The basic unit of eukaryotic chromatin is the nucleosome core, which contains 147 base pairs of DNA wrapped around an octamer of core histone proteins. Linker histones bind through their globular domain at the nucleosome dyad and to internucleosomal DNA through their C-terminal basic tail. The Saccharomyces cerevisiae linker histone homologue, Hho1p, contains two domains, GI and GII, that have sequence similarity to the globular domain of the canonical linker histone H1. The individual domains of Hho1p differ in their structural and functional properties, for example in 10 mM sodium phosphate GI is folded while GII exists as two species: folded and 'unfolded'. In Chapter 2 the structure of the second globular domain of Hho1p, GII, is further investigated. NMR studies indicate residual structure in the 'unfolded' form of GII, especially at the start of helices I and III. Chapter 3 considers the structural roles of Hho1p within chromatin. Semi-quantitative Western blotting is used to measure the abundance of Hho1p relative to nucleosomes in yeast. Analysis of reconstituted nucleosome arrays containing NGIL (Hho1p with the second globular domain removed) are indistinguishable from those containing full-length Hho1p, in gel-based assays and by analytical ultracentrifugation, suggesting the GII domain may not have a major role in chromatin compaction. Chapter 4 focuses on the interaction of Hho1p with chromatin proteins. Chemical cross-linking and gel filtration indicate that Hho1p does not interact significantly with the putative HMGB1 homologues Hmo1p and Nhp6ap in vitro. Hho1p and Htz1p, the yeast histone H2A.Z subtype, do not appear to interact directly in co-immunoprecipitation and chemical cross-linking assays, while chromatin immunoprecipitation studies show no evidence of colocalisation across the ADH2 and PHO5 genes. Hho1p and Sir2p cross-link in solution, but purification difficulties precluded further investigation. The effect of phosphorylation on the interaction of Hho1p and related truncation proteins with DNA and chromatin are investigated in Chapter 5. Phosphorylation reduces their affinity for linear DNA, but has different effects on the binding to four-way junction DNA for Hho1p and NGIL, compared with LGII (the linker region and GII domain of Hho1p). Phosphorylation has no obvious effect on the affinity of these proteins for chromatin in sucrose gradient centrifugation assays. NMR spectroscopy studies show that the linker region is mostly unstructured, with a short region showing some α-helical character. Phosphorylation of the linker domain changes its structural character.

This research was conducted to determine the effect of Phosphorus 6CH on Attention Deficit Hyperactivity Disorder (ADHD). Phosphorus 6CH is a simplex homoeopathic preparation that through repertorisation of DSM-IV diagnostic criteria of ADHD is found to be well indicated for this disorder. Homoeopathic trials have been conducted previously on complex homoeopathic preparations (Strauss, 1998; Smith, 2001) and have shown overall improvements in the symptoms of ADHD. The use of a simplex homoeopathic remedy has not been effectively documented prior to 2004. ADHD is a commonly diagnosed childhood disorder characterised by inattention, impulsivity, and possibly hyperactivity. Current management of this disorder is predominantly through the use of highly scheduled central nervous system stimulants, which may produce unwanted and serious side effects, and in some children may produce no response at all. A double-blind, placebo controlled clinical trial was conducted. Children between seven and eleven years of age with pre-diagnosed ADHD and taking no other medication for the disorder were included in the trial. Children were randomly assigned to either the medication or the placebo groups. Evaluations were conducted by means of the Barkley and DuPaul Teacher Rating Scale (BDTRS), completed by the child’s teacher, the Parent Symptom Questionnaire (PSQ), completed by the child’s parent or guardian, and the Children’s Checking Task (CCT), completed by the child. Evaluation was conducted before the trial, weekly after two weeks of liquid administration, and again a week after cessation of treatment. Statistical analysis revealed significant improvement in both the BDTRS and the PSQ scores, with the placebo group also showing improvement, although not to as significant a degree as the experimental group. In the CCT, no significant improvement was seen in the total scores of the tests, although there was significant improvement in the time taken to complete the tests. Because of the placebo effect having a large influence on the results of the study, more effective research would need to be done in order to establish whether Phosphorus did in fact account for the more significant improvement found in the experimental group. Further studies need to be conducted on the effect of homeopathic remedies such as Phosphorus, with variable dosage and potency being used. Since all children in the study showed a marked improvement due to the high level of attention met on each child by the teachers and parents involved, it is worth considering a study where no medication is used at all, but where children are given individualised attention and encouragement. It would be a valuable way to assess whether this attention would be sufficient to produce marked improvement in the children over a sustained period of time, or whether the attention given would ultimately no longer be enough but would have to be supplemented with medication. / Dr. Joanne Roohani Mrs. Carolina Henn

Purpose: Adaptive servoventilation (ASV) has been reported to show improvement in patients with sleep-disordered breathing (SDB) and heart failure (HF); however, its role as a second-line or adjunctive treatment is not clear. We conducted a systematic review and meta-analysis of new existing data including cardiac mechanistic factor, geometry, and cardiac biomarkers. Methods: We systematically searched for randomized controlled trials (RCTs) and cohort studies that assessed the efficacy or effectiveness of ASV compared to conventional treatments for SDB and HF in five research databases from their inception to November 2018. Random-effects meta-analyses using the inverse variance method and stratified by study design were performed. Results: We included 15 RCTs (n = 859) and 5 cohorts (n = 162) that met our inclusion criteria. ASV significantly improved left ventricular ejection fraction (LVEF) in cohorts (MD 6.96%, 95% CI 2.58, 11.34, p = 0.002), but not in RCTs. Also, the ASV group had significantly lower apnea-hypopnea index (AHI) in both cohorts (MD − 26.02, 95% CI − 36.94, − 15.10, p < 0.00001) and RCTs (MD − 21.83, 95% CI − 28.17, − 15.49, p < 0.00001). ASV did not significantly decrease the E/e′ ratio in RCTs or in cohorts. Finally, ASV significantly decreased brain natriuretic peptide (BNP) in the cohorts (SMD − 121.99, CI 95% − 186.47, − 57.51, p = 0.0002) but not in RCTs. ASV did not have a significant effect on systolic blood pressure, diastolic blood pressure, and cardiac diameters. Conclusions: ASV therapy is associated with improvements of AHI in comparison to alternative treatments in patients with SDB and HF. ASV did not improve LVEF or E/e′ ratios in randomized trials; other intermediate outcomes did not improve significantly. / Revisión por pares

A dissertation submitted in partial fulfilment for the requirements of the degree of Master of Arts in Clinical Psychology at the University of Zululand, South Africa, 2004. / The use of drug stimulation to treat children who have been diagnosed with Attention Deficit Hyperactivity Disorder (ADHD) sparks much controversy. Parental perception of this practise is crucial since it is the parents that have the task of making this sensitive decision. In order to subjectively explicate parental feelings regarding this issue, a qualitative approach was considered appropriate in this study. The study sought to highlight the views of parents around the use of stimulant medication in the treatment of ADHD. In- depth interviews of the four participants were audio taped and then transcribed verbatim. The interviews were unstructured and an open- ended question guideline was utilised. The interviews underwent stringent thematic analysis. Amongst others, the major themes that emerged were those of guilt, frustration, resignation and the strained mother- child relations associated with infant behaviour and the diagnosis. Findings revealed mixed feelings around the use of medication with Ritalin being the most commonly prescribed. However, even though there are mixed feelings associated with medication use, the positive outcomes of this practise outweigh the negative aspects. Although the benefits are great, the future risk of long-term use of stimulant medication is unknown

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Research on influences of eating disorders have informed diagnosis and treatment of eating disorders, particularly for White cisgender women. A Perfect Biopsychosocial Storm is a theory of influences of disordered eating development: sociocultural influences of rigid body shape and size ideals, high rates of trauma and violence, experiences of objectification and sexualization, and biological changes (Maine & Bunnell, 2010). For transgender individuals, recent findings suggest disparities and negative mental health outcomes such as elevated prevalence of disordered eating, body image concerns, and self-reported disordered eating. For transgender men and women, researchers found that disordered eating may be related to attempts to masculinize/feminize the body, through effects like suppression of weight and secondary sex characteristics. For nonbinary individuals, motivations are unclear regarding masculinization/feminization. Further, while previous research has implicated experiences of marginalization in reduced body appreciation, impact on disordered eating behaviors in nonbinary individuals have yet to be explored. This study addressed gaps in research regarding experiences of nonbinary individuals with disordered eating. Through Grounded Theory qualitative analysis, I developed a framework to understand disordered eating among nonbinary individuals. Disordered eating was the surface-level manifestations of experiences such as trauma, distress surrounding bodily changes in puberty, and marginalization. Repeated marginalization, like misgendering and identity erasure, created conditions of shame to be associated with identity and self. Shame is a universal emotion that occurs when one does something they perceive as social transgressive and, thus, prevents connection. Shame motivates individuals to reduce socially transgressive behavior to increase connection with others. When one experiences marginalization and repeated shame surrounding identity, identity and self then can be experienced as a social transgression that prevents belonging. For example, participants described feelings of shame in comparison to the stereotypical image of a nonbinary person (White, masculine-leaning/androgynous, thin, tall). Disordered eating facilitated emotional coping, and, for some participants, helped achievement of gender presentation. Disordered eating also was associated with consequences of further shame around eating behaviors, and feelings of lack of control. Recovery and healing was supported through combating shame and disempowerment: being seen and empowerment through choice.

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