Effects of prenatal dexamethasone exposure on adult C57BL/6J mouse metabolism and oxidative stress.

Prenatal glucocorticoid exposure has been shown to alter hypothalamic-pituitary-adrenal axis function resulting in altered fetal development that can persist through adulthood. Fetal exposure to excess dexamethasone, a synthetic glucocorticoid, has been shown to alter adult behaviour and metabolism. This study investigated the effects prenatal dexamethasone exposure had on adult offspring cardiac and liver metabolism and oxidative stress. Pregnant C57BL/6 mice received a dose of 0.4 mg/kg dexamethasone on gestational days 15-17. Once pups were approximately 7 months old, glucose uptake was determined using positron emission tomography and insulin resistance (IR) was determined by homeostatic model assessment (HOMA) IR calculation. Oxidative stress was assessed by measuring 4-hydroxynonenal protein adduct formation and total reactive oxygen species. Female dexamethasone group had significantly increased glucose uptake when insulin stimulated compared to vehicle-treated mice. HOMA IR revealed no evidence of IR in either male or female offspring. There was also no change in oxidative stress markers in either cardiac or liver tissues of male or female offspring. These data suggest that prenatal dexamethasone exposure in male mice does not alter oxidative stress or metabolism. However, prenatal dexamethasone exposure increased glucocorticoids, cardiac glucose uptake, and pAkt signaling in female heart tissues in adult mice, suggesting there are sex differences in prenatal dexamethasone exposure.

The effects of exercise and active assisted cycle ergometry in post-operative total knee arthroplasty patients - a randomized controlled trial.

PURPOSE: The purpose of this study was to examine the effect of the use of an active assisted cycle ergometer as an adjunct to post-operative treatment following total knee arthroplasty. METHOD: A total of 55 participants aged 50-80 years who had undergone unilateral total knee arthroplasty were randomly assigned to either the control group (standard of care) or the active assisted cycle ergometer (AACE) group. The effect on patient motivation, blood biomarkers, and knee pain, function, range of motion (ROM), strength, and swelling was examined. Qualitative feedback was also obtained post-operatively. RESULTS: Although there was no statistically significant difference in the standard of care compared to the AACE group, there was a trend for a greater reduction in knee pain on the visual analog scale, improved Lower Extremity Functional Scale scores, and knee extension ROM and strength. A greater percentage of the experimental group demonstrated higher motivation. There was no significant difference in swelling or blood biomarker measures. Qualitative feedback from the AACE group post-operatively was also positive. CONCLUSIONS: The use of an AACE protocol as an adjunct to total knee arthroplasty rehabilitation may improve post-operative clinical outcomes. This study has been registered at clinicaltrials.gov (identifier NCT02265523 , Oct 16 2014). LEVEL OF EVIDENCE: Level 1 - randomized controlled trial. Further research with a larger sample size is needed to confirm the benefits of the ergometer use.

Intervention with Microfinance for AIDS and Gender Equity (IMAGE): Women's Engagement with the Scaled-up IMAGE Programme and Experience of Intimate Partner Violence in Rural South Africa.

The Intervention with Microfinance for AIDS and Gender Equity (IMAGE) programme has been scaled up to three provinces in South Africa. This paper explores associations between women's engagement in the intervention, intimate partner violence (IPV) and factors associated with IPV and partner abuse. We enrolled women receiving group-based microfinance loans plus gender training into the scaled-up IMAGE cohort study (n = 860). We present cross-sectional analysis on participants' characteristics and intervention engagement and use multivariate logistic regression to explore associations. 17% of women reported lifetime (95% CI 15 to 20%) and 7% past year (95% CI 5 to 9%) IPV, 9% past-year economic (95% CI 7 to 11%) and 11% past-year emotional (95% CI 9 to 14%) abuse. Women under 35 years had higher levels of IPV and emotional abuse. 53% of women attended all the trainings, 83% continuously borrowed and 98% agreed the training had a major impact on their life. Attendance was associated with improved partner relationships (χ2p < 0.001), but not lower IPV risk. Odds of past-year IPV decreased the more types of support (e.g. advice) women received from group members (aOR 0.27, p < 0.001 among those reporting all support versus none or some). A similar pattern was seen for economic, but not emotional, abuse. The scaled-up IMAGE intervention is widely acceptable and may support improvements in partner relationships, but younger women need to be targeted. Group support appears to be a potentially important component of the intervention.

N-Alkylated aziridines are easily-prepared, potent, specific and cell-permeable covalent inhibitors of human ß-glucocerebrosidase.

ß-Glucocerebrosidase deficiency leads to Gaucher disease and is a potential marker of Parkinson's disease. We have identified N-octyl conduritol aziridine as a potent and specific covalent inactivator of GBA1 in living cells. This compound is a promising lead towards a positron emission tomography probe intended to image GBA1 activity.

The role of partnership dynamics in determining the acceptability of condoms and microbicides.

Microbicides are a class of substances under development that could reduce the sexual transmission of HIV and other sexually transmitted diseases when applied locally to genital mucosal surfaces. Microbicide acceptability research has largely focused on product characteristics, rather than processes of negotiation within relationships about use. Gender relations, decision-making power and communication within sexual relationships are recognised as important determinants of condom and contraceptive use, and are likely to determine microbicide use also. As part of social science research linked to the Microbicides Development Programme (MDP) we combine relationship-based theories with anthropological work conducted with women and men using a placebo gel. We explore communication and decision-making in gel and condom use, including constructions of risk and trust. During the MDP301 Phase III pilot study, in-depth interviews were conducted at sites in South Africa, Tanzania, Uganda and Zambia. Following four weeks of placebo gel use, women and their partners were asked about gel use and acceptability, partner involvement, sexual practices and condom use. Data from 45 couples at five sites were analysed using a grounded theory approach in NVivo. Participation in the study did not require women to inform their partners, yet our data shows women seeking permission from their partners, negotiating disclosure, exchanging information and persuading or motivating for gel use. Although gel was supposedly 'woman-controlled', men exercised considerable influence in determining whether and how it was used. Despite this, negotiations around use were largely successful, since the gel increased sexual pleasure and provided opportunities for intimate communication and the building of trust. Decisions about condom and microbicide use are made in a dyadic context and involve a complex negotiation of risk and trust. Whilst preferences relating to product characteristics are largely individual, use itself is dependent on partnership dynamics and the broader social context in which sexual risk management occurs.

p21(Cip1) expression is increased in ambient oxygen, compared to estimated physiological (5%) levels in rat muscle precursor cell culture.

OBJECTIVE: While it is common practice to culture cells in the presence of ambient oxygen (approximately 21% O2), O2 level observed in the physiological environment is often much lower. Previous efforts to culture a variety of different stem cells, including muscle precursor cells (MPC), under O2 conditions that better mimic in vivo conditions have resulted in enhanced proliferation. In the present study, we hypothesized that 20% O2 in culture represents a sufficient stimulus to cause increased expression of two key negative regulators of the cell-cycle Cip/Kip family of cyclin-dependent kinase inhibitors, p21(Cip1) and p27(Kip1), in MPCs. MATERIALS AND METHODS: MPCs were isolated from Fischer 344 x Brown Norway F(1) hybrid male rats and O2 was adjusted in culture using a tri-gas incubator. RESULTS: 5-Bromo-2'-deoxyuridine incorporation, cell number and nuclear proliferating cell nuclear antigen expression were all decreased after 48 h culture in 20% O2, compared to 5% O2. Twenty per cent O2 had no effect on either p27(Kip1) promoter activity or protein expression. Although p21(Cip1) promoter activity remained unchanged between 5% and 20% O2, there were significant increases in both p21(Cip1) mRNA and protein expression. Furthermore, 20% O2 caused an increase in p21(Cip1) mRNA stability and p53 transcription factor activity. CONCLUSION: These findings are considered important because they reveal p21(Cip1) as a critical regulatory protein that needs to be considered when interpreting proliferation data from MPCs studied in culture. In addition, O2-dependent regulation of MPC proliferation is relevant to conditions, including sarcopenia, heart failure, cancer and muscular dystrophy, where increased oxidative stress exists.

An exploration of the meanings and experiences of cancer of Chinese people living and working in London.

This paper investigates the meanings and experiences of cancer of Chinese people living and working in London, in order to help the future development of culturally sensitive cancer information for Chinese people in the United Kingdom. A focus group interview method was used. Five focus groups (n = 35) were conducted in 2003 in London; these included Chinese health professionals, asylum seekers, immigrants with unknown status, Chinese young adults and Chinese elders. We found that the participants' understanding of cancer reflected Chinese cultural beliefs about health and illness. There are some misunderstandings and lack of knowledge and information about cancer treatments, but they understand cancer to be life threatening. There is also a great reluctance to talk about cancer. The participants suggested that as well as receiving appropriate and early treatment, by either biomedicine or traditional Chinese medicine, or preferably, a combination of the two, an individual's chances of surviving cancer could be enhanced by being provided with spiritual guidance and by being in a happy, positive mood. There is a need to improve knowledge about cancer in the Chinese community through the provision of culturally appropriate and accessible information on a variety of topics, including healthy lifestyles, cancer prevention and treatments, and by encouraging openness about cancer issues.

Immunotoxicology of beryllium lung disease

Beryllium induces non-caseating granulomatous inflammation in humans exposed to the metal dust or fumes in both occupational and non-occupational settings. The resulting condition, chronic beryllium disease (CBD), affects principally the lungs, lymphatics, and skin and continues to plague modern industry. Beryllium exerts several important immunotoxic effects, including induction of a beryllium-antigen specific adaptive immune response and the triggering of inflammatory and innate immune responses. Genetic susceptibility plays a role in CBD adaptive immune responses, mainly mediated through single nucleotide polymorphisms in HLA-DP and, to a lesser extent, HLA-DR. The adaptive response is characterized by influx and proliferation of CD4+ central and effector memory T cells expressing Th1 cytokines. Insights into the immunopathogenesis of CBD have implications for the understanding of other immune-mediated granulomatous disorders and for metal antigen behavior.

Glycogen debranching enzyme is associated with rat skeletal muscle sarcoplasmic reticulum.

AIMS: Gel electrophoresis revealed a band of molecular weight approximately 160 000 Da associated with the skeletal muscle sarcoplasmic reticulum (SR) vesicle preparations. This investigation sought to examine glycogen debranching enzyme associated with skeletal muscle SR. METHODS: Sarcoplasmic reticulum samples were also taken from muscle whose glycogen content had been reduced either via stimulation of the sciatic nerve or alpha-amylase treatment of muscle homogenates. RESULTS: The stimulation protocol reduced whole muscle glycogen by 86% (7.4 +/- 0.4 vs. 1.0 +/- 0.3 microg mg(-1) wet mass, P < or = 0.05). Glycogen associated with the SR was reduced by 82% in the stimulation protocol (533 +/- 82 vs. 96 +/- 7 microg mg(-1) protein) and by 94% in alpha-amylase treatment (493 +/- 11 vs. 29 +/- 2 microg mg(-1) protein), respectively. Gel electrophoresis and Western blots revealed that the content of glycogen debranching enzyme was reduced by approximately 53% as a result of muscle stimulation and by approximately 46% in alpha-amylase treatment (P < or = 0.05). In addition, glycogen debranching enzyme activity was reduced by 61% in stimulated samples compared with control (20.3 +/- 1.0 vs. 8.0 +/- 1.2 nmol mg(-1) min(-1), respectively), a value consistent with reductions observed from gel electrophoresis and Western blots. CONCLUSION: These results confirm that similar to glycogen phosphorylase, glycogen debranching enzyme is associated with the skeletal muscle SR and is dissociated under exercise conditions.

Ethiopian refugees in the UK: migration, adaptation and settlement experiences and their relevance to health.

OBJECTIVE: The study explores Ethiopian refugees' and asylum seekers' experiences of migration, adaptation and settlement in the UK and their health beliefs and practices. DESIGN: Data was collected using semi-structured depth interviews and a semi-structured questionnaire. The sample consisted of 106 Ethiopians resident in the UK. RESULTS: The majority of the participants fled Ethiopia due to political reasons. Whilst 65% of them had lived in the UK for over five years only 7% had full refugee status. Many of the participants faced difficulties with the immigration system, housing and social services and felt socially isolated. Many also had problems with gaining employment or employment appropriate to their qualifications, and 29% were unemployed. The majority of the participants believe that happiness is a prerequisite to healthiness and also an indication of healthiness. On the other hand the majority believed that sickness is caused by disease and mental illness is caused by both supernatural and psychosocial causes. Most of the participants sought the help of their GP in the first instance of illness although some had experienced difficulties accessing health services due to language problems and poor understanding of the primary healthcare system. The participants also believed that the stress of adaptation and settlement affected their mental health and led to depression. CONCLUSION: Migration, adaptation and settlement experiences impact on the health of refugees and are dependent on a number of barriers and enablers, both at a personal and societal level. These should be taken into account in the provision of health and social care services, in particular services should be provided in a culturally competent manner.

Cancer and communication: similarities and differences of men with cancer from six different ethnic groups.

This paper reports the communication aspects of a pilot study, which explored the cancer meanings and experiences of six men with cancer and their significant others from different ethnic groups. A case study design was applied using the principles of phenomenology. In-depth semi-structured individual interviews were conducted in participants' own homes, in London, UK. This paper will only deal with the communication aspects of the findings. Ten themes emerged from the comparative analysis of the study's data, with communication as a cross-cutting theme. Further analysis of this theme revealed similarities and differences of the participants' experiences of communicating with health professionals; families or friends; and God/Allah. In addition, similarities and differences in communicating meanings of cancer in different cultures were revealed. The findings revealed similarities in the way that men from these six cultures communicate with health professionals and their families following a diagnosis of cancer, and differences in how they communicated with God/Allah, which depended on their religious beliefs and practices.

A phase II study of carboplatin and vinorelbine in patients with poor prognosis small cell lung cancer.

AIM: The aim of this study was to evaluate the activity of the combination of carboplatin and vinorelbine in patients with poor prognosis small cell lung cancer (SCLC). Patients with good prognosis disease were included who were not medically fit to tolerate conventional chemotherapy. Activity was assessed primarily as response rate and secondarily in terms of toxicity, time to progression and survival. PATIENTS AND METHODS: Fifty-eight patients, 37 men and 21 women, with histologically or cytologically confirmed SCLC, who had bi-dimensionally measurable disease, with ECOG performance status > or = 2, with adequate haematological, hepatic and renal function received first-line chemotherapy with carboplatin (AUC x 5) day 1 and vinorelbine (30 mg/m2) days 1 and 8 of a 28-day cycle. Response was assessed after every two cycles of chemotherapy, with patients receiving a maximum of six cycles of treatment. RESULTS: The combination of carboplatin and vinorelbine is an active regimen in the treatment of SCLC, with an overall intention-to-treat response rate of 55% [95% confidence interval (CI): 42-68%] with six (10%) of patients having a complete response. Median time to progression was 18 weeks (95% CI: 15-21 weeks). Median overall survival was 26 weeks (95% CI: 21-31 weeks). Ten patients failed to complete two cycles of treatment, and were not evaluable for response for the following reasons: septic death (1 neutropaenic, 1 no myelotoxicity), non-toxic death (1 tumour eroded through the pulmonary artery, 1 ischaemic heart disease) ischaemic heart disease (1) and patient decision (5). There were a total of three toxic deaths all sepsis-complicating neutropaenia. Forty-four (76%) patients experienced grade 3 or 4 neutropaenia, six (11%) grade 3 or 4 thrombocytopaenia, 10 (13%) grade 3 lethargy, three (5%) grade 3 nausea and two (3%) grade 3 diarrhoea. CONCLUSIONS: The combination of carboplatin and vinorelbine is active against SCLC but the toxicity profile in this group of patients suggests that further evaluation is not appropriate.

Glycogen and glycogen phosphorylase associated with sarcoplasmic reticulum: effects of fatiguing activity.

The purpose of the present study was to investigate the effects of fatiguing muscular activity on glycogen, glycogen phosphorylase (GP), and Ca(2+) uptake associated with the sarcoplasmic reticulum (SR). Tetanic contractions (100 ms, 75 Hz) of the gastrocnemius and plantaris muscles, elicited once per second for 15 min, significantly reduced force to 26.5 +/- 4.0% and whole muscle glycogen to 23% of rested levels. SR glycogen levels were 415.4 +/- 76.6 and 20.4 +/- 2.1 microg/mg SR protein in rested and fatigued samples, respectively. The optical density of GP from SDS-PAGE was reduced to 21% of control, whereas pyridoxal 5'-phosphate concentration, a quantitative indicator of GP content, was significantly reduced to 3% of control. GP activity after exercise, in the direction of glycogen breakdown, was reduced to 4% of control. Maximum SR Ca(2+) uptake rate was also significantly reduced to 81% of control. These data demonstrate that glycogen and GP associated with skeletal muscle SR are reduced after fatiguing activity.

The revised Beliefs About Voices Questionnaire (BAVQ-R).

BACKGROUND: We present a revised Beliefs About Voices Questionnaire (BAVQ-R), a self-report measure of patients' beliefs, emotions and behaviour about auditory hallucinations. AIMS: To improve measurement of omnipotence, a pivotal concept in understanding auditory hallucinations, and elucidate links between beliefs about voices, anxiety and depression. METHODS: Seventy-one participants with chronic auditory hallucinations completed the BAVQ-R, and 58 also completed the Hospital Anxiety and Depression Scale. RESULTS: The mean Cronbach's alpha for the five sub-scales was 0.86 (range 0.74-0.88). The study supports hypotheses about links between beliefs, emotions and behaviour, and presents original data on how these relate to the new omnipotence sub-scale. Original data are also presented on connections with anxiety and depression. CONCLUSIONS: The BAVQ-R is more reliable and sensitive to individual differences than the original version, and reliably measures omnipotence.

Nursing students' early exposure to clinical practice: an innovation in curriculum development.

This paper describes a pilot study addressing issues surrounding the balance and status given to both theory and practice in the foundation part of a pre-registration programme. Contemporary thinking seems to suggest that there is a need to reverse recent trends which have placed an emphasis on theory. To facilitate this a framework for clinical learning was adapted to guide students' early exposure to clinical practice. The focus was to develop the students' observational and reflective skills whilst also providing the students with a frame of reference within which they could explore their theoretical studies. The information and experiences gained as a result of this study have led to the integration of an Orientation Framework to support students' early clinical experiences in a pre-registration programme.

Cancer and men from minority ethnic groups: an exploration of the literature.

The authors reviewed literature which has been published in the last 20 years. Cancer is the second leading cause of death in developed countries and is expected to become a significant cause of death in developing countries. Whilst there are a large number of studies on cancer and men, there is a paucity of data on men from minority ethnic groups. In the USA, African Americans are more likely to develop cancer than any other ethnic group. Although cancer rates amongst minority ethnic groups in the UK are thought to be low, 11% of Indian and African men and 19% of Caribbean men died from cancer during 1979-1983. There is also further evidence in the USA that African American, Filipinos and Native Americans have the lowest cancer survival rates. Service utilization, especially tertiary care, is also thought to be low amongst minority ethnic groups from the USA and the UK. Reasons for these variations include artefactual, cultural, materialist and social selectivist explanations as well as the effects of migration, racism and genetic disposition. This area is under-researched, in particular cultural beliefs about cancer. Further research into this area should apply culturally competent methods to ensure valid data to inform cancer policy, education and practice.

Benefits of nurse teachers returning to clinical practice.

This article outlines an action research study developed to facilitate nurse teachers returning to clinical practice. The article explores how the teachers established partnerships with clinicians through which they were able to share the experience of returning to an area of nursing that they had previously only visited. It discusses four categories: expectations of self and others; entering someone else's world; more awareness of student needs; and teaching theory and practising nursing. These categories emerged following the analysis of journals, focus group interviews and individual interviews and led to a number of recommendations concerning the implications for other teachers wishing to return to clinical practice.

Interpreting the equatorial diffraction pattern of collagenous tissues in the light of molecular motion.

The equatorial diffraction pattern associated with collagenous tissues, particularly type I collagen, is diffuse and clearly unlike that from crystals. Hukins and Woodhead-Galloway proposed a statistical model that they termed a "liquid crystal" for collagen fibers in tendons. Fratzl et al. applied this model to both unmineralized and mineralized turkey leg tendon, a model that ignores the organization imposed by the well-known cross-linking. The justification for adopting this model is that the curve fits the data. It is shown that the data can be equally well matched by fitting a least-squares curve consisting of a second-order polynomial plus a Gaussian. The peak of the Gaussian is taken as the equatorial spacing of the collagen. A physical explanation for this model is given, as is a reason for the changes in the spacing with changes in water content of the tissue. The diffusion is attributed to thermally driven agitation of the molecules, in accordance with the Debye-Waller theory including the Gaussian distribution. The remainder of the diffusion is attributed to other scattering sources like the mineral crystallites.