publisher:("Karolinska Institute")

Karolinska Institute

1. Kuntze Söderqvist, Åsa. Mechanical thrombectomy for acute ischemic stroke .

Degree: 2016, Karolinska Institute

► The overall aim of this doctoral thesis was to study the outcome and safety of mechanical thrombectomy, which is an endovascular technique for treating moderate… (more)

▼ The overall aim of this doctoral thesis was to study the outcome and safety of mechanical thrombectomy, which is an endovascular technique for treating moderate to severe acute ischemic stroke caused by a large cerebral artery occlusion. The technique has been developed over the last two decades. At the onset of this doctoral project, only a limited numbers of studies on the technique had been published, but the results were very promising. This thesis is based on five peer-reviewed publications. In these studies, it was found that: • patients with basilar artery occlusions who were treated using mechanical thrombectomy (at Karolinska University Hospital between September 2005 – November 2010), had a significantly better functional outcome compared to patients in other studies, where intravenous thrombolysis or no reperfusion therapy was given (Study I). • mechanical thrombectomy was a safe and effective method for restoring blood flow in selected patients suffering from a moderate to severe acute ischemic stroke that was caused by a large artery occlusion (Study II). This was concluded from an examination of patients with anterior and posterior circulation strokes who were treated with mechanical thrombectomy at Karolinska University Hospital between September 2005 – December 2011. • neither prior treatment with intravenous thrombolysis, nor advanced age, was significantly associated with a risk of symptomatic intracranial hemorrhage (Study II). • functional outcome three months after mechanical thrombectomy was equally good for those over 80 years of age as for those between 50-64 and 65-79 years of age (Study III). This was concluded from an examination of the subgroup of patients from study II with anterior circulation stroke, selected according to practice at Karolinska University Hospital. • in patients with wake-up stroke, there was no indication of poorer outcome (Study III). • endovascular treatment combined with intravenous thrombolysis led to a higher ratio of patients with improved functional outcome compared to patients treated with intravenous thrombolysis alone, with an absolute risk reduction of 19% (Study IV). This was concluded from a meta-analysis of six randomized controlled trials. • the estimated rate of thrombectomy in Sweden in 2013 might have been more than five times higher than the actual rate, if patients had been selected according to our practice at the Karolinska University Hospital (a practice similar to the recently published updated treatment recommendations from both European and American organisations) (Study V). This was concluded by comparing treatment proportions at our institution by level of stroke severity with stroke data from the rest of Sweden, provided from Riksstroke (the Swedish national stroke registry). In conclusion, it has been shown that mechanical thrombectomy is a safe treatment, which significantly improves the likelihood of functional outcome for patients with moderate…

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APA (6^th Edition):

Kuntze Söderqvist, �. (2016). Mechanical thrombectomy for acute ischemic stroke . (Thesis). Karolinska Institute. Retrieved from http://hdl.handle.net/10616/45342

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Kuntze Söderqvist, Åsa. “Mechanical thrombectomy for acute ischemic stroke .” 2016. Thesis, Karolinska Institute. Accessed February 27, 2021. http://hdl.handle.net/10616/45342.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Kuntze Söderqvist, Åsa. “Mechanical thrombectomy for acute ischemic stroke .” 2016. Web. 27 Feb 2021.

Vancouver:

Kuntze Söderqvist �. Mechanical thrombectomy for acute ischemic stroke . [Internet] [Thesis]. Karolinska Institute; 2016. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10616/45342.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Kuntze Söderqvist �. Mechanical thrombectomy for acute ischemic stroke . [Thesis]. Karolinska Institute; 2016. Available from: http://hdl.handle.net/10616/45342

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Karolinska Institute

2. Tuiskunen, Anne. Characterization of dengue virus isolates from patients experiencing dengue fever, dengue hemorrhagic fever, and dengue shock syndrome .

Degree: 2011, Karolinska Institute

URL: http://hdl.handle.net/10616/40825

► The four serotypes of dengue virus (DENV) belong to the genus flavivirus, and have a positive sense, single-stranded RNA genome of ~11 kb. The DENVs… (more)

▼ The four serotypes of dengue virus (DENV) belong to the genus flavivirus, and have a positive sense, single-stranded RNA genome of ~11 kb. The DENVs cause the most common arthropod-borne viral disease in man with ~100 million infections per year. The sole measure of control is limiting the mosquito vectors Aedes aegypti and Ae. albopictus, and there is an urgent need for an effective vaccine and potent anti-viral drugs. DENV infection can be asymptomatic or a self-limited, acute febrile disease ranging in severity. The classical form, dengue fever (DF), is characterized by high fever, headache, stomach ache, rash, myalgia and arthralgia. Severe dengue, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) are accompanied by thrombocytopenia, vascular leakage and hypotension. The fatal condition DSS is characterized by systemic shock. Dengue research has been hampered by a lack of appropriate animal models of infection and disease. Furthermore, fundamental knowledge such as host cell tropism and virulence markers are still not established. This thesis focuses on the characterization of clinical DENV isolates from all four serotypes and clinical conditions (DF, DHF, and DSS) aimed at identifying viral features involved in pathogenesis. Attempts to develop a strand-specific qRT-PCR to identify primary target cells for DENV replication, failed due to the self-priming phenomenon of the DENV genome. Selfpriming was not restricted to any particular regions of the viral genome, nor to contaminating cellular nucleic acids, nor the lack of a poly(A)-tail at the 3‟ end. Firststrand synthesis in situ of the DENV genome is believed to arise due to spontaneous loopback structures functioning as transient primers for the reverse transcriptase. In vitro studies in mammalian Vero cells revealed a decreased level of replication for all DENV isolates from DSS patients compared to DENV isolates from DF patients. The replication patterns of the DHF isolates resembled either the DF- or DSS-derived DENV isolates depending on serotype. The DSS isolates were further distinguished from milder case DENV isolates by induction of apoptosis in mosquito C6/36 cells. Three DENV-1 isolates representing a DF, DHF, and a DSS case, were further characterized in vivo in BALB/c mice. Infection with the DF and DHF isolates peaked during the first week with viral RNA found primarily in lungs, liver, and to a certain extent in brain. In contrast, the DSS isolate was primarily neurotropic and persisted longer compared to the DF and DHF isolates. Genomic sequencing revealed a preference for amino acid substitutions in the viral envelope protein and the non-structural (NS) protein NS1 and NS5. Thus, these viral proteins may influence pathogenesis either by immunomodulation, and/or host cells tropism and replication. In conclusion, these results based on clinical DENV isolates indicate that DENVs within the same serotype and genotype may have both different phenotypes and genotypes. These intrinsic viral features…

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Tuiskunen, A. (2011). Characterization of dengue virus isolates from patients experiencing dengue fever, dengue hemorrhagic fever, and dengue shock syndrome . (Thesis). Karolinska Institute. Retrieved from http://hdl.handle.net/10616/40825

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Tuiskunen, Anne. “Characterization of dengue virus isolates from patients experiencing dengue fever, dengue hemorrhagic fever, and dengue shock syndrome .” 2011. Thesis, Karolinska Institute. Accessed February 27, 2021. http://hdl.handle.net/10616/40825.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Tuiskunen, Anne. “Characterization of dengue virus isolates from patients experiencing dengue fever, dengue hemorrhagic fever, and dengue shock syndrome .” 2011. Web. 27 Feb 2021.

Vancouver:

Tuiskunen A. Characterization of dengue virus isolates from patients experiencing dengue fever, dengue hemorrhagic fever, and dengue shock syndrome . [Internet] [Thesis]. Karolinska Institute; 2011. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10616/40825.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Tuiskunen A. Characterization of dengue virus isolates from patients experiencing dengue fever, dengue hemorrhagic fever, and dengue shock syndrome . [Thesis]. Karolinska Institute; 2011. Available from: http://hdl.handle.net/10616/40825

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

3. Reithmeier, Anja. Tartrate-resistant acid phosphatase/ACP5 as a driver of cancer : dissection of its oncogenic mechanisms and identification of small molecule inhibitors .

Degree: 2017, Karolinska Institute

URL: http://hdl.handle.net/10616/46123

► Cancer patients diagnosed with metastasis have an increased risk of dying. To be able to predict and target tumors with an increased risk for spreading,… (more)

▼ Cancer patients diagnosed with metastasis have an increased risk of dying. To be able to predict and target tumors with an increased risk for spreading, underlying molecular events need to be better dissected and understood. TRAP is a metalloenzyme existing in two isoforms - a precursor form (TRAP 5a) and a highly enzymatically active form (TRAP 5b). TRAP expression was detected in cancer cells of several primary and metastatic tumors and expression levels were raised with increasing malignancy. TRAP expression was further correlated to clinical parameters of aggressiveness such as reduced tumor- and metastasis-free survival. Underlying molecular processes remain unclear and only a limited amount of studies is addressing the respective role of the TRAP isoforms in cancer. In this thesis, two major milestones were addressed tackling the role of TRAP (isoforms) in cancer cell metastasis. (I) Identification and characterization of previously reported and novel small molecule inhibitors of TRAP (II) Characterization of functional alterations and cellular mechanisms induced by TRAP perturbation. The TRAP inhibitor 5-phenylnicotinic acid (5-PNA/CD13) was previously identified by fragment-based screening. In Paper I, 5-PNA was further characterized for its ability to inhibit the mammalian TRAP, its selectivity for TRAP and its cytotoxicity in a cellular model. TRAP-dependent migration was inhibited by 5-PNA, shown to be selective for the TRAP 5b isoform. By small molecule screening of a library containing drug-like compounds in Paper II, several inhibitors for TRAP activity were found and selected based on a strict filtration strategy. Orthogonal validation, full-concentration responses and isoform selectivity were assessed for a selection of hit compounds. Six potential lead structures were characterized for molecular docking modes. The compound CBK289001 rendered valid as inhibiting TRAP-dependent migration in a cell system and initial structure-activity relationships were derived. The aggressiveness of cancer cells with perturbations of TRAP expression was assessed by functional studies in Paper III. TRAP had a promotive effect on cancer cell elongation, proliferation, migration and invasion. Proteomics and Phospho-proteomics outlined changes in the cellular network associated with extracellular matrix modulation and cell adhesion, and a regulation of TGFβ and CD44 signaling. A list of potential TRAP substrates was generated. The role of TRAP 5b isoform in cancer cell aggressiveness and Cathepsin K (CtsK) in its generation and processing was investigated in Paper IV. TRAP 5b was significantly increased compared to TRAP 5a in cells overexpressing TRAP. Inhibition of CtsK, an enzyme shown to be able to cleave TRAP, resulted in an intermediate processed TRAP 5b form with similar activity and promotive effect on migration. CtsK colocalized highly with TRAP 5b and cleaving changed the subcellular localization of TRAP 5b. In summary, the work presented in this thesis is…

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Reithmeier, A. (2017). Tartrate-resistant acid phosphatase/ACP5 as a driver of cancer : dissection of its oncogenic mechanisms and identification of small molecule inhibitors . (Thesis). Karolinska Institute. Retrieved from http://hdl.handle.net/10616/46123

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Reithmeier, Anja. “Tartrate-resistant acid phosphatase/ACP5 as a driver of cancer : dissection of its oncogenic mechanisms and identification of small molecule inhibitors .” 2017. Thesis, Karolinska Institute. Accessed February 27, 2021. http://hdl.handle.net/10616/46123.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Reithmeier, Anja. “Tartrate-resistant acid phosphatase/ACP5 as a driver of cancer : dissection of its oncogenic mechanisms and identification of small molecule inhibitors .” 2017. Web. 27 Feb 2021.

Vancouver:

Reithmeier A. Tartrate-resistant acid phosphatase/ACP5 as a driver of cancer : dissection of its oncogenic mechanisms and identification of small molecule inhibitors . [Internet] [Thesis]. Karolinska Institute; 2017. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10616/46123.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Reithmeier A. Tartrate-resistant acid phosphatase/ACP5 as a driver of cancer : dissection of its oncogenic mechanisms and identification of small molecule inhibitors . [Thesis]. Karolinska Institute; 2017. Available from: http://hdl.handle.net/10616/46123

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Karolinska Institute

4. Millischer, Vincent. Translational studies on bipolar disorder and anorexia nervosa .

Degree: 2020, Karolinska Institute

URL: http://hdl.handle.net/10616/47021

► Translational medicine aims at closing the gap between basic and clinical sciences in an integrative way. Psychiatry is one of the few medical specialties in… (more)

▼ Translational medicine aims at closing the gap between basic and clinical sciences in an integrative way. Psychiatry is one of the few medical specialties in which diagnosis is primarily based on clinical observation and all mental disorders are defined by abnormal behaviors and cognitions. The lack of biomarkers supporting diagnostic and therapeutic procedures has been a challenge in psychiatry. A better biological understanding is needed to move the field forward, it will enhance diagnostics and treatment, while reducing the stigma that surrounds mental disorders that are so poorly understood. Over the last years, advances in fundamental sciences like genetics and neuroscience have made it clear that there is shared biology between many psychiatric disorders and that integration of methods might lead to new understandings. The studies presented in this thesis focus on bipolar disorder (BD) and anorexia nervosa (AN), both severe mental disorders with high suicide rates, high heritability, and both lacking in biological understanding. BD, formerly known as manic-depressive disorder, is a mood disorder, characterized by manic or hypomanic episodes, often in combination with depressive episodes. AN is an eating disorder characterized by severe weight loss together with pathological behaviors. This thesis includes five main studies on the biology underlying these disorders, based on large, well characterized cohorts, covering several methods, including genetic, imaging and protein markers, as well as preliminary data on the establishment of in vitro models. Specifically, in study I, we attempted to replicate previously published findings on the association between subphenotypes of bipolar disorder and genetic variations in the AKT1 gene. Using frequentist and Bayesian approaches, as well as publicly available results from genome-wide association studies (GWAS), we were able to reject previously proposed associations. In study II, we explored the effects of genetic variations in genes involved in glutamate regulation on glutamate levels in two brain regions and their associations with other phenotypes. We found that the minor allele of rs3812778/rs3829280 in the 5’-untranslated region of SLC1A2, coding for a glutamate transporter, is associated (1) with increased glutamate levels in the anterior cingulate cortex, (2) with increased expression levels, in several brain regions, of the transmembrane receptor gene CD44, which is implicated in inflammation and brain development, as well as (3) with an increased risk for rapid-cycling in bipolar disorder, potentially linking CD44/SLC1A2 to a more severe phenotype of BD. In study III, we investigated the effects of clinical and genetic parameters on lithium pharmacokinetics in order to better understand lithium biology and improve lithium dose prediction models for bipolar patients, using the ratio between serum lithium and daily lithium intake, as outcome. We were able to confirm the association of several…

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Millischer, V. (2020). Translational studies on bipolar disorder and anorexia nervosa . (Thesis). Karolinska Institute. Retrieved from http://hdl.handle.net/10616/47021

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Millischer, Vincent. “Translational studies on bipolar disorder and anorexia nervosa .” 2020. Thesis, Karolinska Institute. Accessed February 27, 2021. http://hdl.handle.net/10616/47021.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Millischer, Vincent. “Translational studies on bipolar disorder and anorexia nervosa .” 2020. Web. 27 Feb 2021.

Vancouver:

Millischer V. Translational studies on bipolar disorder and anorexia nervosa . [Internet] [Thesis]. Karolinska Institute; 2020. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10616/47021.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Millischer V. Translational studies on bipolar disorder and anorexia nervosa . [Thesis]. Karolinska Institute; 2020. Available from: http://hdl.handle.net/10616/47021

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Karolinska Institute

5. Fernandes, Sunjay Jude. Exploring the genomic and transcriptomic landscape of immune cells in multiple sclerosis : towards better biomarkers, diagnosis and treatment.

Degree: 2020, Karolinska Institute

URL: http://hdl.handle.net/10616/47007

► The overall aim of this thesis was to determine the changes in gene regulation taking place in immune cells during the course of Multiple Sclerosis.… (more)

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Fernandes, S. J. (2020). Exploring the genomic and transcriptomic landscape of immune cells in multiple sclerosis : towards better biomarkers, diagnosis and treatment. (Thesis). Karolinska Institute. Retrieved from http://hdl.handle.net/10616/47007

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Fernandes, Sunjay Jude. “Exploring the genomic and transcriptomic landscape of immune cells in multiple sclerosis : towards better biomarkers, diagnosis and treatment. ” 2020. Thesis, Karolinska Institute. Accessed February 27, 2021. http://hdl.handle.net/10616/47007.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Fernandes, Sunjay Jude. “Exploring the genomic and transcriptomic landscape of immune cells in multiple sclerosis : towards better biomarkers, diagnosis and treatment. ” 2020. Web. 27 Feb 2021.

Vancouver:

Fernandes SJ. Exploring the genomic and transcriptomic landscape of immune cells in multiple sclerosis : towards better biomarkers, diagnosis and treatment. [Internet] [Thesis]. Karolinska Institute; 2020. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10616/47007.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Fernandes SJ. Exploring the genomic and transcriptomic landscape of immune cells in multiple sclerosis : towards better biomarkers, diagnosis and treatment. [Thesis]. Karolinska Institute; 2020. Available from: http://hdl.handle.net/10616/47007

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Karolinska Institute

6. Majumder, Khairul. Radiotherapy in prostate cancer : information, quality of life and prostate volume .

Degree: 2016, Karolinska Institute

URL: http://hdl.handle.net/10616/45149

► Prostate cancer (PC) is the most widespread form of cancer among men in Sweden, with an annual incidence of approximately 10,000 new cases. Treatment of… (more)

▼ Prostate cancer (PC) is the most widespread form of cancer among men in Sweden, with an annual incidence of approximately 10,000 new cases. Treatment of localized prostate cancer is controversial. Curative intended treatments for localized disease include radical prostatectomy (RP) and radiotherapy (RT). These treatments considered to be equally effective, but have different side effects. ADT commonly used as neo-adjuvant therapy in curative intended radiotherapy. The various regimens of ADT have different side effect profiles. Thus, patients need information about how the different side effects might influence their health-related quality of life (HRQoL), both concering primary treatment (RP and RT) and about ADT. Providing adequate information to cancer patients facilitate their adjustment to the cancer experience by increasing perceptions of control, reducing feelings of threat and anxiety, and in improving HRQoL.Thus, it is of importance to investigate satisfaction with information in prostate cancer patients treated with curative intention. The aims of Paper 1, were to compare information perception and satisfaction with that and influence on HRQoL in patients primarily treated with RT alone or with salvage RT after failure of RP. Using the EORTC QLQ C-30 and EORTC INFO 25 questionnaires in 660 patients prospectively. Higher levels of satisfaction with information and more favorable HRQoL were found in patients treated with RT primarily compared to surgery + salvage RT. In Paper 2, the aims were to compare HRQoL of RT and RP in a randomized trial of 89 patients in curative setting. EORTC QLQ C-33 questionnaire and 20 specific questions were asked by mailed questionnaires. No differences between the two treatments were found. It was not possible to draw any conclusion about efficacy of the treatments due to insufficient power of the study. In Paper 3, the aims were to compare differences in HRQoL after randomizing antiandrogen versus total androgen blockade in 110 curative intent RT patients. EORTC QLQ C-30 and EORTC QLQ PR25 were used. Statistically significant differences in sexual interest and function were noted, in favour of anti-androgen treated patients. In addition, higher levels of overall quality of life and sexual interest as well as lower levels of fatigue, and urinary problems were found at the three-months assessment in the antiandrogen group compared to the total androgen blockade group. The difference in sexual interest remained to the 18-months assessment. At that point of time, significant difference favoring the anti-androgen group found in cognitive functioning. In Paper 4, the aims were to compare differences in changes of prostate volume and in target volume in patients included in Paper 3. Ultrasound technique was used to investigate differences in PV after neo-adjuvant hormonal therapy according to randomization arm. Total androgen blockade was more effective in decreasing PV. This effect was translated to target volume. PV increased during treatment in a…

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Majumder, K. (2016). Radiotherapy in prostate cancer : information, quality of life and prostate volume . (Thesis). Karolinska Institute. Retrieved from http://hdl.handle.net/10616/45149

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Majumder, Khairul. “Radiotherapy in prostate cancer : information, quality of life and prostate volume .” 2016. Thesis, Karolinska Institute. Accessed February 27, 2021. http://hdl.handle.net/10616/45149.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Majumder, Khairul. “Radiotherapy in prostate cancer : information, quality of life and prostate volume .” 2016. Web. 27 Feb 2021.

Vancouver:

Majumder K. Radiotherapy in prostate cancer : information, quality of life and prostate volume . [Internet] [Thesis]. Karolinska Institute; 2016. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10616/45149.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Majumder K. Radiotherapy in prostate cancer : information, quality of life and prostate volume . [Thesis]. Karolinska Institute; 2016. Available from: http://hdl.handle.net/10616/45149

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Karolinska Institute

7. Luttropp, Karin. Ageing and inflammation with focus on end-stage renal diseases : genetic and epigenetic factors .

Degree: 2016, Karolinska Institute

URL: http://hdl.handle.net/10616/45143

► The presence of ageing-associated disorders at a relatively young age in patients suffering from chronic kidney disease (CKD) has led to the hypothesis that CKD… (more)

▼ The presence of ageing-associated disorders at a relatively young age in patients suffering from chronic kidney disease (CKD) has led to the hypothesis that CKD is characterized by accelerated ageing, resulting in a marked discrepancy between chronological and biological age. Factors that accelerate biological ageing, such as inflammation, oxidative stress, and toxins, impact the processes of cellular senescence and/or apoptosis, thereby shortening the life span of cells, and consequently, of the organism as a whole. Numerous studies have linked increased cellular senescence and apoptosis to disorders commonly associated with ageing, such as cardiovascular disease (CVD), osteoporosis, and cognitive dysfunction – all of which are common in the uremic phenotype. In Study I, we demonstrate that increased arterial gene expression of cyclin-dependent kinase inhibitor 2A (CDKN2A), a known inducer of cellular senescence, is associated with the presence of CVD and vascular calcification (VC) in CKD patients. Furthermore, there is a positive correlation between CDKN2A expression and the expression of matrix Gla protein (MGP) and runt-related transcription factor 2 (RUNX2), both of which are involved in osteogenesis. We also show a tentative relationship between a higher degree of VC and increasing p16INK4a expression, a cognate protein of CDKN2A. In Study II, we use telomere length as a biomarker of biological age, showing that CKD patients have shorter telomeres than non-CKD controls. In addition, our results indicate a possible association between longitudinal telomere length, folate, and immunosuppressive treatment in patients undergoing renal transplantation (RTx). This suggests that anti- metabolite therapy may have an impact on biological ageing in RTx patients. In Study III, we show that the global methylation status in dialysis and RTx patients at baseline and after 12 months of renal replacement therapy (RRT) differs at several sites in the genome from that of age- and gender-matched healthy controls. Furthermore, differences in methylation between patients and controls can be found at CpG sites located in genes with known functional relevance to CKD, cellular ageing, CVD and/or metabolic disease. Continuing our investigations of factors affecting epigenetic status, Study IV investigates the association between the degree of self-reported physical activity and global DNA methylation in Swedish seniors. In this study, we demonstrate that individuals who reported higher physical activity had less global DNA methylation than those who were less physically active. Study V describes the application of a multifactorial mathematical model for predicting the presence of inflammation in a dataset generated from 225 incident dialysis patients. Eight of the ten features with the highest predictive factor were single nucleotide polymorphisms (SNPs), suggesting a large genetic influence on inflammation in CKD patients. In Study VI, the interplay between inflammatory status,…

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Luttropp, K. (2016). Ageing and inflammation with focus on end-stage renal diseases : genetic and epigenetic factors . (Thesis). Karolinska Institute. Retrieved from http://hdl.handle.net/10616/45143

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Luttropp, Karin. “Ageing and inflammation with focus on end-stage renal diseases : genetic and epigenetic factors .” 2016. Thesis, Karolinska Institute. Accessed February 27, 2021. http://hdl.handle.net/10616/45143.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Luttropp, Karin. “Ageing and inflammation with focus on end-stage renal diseases : genetic and epigenetic factors .” 2016. Web. 27 Feb 2021.

Vancouver:

Luttropp K. Ageing and inflammation with focus on end-stage renal diseases : genetic and epigenetic factors . [Internet] [Thesis]. Karolinska Institute; 2016. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10616/45143.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Luttropp K. Ageing and inflammation with focus on end-stage renal diseases : genetic and epigenetic factors . [Thesis]. Karolinska Institute; 2016. Available from: http://hdl.handle.net/10616/45143

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Karolinska Institute

8. Skröder Löveborn, Helena. Early-life selenium status and cognitive development .

Degree: 2018, Karolinska Institute

URL: http://hdl.handle.net/10616/46487

► Selenium is an essential element that is found in food sources such as meat, fish, and cereals. The essentiality of selenium was demonstrated in the… (more)

▼ Selenium is an essential element that is found in food sources such as meat, fish, and cereals. The essentiality of selenium was demonstrated in the 1950s, and the interest in its health effects has been growing ever since. Deficiency is common world-wide, particularly in Europe and south-eastern Asia. It has been estimated that 0.5-1 billion people could be selenium deficient. Previous studies regarding health effects of selenium have focused on the impact of deficiency for the risk of cancer, cardiovascular disease, and decreased fertility and immune function. Lately, the importance for brain function has also become the focus of many studies assessing potential protection against cognitive decline and certain neurodegenerative diseases, such as Alzheimer’s and Parkinson’s disease. However, little is known about the importance for early-life development. In particular, the role of selenium in cognitive development has not been studied, even though the brain is one of the organs with highest selenium priority at deficient intake levels. Therefore, the overall aim of this thesis was to assess whether selenium status in early life is important for cognitive development. The studies included in this thesis were based on data from a large mother-child cohort in rural Bangladesh. The cohort was nested in a randomized food and micronutrient supplementation trial that was established in 2001-2003, called the Maternal and Infant Nutrition Intervention, Matlab (MINIMat). Women were recruited to this nested cohort early in pregnancy (at pregnancy testing), and donated urine and blood samples continuously throughout pregnancy. The subsequently born children were divided into two groups for different outcome assessments. For cognitive assessment, children were followed-up at 1.5, 5, and 10 years, while assessment of immune function and various effect biomarkers was performed in the other group of children at 4.5 and 9 years of age. To evaluate the role of selenium in cognitive development, concentrations of the element were measured in urine and blood from the pregnant women, and also in blood, urine, and hair from the Bangladeshi children at different ages (n=223-1408). Results from the group of children who donated blood, urine, and hair, demonstrated that also hair selenium could be used for assessment of selenium status in the present population. Using multivariable-adjusted regression analyses, we found that adequate selenium status during pregnancy seemed important for the children’s cognitive development. Children born to mothers with higher selenium status performed better on the cognitive tests at 1.5, 5 and 10 years of age. Also the selenium status during early childhood seemed to be important for the cognitive abilities at the 5- and 10-year follow-ups. There was an indication of an upper limit for the positive association, in line with the narrow therapeutic interval for selenium. Assessment of influential factors for the selenium biomarkers indicated that exposure to arsenic and cadmium…

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APA (6^th Edition):

Skröder Löveborn, H. (2018). Early-life selenium status and cognitive development . (Thesis). Karolinska Institute. Retrieved from http://hdl.handle.net/10616/46487

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Skröder Löveborn, Helena. “Early-life selenium status and cognitive development .” 2018. Thesis, Karolinska Institute. Accessed February 27, 2021. http://hdl.handle.net/10616/46487.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Skröder Löveborn, Helena. “Early-life selenium status and cognitive development .” 2018. Web. 27 Feb 2021.

Vancouver:

Skröder Löveborn H. Early-life selenium status and cognitive development . [Internet] [Thesis]. Karolinska Institute; 2018. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10616/46487.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Skröder Löveborn H. Early-life selenium status and cognitive development . [Thesis]. Karolinska Institute; 2018. Available from: http://hdl.handle.net/10616/46487

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Karolinska Institute

9. Hagey, Daniel W. Transcriptional regulation of development in time and space .

Degree: 2017, Karolinska Institute

URL: http://hdl.handle.net/10616/46078

► Human development requires the generation of trillions of cells with myriad functions from a single cell. This requires that restriction of stem cell fate competence… (more)

▼ Human development requires the generation of trillions of cells with myriad functions from a single cell. This requires that restriction of stem cell fate competence and proliferation are precisely temporally and spatially patterned as the embryo grows. To accomplish this, the chromatin landscape of individual stem cells progressively constrains gene expression in a context specific manner in order to guide cell behavior. In turn, this context is provided by the cellular environment and intrinsic determinants via the activity of transcription factors. In paper I, we utilize ChIP-sequencing to study the overlapping and specific activities of the transcription factor sex determining region Y-box 2 (SOX2) in the developing cortex, spinal cord, stomach and lungs. We show that cell type specific binding is associated with tissue specific gene expression, while commonly bound cis-regulatory modules neighbor genes involved in the core processes of stem cell maintenance and proliferation. In paper II, we use DNase- and ChIP-sequencing to demonstrate that, though the accessible chromatin landscape in the spinal cord and cortex are highly overlapping, SOX2 binding is primarily specific to one region. We find that this is due to an association with the specifically expressed partner transcription factors HOXA9 in spinal cord and LHX2 in cortex, which are capable of respecifying gene expression when misexpressed. In paper III, we exploit single cell RNA-sequencing to establish that the stem cell population of the early cortex expresses high levels of S o x2, exhibits features of multipotency, and is enriched for genes involved in mitosis, such as Ccnb1/2. In contrast, the committed progenitor pool expresses high levels of the G1/S-phase genes, including Ccnd1, which is capable of inducing differentiation when overexpressed. In paper IV, we find that Sox2 acts in a dose-dependent fashion to control proliferation in the developing cortex by directly repressing Ccnd1. We show that this is accomplished via the binding of off-consensus sites in the Ccnd1 promoter, and an association with Wnt signal transducing, TCF/LEF, transcription factors and their established co-repressor, TLE1.

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Hagey, D. W. (2017). Transcriptional regulation of development in time and space . (Thesis). Karolinska Institute. Retrieved from http://hdl.handle.net/10616/46078

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Hagey, Daniel W. “Transcriptional regulation of development in time and space .” 2017. Thesis, Karolinska Institute. Accessed February 27, 2021. http://hdl.handle.net/10616/46078.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Hagey, Daniel W. “Transcriptional regulation of development in time and space .” 2017. Web. 27 Feb 2021.

Vancouver:

Hagey DW. Transcriptional regulation of development in time and space . [Internet] [Thesis]. Karolinska Institute; 2017. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10616/46078.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Hagey DW. Transcriptional regulation of development in time and space . [Thesis]. Karolinska Institute; 2017. Available from: http://hdl.handle.net/10616/46078

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Karolinska Institute

10. Dahlström, Jenny. Telomeres and telomerase and their functional applications in myeloproliferative neoplasms and acute myeloid leukemia .

Degree: 2016, Karolinska Institute

URL: http://hdl.handle.net/10616/45328

► Myeloproliferative neoplasms (MPNs) are a group of diseases characterized by hyperproliferation in the myeloid lineages of the bone marrow, leading to increased levels of circulating… (more)

▼ Myeloproliferative neoplasms (MPNs) are a group of diseases characterized by hyperproliferation in the myeloid lineages of the bone marrow, leading to increased levels of circulating mature blood cells from one or more lineages. MPNs consist of polycythemia vera, essential thrombocythemia and primary myelofibrosis. Several recurrent mutations are seen in MPNs, most of them resulting in an activation of the JAK/STAT signaling pathway. Telomeres are non-coding repetitive sequences of DNA located at the end of chromosomes. The telomeres are shortened with every cell division and when they become critically short, the cells enter a permanent growth arrest state called replicative senescence. When the telomeres are very short, the cells become genetically unstable and are more susceptible to genetic aberrations. There is accumulating evidence for a role for telomere dysregulation in the pathogenesis of MPNs and AML, and the overall aim of the studies included in this thesis was to better define this role. To clarify a potential dysregulation of telomeres and telomere associated proteins in MPNs, we studied the telomere length (TL), TERT expression and expression of telomere associated proteins in 81 patients with MPNs and 43 healthy controls. We found that patients with MPNs have shorter telomeres in their granulocytes compared to that of healthy controls, but also compared to the patients’ own lymphoid cells. There was no difference in TERT expression between patients and controls. The expression of two positive regulators of TL was lower, and the expression of two negative regulators of TL was higher in patients with MPNs. The dysregulation of telomere binding proteins may contribute to the telomere shortening seen in MPNs. Genetic variants in the TERT locus are implicated in susceptibility to cancer and other diseases. Recent reports also revealed an association between the SNP TERT rs2736100_CC genotype and the risk of developing MPNs in Caucasian populations. We genotyped patients and healthy controls from Sweden and China and found that the TERT rs2736100_C allele is associated with an increased risk of MPN development in both populations. The association of the C-allele with an increased risk of MPNs was only seen in male MPN patients, who generally have a worse outcome than female MPN patients. Moreover, the Chinese healthy population had significantly lower frequency of the TERT rs2736100_C allele compared to their Swedish counterpart, which may contribute to the lower MPN incidence seen in China compared to that in Europe. Patients with the TERT rs2736100_CC had the highest TERT expression, which may make them more susceptible to develop MPNs. The evolution of an acute promyelocytic leukemia (APL)-clone in a patient with a very late relapse was studied to distinguish between a relapse of the first APL, a secondary APL or a second de novo APL, and thereby guide future treatment decisions. Based on identical breakpoints of the PML-RARα gene, but differences in genetic aberrations and mutations…

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Dahlström, J. (2016). Telomeres and telomerase and their functional applications in myeloproliferative neoplasms and acute myeloid leukemia . (Thesis). Karolinska Institute. Retrieved from http://hdl.handle.net/10616/45328

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Dahlström, Jenny. “Telomeres and telomerase and their functional applications in myeloproliferative neoplasms and acute myeloid leukemia .” 2016. Thesis, Karolinska Institute. Accessed February 27, 2021. http://hdl.handle.net/10616/45328.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Dahlström, Jenny. “Telomeres and telomerase and their functional applications in myeloproliferative neoplasms and acute myeloid leukemia .” 2016. Web. 27 Feb 2021.

Vancouver:

Dahlström J. Telomeres and telomerase and their functional applications in myeloproliferative neoplasms and acute myeloid leukemia . [Internet] [Thesis]. Karolinska Institute; 2016. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10616/45328.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Dahlström J. Telomeres and telomerase and their functional applications in myeloproliferative neoplasms and acute myeloid leukemia . [Thesis]. Karolinska Institute; 2016. Available from: http://hdl.handle.net/10616/45328

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Karolinska Institute

11. Ahnquist, Johanna. Socioeconomic determinants of health : a matter of economic or social capital? .

Degree: 2011, Karolinska Institute

URL: http://hdl.handle.net/10616/40783

► Background: There is currently a growing interest in the role of social structures, social conditions and social relationships in explaining patterns of population health, as… (more)

▼ Background: There is currently a growing interest in the role of social structures, social conditions and social relationships in explaining patterns of population health, as well as the need to connect individual health outcomes to their socio-economic context. This thesis contributes to this young, but fast growing field by analyzing the role of social and economic conditions in determining health. Aim: To study the socioeconomic determinants of health by focusing on the relevance of economic and social capital. Methods: The thesis comprises four studies, three of which are based on cross-sectional data from the National Public Health Survey 2006 (N= 56,889) and 2009 (N= 51,414) (Study II, III and IV) and one based on longitudinal data from the Swedish Survey of Living Conditions (ULF) panel study from the years 1981–1997 (N= 3,780) (Study I). While Study I and II analyzed associations between measures of economic capital and health outcomes, Study III focused on associations between measures of social capital and health outcomes. Finally, in Study IV independent associations, and interactions, of a lack of economic capital and social capital on health outcomes were analyzed. Low economic capital (i.e. economic hardships) was measured by low household income and self-reported financial stress (inability to meet expenses and a lack of cash reserves). Social capital was measured on the individual level by social participation, interpersonal (horizontal) and institutional (vertical) trust. Health outcomes included self-rated health, psychological health (severe anxiety, GHQ-12, anti-depressant medication), physical health (musculoskeletal disorders) and health behaviors (harmful alcohol consumption). Results: In Study I, based on longitudinal data, a dose-response effect on women‟s health was observed with an increasing score of cumulative exposure to financial stress, but not for low income. The results for men were more inconclusive. Cumulative exposure to financial stress seemed to affect men‟s self-rated health, while exposure to low income seemed to affect men‟s psychological distress, and neither exposure to low income nor financial stress seemed to affect men‟s musculoskeletal disorders. In Study II, financial stress (but not low income) was significantly associated with both women‟s and men‟s mental health problems (all indicators). Additionally, a graded association was found between mental health problems and levels of economic hardships (as measured by a combined economic hardships measure capturing both self-reported financial stress and low income). In Study III, low social capital (as measured by institutional trust in ten main welfare institutions in Sweden) was associated with increased likelihood of harmful alcohol consumption. Furthermore, a graded association was found between harmful alcohol consumption and levels of institutional trust. In Study IV, a measure of economic hardships (including both self-reported financial stress and low income) and low social capital (i.e., low interpersonal and…

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Ahnquist, J. (2011). Socioeconomic determinants of health : a matter of economic or social capital? . (Thesis). Karolinska Institute. Retrieved from http://hdl.handle.net/10616/40783

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Ahnquist, Johanna. “Socioeconomic determinants of health : a matter of economic or social capital? .” 2011. Thesis, Karolinska Institute. Accessed February 27, 2021. http://hdl.handle.net/10616/40783.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Ahnquist, Johanna. “Socioeconomic determinants of health : a matter of economic or social capital? .” 2011. Web. 27 Feb 2021.

Vancouver:

Ahnquist J. Socioeconomic determinants of health : a matter of economic or social capital? . [Internet] [Thesis]. Karolinska Institute; 2011. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10616/40783.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Ahnquist J. Socioeconomic determinants of health : a matter of economic or social capital? . [Thesis]. Karolinska Institute; 2011. Available from: http://hdl.handle.net/10616/40783

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Karolinska Institute

12. Tadesse, Birkneh Tilahun. Optimization of pediatrics antiretroviral treatment outcomes among HIV infected children in Ethiopia .

Degree: 2019, Karolinska Institute

URL: http://hdl.handle.net/10616/46970

► Ending the HIV/AIDS epidemic by 2030 is a global agenda. To meet this global goal, having safe and effective antiretroviral therapy is a key requirement.… (more)

▼ Ending the HIV/AIDS epidemic by 2030 is a global agenda. To meet this global goal, having safe and effective antiretroviral therapy is a key requirement. In Ethiopia, the safety and efficacy of combination antiretroviral therapy in HIV infected pediatric population is poorly studied. In this thesis, I aimed at understanding the short- and long-term safety and efficacy of antiretroviral therapy among HIV infected children in Ethiopia. Clinical and laboratory data were recorded for a total of 870 HIV infected children in two parallel cohorts – EPDOS and EPHIC projects. We first investigated the burden and correlates of pretreatment drug resistance (PDR) in Paper I. We observed that the overall rate of PDR was 14%. All cases with PDR had resistance to NNRTIs while ~9% harbored resistance solely to NNRTIs and ~5% harbored resistance to both NNRTIs and NRTIs. No resistance was observed to protease inhibitors. In Paper II, among children who were followed for 48 weeks following initiation of treatment, we assessed virologic outcome of children at one year of cART initiation using Cox Proportional Hazards Model. In total, 94/110 (85.5%) achieved virological suppression to undetectable levels during the first year of treatment. Thirty-six (31.9%) experienced virologic rebound. Tenofovir-containing cART regimen and absence of PDR were associated with higher virologic suppression. In Paper III, we explored burden and correlates of HIV drug resistance among children who failed treatment. Overall, 81% (73/90) of successfully genotyped participants had resistant mutations. From these, 69% (62/90) harbored dual drug class resistance. Strikingly, 42% of the participants harbored resistance to all four NRTIs recommended for second line use in the setting. Longer duration of cART and any regimen changes were associated with occurrence of drug resistance mutations. In Paper IV, we investigated the long term renal and hepatic toxicities associated with antiretroviral therapy among cART experienced children. At study enrolment, 177(25.1%) and 83(11.8%) had high aspartate aminotransferase and alanine aminotransferase (ALT), respectively. Zidovudine or nevirapine containing regimens and viral load >1000 copies/mL were associated with elevated ALT. Twenty-four (3.4%) and 84(12.1%) of the children had elevated creatinine and blood urea nitrogen (BUN), respectively. A progressive increment in BUN and decrement in GFR were observed during the follow up period. Both AST and ALT exhibited a decreasing trend. In Paper V, we compared the prevalence and correlates of dyslipidemia between cART naïve and experienced HIV infected children. Dyslipidemia was more common among cART experienced (70.2%) than naïve (58.1%) HIV infected children (p=0.03). Higher proportion of low HDLc (40.2% versus 23.4%, p=0.006) and hypertriglyceridemia (47.2% versus 35.8%, p= 0.02) was observed among cART experienced HIV infected children as compared to naïve. No difference was observed in the…

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Tadesse, B. T. (2019). Optimization of pediatrics antiretroviral treatment outcomes among HIV infected children in Ethiopia . (Thesis). Karolinska Institute. Retrieved from http://hdl.handle.net/10616/46970

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Tadesse, Birkneh Tilahun. “Optimization of pediatrics antiretroviral treatment outcomes among HIV infected children in Ethiopia .” 2019. Thesis, Karolinska Institute. Accessed February 27, 2021. http://hdl.handle.net/10616/46970.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Tadesse, Birkneh Tilahun. “Optimization of pediatrics antiretroviral treatment outcomes among HIV infected children in Ethiopia .” 2019. Web. 27 Feb 2021.

Vancouver:

Tadesse BT. Optimization of pediatrics antiretroviral treatment outcomes among HIV infected children in Ethiopia . [Internet] [Thesis]. Karolinska Institute; 2019. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10616/46970.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Tadesse BT. Optimization of pediatrics antiretroviral treatment outcomes among HIV infected children in Ethiopia . [Thesis]. Karolinska Institute; 2019. Available from: http://hdl.handle.net/10616/46970

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Karolinska Institute

13. Panezai, Jeneen. Periodontal medicine : oral inflammatory conditions with special emphasis on immunological aspects .

Degree: 2018, Karolinska Institute

URL: http://hdl.handle.net/10616/46518

► Systemic effects of periodontal disease have been a subject of interest for the past century, with intense focus converging since the past decade. Both rheumatoid… (more)

▼ Systemic effects of periodontal disease have been a subject of interest for the past century, with intense focus converging since the past decade. Both rheumatoid arthritis (RA) and periodontal disease (PD) are immuno-inflammatory diseases with osteolysis as its hallmark feature. Activated T cells are known to modulate osteoclastogenesis. This thesis aimed to analyze the influence of PD on systemic inflammatory and immunological markers in both PD and RA subjects. Periodontal parameters, clinical (PI, BOP, PPD 3-<5mm and PPD ≥5mm) and radiographic (marginal bone loss or MBL) were investigated in four groups: RA with PD, RA without PD, PD and healthy groups. Immunosuppression of T cell activation via targeted surface protein was also studied. AIMS Study I aimed to investigate the expression and functional importance of low-density lipoprotein receptor-related protein1 (LRP1) in T cells. Study II aimed to investigate serum cytokines, chemokines, growth factors, enzymes and costimulatory proteins in association with periodontal conditions in PD and RA subjects. Study III aimed to investigate the serum markers osteopontin (OPN), tumor necrosis factor receptors 1 (TNFR1) and 2 (TNFR2) receptor activator of nuclear factor‐kappa B ligand (RANKL) and RANKL/ osteoprotegerin (OPG) ratio and compare them in PD and RA groups. Study IV aimed to investigate the severity of both PD and RA and investigate a correlation between glycemia and periodontal disease parameters using ΣPPD Total and ΣPPD Disease index. RESULTS Study I showed that T cells shed LRP1, which probably explains the low LRP1 expression in T cells. Shedding of LRP1 antagonizes T cell adhesion to integrin ligands and TCR-induced activation. Integrin ligands and CXCL12 antagonize shedding through a TSP-1-dependent pathway, whereas ligation of CD28 antagonizes shedding independent of TSP-1. The disappearance of LRP1 from the cell surface may provide basic immunosuppression at the T-cell level. Study II showed significant positive correlations for ST1A1, FGF-19 and NT-3 whereas EN-RAGE, DNER, CX3CL1 and TWEAK associated inversely with BOP, PPD≥ 5mm and MBL but positively with number of teeth. CD markers (CD244, CD40, CDCP1, LIF-R, IL-10RA, CD5 and CD6) were found to be associated with BOP, shallow and deep pockets, MBL and number of teeth, either directly or inversely. CCL8, CX3CL1, CXCL10, CXCL11, CCL11, CCL4, CCL20, CXCL5, CXCL6, and CCL23 were positively associated with number of teeth. Other growth factors were directly associated with MBL (HGF) and number of teeth (VEGF-A, LAP TGFbeta-1). Study III showed OPN, TNFR1, TNFR2 and RANKL serum levels were the highest in the RA group with PD, while the RA group without PD were comparable to PD subjects only. The RANKL/OPG ratios were comparable between PD group and both RA groups with and without PD. Serum RANKL levels were associated with and PPD ≥ 5mm. Study IV showed that the indices correlated strongly with number of deep pockets. DAS28 score correlated…

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Panezai, J. (2018). Periodontal medicine : oral inflammatory conditions with special emphasis on immunological aspects . (Thesis). Karolinska Institute. Retrieved from http://hdl.handle.net/10616/46518

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Panezai, Jeneen. “Periodontal medicine : oral inflammatory conditions with special emphasis on immunological aspects .” 2018. Thesis, Karolinska Institute. Accessed February 27, 2021. http://hdl.handle.net/10616/46518.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Panezai, Jeneen. “Periodontal medicine : oral inflammatory conditions with special emphasis on immunological aspects .” 2018. Web. 27 Feb 2021.

Vancouver:

Panezai J. Periodontal medicine : oral inflammatory conditions with special emphasis on immunological aspects . [Internet] [Thesis]. Karolinska Institute; 2018. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10616/46518.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Panezai J. Periodontal medicine : oral inflammatory conditions with special emphasis on immunological aspects . [Thesis]. Karolinska Institute; 2018. Available from: http://hdl.handle.net/10616/46518

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Karolinska Institute

14. Vroland Nordstrand, Kristina. Goal setting and skills achievements in children with disabilities .

Degree: 2015, Karolinska Institute

URL: http://hdl.handle.net/10616/44740

► The overall aim of this thesis was to increase knowledge about how children with different types of disabilities can identify performance issues and select goals… (more)

▼ The overall aim of this thesis was to increase knowledge about how children with different types of disabilities can identify performance issues and select goals for intervention. Furthermore, the objective was to study the effects of a goal-directed, task-oriented intervention based on children’s self-identified goals from both quantitative and qualitative perspectives. Establishing intervention goals with families, to improve the ability of children with disabilities to perform tasks that they need, want, or are expected to do, to participate in their everyday lives is a central part of paediatric occupational therapy. Within this process children’s perspectives are of importance; to give greater consideration to children’s needs, the children need to be involved in the goal-setting process. As goal setting is an abstract process, it can be questioned whether children with disabilities can identify goals and whether their goals are functional and achievable. Further knowledge about how the child’s self-identified goals influence goal-directed intervention is sparse or even lacking. A specific interest was directed towards including the children in the goal setting, using the Perceived Efficacy and Goal Setting System (PEGS). The PEGS is a picture-based self-report for children, developed in Canada. It uses children’s self-reported performance on everyday tasks to allow them to choose and prioritize goals for intervention. To be useful in a Swedish context, the PEGS needed to be translated and adapted. In study I, five items in the PEGS required adaptation, and one new item was added. Using the Swedish version of the PEGS, 44 child–parent dyads were able to identify individual strengths and weaknesses in the child’s performance of everyday tasks as well as to select goals for intervention. Children’s self-identified goals in studies I–III included improvements in self-care, and leisure and school tasks. In study II, results from 18 children showed that their goals were relatively stable over time: 78% had an absolute agreement ranging from 50% to 100%. Moreover, in studies II and III goals identified by the children differed from those identified by their parents, and results from 31 child–parent dyads in study II, showed that 48% of the children had no goals identical to those chosen by their parents. In studies III and IV, when goal-directed, task-oriented intervention was provided, children’s self-identified goals were achievable. There was evidence of an increase in mean goal attainment (mean T-scores) in both groups (child-goal (n=17): estimated mean difference [EMD] 27.84, 95% confidence interval [CI] 22.93 to 32.76; parent-goal (n=16): EMD 21.42, 95% CI 16.16 to 26.67). There was no evidence of a differences in mean T-scores post-intervention between the two groups (EMD 6.42, 95% CI -0.80 to 13.65), which indicates that children’s self-identified goals are achievable to the same extent as goals identified by parents. These results were sustained at the 5-month follow-up. …

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Vroland Nordstrand, K. (2015). Goal setting and skills achievements in children with disabilities . (Thesis). Karolinska Institute. Retrieved from http://hdl.handle.net/10616/44740

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Vroland Nordstrand, Kristina. “Goal setting and skills achievements in children with disabilities .” 2015. Thesis, Karolinska Institute. Accessed February 27, 2021. http://hdl.handle.net/10616/44740.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Vroland Nordstrand, Kristina. “Goal setting and skills achievements in children with disabilities .” 2015. Web. 27 Feb 2021.

Vancouver:

Vroland Nordstrand K. Goal setting and skills achievements in children with disabilities . [Internet] [Thesis]. Karolinska Institute; 2015. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10616/44740.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Vroland Nordstrand K. Goal setting and skills achievements in children with disabilities . [Thesis]. Karolinska Institute; 2015. Available from: http://hdl.handle.net/10616/44740

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Karolinska Institute

15. Mujahed, Huthayfa. Genetic and epigenetic studies of acute myeloid leukemia and therapeutic possibilities .

Degree: 2020, Karolinska Institute

URL: http://hdl.handle.net/10616/47062

► Acute myeloid leukaemia (AML) is malignant tumour that forms in the bone marrow and arises from immature myeloid progenitors. Consequently, this leads to excessive accumulation… (more)

▼ Acute myeloid leukaemia (AML) is malignant tumour that forms in the bone marrow and arises from immature myeloid progenitors. Consequently, this leads to excessive accumulation of dysfunctional blast cells and lack of normal blood cells. The molecular and genetic heterogeneity of the disease is substantial which makes the disease challenging to classify and treat. Although the AML classification is updated continuously and more data and research on AML pathophysiology emerges, first line treatment for the vast majority of AML patients remains a combination of cytarabine and an anthracycline. While most patients attain a complete remission, the majority of AML patients relapse and develop drug resistance. Recently, new drugs have been approved for the treatment of specific AML subtypes. However, there is need for better understanding of disease pathogenesis including better genetic and epigenetic risk factors in order to develop more effective treatment regimens to improve the outcome of the disease. In Study I, we studied off-target effects of APR-246, a drug that originally was developed to restore the activity of mutated TP53 protein. Oxidative stress related genes heme oxygenase-1 (HMOX1, also termed HO-1), SLC7A11 and RIT1 were significantly upregulated. Also, Nrf2 that induces the expression of HO-1 was upregulated and depletion of Nrf2 mRNA resulted in increased cytotoxicity of APR-246. Moreover, blocking Nrf2 from translocating into the nucleus by using PI3K and mTOR inhibitors led to enhanced cell killing. This suggests that a combination of APR-246 with PI3K and mTOR inhibitors improves sensitivity to APR-246 by interfering with the cellular response to ROS activation to achieve better anti-leukemic effects of APR-246. In Study II, we aimed to define the potential of using stroma cells in diagnostic AML samples as a source of germline DNA. To obtain germline DNA, together with DNA from leukemic cells, it is essential to reliably define somatic mutations in AML cells. Consequently, we cultivated and expanded bone marrow stroma cells from vitally frozen mononuclear cells from AML patients with monosomy 7 as well as defined somatic mutations. In vitro expanded bone marrow stroma cells were stable after 6 weeks of culture and were able to differentiate into adipocytes or osteocytes. We could also show that cultivated stroma cells do not harbour the somatic mutations found in the malignant cells. Thus, we could conclude that bone marrow stroma cells from diagnostic bone marrow samples could be used as a source of germline DNA in AML patients. In Study III, we studied the binding occupancy of the chromatin organizer CTCF in AML patient cells and compared it to binding in normal CD34+ cells. We found that AML cells display an aberrant increase of CTCF binding. Motif analysis revealed that gained CTCF sites are enriched for transcription factors such as PU.1, RUNX1 and CEBPA, which is found to be important for normal myeloid development. TET2 mutated AML…

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Mujahed, H. (2020). Genetic and epigenetic studies of acute myeloid leukemia and therapeutic possibilities . (Thesis). Karolinska Institute. Retrieved from http://hdl.handle.net/10616/47062

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Mujahed, Huthayfa. “Genetic and epigenetic studies of acute myeloid leukemia and therapeutic possibilities .” 2020. Thesis, Karolinska Institute. Accessed February 27, 2021. http://hdl.handle.net/10616/47062.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Mujahed, Huthayfa. “Genetic and epigenetic studies of acute myeloid leukemia and therapeutic possibilities .” 2020. Web. 27 Feb 2021.

Vancouver:

Mujahed H. Genetic and epigenetic studies of acute myeloid leukemia and therapeutic possibilities . [Internet] [Thesis]. Karolinska Institute; 2020. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10616/47062.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Mujahed H. Genetic and epigenetic studies of acute myeloid leukemia and therapeutic possibilities . [Thesis]. Karolinska Institute; 2020. Available from: http://hdl.handle.net/10616/47062

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Karolinska Institute

16. Iravani, Maryam. Estrogen actions in the growth plate cartilage .

Degree: 2020, Karolinska Institute

URL: http://hdl.handle.net/10616/47035

► Estrogens may influence bone growth locally or systemically via the estrogen receptors alpha (ERα), beta (ERβ) and G protein-coupled estrogen receptor 1 (GPER-1). In Paper… (more)

▼ Estrogens may influence bone growth locally or systemically via the estrogen receptors alpha (ERα), beta (ERβ) and G protein-coupled estrogen receptor 1 (GPER-1). In Paper I, our study showed that the treatment of ovariectomized C57BL/6 mice with a selective ERα agonist 1,3,5-tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole (PPT) reduced growth plate height and hypertrophic zone height suggesting that the effect was induced via ERα. Furthermore, chondrocyte proliferation in the growth plate was also inhibited by 17β-estradiol (E2) or PPT as evaluated by proliferating cell nuclear antigen (PCNA) staining. Furthermore, tibiae and femur bones were shorter in E2- or PPT-treated mice when compared to vehicle-treated controls. In contrast, bone lengths in mice treated with a selective ERβ agonist 2,3-bis(4- hydroxyphenyl)-propionitrile (DPN) were similar to bone lengths in controls. These results showed that estrogenic effects on bone growth and growth plate maturation are mainly mediated via ERα. In contrast, the selective GPER-1 agonist G1 had no effects on either metatarsal bone growth ex vivo or tibia and femur growth in treated metatarsals or mice when compared to control groups. Thus, the results from Paper I and II demonstrated that, ligand stimulation of GPER-1 and ERβ does not influence bone growth in mice. In Paper III, target genes and signaling pathways affected by E2 were identified. The enriched pathways inhibited by E2 included estrogen response early and late, apoptosis, epithelial mesenchymal transition and angiogenesis. Also, the mammalian target of rapamycin (mTOR) signaling pathway, which regulates chondrocyte proliferation and differentiation, was significantly inhibited by E2. Among the most strongly affected genes, the expression of peptide YY, a negative regulator of bone formation and mineral density, was inhibited by E2 treatment. Furthermore, epidermal growth factor and oxidative phosphorylation signalling pathways and subgroups of genes regulated by Myc and genes important for mitotic spindle assembly were among the enriched pathways upregulated by E2. Our data showed that E2 actions on bone growth and growth plate maturation are mainly mediated via ERα. In contrast, ligand stimulation of either ERβ or GPER-1 did not influence bone growth in mice. Also, our study has identified target genes and pathways influenced by E2 in the growth plate. Further studies are required to determine the specific mechanisms involving E2-regulated genes. Our findings may have direct implications for the development of new and more selective treatment modalities of extreme tall stature using selective ER modulators that may have fewer side effects than high-dose E2 treatment.

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Iravani, M. (2020). Estrogen actions in the growth plate cartilage . (Thesis). Karolinska Institute. Retrieved from http://hdl.handle.net/10616/47035

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Iravani, Maryam. “Estrogen actions in the growth plate cartilage .” 2020. Thesis, Karolinska Institute. Accessed February 27, 2021. http://hdl.handle.net/10616/47035.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Iravani, Maryam. “Estrogen actions in the growth plate cartilage .” 2020. Web. 27 Feb 2021.

Vancouver:

Iravani M. Estrogen actions in the growth plate cartilage . [Internet] [Thesis]. Karolinska Institute; 2020. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10616/47035.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Iravani M. Estrogen actions in the growth plate cartilage . [Thesis]. Karolinska Institute; 2020. Available from: http://hdl.handle.net/10616/47035

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Karolinska Institute

17. Celvin, Bettina. Prevention of growth failure caused by glucocorticoids and inflammation .

Degree: 2019, Karolinska Institute

URL: http://hdl.handle.net/10616/46885

► Longitudinal bone growth is a complex process that takes place in the growth plate, and normal growth is dependent on a precise balance of several… (more)

▼ Longitudinal bone growth is a complex process that takes place in the growth plate, and normal growth is dependent on a precise balance of several endocrine and paracrine factors. Growth impairment is common in children with inflammatory diseases and is associated with elevated levels of pro-inflammatory cytokines and long-term glucocorticoid treatment. To date, no treatments are available to treat growth impairment caused by glucocorticoids and there is a need to find new strategies to counteract the negative side effects of glucocorticoids on bone growth. The aim of this thesis was to study bone growth impairment induced by glucocorticoids and inflammation and the underlying molecular mechanisms. The aim was also to address whether the mitochondrial derived peptide humanin potentially could rescue from glucocorticoid-induced bone growth impairment and apoptosis in the growth plate, without interfering with the anti-inflammatory effect of glucocorticoids. In study I the effect of glucocorticoids and humanin on bone growth was assessed in several different experimental models. We discovered that the synthetic humanin analogue, HNG, completely rescued from dexamethasone-induced bone growth impairment and that humanin over-expressing mice were resistant to glucocorticoid-induced growth impairment. In addition, our results indicate that humanin is a novel regulator of Hedgehog signaling. In study II we assessed whether HNG could rescue from glucocorticoid-induced apoptosis in the growth plate in a model of chronic inflammation. We showed that HNG treatment suppressed apoptosis in both growth plate and articular cartilage. Importantly, we found that HNG did not interfere with the anti-inflammatory effect of dexamethasone. In study III we investigated the effect of dexamethasone on bone growth and chondrogenesis in a disease model of chronic inflammation. By using the transgenic TNF over-expressing mouse model (tgTNF) we found that chronic inflammation by itself suppressed bone growth and that dexamethasone treatment further suppressed bone growth despite its anti-inflammatory actions. We also showed that Indian hedgehog and humanin expression levels were suppressed in the growth plate of the tgTNF mice, suggesting a new mechanism for inflammation induced growth impairment.

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Celvin, B. (2019). Prevention of growth failure caused by glucocorticoids and inflammation . (Thesis). Karolinska Institute. Retrieved from http://hdl.handle.net/10616/46885

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Celvin, Bettina. “Prevention of growth failure caused by glucocorticoids and inflammation .” 2019. Thesis, Karolinska Institute. Accessed February 27, 2021. http://hdl.handle.net/10616/46885.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Celvin, Bettina. “Prevention of growth failure caused by glucocorticoids and inflammation .” 2019. Web. 27 Feb 2021.

Vancouver:

Celvin B. Prevention of growth failure caused by glucocorticoids and inflammation . [Internet] [Thesis]. Karolinska Institute; 2019. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10616/46885.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Celvin B. Prevention of growth failure caused by glucocorticoids and inflammation . [Thesis]. Karolinska Institute; 2019. Available from: http://hdl.handle.net/10616/46885

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

18. Regardt, Malin. Hand function, activity limitation and health-related quality of life in patients with polymyositis and dermatomyositis .

Degree: 2014, Karolinska Institute

URL: http://hdl.handle.net/10616/41985

► Background: Polymyositis (PM) and dermatomyositis (DM) are rare idiopathic inflammatory myopathies. Common clinical features are proximal muscle weakness and reduced muscle endurance, which can lead… (more)

▼ Background: Polymyositis (PM) and dermatomyositis (DM) are rare idiopathic inflammatory myopathies. Common clinical features are proximal muscle weakness and reduced muscle endurance, which can lead to activity limitation and reduced healthrelated quality of life (HRQoL). The current body of knowledge about hand function, activity limitation, and HRQoL in patients with PM and DM is limited. Aim: The overall aim of this thesis was to describe and explore hand function, activity limitation, work ability, and HRQoL in patients with PM and DM. Method: Four papers with cross-sectional, over-time, or intervention pilot study designs have been applied in this thesis. Descriptive, comparable, over time, and correlational statistics have been used. In all, 143 patients with PM and DM participated in the studies. Results: The results in this thesis showed that both women and men with PM and DM have reduced grip force and HRQoL compared to gender- and age-matched values from the literature. The reduced grip force and HRQoL were measured at the time of diagnosis in both women and men. Women had a reduced grip force at years 1-4 and at 6 years after diagnosis, while the men were affected up to 2 years after diagnosis. The HRQoL was rated lower than the normative values up to 6 years after diagnosis in women and 2 years following diagnosis in men. The grip force had a moderate to high correlation to the HRQoL dimensions of Role Physical, General Health, Vitality, and Mental Health. A hand exercise intervention seemed to be feasible to perform with good adherence but generated few individual improvements in hand function and activity performance why the protocol needs to be adjusted. Patients with reduced hand grip strength also demonstrated activity limitation (according to the Disability of the Arm, Shoulder, and Hand questionnaire) and reduced dexterity. In patients with PM and DM, 44% worked fulltime (40 h/week), 31% worked part-time, and 25% were on full-time sick leave. More than 50% of patients with PM and DM self-rated their work ability as “poor” or “less good”. Physically strenuous work components were present “quite often” to “very often” in up to 79% of the patients and were more prevalent in patients on sick leave =2 years. For those working, interfering factors in the work environment concerned task and time demands. Supporting factors were the meaning of their work, interactions with coworkers, and others. A low self-rated work ability was correlated moderate-high with a low percentage of full-time employment, the presence of work-related risk factors, and constraints in the work environment. Conclusion: Patients with PM and DM have reduced hand grip strength, lower ratings on HRQoL, and poor to less good self-rated work ability and the low grip strength may influence HRQoL whereas the proximal weakness seems to affect the ability to work. Measures of hand function and work ability should be included in care of patients with PM and…

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Regardt, M. (2014). Hand function, activity limitation and health-related quality of life in patients with polymyositis and dermatomyositis . (Thesis). Karolinska Institute. Retrieved from http://hdl.handle.net/10616/41985

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Regardt, Malin. “Hand function, activity limitation and health-related quality of life in patients with polymyositis and dermatomyositis .” 2014. Thesis, Karolinska Institute. Accessed February 27, 2021. http://hdl.handle.net/10616/41985.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Regardt, Malin. “Hand function, activity limitation and health-related quality of life in patients with polymyositis and dermatomyositis .” 2014. Web. 27 Feb 2021.

Vancouver:

Regardt M. Hand function, activity limitation and health-related quality of life in patients with polymyositis and dermatomyositis . [Internet] [Thesis]. Karolinska Institute; 2014. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10616/41985.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Regardt M. Hand function, activity limitation and health-related quality of life in patients with polymyositis and dermatomyositis . [Thesis]. Karolinska Institute; 2014. Available from: http://hdl.handle.net/10616/41985

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Karolinska Institute

19. Hertz, Ellen. Translational studies of molecular interactions in Parkinson's disease .

Degree: 2020, Karolinska Institute

URL: http://hdl.handle.net/10616/47114

► Interactions between molecules are the basis of cellular function. In disease, these tightly regulated systems are often disturbed. Parkinson’s disease (PD) is recognized by protein… (more)

▼ Interactions between molecules are the basis of cellular function. In disease, these tightly regulated systems are often disturbed. Parkinson’s disease (PD) is recognized by protein aggregates in the brain of erroneously interacting molecules, directly linking the clinical picture to the molecular mechanisms. The currently incomplete understanding of the mechanisms behind PD pathogenesis impedes the development of disease-modifying treatment and new targets are needed since today’s dopaminergic treatment does not fully alleviate the symptoms. G protein-coupled receptors (GPCRs) are a wide group of transmembrane receptors usually targeted by drugs due to their ability to convey extracellular information into definite cellular responses. This Thesis focuses on protein interactions, from cellular models of a Parkinson-linked GPCR, GPR37, to detection of nanoaggregates in serum from PD patients as a sign of disease. The main findings relate to the interactome of GPR37 as a factor regulating cell survival. GPR37 has been suggested to accumulate and cause dopaminergic cell death in PD when improperly folded but is able to elicit cytoprotective function when correctly matured and trafficked to the cell surface. We report that GPR37 interaction with ganglioside GM1-enriched lipid rafts and a proposed ligand prosaposin affects trafficking of GPR37 to the plasma membrane. Since the role of lipids in PD pathogenesis is increasingly acknowledged and GM1 has been suggested to slow down PD progression in clinical studies, we further studied the mechanism of the GPR37-GM1 interaction. We propose that exogenous GM1 treatment increase cellular resistance to a neurotoxin partly through a GPR37-dependent mechanism. This suggests yet another molecular mechanism of GM1 cytoprotection. Moreover, GPR37 has been suggested to be a modulator of dopaminergic transmission why we investigated the proposed interaction with dopamine D2 receptor (D2R) and GPR37 in live cells. The levels of heterodimerization where generally low in our cellular system. However, it could be augmented both by chaperone treatment, inducing trafficking of GPR37, and by clinically used dopamine agonist treatment. Shifting the heterodimerization level of GPCRs is known to alter molecular response. Therefore, the physiological outcome of this interaction needs to deciphered to understand effects and side effects of dopamine agonist treatment. We also investigate improper protein interactions as a potential biomarker in serum from PD patients by detection of β-sheet enriched nanoaggregates. We report a higher detected frequency of nanoamyloids in patients compared to healthy controls and a bimodal distribution of amyloid size in serum. However, the frequency of nanoamyloids did not correlate robustly with neither disease progression or disease symptoms. Potentially this is due to heterogeneity, both clinical and molecular, in the disease. This emphasizes the need of understanding the molecular interactions in a clinical context.

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Hertz, E. (2020). Translational studies of molecular interactions in Parkinson's disease . (Thesis). Karolinska Institute. Retrieved from http://hdl.handle.net/10616/47114

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Hertz, Ellen. “Translational studies of molecular interactions in Parkinson's disease .” 2020. Thesis, Karolinska Institute. Accessed February 27, 2021. http://hdl.handle.net/10616/47114.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Hertz, Ellen. “Translational studies of molecular interactions in Parkinson's disease .” 2020. Web. 27 Feb 2021.

Vancouver:

Hertz E. Translational studies of molecular interactions in Parkinson's disease . [Internet] [Thesis]. Karolinska Institute; 2020. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10616/47114.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Hertz E. Translational studies of molecular interactions in Parkinson's disease . [Thesis]. Karolinska Institute; 2020. Available from: http://hdl.handle.net/10616/47114

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Karolinska Institute

20. Walusimbi, Simon. Tuberculosis and HIV : evaluation of new tests for diagnostic accuracy, cost-effectiveness and effect on treatment of tuberculosis in Smear-Negative HIV-positive patients in Uganda .

Degree: 2015, Karolinska Institute

URL: http://hdl.handle.net/10616/44645

► Background: Despite tremendous progress in the control of the global tuberculosis (TB) epidemic during the past decade, it is still a major health problem even… (more)

▼ Background: Despite tremendous progress in the control of the global tuberculosis (TB) epidemic during the past decade, it is still a major health problem even today. The burden of TB is particularly severe in sub-Sahara Africa where TB and HIV co-infection is common, especially in those who are smear-negative. Such patients are twice more likely to die from TB than their counterparts because of delayed diagnosis and treatment. This thesis focuses on the evaluation of currently available new tests which have been developed to facilitate rapid diagnosis and early treatment of TB. Aims: The purpose of this thesis was to increase knowledge about the diagnostic accuracy, cost-effectiveness and effect on treatment of TB of the new tests in smear-negative HIV-positive patients in a context where resources are limited. Methods: In study I, a systematic review was performed to summarize and compare the over-all accuracy for smearnegative TB of the existing traditional TB tests (WHO 2007 TB algorithm) and two new tests: Xpert MTB/Rif test (a molecular-based method) and Microscopic Observation Drug Susceptibility test (a culture-based method). In study II, a cross-sectional study was performed to collect primary laboratory data on the diagnostic accuracy for smear-negative TB of Xpert MTB/Rif (GeneXpert), Microscopic Observation Drug Susceptibility test (MODS) and Nitrate Reductase Assay (NRA) in HIV-positive patients. The results of the three tests were compared with traditional solid Löwenstein-Jensen (L-J) TB culture and a new conventional liquid (MGIT) TB culture method. In study III, we modelled the cost-effectiveness of using MODS or GeneXpert-based algorithm for diagnosis of pulmonary TB in HIV-positive patients. Finally, in study IV, we investigated how best to treat patients with presumptive pulmonary TB who were both Smear and GeneXpert negative. Results: From study I, we found that the sensitivity of the tests for smear-negative TB was moderate (61-73%). The specificity was high for both GeneXpert (98%) and MODS (91%) but moderate for the WHO 2007 TB algorithm (69%). From study II, we found that GeneXpert, MODS and NRA had low sensitivity for smearnegative TB in HIV-positive patients (24-49%). However, the specificity of all three tests was high (92-98%). From study III, we found that utilizing a MODS-based algorithm for diagnosis of pulmonary TB in HIVpositive patients was more cost-effective than utilizing a GeneXpert-based algorithm (US 34 versus US 71 per TB patient diagnosed). From study IV, we found that a smear and GeneXpert-negative test result had a high negative predictive value for TB. Thus, despite the low-moderate sensitivity of GeneXpert for smear-negative TB, a majority of patients (88%) responded fully to antibiotic treatment and empiric TB treatment was initiated in only a few (8%) of them. Conclusions: GeneXpert, MODS and NRA are useful for diagnosis of TB in smear-negative patients including those who are HIV-positive.…

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Walusimbi, S. (2015). Tuberculosis and HIV : evaluation of new tests for diagnostic accuracy, cost-effectiveness and effect on treatment of tuberculosis in Smear-Negative HIV-positive patients in Uganda . (Thesis). Karolinska Institute. Retrieved from http://hdl.handle.net/10616/44645

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Walusimbi, Simon. “Tuberculosis and HIV : evaluation of new tests for diagnostic accuracy, cost-effectiveness and effect on treatment of tuberculosis in Smear-Negative HIV-positive patients in Uganda .” 2015. Thesis, Karolinska Institute. Accessed February 27, 2021. http://hdl.handle.net/10616/44645.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Walusimbi, Simon. “Tuberculosis and HIV : evaluation of new tests for diagnostic accuracy, cost-effectiveness and effect on treatment of tuberculosis in Smear-Negative HIV-positive patients in Uganda .” 2015. Web. 27 Feb 2021.

Vancouver:

Walusimbi S. Tuberculosis and HIV : evaluation of new tests for diagnostic accuracy, cost-effectiveness and effect on treatment of tuberculosis in Smear-Negative HIV-positive patients in Uganda . [Internet] [Thesis]. Karolinska Institute; 2015. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10616/44645.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Walusimbi S. Tuberculosis and HIV : evaluation of new tests for diagnostic accuracy, cost-effectiveness and effect on treatment of tuberculosis in Smear-Negative HIV-positive patients in Uganda . [Thesis]. Karolinska Institute; 2015. Available from: http://hdl.handle.net/10616/44645

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Karolinska Institute

21. Wallerstedt, Anna. Outcomes after surgical treatment of localized prostate cancer with focus on urinary incontinence and short term complications .

Degree: 2015, Karolinska Institute

URL: http://hdl.handle.net/10616/42343

► Background: Urinary incontinence is a significant long-term complication after radical prostatectomy. The aim was to evaluate clinically significant definitions of urinary incontinence and to investigate… (more)

▼ Background: Urinary incontinence is a significant long-term complication after radical prostatectomy. The aim was to evaluate clinically significant definitions of urinary incontinence and to investigate its potential predictors. Robot-assisted radical prostatectomy has become a widespread surgical technique in prostate cancer despite the lack of randomised trials showing its superiority compared to open surgery. A further aim was to compare shortterm results three months after the two surgical techniques. Material and methods: Data for this thesis derives from two sources. The first cohort is a consecutive series of 1411 men who underwent radical prostatectomy at Karolinska University Hospital from 2002 to 2006 and completed a study-specific validated questionnaire. The second cohort derives from the LAPPRO study, a multicentre, prospective controlled trial of men who underwent radical prostatectomy between 2008 and 2011 (n=4003). Data was collected prospectively with validated patient questionnaires and case report forms which were completed by health-care personnel. Results: Urinary leakage as a long-term side effect after radical prostatectomy proved to cause the patient a lot of bother. Even a proportion of those who had occasional leakage reported significant bother. Increased age at surgery increases the risk of urinary incontinence one year after surgery and this increases exponentially with age. Furthermore patients with preoperative urinary leakage have an increased risk of postoperative incontinence. When evaluating short-term outcomes and comparing open radical prostatectomy to robot-assisted radical prostatectomy, re-operation during initial hospital stay was more frequent after open surgery. Men operated by open surgery also sought medical care more frequently compared to men operated by robot-assisted surgery within three months after surgery. Men who underwent lymph-node dissection proved to have an increased risk for readmission as well as a greatly increased risk for thromboembolic events, such as deep venous thrombosis and pulmonary embolism. Regardless of whether lymph-node dissection was preformed or not, men who underwent open prostatectomy appeared to have an increased risk of thromboembolic events compared to those who had robot-assisted surgery. Conclusions: If the definition of continence consists of the use of pads, a certain number of men that are bothered significantly by urinary leakage will be defined as continent. When planning a patient for radical prostatectomy, one must take age and preoperative urinary leakage into consideration as risk factors for postoperative incontinence. The robot-assisted radical prostatectomy is a safe procedure and has some short-term advantages compared to open surgery. Lymph-node dissection during radical prostatectomy increases the risk for thromboembolic events, the risk is higher in open surgery compared to robot-assisted surgery.

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Wallerstedt, A. (2015). Outcomes after surgical treatment of localized prostate cancer with focus on urinary incontinence and short term complications . (Thesis). Karolinska Institute. Retrieved from http://hdl.handle.net/10616/42343

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Wallerstedt, Anna. “Outcomes after surgical treatment of localized prostate cancer with focus on urinary incontinence and short term complications .” 2015. Thesis, Karolinska Institute. Accessed February 27, 2021. http://hdl.handle.net/10616/42343.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Wallerstedt, Anna. “Outcomes after surgical treatment of localized prostate cancer with focus on urinary incontinence and short term complications .” 2015. Web. 27 Feb 2021.

Vancouver:

Wallerstedt A. Outcomes after surgical treatment of localized prostate cancer with focus on urinary incontinence and short term complications . [Internet] [Thesis]. Karolinska Institute; 2015. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10616/42343.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Wallerstedt A. Outcomes after surgical treatment of localized prostate cancer with focus on urinary incontinence and short term complications . [Thesis]. Karolinska Institute; 2015. Available from: http://hdl.handle.net/10616/42343

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Karolinska Institute

22. Steglich, Babett. Interplay of chromatin remodeling, transcriptional regulation, and nuclear organization .

Degree: 2015, Karolinska Institute

URL: http://hdl.handle.net/10616/44637

► Transcription is regulated on different levels to ensure that genes are expressed at the correct time and in the amounts required. At the chromatin level,… (more)

▼ Transcription is regulated on different levels to ensure that genes are expressed at the correct time and in the amounts required. At the chromatin level, DNA is wound onto histone proteins, forming nucleosomes that influence accessibility of DNA elements. Modifications on those histones and interactions with other chromatin proteins can either encourage or inhibit recruitment of the transcription machinery. Genomic regions of similar character form chromatin domains, organizing the genome based on their transcription states. Within the nucleus, both individual loci and entire chromosomes assume non-random positions, based on their transcription levels and interactions with nuclear landmarks. This thesis examines the effects of the Fun30 chromatin remodeling enzymes on transcription regulation and nuclear organization, both on the local chromatin level as well as on a genome-wide scale. Using the fission yeast Schizosaccharomyces pombe as a model organism, we mapped the interactions between the genome and two inner nuclear membrane proteins, Ima1 and Man1. We observed a preference for lowly expressed genes to associate with the nuclear envelope, similar to what had been observed in mammalian and fruit fly cells. When comparing Ima1 and Man1 binding patterns, we found both common and separate target sites, suggesting a role for inner nuclear membrane proteins in organizing the fission yeast genome. Following up on these results, we went on to examine subtelomeric chromatin domains, which are regulated through the Fun30 remodeler Fft3. These domains contain repressed genes, whose transcription levels increase in cells carrying an fft3Δ deletion. While the subtelomeres associate with the nuclear envelope through Man1 in wild-type cells, this interaction is lost in fft3Δ cells. In these cells, we also observed changes in nucleosome occupancy at the subtelomeric borders. Interestingly, a strain carrying a catalytically inactive version of the Fft3 remodeler showed the same behavior as the deletion strain, with upregulation of subtelomeric genes and loss of Man1 interactions. Together, these results point to an active role of Fft3 in regulating subtelomeric chromatin, transcription, and nuclear periphery interactions. In addition to their role at subtelomeres, Fun30 remodelers also control transcription in other parts of the genome. When we examined a strain lacking Fft2, a paralog of Fft3, we found increased transcription of the fission yeast Tf2 retrotransposons. This increase is accompanied by a shift in transcription start site (TSS) further upstream and is especially pronounced when both fft2 and fft3 are deleted. By mapping nucleosome positioning, we were able to establish that Fft2 and Fft3 collaborate in stabilizing a nucleosome over the upstream TSS, resulting in transcription initiation further downstream and production of an mRNA incapable of transposition. Expression of both remodelers is downregulated in stress conditions, allowing for production of the…

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APA (6^th Edition):

Steglich, B. (2015). Interplay of chromatin remodeling, transcriptional regulation, and nuclear organization . (Thesis). Karolinska Institute. Retrieved from http://hdl.handle.net/10616/44637

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Steglich, Babett. “Interplay of chromatin remodeling, transcriptional regulation, and nuclear organization .” 2015. Thesis, Karolinska Institute. Accessed February 27, 2021. http://hdl.handle.net/10616/44637.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Steglich, Babett. “Interplay of chromatin remodeling, transcriptional regulation, and nuclear organization .” 2015. Web. 27 Feb 2021.

Vancouver:

Steglich B. Interplay of chromatin remodeling, transcriptional regulation, and nuclear organization . [Internet] [Thesis]. Karolinska Institute; 2015. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10616/44637.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Steglich B. Interplay of chromatin remodeling, transcriptional regulation, and nuclear organization . [Thesis]. Karolinska Institute; 2015. Available from: http://hdl.handle.net/10616/44637

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Karolinska Institute

23. Lundberg, H Johan. On endovascular methods for cell transplantantion - exploring the selective intra-arterial and trans-vessel wall routes .

Degree: 2011, Karolinska Institute

URL: http://hdl.handle.net/10616/40413

► Background: Cell based transplantation methods are a pivotal part of the emerging field of regenerative medicine. These transplantation methods could possible produce curative treatments where,… (more)

▼ Background: Cell based transplantation methods are a pivotal part of the emerging field of regenerative medicine. These transplantation methods could possible produce curative treatments where, previously, expectations of such feats were low. Diseases for which treatments are evaluated are in such diverging physiological systems as e.g. the CNS with ischemic or traumatic injuries, the endocrine system with type I diabetes mellitus, or musculo-skeletal system with dystrophies, hematological system with leukemia and cardiovascular system with ischemic heart disease among others. Transplantation methods for cells span from open surgical/percutaneous, over intravenous, to specific intra-arterial methods. The method for delivery of cells is in fact an important part of the translation of cell based therapies to clinical practice. With that said, the use of endovascular techniques opens attractive routes of transplantation that needs to be thoroughly studied in order to achieve maximum efficacy. Methods: We have utilized a model of traumatic brain injury in the rat where cell transplantations have been performed by selective intra-arterial methods and compared to intravenous administration. Analysis of engraftment has been performed by immunohistochemistry and cell characterization has been performed by microarray and RT-qPCR. Further, we have developed the Extroducer catheter system, a “nano”-catheter aimed for trans-vessel wall technique passage, in simulator, ex vivo, in vivo in rat and with full clinical integration in rabbit and swine. Long term follow-up studies have been performed both in rat (14 days) and rabbit (5, 30 and 80 days). Results and Conclusions: We first show that selective intra-arterial methods increase engraftment levels up to fifteen-folds higher compared to intravenous controls. However, not all cell systems are found to be optimal for intra-luminal transplantation methods. Some of the factors limiting engraftment were thus explored within the cell systems themselves. These findings indicated that lack of engraftment might be dependent on integrin expression and endothelial interactions. For cells that lack the capacity of diapedesis and especially for more specific niche cell systems, such as insulin producing cells in the pancreas, the Extroducer can create direct parenchymal access via the endovascular route. Thus, the Extroducer system, developed within this thesis, offers a working channel between the proximal end of an endovascular catheter and the parenchyma of any organ of the body. Development and testing verified integration with clinical routine catheters. No long term adverse events were observed in the rat or the rabbit following the trans-vessel wall passage. In conclusion, endovascular intervention can provide a number of conceptually different methods for cell transplantation.

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Lundberg, H. J. (2011). On endovascular methods for cell transplantantion - exploring the selective intra-arterial and trans-vessel wall routes . (Thesis). Karolinska Institute. Retrieved from http://hdl.handle.net/10616/40413

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Lundberg, H Johan. “On endovascular methods for cell transplantantion - exploring the selective intra-arterial and trans-vessel wall routes .” 2011. Thesis, Karolinska Institute. Accessed February 27, 2021. http://hdl.handle.net/10616/40413.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Lundberg, H Johan. “On endovascular methods for cell transplantantion - exploring the selective intra-arterial and trans-vessel wall routes .” 2011. Web. 27 Feb 2021.

Vancouver:

Lundberg HJ. On endovascular methods for cell transplantantion - exploring the selective intra-arterial and trans-vessel wall routes . [Internet] [Thesis]. Karolinska Institute; 2011. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10616/40413.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Lundberg HJ. On endovascular methods for cell transplantantion - exploring the selective intra-arterial and trans-vessel wall routes . [Thesis]. Karolinska Institute; 2011. Available from: http://hdl.handle.net/10616/40413

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Karolinska Institute

24. Cerrato, Ruha. Studies on the regulation of endothelial nitric oxide synthase in endothelial dysfunction .

Degree: 2016, Karolinska Institute

URL: http://hdl.handle.net/10616/45160

► Ischaemic heart disease and cerebrovascular disease are the leading causes of morbidity and mortality in the world. The underlying progression of the disease is linked… (more)

▼ Ischaemic heart disease and cerebrovascular disease are the leading causes of morbidity and mortality in the world. The underlying progression of the disease is linked to a reduction in the bioavailability of nitric oxide. One factor contributing to this is an increase in the production of superoxide radicals. A combination of increased oxidative stress, inappropriate lipid metabolism and cell death sets the stage for what will subsequently develop into atherosclerosis. The process of atherogenesis can slow down if patients at risk are identi ed early, receive the necessary pharmacological treatment and change to a healthier lifestyle. The aim of the following studies was to identify whether the uptake, synthesis and recycling of tetrahydrobiopterin (BH4), the essential co-factor of endothelial nitric oxide synthase (eNOS), could in uence oxidative stress in human vasculature. We also sought to elucidate whether endothelin-1 (ET-1), a potent vasoconstrictor, played an important role in oxidative stress in human vasculature and the potential mechanisms underlying this in uence. In Study I, 49 patients with coronary artery disease took part in a placebo-controlled clinical trial with the aim of determining the mechanisms of exogenous BH4 in relation to vascular function. Oral BH4 treatment signi cantly elevates the levels of BH4 in blood, but this effect is limited by the rapid systemic oxidation of exogenous BH4. The ratio of reduced to oxidised biopterins in blood and vascular tissue is unchanged by exogenous BH4 treatment, resulting in no net effect on vascular superoxide production or endothelial function. In Study II, the aim was to explore the regulation of endogenous BH4 and subsequent effects on endothelial function in patients with coronary artery disease. In three clinical models and one in vitro model, involving 465 subjects, we observed that an inability to increase vascular BH4 synthesis leads to signi cant impairment of endothelial function. In Study III, the aim was to explore the role of ET-1 in endothelial dysfunction, speci cally with regard to superoxide production. ET-1 increases superoxide production in human coronary artery bypass grafts via a receptor-driven mechanism involving, the largest contributor of superoxide in the vascular wall, nicotine amide dinucleotide phosphate (NADPH) oxidase. In Study IV, I applied what I had learned from Study I and Study II and sought to further delineate whether endothelin-1 in uences biopterin homeostasis in both human and animal tissues. ET-1 did not have any effect on BH4 in human coronary artery bypass grafts or resistance arteries, endothelial cells and mice with an over-expression of ET-1 in the endothelium (ET-transgenic mice).

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Cerrato, R. (2016). Studies on the regulation of endothelial nitric oxide synthase in endothelial dysfunction . (Thesis). Karolinska Institute. Retrieved from http://hdl.handle.net/10616/45160

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Cerrato, Ruha. “Studies on the regulation of endothelial nitric oxide synthase in endothelial dysfunction .” 2016. Thesis, Karolinska Institute. Accessed February 27, 2021. http://hdl.handle.net/10616/45160.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Cerrato, Ruha. “Studies on the regulation of endothelial nitric oxide synthase in endothelial dysfunction .” 2016. Web. 27 Feb 2021.

Vancouver:

Cerrato R. Studies on the regulation of endothelial nitric oxide synthase in endothelial dysfunction . [Internet] [Thesis]. Karolinska Institute; 2016. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10616/45160.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Cerrato R. Studies on the regulation of endothelial nitric oxide synthase in endothelial dysfunction . [Thesis]. Karolinska Institute; 2016. Available from: http://hdl.handle.net/10616/45160

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Karolinska Institute

25. Chen, Qi. What can genetically informative designs add to the understanding of ADHD? .

Degree: 2016, Karolinska Institute

URL: http://hdl.handle.net/10616/45027

► Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent and clinically heterogeneous neurodevelopmental disorder affecting approximately 3.4–7.3% children and adolescents and 2.5–3.4% adults worldwide, leading to adverse… (more)

▼ Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent and clinically heterogeneous neurodevelopmental disorder affecting approximately 3.4–7.3% children and adolescents and 2.5–3.4% adults worldwide, leading to adverse consequences for affected individuals, their families, and society at large. Despite the growing body of research, the etiology of ADHD remains obscure. Epidemiologic research is crucial for detecting disease risk factors. However, prior studies have rarely moved beyond identifying associations between proposed risk factors and later outcomes to rigorously testing the causality of these associations. The stagnation is partly due to the intrinsic limitations of observational studies, such as insufficient adjustment for genetic confounding. Large register-based data enable researchers to incorporate classical epidemiologic designs into genetically informative samples. Such genetically informative study designs are useful tools for unraveling the role of genetic and environmental factors in the development of diseases. In this thesis, the four studies used genetically informative designs to enhance the current understanding of the etiology of ADHD and the mechanisms underlying the associations between ADHD and its adverse health outcomes, including high body mass index (BMI) and suicidal behavior. In Study I, we attempted to quantify the familial aggregation of ADHD in a large representative Swedish family sample, consisting of siblings and cousins of varying degrees of genetic relatedness. The results demonstrated that the familial aggregation of ADHD generally increased with increasing genetic relatedness between family members. Persistence of ADHD into adulthood in family members was associated with higher degree of the familial aggregation compared to remission of ADHD prior to adulthood. In Study II, we assessed the co-aggregation of ADHD and overweight/obesity within families and further tested the hypothesis that the familial co-aggregation of the two conditions is at least in part due to common familial causes. The findings suggested an etiological overlap between ADHD and overweight/obesity. In Study III, we investigated the association between high maternal pre-pregnancy BMI and offspring ADHD both at the population level and within siblings. The findings indicated the contribution of shared familial factors to the association, which supported the conclusion from Study II. A direct causal effect of high maternal pre-pregnancy BMI on offspring ADHD was, however, not evident. In Study IV we examined the association between the use of ADHD medication and concomitant suicidal behavior. When the same individual was compared with him of herself for the rate of suicide-related events during on- and off-treatment periods, the results did not support that the use of ADHD medication increased the risk of concomitant suicidal behavior. In conclusion, observational studies using genetically informative designs may provide…

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Chen, Q. (2016). What can genetically informative designs add to the understanding of ADHD? . (Thesis). Karolinska Institute. Retrieved from http://hdl.handle.net/10616/45027

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Chen, Qi. “What can genetically informative designs add to the understanding of ADHD? .” 2016. Thesis, Karolinska Institute. Accessed February 27, 2021. http://hdl.handle.net/10616/45027.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Chen, Qi. “What can genetically informative designs add to the understanding of ADHD? .” 2016. Web. 27 Feb 2021.

Vancouver:

Chen Q. What can genetically informative designs add to the understanding of ADHD? . [Internet] [Thesis]. Karolinska Institute; 2016. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10616/45027.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Chen Q. What can genetically informative designs add to the understanding of ADHD? . [Thesis]. Karolinska Institute; 2016. Available from: http://hdl.handle.net/10616/45027

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Karolinska Institute

26. Sekharappa, Harsha Madapura. Regulatory mechanisms contributing to the homeostasis of normal and malignant hematopoietic cells .

Degree: 2016, Karolinska Institute

URL: http://hdl.handle.net/10616/45100

► Bone marrow is the site of origin of diverse population of hematological cells with lineage specific function. The different lineages of cells originate from a… (more)

▼ Bone marrow is the site of origin of diverse population of hematological cells with lineage specific function. The different lineages of cells originate from a common progenitor that has a strong self-renewable capability giving rise to myeloid and lymphoid progenitor cells. The myeloid progenitor cells terminally differentiate to monocytes, granulocytes, erythrocytes and thrombocytes, while the lymphoid progenitor cells terminally differentiate to B, T and NK cells. A plethora of extracellular and intracellular factors in a complex yet tightly regulated orchestra controls the genesis and function of each cell type. However, breakdown of one or more regulatory processes can steer cells towards becoming cancerous, characterized by the loss of normal cellular functions and/or morphology. This thesis analyses; The contribution of p53 in the regulation of normal T cell homeostasis; A mechanism evolved by EBV for its sustenance in B cells and, a mechanism contributing to the development/survival of malignant hematopoietic cells. The first half of the thesis describes the contribution of the tumor suppressor p53 in the regulation of T cell homeostasis. Paper I demonstrates the regulation of pro-apoptotic SAP by p53 in activated T cells. p53 and SAP were upregulated in activated but not in unstimulated T cells. To determine the effect of p53 on SAP expression, p53 was selectively induced by nutlin-3 in unstimulated T cells. This induced SAP mRNA and protein expression. Further, chromatin immuno-precipitation confirmed the binding of p53 to the SAP promoter in activated T cells. Paper II demonstrated the cMyc-p53 feedback mechanism contributing to T cell homeostasis. cMyc, p53 and p14ARF expression was induced in activated T cells. Further elevation of p53 in activated T cells by nutlin-3 treatment decreased cell proliferation, cMyc and p14ARF expression. At the other end of the feedback loop, inhibition of Notch (DAPT) signaling or cMyc (10058-F4) in activated primary T cells decreased proliferation accompanied by decreased cMyc, p14ARF and p53 expression. Thus, inhibition of cMyc expression had a negative outcome on p53 expression, and induction of p53 had a negative consequence on cMyc expression in activated T cells. Nutlin-3 induced p53 and 10058-F4 mediated cMyc inhibition in activated T cells had a combined effect of apoptosis and cell cycle arrest. On the contrary, activated T cells treated with nutlin-3 or cMyc inhibitor (10058-F4) retained the cytotoxic function despite the diminished proliferation. The second half of the thesis explores mechanisms that virus infected and tumor cells exploit for their manifestation. In paper III we studied the role of CD4+T cells in the establishment and regulation of EBV latency. Our results showed that activated CD4+T cells from healthy donors downregulated the latency III protein EBNA2 (and its transcript, Cp) in LCLs, thus indicating that they induce a shift in latency towards II. By exploiting the transwell system we demonstrated that cell-cell contact is not…

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Sekharappa, H. M. (2016). Regulatory mechanisms contributing to the homeostasis of normal and malignant hematopoietic cells . (Thesis). Karolinska Institute. Retrieved from http://hdl.handle.net/10616/45100

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Sekharappa, Harsha Madapura. “Regulatory mechanisms contributing to the homeostasis of normal and malignant hematopoietic cells .” 2016. Thesis, Karolinska Institute. Accessed February 27, 2021. http://hdl.handle.net/10616/45100.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Sekharappa, Harsha Madapura. “Regulatory mechanisms contributing to the homeostasis of normal and malignant hematopoietic cells .” 2016. Web. 27 Feb 2021.

Vancouver:

Sekharappa HM. Regulatory mechanisms contributing to the homeostasis of normal and malignant hematopoietic cells . [Internet] [Thesis]. Karolinska Institute; 2016. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10616/45100.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Sekharappa HM. Regulatory mechanisms contributing to the homeostasis of normal and malignant hematopoietic cells . [Thesis]. Karolinska Institute; 2016. Available from: http://hdl.handle.net/10616/45100

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Karolinska Institute

27. Engstrand, Jennie. Liver metastases from colorectal cancer .

Degree: 2017, Karolinska Institute

URL: http://hdl.handle.net/10616/45551

► Introduction: Colorectal cancer (CRC) is the third most common cancer worldwide. At diagnosis of CRC 20-25% of patients have metastatic disease. The liver is the… (more)

▼ Introduction: Colorectal cancer (CRC) is the third most common cancer worldwide. At diagnosis of CRC 20-25% of patients have metastatic disease. The liver is the most common metastatic site and liver metastases are detected in 25-30% of all patients. A quarter of these patients are amenable for liver resection that results in a five-year survival exceeding 50%. The indications for liver resection continue to broaden and are no longer limited by number and size of liver metastases nor the presence of extrahepatic metastases. Currently liver resection is indicated when macroscopic tumour clearance can be achieved with preservation of a sufficient future liver remnant. Different strategies to improve resectability exist such as portal vein occlusion, two-stage resections, associating liver partition and portal vein ligation for staged hepatectomy and thermal ablation, mainly radiofrequency ablation or microwave ablation (MWA). Decisions on management of patients with metastatic CRC should ideally be made in a multidisciplinary team (MDT) setting. Failing to do so may result in suboptimal management and patients that could be resected are not necessarily offered curative-intended treatment. As a result of this there are known regional differences in the treatment of patients with liver metastases that may affect survival. For patients not suitable for resection, either due to the metastatic burden or comorbidity omitting extensive surgery, local ablation is an option. Aims: The aim of Study I was to provide detailed population-based data of liver metastatic patterns, treatment and survival in patients with metastatic CRC. In Study II, the potentially improved resection rates were evaluated in a scenario where all patients with liver metastatic disease, irrespective of extrahepatic metastases, were assessed by a liver MDT. Study III aimed to describe the feasibility and safety of a multiple MWA strategy in patients with initially unresectable liver metastases. The primary aim of Study IV was to evaluate the accuracy and safety of antenna placement in stereotactic computed tomography-guided MWA of primary and secondary liver tumours. The secondary aims of Study IV were to evaluate the feasibility of the navigation system, to measure the procedure-related radiation dose and to assess the safety of high-frequency jet ventilation for target motion control. Patients and Methods: In Studies I and II, a population-based cohort consisting of all patients diagnosed with CRC in the Stockholm and Gotland region during 2008, identified from the Swedish Colorectal Cancer Registry, was used. Details of metastatic spread, referral to a MDT conference and oncologic and surgical treatment were retrieved from electronic patient charts and recorded during a five-year follow-up period or until death. Predictors of survival in Studies I and III were estimated using a Cox proportional hazards model. Survival curves were illustrated using Kaplan-Meier estimates and survival functions were compared using the log-rank test…

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Engstrand, J. (2017). Liver metastases from colorectal cancer . (Thesis). Karolinska Institute. Retrieved from http://hdl.handle.net/10616/45551

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Engstrand, Jennie. “Liver metastases from colorectal cancer .” 2017. Thesis, Karolinska Institute. Accessed February 27, 2021. http://hdl.handle.net/10616/45551.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Engstrand, Jennie. “Liver metastases from colorectal cancer .” 2017. Web. 27 Feb 2021.

Vancouver:

Engstrand J. Liver metastases from colorectal cancer . [Internet] [Thesis]. Karolinska Institute; 2017. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10616/45551.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Engstrand J. Liver metastases from colorectal cancer . [Thesis]. Karolinska Institute; 2017. Available from: http://hdl.handle.net/10616/45551

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Karolinska Institute

28. Levander, Sepideh. Development of vaccines and mouse models for chronic hepatitis C virus infection .

Degree: 2016, Karolinska Institute

URL: http://hdl.handle.net/10616/45172

► Chronic hepatitis C virus (HCV) infection is a major causative agent for severe liver disease and cancer worldwide. Globally, it is estimated that approximately 185… (more)

▼ Chronic hepatitis C virus (HCV) infection is a major causative agent for severe liver disease and cancer worldwide. Globally, it is estimated that approximately 185 million people are infected with HCV and 130-170 million of these are chronic carriers of the virus (1, 2). The HCV infection is one of the major causes of liver disease and the infection is characterized by a slow and silent progression. Patients infected with HCV have an increased risk of developing fibrosis, cirrhosis and hepatocellular carcinoma. Importantly, this infection is today considered curable in the majority of individuals receiving the recently introduced direct-acting antiviral (DAA) therapy (3-5). Therefore the urgency for a HCV vaccine has reduced. However, only 10% of all chronic HCV carriers receive any treatment due to high cost of treatment and the majority of the chronic carriers live in resource-poor countries. Hence, there is still an urgent need to prevent the spread of HCV through a vaccine. Today, no prophylactic or therapeutic vaccines are available. However, numerous vaccines have been developed and tested for efficacy in clinical trials (6-9). A few HCV vaccines are currently being tested for both protective and therapeutic effects (10). A key feature of patients with chronic HCV is their lack of functional T cell responses to HCV (11-13). Interestingly, a recent study showed that DAA induced cure of HCV rapidly restores at least partly HCV-specific T cell responses. However, these responses do not seem to protect against reinfection (14, 15). Thus, it may be of importance to broaden the post-cure T cell responses through vaccination to reduce the risk of reinfection. This will save significant costs and reduce HCV associated morbidity and mortality. In this thesis we have evaluated our in-house therapeutic DNA vaccine in 12 patients with chronic HCV infection. The phase I clinical trial was performed in treatment naive HCV genotype 1 patients, receiving four monthly vaccinations in the deltoid muscles with 167, 500, or 1,500 μg codon-optimized HCV nonstructural (NS) 3/4A-expressing DNA vaccine delivered by in vivo electroporation (EP). This first-in-man therapeutic HCV DNA vaccine study with a DNA vaccine delivered by in vivo EP showed a good tolerability and safety with no severe adverse events. In addition, a transient immune activation and transient reductions in serum HCV RNA levels was seen in a few patients at the time of the vaccinations. Thus, DNA-based vaccines may be explored as a therapeutic or prophylactic tool in hepatitis C. There are many ways to make a DNA vaccine more potent to get a good effect and fully utilize the vaccines effect. One approach is to use molecular adjuvants to obtain the most potent immune modulatory effect of a DNA vaccination. Other methods to increase the immunogenicity of the DNA vaccine can also be to make the delivery method more effective, like EP and in vivo intracellular injection (IVIN) device. The importance here is to be able to activate and reactivate the…

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Levander, S. (2016). Development of vaccines and mouse models for chronic hepatitis C virus infection . (Thesis). Karolinska Institute. Retrieved from http://hdl.handle.net/10616/45172

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Levander, Sepideh. “Development of vaccines and mouse models for chronic hepatitis C virus infection .” 2016. Thesis, Karolinska Institute. Accessed February 27, 2021. http://hdl.handle.net/10616/45172.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Levander, Sepideh. “Development of vaccines and mouse models for chronic hepatitis C virus infection .” 2016. Web. 27 Feb 2021.

Vancouver:

Levander S. Development of vaccines and mouse models for chronic hepatitis C virus infection . [Internet] [Thesis]. Karolinska Institute; 2016. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10616/45172.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Levander S. Development of vaccines and mouse models for chronic hepatitis C virus infection . [Thesis]. Karolinska Institute; 2016. Available from: http://hdl.handle.net/10616/45172

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Karolinska Institute

29. Neovius, Erik. Development of surgical techniques in craniofacial reconstruction .

Degree: 2016, Karolinska Institute

URL: http://hdl.handle.net/10616/45351

► Introduction: Facial fractures are common and either the injury or the surgical treatment may cause sequelae including diplopia, visual loss, dystopia, enophthalmos, scarring, soft tissue… (more)

▼ Introduction: Facial fractures are common and either the injury or the surgical treatment may cause sequelae including diplopia, visual loss, dystopia, enophthalmos, scarring, soft tissue affection and sensory disturbances. Severe facial fractures may also lead to bone defects due to resorption. In bone reconstruction after facial fractures, tumor surgery or anomalies, replacement using autologous bone is the gold standard treatment. However, in order to avoid donor-site morbidity and risks, reduce surgery time and hospital stay; the interest in artificial bone substitutes is increasing. The aim with these studies was to better understand risks and complications related to craniofacial surgery and thereby improve surgical treatment. Additionally, to explore bone substitutes in order to avoid donor site morbidity. Methods: In study I-II patients with facial fractures were grouped based on the severity and location of injury and examined three years or more after surgery regarding vision, diplopia, dystopia, enophthalmos and infraorbital nerve (ION) sensibility. Study III included patients treated for a facial fracture including lower eyelid incisions. The outcome after subciliary and transconjunctival incisions with regards to the long-term occurrence of ectropion, scleral show, entropion and canthal malposition was examined. Study IV was a prospective randomized study comparing the healing capacity between BMP-2 (250 μg/ml) in hydrogel, hydrogel without BMP-2, SpongostanTM (negative control) or TisseelTM with autologous bone matrix (positive control) in critical size cranial bone defects in neurosurgery. Study V was a prospective randomized study investigating the healing capacity of BMP-2 (50 μg/ml or 250 μg/ml) in hydrogel compared to treatment with autologous bone in alveolar cleft surgery. Results: In Study I and II, 81 patients attended to follow-up. Diplopia occurred in 3.7%, visual loss in 2.5%, dystopia in 4.9% and visible enophthalmos (>2 mm) in 8.6% (Study I). Severe diplopia was found in two patients (2.5%) and was due to nerve injuries, the trochlear and abducens nerve respectively. Complex fractures had a higher incidence of any sequelae. In Study II we found affected ION sensibility in 20% and severely affected sensibility in 7.4% but there was no statistically significant correlation between questionnaire results and log von Frey values. In Study III, including 128 patients, 8.1% had ectropion and 11% had scleral show in the subciliary group whereas 2.2% had ectropion, 4.4% had scleral show and 2.2% had a canthal malposition in the transconjunctival group. This difference was not statistically significant. In Study IV we found that TisseelTM with autograft, hydrogel and hydrogel with BMP-2 had a significantly better bone healing capacity than negative controls (SpongostanTM). Frontal bone originating from the neural crest had significantly better bone healing than parietal/temporal bone originating from the mesoderm. In Study V the bone healing capacity was comparable…

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Neovius, E. (2016). Development of surgical techniques in craniofacial reconstruction . (Thesis). Karolinska Institute. Retrieved from http://hdl.handle.net/10616/45351

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Neovius, Erik. “Development of surgical techniques in craniofacial reconstruction .” 2016. Thesis, Karolinska Institute. Accessed February 27, 2021. http://hdl.handle.net/10616/45351.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Neovius, Erik. “Development of surgical techniques in craniofacial reconstruction .” 2016. Web. 27 Feb 2021.

Vancouver:

Neovius E. Development of surgical techniques in craniofacial reconstruction . [Internet] [Thesis]. Karolinska Institute; 2016. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10616/45351.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Neovius E. Development of surgical techniques in craniofacial reconstruction . [Thesis]. Karolinska Institute; 2016. Available from: http://hdl.handle.net/10616/45351

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Karolinska Institute

30. Avelar Pereira, Bárbara. Multimodal imaging : functional, structural, and molecular brain correlates of cognitive aging .

Degree: 2019, Karolinska Institute

URL: http://hdl.handle.net/10616/46826

► Aging is associated with a decline in many (but not all) cognitive abilities. Although it remains largely unknown how changes in brain integrity relate to… (more)

▼ Aging is associated with a decline in many (but not all) cognitive abilities. Although it remains largely unknown how changes in brain integrity relate to cognitive deficits, these changes are likely expressed across interrelated functional, structural, and molecular layers. This complexity calls for a multimodal imaging approach in age-related mind-brain research. Hence, in this thesis, different imaging modalities were combined in order to study the neural basis of cognitive aging. Study I investigated functional connectivity patterns among three large-scale functional brain networks (i.e., default mode [DMN], frontoparietal control [FPN], and dorsal attention [DAN] networks) during rest and task in younger and older adults. The FPN was flexible in its affiliation to other networks, given that it was more functionally connected to the DMN during rest and to the DAN during task performance. Age-related differences were stable across states for the FPN, but were only present for connectivity between the DMN and DAN during the task. Taken together, these results suggest that resting-state is not sufficient to uncover the entire functional connectome of the human brain. Study II identified brain iron as a potential source of age-related differences in connectivity. Greater striatal iron content was associated with lower intrinsic functional connectivity of the caudate and putamen. Additionally, more iron was associated with less connectivity between the putamen and the rest of the brain. Functional connectivity within the putamen was also linked to motor ability, indicating that iron-related connectivity features are behaviorally meaningful. Study III explored the relationship between functional and structural connectivity, and showed that increased homotopic functional connectivity in the prefrontal cortex was associated with worse microstructural degeneration of the corpus callosum, and exacerbated working memory decline. However, given that the association between function and structure was weak, results also suggest that homotopic functional connectivity can be resilient to change in the integrity of its structural paths. Study IV found that dopamine and iron in the putamen were positively associated, but only up until middle age. Together with the fact that dopamine requires iron for its synthesis, these results indicate that, for individuals without excessive iron accumulation, more iron is associated with higher dopaminergic activity. Higher iron load in the putamen was also linked to better processing speed for those in middle age. Collectively, the studies show that functional connectivity is influenced by mental state, white-matter changes, and molecular properties, with the latter also being interrelated among themselves. These different features are associated with performance and interact with each other, suggesting that cognitive decline is linked to a multitude of changes in brain integrity, and that age-related alterations in the human …

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Avelar Pereira, B. (2019). Multimodal imaging : functional, structural, and molecular brain correlates of cognitive aging . (Thesis). Karolinska Institute. Retrieved from http://hdl.handle.net/10616/46826

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Avelar Pereira, Bárbara. “Multimodal imaging : functional, structural, and molecular brain correlates of cognitive aging .” 2019. Thesis, Karolinska Institute. Accessed February 27, 2021. http://hdl.handle.net/10616/46826.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Avelar Pereira, Bárbara. “Multimodal imaging : functional, structural, and molecular brain correlates of cognitive aging .” 2019. Web. 27 Feb 2021.

Vancouver:

Avelar Pereira B. Multimodal imaging : functional, structural, and molecular brain correlates of cognitive aging . [Internet] [Thesis]. Karolinska Institute; 2019. [cited 2021 Feb 27]. Available from: http://hdl.handle.net/10616/46826.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Avelar Pereira B. Multimodal imaging : functional, structural, and molecular brain correlates of cognitive aging . [Thesis]. Karolinska Institute; 2019. Available from: http://hdl.handle.net/10616/46826

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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Open Access Theses and Dissertations