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FLAVONOIDS, TRP channels, INTRACELLULAR calcium, TRADITIONAL medicine, CHROMONES, CALCIUM metabolism, ANIMAL experimentation, CARRIER proteins, CELLS, CHEMICAL elements, COMPARATIVE studies, EPITHELIAL cells, RESEARCH methodology, MEDICAL cooperation, MICE, RESEARCH, RESEARCH funding, and EVALUATION research

Background and Purpose: The TRPC5 proteins assemble to create calcium-permeable, non-selective, cationic channels. We sought novel modulators of these channels through studies of natural products.Experimental Approach: Intracellular calcium measurements and patch clamp recordings were made from cell lines. Compounds were generated by synthetic chemistry.Key Results: Through a screen of natural products used in traditional Chinese medicines, the flavonol galangin was identified as an inhibitor of lanthanide-evoked calcium entry in TRPC5 overexpressing HEK 293 cells (IC50 0.45 μM). Galangin also inhibited lanthanide-evoked TRPC5-mediated current in whole-cell and outside-out patch recordings. In differentiated 3T3-L1 cells, it inhibited constitutive and lanthanide-evoked calcium entry through endogenous TRPC5-containing channels. The related natural flavonols, kaempferol and quercetin were less potent inhibitors of TRPC5. Myricetin and luteolin lacked effect, and apigenin was a stimulator. Based on structure-activity relationship studies with natural and synthetic flavonols, we designed 3,5,7-trihydroxy-2-(2-bromophenyl)-4H-chromen-4-one (AM12), which inhibited lanthanide-evoked TRPC5 activity with an IC50 of 0.28 μM. AM12 also inhibited TRPC5 activity evoked by the agonist (-)-Englerin A and was effective in excised outside-out membrane patches, suggesting a relatively direct effect. It inhibited TRPC4 channels similarly, but its inhibitory effect on TRPC1-TRPC5 heteromeric channels was weaker.Conclusions and Implications: The data suggest that galangin (a natural product from the ginger family) is a TRPC5 inhibitor and that other natural and synthetic flavonoids contain antagonist or agonist capabilities at TRPC5 and closely related channels depending on the substitution patterns of both the chromone core and the phenyl ring. [ABSTRACT FROM AUTHOR]

ATHEROSCLEROSIS treatment, TYPE 2 diabetes treatment, GLUCOSE intolerance, THERAPEUTIC use of monoclonal antibodies, DISEASE progression, ATHEROSCLEROSIS complications, TYPE 2 diabetes complications, ARTERIES, ATHEROSCLEROSIS, CLINICAL trials, COMPARATIVE studies, INTERLEUKIN-1, RESEARCH methodology, MEDICAL cooperation, MONOCLONAL antibodies, RESEARCH, EVALUATION research, RANDOMIZED controlled trials, BLIND experiment, CHEMICAL inhibitors, and DISEASE complications

Background: Evidence suggests that interleukin (IL)-1β is important in the pathogenesis of atherosclerosis and its complications and that inhibiting IL-1β may favorably affect vascular disease progression.Objectives: The goal of this study was to evaluate the effects of IL-1β inhibition with canakinumab versus placebo on arterial structure and function, determined by magnetic resonance imaging.Methods: Patients (N = 189) with atherosclerotic disease and either type 2 diabetes mellitus or impaired glucose tolerance were randomized to receive placebo (n = 94) or canakinumab 150 mg monthly (n = 95) for 12 months. They underwent magnetic resonance imaging of the carotid arteries and aorta.Results: There were no statistically significant differences between canakinumab compared with placebo in the primary efficacy and safety endpoints. There was no statistically significant change in mean carotid wall area and no effect on aortic distensibility, measured at 3 separate anatomic sites. The change in mean carotid artery wall area was -3.37 mm2 after 12 months with canakinumab versus placebo. High-sensitivity C-reactive protein was significantly reduced by canakinumab compared with placebo at 3 months (geometric mean ratio [GMR]: 0.568; 95% confidence interval [CI]: 0.436 to 0.740; p < 0.0001) and 12 months (GMR: 0.56; 95% CI: 0.414 to 0.758; p = 0.0002). Lipoprotein(a) levels were reduced by canakinumab compared with placebo (-4.30 mg/dl [range: -8.5 to -0.55 mg/dl]; p = 0.025] at 12 months), but triglyceride levels increased (GMR: 1.20; 95% CI: 1.046 to 1.380; p = 0.01). In these patients with type 2 diabetes mellitus or impaired glucose tolerance, canakinumab had no effect compared with placebo on any of the measures assessed by using a standard oral glucose tolerance test.Conclusions: There were no statistically significant effects of canakinumab on measures of vascular structure or function. Canakinumab reduced markers of inflammation (high-sensitivity C-reactive protein and interleukin-6), and there were modest increases in levels of total cholesterol and triglycerides. (Safety & Effectiveness on Vascular Structure and Function of ACZ885 in Atherosclerosis and Either T2DM or IGT Patients; NCT00995930). [ABSTRACT FROM AUTHOR]

DIARRHEA -- Risk factors, GERIATRIC assessment, ANTIBIOTICS, CLOSTRIDIUM diseases, CONFIDENCE intervals, DIARRHEA, DRUG prescribing, FACTOR analysis, FRAIL elderly, LONGITUDINAL method, MEDICAL cooperation, NURSING home patients, NURSING care facilities, NUTRITIONAL assessment, PROBABILITY theory, RESEARCH, RESEARCH funding, STATISTICS, PHYSICIAN practice patterns, MULTIPLE regression analysis, PROPORTIONAL hazards models, DATA analysis software, DESCRIPTIVE statistics, and ODDS ratio

Background: the risk factors for and frequency of antibiotic prescription and antibiotic-associated diarrhoea (AAD) among care home residents are unknown. Aim: to prospectively study frequency and risks for antibiotic prescribing and AAD for care home residents. Design and setting: a 12-month prospective cohort study in care homes across South Wales. Method: antibiotic prescriptions and the development of AAD were recorded on case report forms. We defined AAD as three or more loose stools in a 24-h period occurring within 8 weeks of exposure to an antibiotic. Results: we recruited 279 residents from 10 care homes. The incidence of antibiotic prescriptions was 2.16 prescriptions per resident year (95% CI: 1.90-2.46). Antibiotics were less likely to be prescribed to residents from dual-registered homes (OR compared with nursing homes: 0.38, 95% CI: 0.18-0.79). For those who were prescribed antibiotics, the incidence of AAD was 0.57 episodes per resident year (95% CI: 0.41-0.81 episodes). AAD was more likely in residents who were prescribed coamoxiclav (hazards ratio, HR = 2.08, 95% confidence interval, CI: 1.18-3.66) or routinely used incontinence pads (HR = 2.54, 95% CI: 1.26-5.13) and less likely in residents from residential homes (HR compared with nursing homes: 0.14, 95% CI: 0.06-0.32). Conclusion: residents of care homes, particularly of nursing homes, are frequently prescribed antibiotics and often experience diarrhoea following such prescriptions. Co-amoxiclav is associated with greater risk of AAD. [ABSTRACT FROM AUTHOR]

HYPERGLYCEMIA prevention, HYPOGLYCEMIA, DRUG delivery systems, DRUGS, EXPERIMENTAL design, GLYCOSYLATED hemoglobin, INSULIN, TYPE 1 diabetes, LONGITUDINAL method, RESEARCH methodology, MEDICAL cooperation, PATIENT compliance, PHARMACEUTICAL arithmetic, RESEARCH, RANDOMIZED controlled trials, and PREVENTION

Background: People with T1DM and insulin-treated T2DM often do not follow and/or adjust their insulin regimens as needed. Key contributors to treatment non-adherence are fear of hypoglycaemia, difficulty and lack of self-efficacy associated with insulin dose determination. Because manual calculation of insulin boluses is both complex and time consuming, people may rely on empirical estimates, which can result in persistent hypoglycaemia and/or hyperglycaemia. Use of automated bolus advisors (BA) has been shown to help insulin pump users to more accurately meet prandial insulin dosage requirements, improve postprandial glycaemic excursions, and achieve optimal glycaemic control with an increased time within optimal range. Use of a BA containing an early algorithm based on sliding scales for insulin dosing has also been shown to improve HbA1c levels in people treated with multiple daily insulin injections (MDI). We designed a study to determine if use of an automated BA can improve clinical and psychosocial outcomes in people treated with MDI. Methods/design: The Automated Bolus Advisor Control and Usability Study (ABACUS) is a 6-month, prospective, randomised, multi-centre, multi-national trial to determine if automated BA use improves glycaemic control as measured by a change in HbA1c in people using MDI with elevated HbA1c levels (>7.5%). A total of 226 T1DM and T2DM participants will be recruited. Anticipated attrition of 20% will yield a sample size of 90 participants, which will provide >80% power to detect a mean difference of 0.5%, with SD of 0.9%, using a one-sided 5% t-test, with 5% significance level. Other measures of glycaemic control, self-care behaviours and psychosocial issues will also be assessed. Discussion: It is critical that healthcare providers utilise available technologies that both facilitate effective glucose management and address concerns about safety and lifestyle. Automated BAs may help people using MDI to manage their diabetes more effectively and minimise the risk of long-term diabetes related complications. Findings from a recent study suggest that BA use positively addresses both safety and lifestyle concerns; however, randomised trials are needed to confirm these perceptions and determine whether bolus advisor use improves clinical outcomes. Our study is designed to make these assessments. Trial registration: NCT01460446 [ABSTRACT FROM AUTHOR]

BODY image in women, WOMEN college students, FOOD habits, AEROBIC exercises, BODY size, SELF-esteem in women, EXERCISE & psychology, INGESTION, BODY image, BREAKFASTS, COMPARATIVE studies, RESEARCH methodology, MEDICAL cooperation, RESEARCH, SATISFACTION, SELF-perception, EVALUATION research, RANDOMIZED controlled trials, and PSYCHOLOGY

Food intake and exercise have been shown to alter body satisfaction in a state-dependent manner. One-time consumption of food perceived as unhealthy can be detrimental to body satisfaction, whereas an acute bout of moderate-intensity aerobic exercise can be beneficial. The current study examined the effect of exercise on state body image and appearance-related self-esteem following consumption of isocaloric foods perceived as healthy or unhealthy in 36 female college students (18-30 years old) in the Northeastern United States. Using a randomized-controlled design, participants attended six study sessions with breakfast conditions (healthy, unhealthy, no food) and activity (exercise, quiet rest) as within-participants factors. Body image questionnaires were completed prior to breakfast condition, between breakfast and activity conditions, and following activity condition. Results showed that consumption of an unhealthy breakfast decreased appearance self-esteem and increased body size perception, whereas consumption of a healthy breakfast did not influence appearance self-esteem but increased body size perception. Exercise did not influence state body image attitudes or perceptions following meal consumption. Study findings suggest that morning meal type, but not aerobic exercise, influence body satisfaction in college-aged females. [ABSTRACT FROM AUTHOR]

COMMITMENT (Psychology), MENTAL depression, PSYCHOSES, QUALITY of life, SCHIZOPHRENIA, ANTIDEPRESSANTS, ANTIPSYCHOTIC agents, COMPARATIVE studies, LONGITUDINAL method, RESEARCH methodology, MEDICAL cooperation, PSYCHOLOGICAL tests, PSYCHOLOGY, RESEARCH, RESEARCH funding, STATISTICAL sampling, PILOT projects, EVALUATION research, ACCEPTANCE & commitment therapy, RANDOMIZED controlled trials, TREATMENT effectiveness, BLIND experiment, and RESEARCH evaluation

Background: Depression is one of the major contributors to poorer quality of life amongst individuals with psychosis and schizophrenia. The study was designed as a Pilot Trial to determine the parameters of a larger, definitive pragmatic multi-centre randomised controlled trial of Acceptance and Commitment Therapy for depression after psychosis (ACTdp) for individuals with a diagnosis of schizophrenia who also meet diagnostic criteria for major depression.Methods: Participants were required to meet criteria for schizophrenia and major depression. Blinded follow-ups were undertaken at 5-months (end of treatment) and at 10-months (5-months posttreatment). Primary outcomes were depression as measured by the Calgary Depression Scale for Schizophrenia (CDSS) and the Beck Depression Inventory (BDI).Results: A total of 29 participants were randomised to ACTdp + Standard Care (SC) (n=15) or SC alone (n=14). We did not observe significant differences between groups on the CDSS total score at 5-months (Coeff=-1.43, 95%CI -5.17, 2.32, p=0.45) or at 10-months (Coeff=1.8, 95%CI -2.10, 5.69, p=0.36). In terms of BDI, we noted a statistically significant effect in favour of ACTdp+SC at 5-months (Coeff=-8.38, 95%CI -15.49, -1.27, p=0.02) but not at 10-months (Coeff=-4.85, 95%CI -12.10, 2.39, p=0.18). We also observed significant effects on psychological flexibility at 5-months (Coeff=-8.83, 95%CI -14.94, -2.71, p<0.01) but not 10-months (Coeff=-4.92, 95%CI -11.09, 1.25, p=0.11).Implications: In this first RCT of a psychological therapy with depression as the primary outcome, ACT is a promising intervention for depression in the context of psychosis. A further large-scale definitive randomised controlled trial is required to determine effectiveness.Trial Registration: ISRCTN: 33306437. [ABSTRACT FROM AUTHOR]

SCHIZOPHRENIA, PSYCHOSES, DELUSIONS, HALLUCINATIONS & illusions, DIAGNOSIS of schizophrenia, SIBLINGS, CHI-squared test, COMPARATIVE studies, DEMOGRAPHY, FACTOR analysis, FAMILY health, RESEARCH methodology, MEDICAL cooperation, PSYCHOLOGICAL tests, PSYCHOLOGY, RESEARCH, EVALUATION research, and SEVERITY of illness index

Abstract: Careful phenotyping and the identification of subtypes of schizophrenia can contribute significantly to the success of genetic studies in schizophrenia. The phenomenology of schizophrenia in affected sib pairs has been well-described in Caucasian populations, however a paucity of data exists for African populations. This study therefore investigated symptom dimensions in a sizeable group of affected Xhosa sib pairs as a means of evaluating the role of shared familial factors in the psychosis of schizophrenia. Five hundred and thirteen participants were interviewed with the Diagnostic Interview for Genetic Studies (DIGS), which included the Schedules for the Assessment of Negative and Positive symptoms (SANS/SAPS). One hundred and four sib pairs were then extracted (N =208) for analysis of concordance for lifetime psychotic symptoms and an exploratory factor analysis of the SANS/SAPS. Concordance analysis of life-time symptoms indicated a significant concordance for olfactory hallucinations, persecutory delusions, jealousy, somatic, reference and control delusions as well as thought insertion and withdrawal. The factor analysis of the global scores of the SAPS and SANS revealed a five factor best-fit model and accounted for 92.5% of variance. The factors included a negative symptom factor, a positive symptom factor, a positive thought disorder and a bizarre behaviour component. The core symptomatology of schizophrenia in this sib pair sample was similar to that reported in Caucasian populations with the exception of higher rates of auditory hallucinations and delusions of persecution. In summary therefore; although the factor analysis only supported the concept of the universality of psychotic symptoms in schizophrenia, the concordance analysis of these symptoms did reveal hallucinations as well as delusions of control as possible candidates relevant for future research into genotype–phenotype relationships. [Copyright &y& Elsevier]