Thesis (MMed in Psychiatry) -- University of Limpopo, 2010 / Background: Bipolar disorder is a lifelong illness typically presenting with frequent relapses and/or recurrences. Bipolar disorder carries a high morbidity and mortality and can cause significant functional impairment. In understanding the relapsing course of the illness, chronicity may be reduced by preventing or delaying the occurrence of new episodes. Objectives: The objectives of this study were to establish the prevalence of new episodes in patients with bipolar I disorder and to determine predictors of new episodes. Methods: This was a retrospective, descriptive study based on the review of medical records of patients with bipolar I disorder seen at Dr. George Mukhari Hospital – psychiatry unit between the period of 1 June 2007 to 1 June 2008. Data concerning sociodemographic parameters of the patients and psychiatric information was collected using a data collection sheet. Results: Data was extracted and analysed from a total of 143 patient records. Ninety (63%) experienced new episodes and fifty-three patients (37%) did not have any new episodes. Seventy-nine patients (55%) had one or more manic episodes (mean=0.64) and nineteen (13.38 %) had one or more depressive episodes. (Mean=0.14). The maximum number of new episodes was 2 and the mean was 0.78. The most recent episode was manic in seventy-six patients (84%). The mean number of hospital admissions was 0.88. Of the patients that had new episodes, the age ranged from 18 to more than 55 years, the vast majority were black (94%) and of Christian faith (97%). More than half were female (58%) and single (49%), with 1-2 children (48%). The majority achieved high school education (60%), and were unemployed (70%). Only 47% were receiving a disability grant. New episodes were more prevalent in patients who experienced a younger age of onset of illness (41% in the 18-24 year age group) and who were ill for more than ten years (43%). Less than half had a positive family history of mental illness (43%), 39% had a history of substance use, the most common substance being alcohol (54%), and 39% suffered from one or more comorbid medical illnesses. 78% of the patients who had new episodes were on antipsychotics, 93% were on mood stabilisers, and 69% were on a xii combination of mood stabilisers and antipsychotics. The only factor that was significantly predictive of new episodes was poor compliance. Conclusion: There is a high prevalence of relapse in patients with bipolar I disorder, particularly to the manic pole. Compliance with medication remains a serious problem and is associated with the occurrence of new episodes. Improved treatments should include biopsychosocial strategies, identification of risk factors for relapse/recurrence and early and consistent intervention.

Thesis (M Med (Psychiatry))University of Limpopo (Medunsa Campus), 2010. / Background: Bipolar disorder is a lifelong illness typically presenting with frequent relapses and/or recurrences. Bipolar disorder carries a high morbidity and mortality and can cause significant functional impairment. In understanding the relapsing course of the illness, chronicity may be reduced by preventing or delaying the occurrence of new episodes. Objectives: The objectives of this study were to establish the prevalence of new episodes in patients with bipolar I disorder and to determine predictors of new episodes. Methods: This was a retrospective, descriptive study based on the review of medical records of patients with bipolar I disorder seen at Dr. George Mukhari Hospital – psychiatry unit between the period of 1 June 2007 to 1 June 2008. Data concerning sociodemographic parameters of the patients and psychiatric information was collected using a data collection sheet. Results: Data was extracted and analysed from a total of 143 patient records. Ninety (63%) experienced new episodes and fifty-three patients (37%) did not have any new episodes. Seventy-nine patients (55%) had one or more manic episodes (mean=0.64) and nineteen (13.38 %) had one or more depressive episodes. (Mean=0.14). The maximum number of new episodes was 2 and the mean was 0.78. The most recent episode was manic in seventy-six patients (84%). The mean number of hospital admissions was 0.88. Of the patients that had new episodes, the age ranged from 18 to more than 55 years, the vast majority were black (94%) and of Christian faith (97%). More than half were female (58%) and single (49%), with 1-2 children (48%). The majority achieved high school education (60%), and were unemployed (70%). Only 47% were receiving a disability grant. New episodes were more prevalent in patients who experienced a younger age of onset of illness (41% in the 18-24 year age group) and who were ill for more than ten years (43%). Less than half had a positive family history of mental illness (43%), 39% had a history of substance use, the most common substance being alcohol (54%), and 39% suffered from one or more comorbid medical illnesses. 78% of the patients who had new episodes were on antipsychotics, 93% were on mood stabilisers, and 69% were on a xii combination of mood stabilisers and antipsychotics. The only factor that was significantly predictive of new episodes was poor compliance. Conclusion: There is a high prevalence of relapse in patients with bipolar I disorder, particularly to the manic pole. Compliance with medication remains a serious problem and is associated with the occurrence of new episodes. Improved treatments should include biopsychosocial strategies, identification of risk factors for relapse/recurrence and early and consistent intervention.

<p>Playing related musculoskeletal disorder (PRMD) is common among instrumentalists, professionals, amateurs and music students with a prevalence ranging from 39-47% with an impact on playing and performance. This is synonymous to the prevalence of musculoskeletal disorders among other work population. Risk factors such as lack of warm ups, awkward posture, long playing hours and bad techniques has been consistently indicated as risk factors influencing the incidence of PRMDs among instrumentalists. The aim of this study is to design a warm up programme for instrumentalists. The study population and sample are instrumentalists at the Centre for Performing Arts, University of the Western Cape. A cross sectional study design with a quantitative approach was utilized in this study to determine the prevalence, severity, distribution of PRMDs and its association with quality of life. All the instrumentalists learning or playing a musical instrument of the Centre for Performing Arts was approached to participate in this study. In the first phase of the study, a self administered questionnaire was used to collect data regarding prevalence, distribution and the severity of PRMDs and health related quality of life. The instruments for this study are the standard NORDIC questionnaire for musculoskeletal disorders to determine pain distribution and prevalence, the visual analogue scale to determine the pain severity and the WHOQOL &ndash / BREF, a quality of life questionnaire and an adapted questionnaire to determine the knowledge of instrumentalists about injury prevention strategies. The second phase of the study, a systematic review of evidence was done on the pattern of warm up and practice habits of instrumentalists. The third phase of the study to design the content of the study was done using a Delphi study. The Statistical Package for Social Sciences (SPSS) was used for descriptive and inferential statistics. Chi square was used to determine the association of prevalence, distribution and severity on quality of life. Alpha level was set at 0.05. Ethical clearance and permission to conduct study was sought, written informed consents from participants was sought clearly stating the right to participate and withdraw from study was respected and anonymity and confidentiality was be ensured. The results of the study show that 82.4 % lifetime prevalence and current prevalence of 23.5 % among instrumental musicians in a Centre for Performing Arts. The shoulder (41.2 %), neck (29.4 %) and the wrists and hands (29.4%) are the mostly affected region on the body. The most common symptoms are tightness and soreness. However, the results of the systematic review shows that there is a lack of operational term for warm up in the performing arts and this therefore could be responsible for the variations in the influence of warm up on the prevention of PRMDs. The content of the warm up programme was designed using a Delphi study and stretching and postural awareness were included with musical warm up as part of a regular warm up exercise, although, consensus was not reached on the duration of the warm up programme. Strengthening and conditioning were included to in a different exercise program done three times per week. Education on injury prevention strategies were also included in the programme and the mode of instruction agreed on was active learning and group instruction in classroom. The role of warm up exercise in the prevention of PRMDs using this model could reduce the incidence of PRMDs. However, it is important to note that the programme should be tested in order to determine the overall effect it has on PRMDs.</p>

<p>Playing related musculoskeletal disorder (PRMD) is common among instrumentalists, professionals, amateurs and music students with a prevalence ranging from 39-47% with an impact on playing and performance. This is synonymous to the prevalence of musculoskeletal disorders among other work population. Risk factors such as lack of warm ups, awkward posture, long playing hours and bad techniques has been consistently indicated as risk factors influencing the incidence of PRMDs among instrumentalists. The aim of this study is to design a warm up programme for instrumentalists. The study population and sample are instrumentalists at the Centre for Performing Arts, University of the Western Cape. A cross sectional study design with a quantitative approach was utilized in this study to determine the prevalence, severity, distribution of PRMDs and its association with quality of life. All the instrumentalists learning or playing a musical instrument of the Centre for Performing Arts was approached to participate in this study. In the first phase of the study, a self administered questionnaire was used to collect data regarding prevalence, distribution and the severity of PRMDs and health related quality of life. The instruments for this study are the standard NORDIC questionnaire for musculoskeletal disorders to determine pain distribution and prevalence, the visual analogue scale to determine the pain severity and the WHOQOL &ndash / BREF, a quality of life questionnaire and an adapted questionnaire to determine the knowledge of instrumentalists about injury prevention strategies. The second phase of the study, a systematic review of evidence was done on the pattern of warm up and practice habits of instrumentalists. The third phase of the study to design the content of the study was done using a Delphi study. The Statistical Package for Social Sciences (SPSS) was used for descriptive and inferential statistics. Chi square was used to determine the association of prevalence, distribution and severity on quality of life. Alpha level was set at 0.05. Ethical clearance and permission to conduct study was sought, written informed consents from participants was sought clearly stating the right to participate and withdraw from study was respected and anonymity and confidentiality was be ensured. The results of the study show that 82.4 % lifetime prevalence and current prevalence of 23.5 % among instrumental musicians in a Centre for Performing Arts. The shoulder (41.2 %), neck (29.4 %) and the wrists and hands (29.4%) are the mostly affected region on the body. The most common symptoms are tightness and soreness. However, the results of the systematic review shows that there is a lack of operational term for warm up in the performing arts and this therefore could be responsible for the variations in the influence of warm up on the prevention of PRMDs. The content of the warm up programme was designed using a Delphi study and stretching and postural awareness were included with musical warm up as part of a regular warm up exercise, although, consensus was not reached on the duration of the warm up programme. Strengthening and conditioning were included to in a different exercise program done three times per week. Education on injury prevention strategies were also included in the programme and the mode of instruction agreed on was active learning and group instruction in classroom. The role of warm up exercise in the prevention of PRMDs using this model could reduce the incidence of PRMDs. However, it is important to note that the programme should be tested in order to determine the overall effect it has on PRMDs.</p>

Thesis (doctoral)--Universität Hamburg, 1978.

Submitted to the faculty of the Indiana University School of Informatics Graduate School in partial fulfillment of the requirements for the degree Master of Sciences in Bioinformatics, August 2005 / Reported evidence suggested that high abundance of intrinsic disorder in eukaryotic genomes in comparison to bacteria and archaea may reflect the greater need for disorder-associated signaling and transcriptional regulation in nucleated cells. The major advantage of intrinsically disordered proteins or disordered regions is their inherent plasticity for molecular recognition, and this advantage promotes disordered proteins or disordered regions in binding their targets with high specificity and low affinity and with numerous partners. Although several well-characterized examples of intrinsically disordered proteins in transcriptional regulation have been reported and the biological functions associated with their corresponding structural properties have been examined, so far no specific systematic analysis of intrinsically disordered proteins has been reported. To test for a generalized prevalence of intrinsic disorder in transcriptional regulation, we first used the Predictor Of Natural Disorder Regions (PONDR VL-XT) to systematically analyze the intrinsic disorder in three Transcription Factor (TF) datasets (TFSPTRENR25, TFSPNR25, TFNR25) and two control sets (PDBs25 and RandomACNR25). PONDR VL-XT predicts regions of ≥30 consecutive disordered residues for 94.13%, 85.19%, 82.63%, 54.51%, and 18.64% of the proteins from TFNR25, TFSPNR25, TFSPTRENR25, RandomACNR25, and PDBs25, respectively, indicating significant abundance of intrinsic disorder in TFs as compared to the two control sets. We then used Cumulative Distribution Function (CDF) and charge-hydropathy plots to further confirm this propensity for intrinsic disorder in TFs. The amino acid compositions results showed that the three TF datasets differed significantly 5 from the two control sets. All three TF datasets were substantially depleted in order-promoting residues such as W, F, I, Y, and V, and significantly enriched in disorder-promoting residues such as Q, S, and P. H and C were highly over-represented in TF datasets because nearly a half of TFs contain several zinc-fingers and the most popular type of zinc-finger is C2H2. High occurrence of proline and glutamine in these TF datasets suggests that these residues might contribute to conformational flexibility needed during the process of binding by co-activators or repressors during transcriptional activation or repression. The data for disorder predictions on TF domains showed that the AT-hooks and basic regions of DNA Binding Domains (DBDs) were highly disordered (the overall disorder scores are 99% and 96% respectively). The C2H2 zinc-fingers were predicted to be highly ordered; however, the longer the zinc finger linkers, the higher the predicted magnitude of disorder. Overall, the degree of disorder in TF activation regions was much higher than that in DBDs. Our studies also confirmed that the degree of disorder was significantly higher in eukaryotic TFs than in prokaryotic TFs, and the results reflected the fact that the eukaryotes have well-developed elaborated gene transcription mechanism, and such a system is in great need of TF flexibility. Taken together, our data suggests that intrinsically disordered TFs or partially unstructured regions in TFs play key roles in transcriptional regulation, where folding coupled to binding is a common mechanism.

A thesis submitted to the Faculty of Science, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of Doctor of Philosophy. Johannesburg, 2015. / FOXP2 is the gene product of the so-called “language gene” and is the only protein known to be involved in a monogenetic autosomally inherited language disorder. This disorder has been termed Speech-Language Disorder 1. In addition to the role it plays in language, FOXP2 is thought to be involved in cancer, autism and schizophrenia. FOXP2 is a member of the P subfamily of FOX transcription factors, the DNA-binding domain of which is the forkhead domain. The aim of this work was to investigate the binding mechanism of the FOXP2 forkhead domain and various DNA sequences in order to assess affinity and specificity. It was shown by surface plasmon resonance that the FOXP2 forkhead domain can recognise a variety of DNA sequences, including a novel sequence, identified by systematic evolution of ligands by exponential enrichment. This motif has not previously been reported as a binding motif of the FOXP2 forkhead domain. Kinetic analysis by surface plasmon resonance showed that the novel sequence, as well as other published cognate sequences, each binds to the FOXP2 forkhead domain with different rates and affinities. Molecular docking of the DNA sequences to the FOXP2 forkhead domain revealed that electrostatic interactions between positively charged amino acids and the DNA backbone, as well as basespecific interactions between His554 and the DNA appear to be key in determining rates and affinities of binding interactions of the FOXP2 forkhead domain and DNA. Based on these findings, three types of DNA-binding are proposed for the FOXP2 forkhead domain. These types are: low affinity, nonfunctional binding; moderate affinity, non-functional binding and high affinity, functional binding. It is probable that each type of binding serves to control the vii spatial location of the protein within the nucleus, as well as the local concentration of protein. The proposed mechanism of binding for the forkhead domain of FOXP2 may have a future impact on the binding and function of full length FOXP2.

The study was based on the clinical data summaries ("item sheets") of children who attended the Maudsley Hospital during the late 1960s and early 1970s. These summaries were used to identify a group of 80 child and adolescent psychiatric patients with an operationally defined depressive syndrome. The depressed children were individually matched with 80 non-depressed psychiatric controls on demographic variables and non-depressive childhood symptoms by a computer algorithm. At follow-up, on average 18 years after the initial contact, information was obtained on the adult psychiatric status of 82% of the total sample. Adult assessments were made "blind" to case/control status, and included standardized measures of "lifetime" psychiatric disorder and psychosocial functioning. The depressed group was at increased risk for affective disorder in adult life, and had elevated risks of psychiatric hospitalization and psychiatric treatment. Depressed children were no more likely than control children to have non-depressive adult psychiatric disorders. These findings suggest that there is substantial specificity in the continuity of affective disturbances between childhood and adult life.

Thesis (doctoral)--University of Uppsala, 1981. / Bibliography: p. 47-56.

Thesis (Ph.D.)--Boston University / Research suggests that "eating disorder not otherwise specified" (EDNOS) is particularly prevalent among individuals with borderline personality disorder (BPD). However, longitudinal data concerning course and predictors of outcome among different subtypes of EDNOS are scarce, particularly with comorbid BPD. The purpose of this study was to examine the longitudinal course of ED NOS subtypes and baseline predictors of outcome of ED NOS over 1 0 years of prospective follow-up in borderline patients. Two hundred and ninety patients who met Revised Diagnostic Interview for Borderlines (DIB-R) and Diagnostic and Statistical Manual of Mental Disorders, 3rd Edition, Revised (DSM-111-R) criteria for BPD were followed prospectively over 10 years. Five subtypes of Structured Clinical Interview for DSM-111-R Axis I Disorders (SCID-1) diagnosed EDNOS were identified: subthreshold anorexia nervosa (AN) above the low-weight cut-off; subthreshold AN without loss of menses, subthreshold bulimia nervosa (BN); binge eating disorder (BED); and purging disorder. At baseline, 20% of the sample met criteria for an EDNOS subtype. In the first study, generalized estimating equations were first conducted to determine the prevalence of EDNOS subtypes over time. We used Kaplan-Meier survival analyses to examine time-to-remission, recurrence, and new onsets of the EDNOS subtypes. In the second study, baseline body mass index (BMI), socioeconomic status (SES), global assessment of functioning (GAF), social security disability income (SSOI), polypharmacy, and severity of childhood neglect, sexual abuse, and "other abuse" (e.g., physical, verbal, emotional) were examined as predictors of the course of EDNOS. Findings from the first study indicate that over time, rates of EDNOS were observed to decrease, and remissions were common. Among the EDNOS subtypes, BED was observed to have a particularly slow rate of remission and moderate rates of new onsets. Subthreshold AN without low weight had high rates of recurrence and new onsets. Findings of the second study indicate that borderline patients with EDNOS who were receiving SSDI at baseline were less likely to experience a remission of EDNOS and more likely to experience a recurrence. Additionally, severity of childhood adversity predicted new onsets of EDNOS. Findings suggest that receiving SSOI and severity of childhood adversity importantly impact the course of EDNOS in BPD.