Effect of cholecalciferol on unsaturated model membranes

Vitamin D plays an important role in many physiological processes, particularly calcium and phosphorous homeostasis. The biochemistry of vitamin D is also complex, encompassing a range of active molecules that may be either endogenous or dietary in origin. The role of lipids and fats in the production, processing and use of vitamin D is an interesting one, with a relative paucity of model studies into the interactions of vitamin D with lipidic systems such as micelles and vesicles. Here, we have studied the effect of vitamin D3 in simple unsaturated phospholipid systems. We used NMR and FTIR spectroscopy to investigate the effect of increasing vitamin D concentration on the structure and dynamics of the lipid chains and interfacial region. In order to link these model studies with more complex biomimetic environments, we compare results in the presence of buffer and vitamin D binding protein. We have also used DLS to determine that vitamin D3-DOPC vesicles can retain their size distribution for varying amounts of time in different conditions. We find that the acyl chain region of vitamin D3-DOPC membranes are generally disordered, and that the addition of buffer and/or protein alters the properties of the interfacial region

Pain in castration-resistant prostate cancer with bone metastases: a qualitative study

<p>Abstract</p> <p>Background</p> <p>Bone metastases are a common painful and debilitating consequence of castration-resistant prostate cancer (CPRC). Bone pain may predict patients' prognosis and there is a need to further explore CRPC patients' experiences of bone pain in the overall context of disease pathology. Due to the subjective nature of pain, assessments of pain severity, onset and progression are reliant on patient assessment. Patient reported outcome (PRO) measures, therefore, are commonly used as key endpoints for evaluating the efficacy of CRPC treatments. Evidence of the content validity of leading PRO measures of pain severity used in CRPC clinical trials is, however, limited.</p> <p>Methods</p> <p>To document patients' experience of CRPC symptoms including pain, and their impact on health-related quality of life (HRQL), semi-structured in-depth qualitative interviews were conducted with 17 patients with CRPC and bone metastases. The content validity of the Present Pain Intensity (PPI) scale from the McGill Pain Questionnaire (MPQ), and the 'Average Pain' and 'Worst Pain' items of the Brief Pain Inventory Short-Form (BPI-SF) was also assessed.</p> <p>Results</p> <p>Patients with CRPC and bone metastases present with a constellation of symptoms that can have a profound effect on HRQL. For patients in this study, bone pain was the most prominent and debilitating symptom associated with their condition. Bone pain was chronic and, despite being generally well-managed by analgesic medication, instances of breakthrough cancer pain (BTcP) were common. Cognitive debriefing of the selected PRO measures of pain severity highlighted difficulties among patients in understanding the verbal response scale (VRS) of the MPQ PPI scale. There were also some inconsistencies in the way in which the BPI-SF 'Average Pain' item was interpreted by patients. In contrast, the BPI-SF 'Worst Pain' item was well understood and interpreted consistently among patients.</p> <p>Conclusions</p> <p>Study findings support the importance of PRO measures of pain severity as key endpoints for evaluating the efficacy of treatments for CRPC, particularly for patients with bone metastases where episodes of BTcP are common. Qualitative evidence from CRPC patients supports the content validity of the BPI-SF ''Worst Pain' item and promotes use of this item for measuring pain severity in this population.</p

Reorganization of mental health services: from institutional to community-based models of care.

Mental health services in the Eastern Mediterranean Region are predominantly centralized and institutionalized, relying on scarce specialist manpower. This creates a major treatment gap for patients with common and disabling mental disorders and places an unnecessary burden on the individual, their family and society. Six steps for reorganization of mental health services in the Region can be outlined: (1) integrate delivery of interventions for priority mental disorders into primary health care and existing priority programmes; (2) systematically strengthen the capacity of non-specialized health personnel for providing mental health care; (3) scale up community-based services (community outreach teams for defined catchment, supported residential facilities, supported employment and family support); (4) establish mental health services in general hospitals for outpatient and acute inpatient care; (5) progressively reduce the number of long-stay beds in mental hospitals through restricting new admissions; and (6) provide transitional/bridge funding over a period of time to scale up community-based services and downsize mental institutions in parallel

Turkdean Roman Villa, Gloucestershire: archaeological investigations 1997-1998

Before the transmission of the first ‘live’ Time Team television programme on 23 August 1997, the existence of a Roman villa near Chalkhill Barn in the parish of Turkdean, 12 miles north-east of Cirencester and 2 miles from the Fosse Way, was hardly known to the archaeological community (FIG. 1). That a Roman building did exist in this location had, however, been suspected for a number of years by the landowner, the late Mr Wilf Mustoe. Distinctive linear parchmarks suggestive of buildings had been clearly visible at ground level in the grass pasture each dry summer, and in 1976 Mr Mustoe made a measured sketch plan of them on the back of an envelope. Subsequently the sketch was drawn up into a scale plan entitled ‘Roman villa’ by Simon Goddard, a relation. There was little knowledge of the site outside of Mr Mustoe's family until it was independently ‘discovered’ by local archaeologist Roger Box in August 1996 whilst fortuitously flying over the site in a helicopter. In the evening light Mr Box instantly recognised the parchmarks of an unmistakable Roman villa and took a series of photographs (FIG. 2). Mr Box showed his photographs to Mr Mustoe, and with his agreement wrote to Time Team suggesting that this would be an excellent site for a television programme. Arrangements were duly set in place and the evidence of the cropmarks was confirmed by a trial geophysical survey in March 199

The pathways to psychiatric care: a cross-cultural study

This paper describes the referral pathways taken by 1554 patients newly referred to the mental health services in 11 countries, and documents factors associated with delays in referral. The pathways in centres relatively well provided with psychiatric staff were dominated by general practitioners and to a lesser extent hospital doctors: the relatively less well resourced centres showed a variety of pathways with native healers often playing an important part. Delays were remarkably short in all centres regardless of psychiatric resources, but in some centres we found longer delays on pathways involving native healers. Somatic problems were a common presentation in all centres, and in some centres there was a tendency for patients presenting with somatic problems to have longer delays than those with symptoms of depression or anxiety. The implications of these findings are discussed in the context of an ongoing programme of WHO research activities aimed at improving the quality of mental illness care available in community setting

Utilisation of the static Evans method to measure magnetic susceptibilities of transition metal acetylacetonate complexes as part of an undergraduate inorganic laboratory class

The Evans method is routinely utilised to collect paramagnetic susceptibility data via the employment of relevant Nuclear Magnetic Resonance (NMR) methods. As the sample is normally spun, the lack of such a function on benchtop NMR instrumentation required a “static” approach to be employed. We have utilised the static Evan’s method approach to measure the magnetic susceptibilities, and subsequently the effective magnetic moment, of a series of synthesised transition metal acetylacetonate complexes in order to appraise the d-electron configuration. The obtained values were compared to those obtained using a Guoy balance and theoretical calculations. The collection of T1 relaxation data further exemplifies the effect of the paramagnetic centre in terms of aiding relaxation, and therefore links to Magnetic Resonance Imaging (MRI) contrast agents, thus providing students with real-world perspective of the experiment conducted

Widespread sex differences in gene expression and splicing in the adult human brain

There is strong evidence to show that men and women differ in terms of neurodevelopment, neurochemistry and susceptibility to neurodegenerative and neuropsychiatric disease. The molecular basis of these differences remains unclear. Progress in this field has been hampered by the lack of genome-wide information on sex differences in gene expression and in particular splicing in the human brain. Here we address this issue by using post-mortem adult human brain and spinal cord samples originating from 137 neuropathologically confirmed control individuals to study whole-genome gene expression and splicing in 12 CNS regions. We show that sex differences in gene expression and splicing are widespread in adult human brain, being detectable in all major brain regions and involving 2.5% of all expressed genes. We give examples of genes where sex-biased expression is both disease-relevant and likely to have functional consequences, and provide evidence suggesting that sex biases in expression may reflect sex-biased gene regulatory structures

Exploring behaviors, treatment beliefs, and barriers to oral chemotherapy adherence among adult leukemia patients in a rural outpatient setting

Objective: Adherence to oral chemotherapy is essential for patients with chronic myeloid leukemia (CML) and multiple myeloma (MM) to remain in remission. Few studies have used a Likert-type scale to measure medication adherence in CML and MM patients. We applied a validated treatment adherence tool, the ASK-12 (Adherence Starts with Knowledge®) survey, which assessed inconvenience and forgetfulness, treatment beliefs, and medication-taking behaviors recorded on a five-point Likert-type scale at two visits. Results: A medication adherence survey was administered to 42 newly diagnosed or pre-existing CML or MM patients at two outpatient oncology clinics affiliated with an academic medical center in rural eastern North Carolina. Thirty-one patients completed surveys at visit 1 and visit 2 (median 4.5 months apart). Most patients were treated for MM (65%), were non-Hispanic black (68%) and female (58%). Within subscales, mean adherence scores decreased between visits, signaling better adherence. Overall, visit scores were correlated (0.63, p = 0.001). Forgetting to take medication sometimes was the most common reason for non-adherence. Medication costs were not a barrier for MM patients. Greater patient–provider informed decision-making was identified as an opportunity for quality improvement among CML patients. The ASK-12 survey provided a strategy to obtain robust information on medication adherence

Disease acceptance and adherence to imatinib in Taiwanese chronic myeloid leukaemia outpatients

Background The launch of imatinib has turned chronic myeloid leukaemia (CML) into a chronic illness due to the dramatic improvement in survival. Several recent studies have demonstrated that poor adherence to imatinib may hamper the therapeutic outcomes and result in increased medical expenditures, whilst research on exploring the reasons for non-adherence to imatinib is still limited. Objective This study aimed to explore the experience of patients as they journey through their CML treatments and associated imatinib utilisation in order to understand the perceptions, attitudes and concerns that may influence adherence to imatinib treatment. Setting This study was conducted at oncology outpatient clinics in a medical centre in southern Taiwan. Methods CML patients who regularly attended the oncology outpatient clinics to receive imatinib treatment from October 2011 to March 2012 were invited to participate in the study. Semi-structured face-to-face interviews were used to explore patients’ experiences and views of their treatment, their current CML status and CML-related health conditions, their concerns about imatinib treatment and imatinib-taking behaviours. Patient interviews were recorded, transcribed verbatim and thematically analysed using the constant comparison approach. Main outcome measure Themes related to patients’ views of the disease and health conditions, worries and concerns influencing imatinib utilisation behaviours are reported. Results Forty-two CML patients participated in the interviews. The emerging themes included: acceptance of current disease and health status, misconceptions about disease progression, factors associated with adherence to imatinib, concerns and management of adverse drug effects. Participants regarded CML as a chronic disease but had misconceptions about disease progression, therapeutic monitoring, resistance to imatinib and symptoms of side effects. Participants were generally adherent to imatinib and favoured long-term prescriptions to avoid regular outpatient visits for medication refills. Experiencing adverse effect was the main reason influencing adherence and led to polypharmacy. Most participants altered medicine-taking behaviours to maintain long-term use of imatinib. Conclusion Taiwanese CML patients are adherent to imatinib but report changing their medication-taking behaviour due to adverse drug effects and associated polypharmacy. Patients’ misconceptions of the disease and medication suggests that it is necessary to improve communication between patients and healthcare professionals. Routinely providing updated information as part of the patient counselling process should be considered as a means of improving this communication