Newly qualified physical education teachers’ experiences of developing subject knowledge prior to, during and after a Postgraduate Certificate in Education course

Office for Standards in Education (OFSTED) inspections of secondary Postgraduate Certificate in Education (PGCE) physical education courses in England between 1996 and 1998 (OFSTED, 1999) were critical of student teachers' subject knowledge. The purpose of this study was to investigate the development of subject knowledge and influences on the development of that subject knowledge in a sample of three newly qualified teachers (NQTs) who had completed a PGCE physical education course in England. The research comprised semi-structured interviews and analysis of documentation. Among these three NQTs there were some similarities, but more differences in terms of the development of subject knowledge as well as different influences on the development of subject knowledge. These results suggest that teacher educators may need to be flexible in how they approach and support the development of student teachers' subject knowledge. Results also suggest that teacher educators should work more closely with colleagues teaching sports-related undergraduate degree courses to support the development of subject knowledge for those students who wish to progress to a PGCE physical education course

Emerging pharmacotherapy of tinnitus

Tinnitus, the perception of sound in the absence of an auditory stimulus, is perceived by about 1 in 10 adults, and for at least 1 in 100, tinnitus severely affects their quality of life. Because tinnitus is frequently associated with irritability, agitation, stress, insomnia, anxiety and depression, the social and economic burdens of tinnitus can be enormous. No curative treatments are available. However, tinnitus symptoms can be alleviated to some extent. The most widespread management therapies consist of auditory stimulation and cognitive behavioral treatment, aiming at improving habituation and coping strategies. Available clinical trials vary in methodological rigor and have been performed for a considerable number of different drugs. None of the investigated drugs have demonstrated providing replicable long-term reduction of tinnitus impact in the majority of patients in excess of placebo effects. Accordingly, there are no FDA or European Medicines Agency approved drugs for the treatment of tinnitus. However, in spite of the lack of evidence, a large variety of different compounds are prescribed off-label. Therefore, more effective pharmacotherapies for this huge and still growing market are desperately needed and even a drug that produces only a small but significant effect would have an enormous therapeutic impact. This review describes current and emerging pharmacotherapies with current difficulties and limitations. In addition, it provides an estimate of the tinnitus market. Finally, it describes recent advances in the tinnitus field which may help overcome obstacles faced in the pharmacological treatment of tinnitus. These include incomplete knowledge of tinnitus pathophysiology, lack of well-established animal models, heterogeneity of different forms of tinnitus, difficulties in tinnitus assessment and outcome measurement and variability in clinical trial methodology. © 2009 Informa UK Ltd.Fil: Langguth, Berthold. Universitat Regensburg; AlemaniaFil: Salvi, Richard. State University of New York; Estados UnidosFil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentin

Challenges to access and provision of palliative care for people who are homeless : a systematic review of qualitative research

Background: People who are homeless or vulnerably housed are a marginalized group who often experience high rates of morbidity and die young as a result of complex problems. Access to health care and support can be challenging, with access to palliative care even more so. This review presents a synthesis of published qualitative research exploring from the perspective of homeless people and those working to support them, current challenges to palliative care access and provision, in addition to suggestions for what may improve palliative care for this population. Methods: Systematic review of qualitative research analysed using thematic synthesis. PsycINFO, Medline, Sociological Abstracts, Social Services Abstracts, Science citations index and CINAHL were searched up to September 2016. Thematic synthesis involved a three-step inductive process to develop a deeper understanding of the challenges to and suggestions for the access and provision of palliative care for homeless people. Results: Thirteen qualitative articles, reporting nine studies were identified. The challenges to access and provision to palliative care were drawn from the data covering three broad areas, namely “the chaotic lifestyles sometimes associated with being homeless”, “the delivery of palliative care within a hostel for homeless people” and provision within “mainstream health care systems”. Obstacles were related to homeless persons competing day-to-day priorities, their experience of stigma in mainstream settings, the high burden on hostel staff in supporting residents at the end of life and inflexibility in mainstream health care systems. Suggestions for improving access to palliative care include building trust between homeless persons and health professionals, increasing collaboration between and flexibility within services, and providing more training and support for all professionals. Conclusions: The provision of palliative care can be complicated for all populations, however delivering palliative care for people who are homeless is influenced by a potentially greater and more varied range of factors, on both individual and systemic levels, than providing palliative care for the housed population. Careful consideration and potentially great changes will be needed within health care systems to ensure homeless populations have equitable access to palliative care

Altered networks in bothersome tinnitus: a functional connectivity study

<p>Abstract</p> <p>Background</p> <p>The objective was to examine functional connectivity linked to the auditory system in patients with bothersome tinnitus. Activity was low frequency (< 0.1 Hz), spontaneous blood oxygenation level-dependent (BOLD) responses at rest. The question was whether the experience of chronic bothersome tinnitus induced changes in synaptic efficacy between co-activated components. Functional connectivity for seed regions in auditory, visual, attention, and control networks was computed across all 2 mm³brain volumes in 17 patients with moderate-severe bothersome tinnitus (<it>Tinnitus Handicap Index: average </it>53.5 ± 3.6 (range 38-76)) and 17 age-matched controls.</p> <p>Results</p> <p>In bothersome tinnitus, negative correlations reciprocally characterized functional connectivity between auditory and occipital/visual cortex. Negative correlations indicate that when BOLD response magnitudes increased in auditory or visual cortex they decreased in the linked visual or auditory cortex, suggesting reciprocally phase reversed activity between functionally connected locations in tinnitus. Both groups showed similar connectivity with positive correlations within the auditory network. Connectivity for primary visual cortex in tinnitus included extensive negative correlations in the ventral attention temporoparietal junction and in the inferior frontal gyrus and rostral insula - executive control network components. Rostral insula and inferior frontal gyrus connectivity in tinnitus also showed greater negative correlations in occipital cortex.</p> <p>Conclusions</p> <p>These results imply that in bothersome tinnitus there is dissociation between activity in auditory cortex and visual, attention and control networks. The reciprocal negative correlations in connectivity between these networks might be maladaptive or reflect adaptations to reduce phantom noise salience and conflict with attention to non-auditory tasks.</p

The Hippocampus Is Coupled with the Default Network during Memory Retrieval but Not during Memory Encoding

The brain's default mode network (DMN) is activated during internally-oriented tasks and shows strong coherence in spontaneous rest activity. Despite a surge of recent interest, the functional role of the DMN remains poorly understood. Interestingly, the DMN activates during retrieval of past events but deactivates during encoding of novel events into memory. One hypothesis is that these opposing effects reflect a difference between attentional orienting towards internal events, such as retrieved memories, vs. external events, such as to-be-encoded stimuli. Another hypothesis is that hippocampal regions are coupled with the DMN during retrieval but decoupled from the DMN during encoding. The present fMRI study investigated these two hypotheses by combining a resting-state coherence analysis with a task that measured the encoding and retrieval of both internally-generated and externally-presented events. Results revealed that the main DMN regions were activated during retrieval but deactivated during encoding. Counter to the internal orienting hypothesis, this pattern was not modulated by whether memory events were internal or external. Consistent with the hippocampal coupling hypothesis, the hippocampus behaved like other DMN regions during retrieval but not during encoding. Taken together, our findings clarify the relationship between the DMN and the neural correlates of memory retrieval and encoding

Tau Reduction Does Not Prevent Motor Deficits in Two Mouse Models of Parkinson's Disease

Many neurodegenerative diseases are increasing in prevalence and cannot be prevented or cured. If they shared common pathogenic mechanisms, treatments targeting such mechanisms might be of benefit in multiple conditions. The tau protein has been implicated in the pathogenesis of diverse neurodegenerative disorders, including Alzheimer's disease (AD) and Parkinson's disease (PD). Tau reduction prevents cognitive deficits, behavioral abnormalities and other pathological changes in multiple AD mouse models. Here we examined whether tau reduction also prevents motor deficits and pathological alterations in two mouse models of PD, generated by unilateral striatal injection of 6-hydroxydopamine (6-OHDA) or transgene-mediated neuronal expression of human wildtype α-synuclein. Both models were evaluated on Tau+/+, Tau+/– and Tau–/– backgrounds in a variety of motor tests. Tau reduction did not prevent motor deficits caused by 6-OHDA and slightly worsened one of them. Tau reduction also did not prevent 6-OHDA-induced loss of dopaminergic terminals in the striatum. Similarly, tau reduction did not prevent motor deficits in α-synuclein transgenic mice. Our results suggest that tau has distinct roles in the pathogeneses of AD and PD and that tau reduction may not be of benefit in the latter condition

Altered Energy Homeostasis and Resistance to Diet-Induced Obesity in KRAP-Deficient Mice

Obesity and related metabolic disorders have become leading causes of adult morbidity and mortality. KRAP (Ki-ras-induced actin-interacting protein) is a cytoskeleton-associated protein and a ubiquitous protein among tissues, originally identified as a cancer-related molecule, however, its physiological roles remain unknown. Here we demonstrate that KRAP-deficient (KRAP−/−) mice show enhanced metabolic rate, decreased adiposity, improved glucose tolerance, hypoinsulinemia and hypoleptinemia. KRAP−/− mice are also protected against high-fat diet-induced obesity and insulin resistance despite of hyperphagia. Notably, glucose uptake in the brown adipose tissue (BAT) in KRAP−/− mice is enhanced in an insulin-independent manner, suggesting that BAT is involved in altered energy homeostasis in KRAP−/− mice, although UCP (Uncoupling protein) expressions are not altered. Of interest is the down-regulation of fatty acid metabolism-related molecules, including acetyl-CoA carboxylase (ACC)-1, ACC-2 and fatty acid synthase in the liver of KRAP−/− mice, which could in part account for the metabolic phenotype in KRAP−/− mice. Thus, KRAP is a novel regulator in whole-body energy homeostasis and may be a therapeutic target in obesity and related diseases

High exposures to bioactivated cyclophosphamide are related to the occurrence of veno-occlusive disease of the liver following high-dose chemotherapy

We investigated whether the occurrence of veno-occlusive disease of the liver (VOD) may be associated with individual variations in the pharmacokinetics of high-dose cyclophosphamide. Patients received single or multiple courses of cyclophosphamide (1000 or 1500 mg m−2 day−1), thiotepa (80 or 120 mg m−2 day−1) and carboplatin (265–400 mg m−2 day−1) (CTC) for 4 consecutive days. The area under the plasma concentration–time curves (AUCs) were calculated for cyclophosphamide and its activated metabolites 4-hydroxycyclophosphamide and phosphoramide mustard based on multiple blood samples. Possible relationships between the AUCs and the occurrence of VOD were studied. A total of 59 patients (115 courses) were included. Four patients experienced VOD after a second CTC course. The first-course AUC of 4-hydroxycyclophosphamide (P=0.003) but not of phosphoramide mustard (P=0.101) appeared to be predictive of the occurrence of VOD after multiple courses. High exposures to bioactivated cyclophosphamide may lead to increased organ toxicity

Evaluation of short‐term safety of ultrasound‐guided foetal fluid sampling in the dog (Canis lupus familiaris)

Background: In humans, analysis of amniotic fluid is widely used for diagnostic and prognostic purposes. Amniocentesis has scarcely been used in veterinary medicine to date, despite a tremendous potential for clinical and research applications in dogs. Our study aimed to establish a safe method for foetal fluid sampling in female dogs. Methods: Two transabdominal ultrasound-guided methods were assessed: the "free hand" and the needle-guided bracket sampling. In addition, through a subsequent routinely scheduled ovariohysterectomy, fluid was directly collected. Samples from 98 conceptuses were collected at day 46.7 +/- 7.5 of pregnancy. Results: The amount of fluid retrieved varied between 0.5 and 5.0 ml per collection. Macroscopic examination of the uterus and conceptuses identified 53% of the puncture sites. Neither fluid leakage nor foetal injury was detected, and six hematomas (5.8%) were visible. Ultrasound-guided foetal fluid collection was found to be potentially safe, and it can be performed by using either transabdominal method. Conclusion: Foetal fluid collection is possible with relative ease and low short-term risk, and may open paths for diagnostic, therapeutic and research purposes in dogs. The procedure can provide new insights into prenatal clinical medicine, including diagnostics of foetal deaths, early identification of heritable diseases and so on

Enhancement of Naringenin Bioavailability by Complexation with Hydroxypropoyl-β-Cyclodextrin

The abundant flavonoid aglycone, naringenin, which is responsible for the bitter taste in grapefruits, has been shown to possess hypolipidemic and anti-inflammatory effects both in vitro and in vivo. Recently, our group demonstrated that naringenin inhibits hepatitis C virus (HCV) production, while others demonstrated its potential in the treatment of hyperlipidemia and diabetes. However, naringenin suffers from low oral bioavailability critically limiting its clinical potential. In this study, we demonstrate that the solubility of naringenin is enhanced by complexation with β-cyclodextrin, an FDA approved excipient. Hydroxypropoyl-β-cyclodextrin (HPβCD), specifically, increased the solubility of naringenin by over 400-fold, and its transport across a Caco-2 model of the gut epithelium by 11-fold. Complexation of naringenin with HPβCD increased its plasma concentrations when fed to rats, with AUC values increasing by 7.4-fold and Cmax increasing 14.6-fold. Moreover, when the complex was administered just prior to a meal it decreased VLDL levels by 42% and increased the rate of glucose clearance by 64% compared to naringenin alone. These effects correlated with increased expression of the PPAR co-activator, PGC1α in both liver and skeletal muscle. Histology and blood chemistry analysis indicated this route of administration was not associated with damage to the intestine, kidney, or liver. These results suggest that the complexation of naringenin with HPβCD is a viable option for the oral delivery of naringenin as a therapeutic entity with applications in the treatment of dyslipidemia, diabetes, and HCV infection.National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) (K01DK080241)Harvard Clinical Nutrition Research Center (P30-DK040561)European Research Council (Starting Grant (TMIHCV 242699))Massachusetts General Hospital (BioMEMS Resource Center (P41 EB-002503))Alexander Silberman Institute of Life Science