Comparative efficacy of two fipronil spot-on formulations against experimental tick infestations (Ixodes ricinus) in dogs

A parallel-group-design, randomized, unicentre and blinded controlled study was undertaken to assess the efficacy of a new fipronil-based spot-on formulation applied once to dogs against experimental Ixodes ricinus infestations. Six dogs served as negative controls (group 1), six dogs served as positive controls (group 2) receiving the original fipronil spot-on (Frontline® spot-on Dog, Merial) at a dosage of 0.67 mL for a dog weighing from 2 to 10 kg and 1.34 mL for a dog weighing from 10.1 to 20 kg and six dogs were treated with a 10% w/v fipronil-based spot-on solution (Effipro® Spot-on, Virbac SA) at an identical dosage (group 3, 0.67 mL for a dog weighing from 2 to 10 kg and 1.34 mL for a dog weighing from 10.1 to 20 kg). Each dog was sedated and subsequently infested with 50 unfed adult I. ricinus on days −7, −2, 7, 14, 21, 28 and 35. Forty-eight hours after the treatment and 48 h after each challenge (days −5, 2, 9, 16, 23, 30 and 37), the population of the remaining ticks was assessed for each animal. Geometric mean tick counts obtained were reduced by 99% and 94% on day 2 in groups 2 and 3, respectively, compared to the negative control group. Dogs were protected from re-infestations with an efficacy of >90% for 3 weeks in group 2 and for 5 weeks in group 3. Both 10% w/v fipronil-based spot-on solutions, despite different vehicles, were equally able to eradicate tick infestation, to prevent new infestations and were equally well tolerated

Gender perspectives on views and preferences of older people on exercise to prevent falls: a systematic mixed studies review

Background: To offer fall prevention exercise programs that attract older people of both sexes there is a need to understand both womens and mens views and preferences regarding these programs. This paper aims to systematically review the literature to explore any underlying gender perspectives or gender interpretations on older peoples views or preferences regarding uptake and adherence to exercise to prevent falls. Methods: A review of the literature was carried out using a convergent qualitative design based on systematic searches of seven electronic databases (PubMed, CINAHL, Amed, PsycINFO, Scopus, PEDro, and OTseeker). Two investigators identified eligible studies. Each included article was read by at least two authors independently to extract data into tables. Views and preferences reported were coded and summarized in themes of facilitators and barriers using a thematic analysis approach. Results: Nine hundred and nine unique studies were identified. Twenty five studies met the criteria for inclusion. Only five of these contained a gender analysis of mens and womens views on fall prevention exercises. The results suggests that both women and men see women as more receptive to and in more need of fall prevention messages. The synthesis from all 25 studies identified six themes illustrating facilitators and six themes describing barriers for older people either starting or adhering to fall prevention exercise. The facilitators were: support from professionals or family; social interaction; perceived benefits; a supportive exercise context; feelings of commitment; and having fun. Barriers were: practical issues; concerns about exercise; unawareness; reduced health status; lack of support; and lack of interest. Considerably more women than men were included in the studies. Conclusion: Although there is plenty of information on the facilitators and barriers to falls prevention exercise in older people, there is a distinct lack of studies investigating differences or similarities in older womens and mens views regarding fall prevention exercise. In order to ensure that fall prevention exercise is appealing to both sexes and that the inclusion of both men and women are encouraged, more research is needed to find out whether gender differences exists and whether practitioners need to offer a range of opportunities and support strategies to attract both women and men to falls prevention exercise.Funding Agencies|Swedish Research Council [2015-03481]; Strategic Research Programme in Care Sciences, Umea University; Karolinska Institute, Sweden; Umea University</p

Evo-devo of human adolescence: beyond disease models of early puberty

Despite substantial heritability in pubertal development, much variation remains to be explained, leaving room for the influence of environmental factors to adjust its phenotypic trajectory in the service of fitness goals. Utilizing evolutionary development biology (evo-devo), we examine adolescence as an evolutionary life-history stage in its developmental context. We show that the transition from the preceding stage of juvenility entails adaptive plasticity in response to energy resources, other environmental cues, social needs of adolescence and maturation toward youth and adulthood. Using the evolutionary theory of socialization, we show that familial psychosocial stress fosters a fast life history and reproductive strategy rather than early maturation being just a risk factor for aggression and delinquency. Here we explore implications of an evolutionary-developmental-endocrinological-anthropological framework for theory building, while illuminating new directions for research

Approaches to discontinuing efalizumab: an open-label study of therapies for managing inflammatory recurrence

BACKGROUND: Efalizumab is a humanised recombinant monoclonal IgG1 antibody for the treatment of moderate-to-severe plaque psoriasis. When treatment discontinuation is necessary, however, some patients may experience inflammatory recurrence of the disease, which can progress to rebound if untreated. This analysis evaluated approaches for managing inflammatory recurrence after discontinuation of efalizumab. METHODS: An open-label, multicentre, investigational study was performed in 41 patients with moderate-to-severe plaque psoriasis who had recently completed clinical studies with efalizumab and had developed signs of inflammatory recurrence following abrupt cessation of treatment. Patients were assigned by the attending physicians to receive one of five standardised alternative systemic psoriasis treatment regimens for 12 weeks. Efficacy of the different therapy options was assessed using the physician's global assessment (PGA) of change over time. RESULTS: More favourable PGA responses were observed in patients changing to cyclosporin (PGA of 'good', 'excellent' or 'cleared': 7/10 patients, 70.0%) or methotrexate (9/20, 45.0%), compared with those receiving systemic corticosteroids (2/8, 25.0%), retinoids (0/1, 0.0%) or combined corticosteroids plus methotrexate (0/2, 0.0%). While the majority (77.8%) of patients showed inflammatory morphology at baseline, following 12 weeks of the alternative therapies the overall prevalence of inflammatory disease was decreased to 19.2%. CONCLUSION: Inflammatory recurrence after discontinuation of efalizumab therapy is a manageable event, with a number of therapies and approaches available to physicians, including short courses of cyclosporin or methotrexate

Production and Characterization of Antifungal Compounds Produced by Lactobacillus plantarum IMAU10014

Lactobacillus plantarum IMAU10014 was isolated from koumiss that produces a broad spectrum of antifungal compounds, all of which were active against plant pathogenic fungi in an agar plate assay. Two major antifungal compounds were extracted from the cell-free supernatant broth of L. plantarum IMAU10014. 3-phenyllactic acid and Benzeneacetic acid, 2-propenyl ester were carried out by HPLC, LC-MS, GC-MS, NMR analysis. It is the first report that lactic acid bacteria produce antifungal Benzeneacetic acid, 2-propenyl ester. Of these, the antifungal products also have a broad spectrum of antifungal activity, namely against Botrytis cinerea, Glomerella cingulate, Phytophthora drechsleri Tucker, Penicillium citrinum, Penicillium digitatum and Fusarium oxysporum, which was identified by the overlay and well-diffusion assay. F. oxysporum, P. citrinum and P. drechsleri Tucker were the most sensitive among molds

Attentional capture by alcohol-related stimuli may be activated involuntarily by top-down search goals

Previous research has found that the attention of social drinkers is preferentially oriented towards alcohol related stimuli (attentional capture). This is argued to play a role in escalating craving for alcohol that can result in hazardous drinking. According to Incentive theories of drug addiction, the stimuli associated with the drug reward acquire learned incentive salience, and grab attention. However, it is not clear whether the mechanism by which this bias is created is a voluntary or an automatic one, although some evidence suggests a stimulus-driven mechanism. Here we test for the first time whether this attentional capture could reflect an involuntary consequence of a goal-driven mechanism. Across three experiments, participants were given search goals to detect either an alcoholic or a non-alcoholic object (target) in a stream of briefly presented objects unrelated to the target. Prior to the target, a task-irrelevant parafoveal distractor appeared. This could either be congruent or incongruent with the current search goal. Applying a meta-analysis, we combined the results across the three experiments and found consistent evidence of goal-driven attentional capture; whereby alcohol distractors impeded target detection when the search goal was for alcohol. By contrast, alcohol distractors did not interfere with target detection while participants were searching for a non-alcoholic category. A separate experiment revealed that the goal-driven capture effect was not found when participants held alcohol features active in memory but did not intentionally search for them. These findings suggest a strong goal-driven account of attentional capture by alcohol cues in social drinkers

The Genetics of Obesity

Obesity is a result of excess body fat accumulation. This excess is associated with adverse health effects such as CVD, type 2 diabetes, and cancer. The development of obesity has an evident environmental contribution, but as shown by heritability estimates of 40% to 70%, a genetic susceptibility component is also needed. Progress in understanding the etiology has been slow, with findings largely restricted to monogenic, severe forms of obesity. However, technological and analytical advances have enabled detection of more than 20 obesity susceptibility loci. These contain genes suggested to be involved in the regulation of food intake through action in the central nervous system as well as in adipocyte function. These results provide plausible biological pathways that may, in the future, be targeted as part of treatment or prevention strategies. Although the proportion of heritability explained by these genes is small, their detection heralds a new phase in understanding the etiology of common obesity

Prevalence of lipid abnormalities before and after introduction of lipid modifying therapy among Swedish patients with dyslipidemia (PRIMULA)

<p>Abstract</p> <p>Background</p> <p>Data on the prevalence of dyslipidemia and attainment of goal/normal lipid levels in a Swedish population are scarce. The objective of this study is to estimate the prevalence of dyslipidemia and attainment of goal/normal lipid levels in patients treated with lipid modifying therapy (LMT).</p> <p>Methods</p> <p>This longitudinal retrospective observational study covers time periods before and after treatment. Data were collected from 1994-2007 electronic patient records in public primary healthcare centers in Uppsala County, Sweden. Patients were included if they had been treated with LMT and had at least one lipid abnormality indicating dyslipidemia and if complete lipid profile data were available. Thresholds levels for lipids were defined as per Swedish guidelines.</p> <p>Results</p> <p>Among 5,424 patients included, at baseline, the prevalence of dyslipidemia (≥1 lipid abnormality) was by definition 100%, while this figure was 82% at follow-up. At baseline, 60% had elevated low-density lipoprotein (LDL-C) combined with low high-density lipoprotein (HDL-C) and/or elevated triglycerides (TG s), corresponding figure at follow-up was 36%. Low HDL-C and/or elevated TGs at follow-up remained at 69% for patients with type 2 diabetes mellitus (T2DM), 50% among patients with coronary heart disease (CHD) and 66% among patients with 10 year CHD risk >20%. Of the total sample, 40% attained goal levels of LDL-C and 18% attained goal/normal levels on all three lipid parameters.</p> <p>Conclusions</p> <p>Focusing therapy on LDL-C reduction allows 40% of patients to achieve LDL-C goal and helps reducing triglyceride levels. Almost 60% of patients experience persistent HDL-C and/or triglyceride abnormality independently of LDL-C levels and could be candidates for additional treatments.</p

A Systematic Study of Gene Mutations in Urothelial Carcinoma; Inactivating Mutations in TSC2 and PIK3R1

Abstract BACKGROUND: Urothelial carcinoma (UC) is characterized by frequent gene mutations of which activating mutations in FGFR3 are the most frequent. Several downstream targets of FGFR3 are also mutated in UC, e.g., PIK3CA, AKT1, and RAS. Most mutation studies of UCs have been focused on single or a few genes at the time or been performed on small sample series. This has limited the possibility to investigate co-occurrence of mutations. METHODOLOGY/PRINCIPAL FINDINGS: We performed mutation analyses of 16 genes, FGFR3, PIK3CA, PIK3R1 PTEN, AKT1, KRAS, HRAS, NRAS, BRAF, ARAF, RAF1, TSC1, TSC2, APC, CTNNB1, and TP53, in 145 cases of UC. We show that FGFR3 and PIK3CA mutations are positively associated. In addition, we identified PIK3R1 as a target for mutations. We demonstrate a negative association at borderline significance between FGFR3 and RAS mutations, and show that these mutations are not strictly mutually exclusive. We show that mutations in BRAF, ARAF, RAF1 rarely occurs in UC. Our data emphasize the possible importance of APC signaling as 6% of the investigated tumors either showed inactivating APC or activating CTNNB1 mutations. TSC1, as well as TSC2, that constitute the mTOR regulatory tuberous sclerosis complex were found to be mutated at a combined frequency of 15%. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate a significant association between FGFR3 and PIK3CA mutations in UC. Moreover, the identification of mutations in PIK3R1 further emphasizes the importance of the PI3-kinase pathway in UC. The presence of TSC2 mutations, in addition to TSC1 mutations, underlines the involvement of mTOR signaling in UC