Avian blood parasites in an endangered columbid: Leucocytozoon marchouxi in the Mauritian Pink Pigeon Columba mayeri

There is increasing evidence that pathogens can play a significant role in species decline. This study of a complete free-living species reveals a cost of blood parasitism to an endangered host, the Pink Pigeon Columba mayeri, endemic to Mauritius. We investigated the prevalence and effect of infection of the blood parasite, Leucocytozoon marchouxi, in the free-living Pink Pigeon population. Overall, L. marchouxi infection prevalence detected was 18·3%. Juveniles were more likely to be infected than older birds and there was geographical variation in infection prevalence. Survival of birds infected with L. marchouxi was lower than that of uninfected birds to 90 days post-sampling. This study suggests that while common haematozoa are well tolerated in healthy adults, these parasites may have greater pathogenic potential in susceptible juveniles. The study is unusual given its completeness of species sampling (96%) within a short time-period, the accurate host age data, and its focus on blood parasites in a threatened bird species. Species for which long-term life-history data are available for every individual serve as valuable models for dissecting the contribution of particular pathogens to species decline

Patterns and predictors of statin prescription in patients with type 2 diabetes

<p>Abstract</p> <p>Background</p> <p>The benefit of statins for prevention of cardiovascular events in type 2 diabetes is established, but a gap exists between guideline recommendations and clinical practice. The aim of the study was to identify patient-related factors predicting statin prescription.</p> <p>Methods</p> <p>We assessed the quality of care in 51,640 patients with type 2 diabetes in a German diabetes registry. Patients were stratified according to primary and secondary prevention. Five-year risk for cardiovascular events was calculated in primary prevention patients. A multivariate adjusted logistic regression model was constructed to determine which parameters influenced statin prescription.</p> <p>Results</p> <p>34% had established atherosclerotic disease and 25.5% received a statin. Prescription was significantly higher in the secondary compared to the primary prevention group (38.1% [95% CI 37.4–38.9%] vs. 18.5% [95% CI 18.0–19.0%], respectively). In primary prevention the odds for statin prescription increased with estimated cardiovascular risk (OR 1.17 per 5% increase in 5-year risk, 95% CI 1.11–1.22). Positive predictors for statin prescription were secondary prevention, hypertension, former smoking, baseline LDL-cholesterol, and microalbuminuria. The odds of receiving a statin had an inverted U-shaped relation with age (nadir, 66 years), age at first diagnosis of diabetes (nadir, 56 years), and body mass index (nadir, 32 kg/m²). The model predicted prescription in 70% of the patients correctly.</p> <p>Conclusion</p> <p>The majority of patients with type 2 diabetes are not receiving statins. The predominant factors determining statin prescription are the patient's prevention status and, in primary prevention, estimated cardiovascular risk. The results suggest that although physicians are aware of the general concept of cardiovascular risk, they fail to consistently implement guidelines.</p

Ezetimibe alone or in combination with simvastatin increases small dense low-density lipoproteins in healthy men: a randomized trial

Aims The predominance of small dense low-density lipoproteins (sdLDLs) has been associated with increased cardiovascular risk. The effect of ezetimibe on LDL subfraction distribution has not been fully elucidated. This study assessed by gradient gel electrophoresis the effects of ezetimibe alone, simvastatin alone, and their combination on sdLDL subfraction distribution. Methods and results A single-centre, randomized, parallel three-group open-label study was performed in 72 healthy men with a baseline LDL-cholesterol (LDL-C) concentration of 111 ± 30 mg/dL (2.9 ± 0.8 mmol/L). They were treated with ezetimibe (10 mg/day, n = 24), simvastatin (40 mg/day, n = 24), or their combination (n = 24) for 14 days. Blood was drawn before and after the treatment period. Generalized estimating equations were used to assess the influence of drug therapy on LDL subfraction distribution, controlling for within-subject patterns (clustering). We adjusted for age, body mass index, and baseline concentrations of LDL-C and triglycerides. Ezetimibe alone changed LDL subfraction distribution towards a more atherogenic profile by significantly increasing sdLDL subfractions (LDL-IVA +14.2%, P = 0.0216 and LDL-IVB +16.7%, P = 0.039; fully adjusted Wald χ2 test). In contrast, simvastatin alone significantly decreased the LDL-IVB subfraction (−16.7%, P = 0.002). This effect was offset when simvastatin was combined with ezetimibe (LDL-IVB +14.3%, P = 0.44). All three treatments decreased the large, more buoyant LDL-I subfraction, the effects of ezetimibe being the most pronounced (ezetimibe -13.9%, P < 0.0001; combination therapy −7.3%, P = 0.0743; simvastatin −4.6%, P < 0.0001). Conclusion In healthy men, treatment with ezetimibe alone is associated with the development of a pro-atherogenic LDL subfraction profile. Potentially atheroprotective effects of simvastatin are offset by ezetimibe. This study is registered with ClinicalTrials.gov, identifier no. NCT0031799

Child sexual abuse material in child-centred institutions: situational crime prevention approaches

This paper focuses on the potential for child-centred institutions to use situational crime prevention (SCP) strategies to prevent or reduce child sexual abuse material (CSAM)1 offending as a distinct form of child sexual abuse (CSA). We discuss the failure of the Royal Commission into Institutional Responses to Child Sexual Abuse in Australia to address the potential for CSAM offending to occur in child-centred institutions. Our premise is that CSAM offending is markedly shaped by the situation in which it occurs, rather than by any pre-existing preparedness to offend sexually against children. In this context, SCP for CSAM offending must be considered as part of overall strategies to combat CSA in institutional settings. However, we acknowledge that effective implementation of SCP in this area is not straightforward. We consider some of the challenges in implementing SCP at an institutional level

Bidirectional crosstalk between hypoxia-inducible factor and glucocorticoid signalling in zebrafish larvae

In the last decades in vitro studies highlighted the potential for crosstalk between Hypoxia-Inducible Factor-(HIF) and glucocorticoid-(GC) signalling pathways. However, how this interplay precisely occurs in vivo is still debated. Here, we use zebrafish larvae (Danio rerio) to elucidate how and to what degree hypoxic signalling affects the endogenous glucocorticoid pathway and vice versa, in vivo. Firstly, our results demonstrate that in the presence of upregulated HIF signalling, both glucocorticoid receptor (Gr) responsiveness and endogenous cortisol levels are repressed in 5 days post fertilisation larvae. In addition, despite HIF activity being low at normoxia, our data show that it already impedes both glucocorticoid activity and levels. Secondly, we further analysed the in vivo contribution of glucocorticoids to HIF activity. Interestingly, our results show that both glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) play a key role in enhancing it. Finally, we found indications that glucocorticoids promote HIF signalling via multiple routes. Cumulatively, our findings allowed us to suggest a model for how this crosstalk occurs in vivo

Ferredoxin 1b deficiency leads to testis disorganization, impaired spermatogenesis and feminization in zebrafish

The roles of steroids in zebrafish sex differentiation, gonadal development and function of the adult gonad are poorly understood. Herein, we have employed a ferredoxin 1b (fdx1b) mutant zebrafish to explore such processes. Fdx1b is an essential electron-providing cofactor to mitochondrial steroidogenic enzymes, which are crucial for glucocorticoid and androgen production in vertebrates. Fdx1b-/- zebrafish mutants develop into viable adults, in which concentrations of androgens and the glucocorticoid, cortisol, are significantly reduced. Adult fdx1b-/- mutant zebrafish display predominantly female secondary sex characteristics but may possess either ovaries or testes, confirming that androgen signaling is dispensable for testicular differentiation in this species, as previously demonstrated in androgen receptor mutant zebrafish. Adult male fdx1b-/- mutant zebrafish do not exhibit characteristic breeding behaviors, and sperm production is reduced, resulting in infertility in standard breeding scenarios. However, eggs collected from wild-type females can be fertilized by the sperm of fdx1b-/- mutant males by IVF. The testes of fdx1b-/- mutant males are disorganized and lack defined seminiferous tubule structure. Expression of several pro-male and spermatogenic genes is decreased in the testes of fdx1b-/- mutant males, including pro-male transcription factor SRY-box 9a (sox9a) and spermatogenic genes insulin-like growth factor 3 (igf3) and insulin-like 3 (insl3). This study establishes an androgen- and cortisol-deficient fdx1b zebrafish mutant as a model for understanding the impacts of steroid deficiency on sex development and reproductive function. This model will be particularly useful for further investigation of the roles of steroids in spermatogenesis, gonadal development and regulation of reproductive behavior, thus enabling further elucidation of the physiological consequences of endocrine disruption in vertebrates

Effects of Lipid-Lowering Drugs on Irisin in Human Subjects In Vivo and in Human Skeletal Muscle Cells Ex Vivo

Context and Objective The myokine irisin has been proposed to regulate energy homeostasis. Little is known about its association with metabolic parameters and especially with parameters influencing pathways of lipid metabolism. In the context of a clinical trial, an exploratory post hoc analysis has been performed in healthy subjects to determine whether simvastatin and/or ezetimibe influence serum irisin levels. The direct effects of simvastatin on irisin were also examined in primary human skeletal muscle cells (HSKMCs). Design and Participants A randomized, parallel 3-group study was performed in 72 men with mild hypercholesterolemia and without apparent cardiovascular disease. Each group of 24 subjects received a 14-day treatment with either simvastatin 40 mg, ezetimibe 10 mg, or their combination. Results: Baseline irisin concentrations were not significantly correlated with age, BMI, estimated GFR, thyroid parameters, glucose, insulin, lipoproteins, non-cholesterol sterols, adipokines, inflammation markers and various molecular markers of cholesterol metabolism. Circulating irisin increased significantly in simvastatin-treated but not in ezetimibe-treated subjects. The changes were independent of changes in LDL-cholesterol and were not correlated with changes in creatine kinase levels. In HSKMCs, simvastatin significantly increased irisin secretion as well as mRNA expression of its parent peptide hormone FNDC5. Simvastatin significantly induced cellular reactive oxygen species levels along with expression of pro- and anti-oxidative genes such as Nox2, and MnSOD and catalase, respectively. Markers of cellular stress such as atrogin-1 mRNA and Bax protein expression were also induced by simvastatin. Decreased cell viability and increased irisin secretion by simvastatin was reversed by antioxidant mito-TEMPO, implying in part that irisin is secreted as a result of increased mitochondrial oxidative stress and subsequent myocyte damage. Conclusions: Simvastatin increases irisin concentrations in vivo and in vitro. It remains to be determined whether this increase is a result of muscle damage or a protective mechanism against simvastatin-induced cellular stress. Trial Registration ClinicalTrials.gov NCT00317993 NCT00317993

Risk of Major Complications From Coronary Angioplasty Performed Immediately After Diagnostic Coronary Angiography: Results From the Registry of the Society for Cardiac Angiography and Interventions

AbstractObjectives. This study was designed to determine the risk of performing percutaneous transluminal coronary angioplasty (PTCA) at the time of diagnostic catheterization (“combined procedures”).Background. Health care providers are under increasing pressure to combine diagnostic and interventional coronary procedures to reduce costs. However, the risk associated with combined procedures has not been rigorously assessed.Methods. A multicenter cohort study of 35,700 patients undergoing elective PTCA from 1992 through 1995 was performed to determine the risk of major complications (myocardial infarction, emergency coronary artery bypass graft surgery or death) from combined relative to staged procedures (i.e., performing PTCA at a session subsequent to diagnostic catheterization).Results. The risks of major complications from combined and staged procedures were 2.0% and 1.6%, respectively (unadjusted odds ratio [OR] 1.28, 95% confidence interval [CI] 1.05 to 1.57). After adjusting for clinical and angiographic differences and clustering by laboratory, the risk from combined procedures was not significantly elevated (multivariable OR 1.18, 95% CI 0.89 to 1.55). However, several subgroups of patients did have an increased risk from combined procedures: patients with multivessel disease (multivariable OR 1.64, 95% CI 1.13 to 2.39); women (multivariable OR 1.64, 95% CI 1.05 to 2.55); patients >65 years old (multivariable OR 1.40, 95% CI 1.02 to 1.93); and patients undergoing multilesion PTCA (multivariable OR 1.53, 95% CI 1.06 to 2.21). The risk of combined relative to staged procedures decreased over the 4-year period (multivariable p = 0.029).Conclusions. Combining PTCA with diagnostic catheterization appears to be safe in many patients. However, several subgroups of patients may be at increased risk. Careful patient selection will most likely remain critical to ensuring the safety of combined procedures.(J Am Coll Cardiol 1997;30:193–200

Emergency care provided to refugee children in Europe: RefuNET: A cross-sectional survey study

Background Refugee children and young people have complex healthcare needs. However, issues related to acute healthcare provision for refugee children across Europe remain unexplored. This study aimed to describe the urgent and emergency healthcare needs of refugee children in Europe, and to identify obstacles to providing this care.Methods An online cross-sectional survey was distributed to European healthcare professionals via research networks between 1 February and 1 October 2017 addressing health issues of children and young people age

Neutrino propagation in a random magnetic field

The active-sterile neutrino conversion probability is calculated for neutrino propagating in a medium in the presence of random magnetic field fluctuations. Necessary condition for the probability to be positive definite is obtained. Using this necessary condition we put constraint on the neutrino magnetic moment from active-sterile electron neutrino conversion in the early universe hot plasma and in supernova.Comment: 11 page