The Health and Well-Being of Lesbian, Gay, and Bisexual Youth in New Mexico

Ensuring a safe and healthy environment for youth is critical for them to thrive, both academically and physically. However, a safe and healthy environment is not always available to many lesbian, gay, bisexual, transgender, and questioning (LGBTQ) students. In order to better understand and address the health inequities that LGBTQ students face, this report describes health status data from the New Mexico Youth Risk and Resiliency Survey (NM-YRRS) by sexual orientation

Work hard, party harder:drug use and sexual behaviour in young British casual workers in Ibiza, Spain

Background: Every summer, young people flock to nightlife-focused holiday resorts around the world to find casual work. Despite being exposed to hedonistic environments, often for several months, little is known about their substance use, sexual activity and health service needs over this extended amount of time abroad. Methods: A short anonymous questionnaire examining alcohol and drug use, sexual behaviour and use of health services was administered to young British casual workers aged 16–35 in San Antonio, Ibiza (n = 171). Results: 97.7% of casual workers used alcohol in Ibiza, and the majority (85.3%) used drugs. Almost half (43.5%) of all participants used a drug in Ibiza that they had never used in the UK. Most casual workers arrived in Ibiza without a partner or spouse (86.5%). Of these, 86.9% had sex during their stay and 50.0% had unprotected sex; often while under the influence of alcohol. Only 14.3% of those having unprotected sex with a new partner sought a sexual health check-up in Ibiza, although 84.1% intended to do this on their return to the UK. Conclusion: Substance use and sexual risk taking is widespread among young British casual workers in Ibiza. Such international nightlife resorts represent key settings for substance-related health and social problems, and for the international spread of sexually transmitted infections. Addressing the health needs of casual workers and the environments that permit and promote their excessive behaviour requires collaboration between authorities in home and destination countries and the tourism industry

Plasticity of microvascular oxygenation control in rat fast-twitch muscle: effects of experimental creatine depletion

Aging, heart failure and diabetes each compromise the matching of O2 delivery (QO2)-to-metabolic requirements (O2 uptake, VO2) in skeletal muscle such that the O2 pressure driving blood-myocyte O2 flux (microvascular PO2, PmvO2) is reduced and contractile function impaired. In contrast, β-guanidinopropionic acid (β-GPA) treatment improves muscle contractile function, primarily in fast-twitch muscle (Moerland and Kushmerick, 1994). We tested the hypothesis that β-GPA (2% wt/BW in rat chow, 8 wk; n=14) would improve QO2-to-VO2 matching (elevated PmvO2) during contractions (4.5 V @ 1 Hz) in mixed (MG) and white (WG) portions of the gastrocnemius, both predominantly fast-twitch). Compared with control (CON), during contractions PmvO2 fell less following β-GPA (MG -54%, WG -26%, p<0.05), elevating steady-state PmvO2 (CON, MG: 10±2, WG: 9±1; β-GPA, MG 16±2, WG 18±2 mmHg, P<0.05). This reflected an increased QO2/VO2 ratio due primarily to a reduced VO2 in β-GPA muscles. It is likely that this adaptation helps facilitate the β-GPA-induced enhancement of contractile function in fast-twitch muscles

The Guinea Pig as a Model of Infectious Diseases

The words ‘guinea pig’ are synonymous with scientific experimentation, but much less is known about this species than many other laboratory animals. This animal model has been used for approximately 200 y and was the first to be used in the study of infectious diseases such as tuberculosis and diphtheria. Today the guinea pig is used as a model for a number of infectious bacterial diseases, including pulmonary, sexually transmitted, ocular and aural, gastrointestinal, and other infections that threaten the lives of humans. Most studies on the immune response to these diseases, with potential therapies and vaccines, have been conducted in animal models (for example, mouse) that may have less similarity to humans because of the large number of immunologic reagents available for these other species. This review presents some of the diseases for which the guinea pig is regarded as the premier model to study infections because of its similarity to humans with regard to symptoms and immune response. Furthermore, for diseases in which guinea pigs share parallel pathogenesis of disease with humans, they are potentially the best animal model for designing treatments and vaccines. Future studies of immune regulation of these diseases, novel therapies, and preventative measures require the development of new immunologic reagents designed specifically for the guinea pig

Parkinsonian motor impairment predicts personality domains related to genetic risk and treatment outcomes in schizophrenia

Identifying endophenotypes of schizophrenia is of critical importance and has profound implications on clinical practice. Here we propose an innovative approach to clarify the mechanims through which temperament and character deviance relates to risk for schizophrenia and predict long-term treatment outcomes. We recruited 61 antipsychotic naïve subjects with chronic schizophrenia, 99 unaffected relatives, and 68 healthy controls from rural communities in the Central Andes. Diagnosis was ascertained with the Schedules of Clinical Assessment in Neuropsychiatry; parkinsonian motor impairment was measured with the Unified Parkinson’s Disease Rating Scale; mesencephalic parenchyma was evaluated with transcranial ultrasound; and personality traits were assessed using the Temperament and Character Inventory. Ten-year outcome data was available for ~40% of the index cases. Patients with schizophrenia had higher harm avoidance and self-transcendence (ST), and lower reward dependence (RD), cooperativeness (CO), and self-directedness (SD). Unaffected relatives had higher ST and lower CO and SD. Parkinsonism reliably predicted RD, CO, and SD after correcting for age and sex. The average duration of untreated psychosis (DUP) was over 5 years. Further, SD was anticorrelated with DUP and antipsychotic dosing at follow-up. Baseline DUP was related to antipsychotic dose-years. Further, ‘explosive/borderline’, ‘methodical/obsessive’, and ‘disorganized/schizotypal’ personality profiles were associated with increased risk of schizophrenia. Parkinsonism predicts core personality features and treatment outcomes in schizophrenia. Our study suggests that RD, CO, and SD are endophenotypes of the disease that may, in part, be mediated by dopaminergic function. Further, SD is an important determinant of treatment course and outcome

Transgenic Mice Expressing Porcine Prion Protein Resistant to Classical Scrapie but Susceptible to Sheep Bovine Spongiform Encephalopathy and Atypical Scrapie

Atypical scrapie strain phenotypes may shift when transmitted to a new host

Parkinsonian motor impairment predicts personality domains related to genetic risk and treatment outcomes in schizophrenia

Identifying endophenotypes of schizophrenia is of critical importance and has profound implications on clinical practice. Here we propose an innovative approach to clarify the mechanims through which temperament and character deviance relates to risk for schizophrenia and predict long-term treatment outcomes. We recruited 61 antipsychotic naïve subjects with chronic schizophrenia, 99 unaffected relatives, and 68 healthy controls from rural communities in the Central Andes. Diagnosis was ascertained with the Schedules of Clinical Assessment in Neuropsychiatry; parkinsonian motor impairment was measured with the Unified Parkinson\u27s Disease Rating Scale; mesencephalic parenchyma was evaluated with transcranial ultrasound; and personality traits were assessed using the Temperament and Character Inventory. Ten-year outcome data was available for ~40% of the index cases. Patients with schizophrenia had higher harm avoidance and self-transcendence (ST), and lower reward dependence (RD), cooperativeness (CO), and self-directedness (SD). Unaffected relatives had higher ST and lower CO and SD. Parkinsonism reliably predicted RD, CO, and SD after correcting for age and sex. The average duration of untreated psychosis (DUP) was over 5 years. Further, SD was anticorrelated with DUP and antipsychotic dosing at follow-up. Baseline DUP was related to antipsychotic dose-years. Further, \u27explosive/borderline\u27, \u27methodical/obsessive\u27, and \u27disorganized/schizotypal\u27 personality profiles were associated with increased risk of schizophrenia. Parkinsonism predicts core personality features and treatment outcomes in schizophrenia. Our study suggests that RD, CO, and SD are endophenotypes of the disease that may, in part, be mediated by dopaminergic function. Further, SD is an important determinant of treatment course and outcome

Pulmonary Immunization Using Antigen 85-B Polymeric Microparticles to Boost Tuberculosis Immunity

This study aims to evaluate immunization with polymeric microparticles containing recombinant antigen 85B (rAg85B) delivered directly to the lungs to protect against tuberculosis. rAg85B was expressed in Escherichia coli and encapsulated in poly(lactic-co-glycolic acid) microparticles (P-rAg85B). These were delivered as dry powders to the lungs of guinea pigs in single or multiple doses of homologous and heterologous antigens. Bacille Calmette-Guérin (BCG) delivered subcutaneously was employed as the positive control and as part of immunization strategies. Immunized animals were challenged with a low-dose aerosol of Mycobacterium tuberculosis (MTB) H37Rv to assess the extent of protection measured as reduction in bacterial burden (CFU) in the lungs and spleens of guinea pigs. Histopathological examination and morphometric analysis of these tissues were also performed. The heterologous strategy of BCG prime-P-rAg85B aerosol boosts appeared to enhance protection from bacterial infection, as indicated by a reduction in CFU in both the lungs and spleens compared with untreated controls. Although the CFU data were not statistically different from the BCG and BCG-BCG groups, the histopathological and morphometric analyses indicated the positive effect of BCG-P-rAg85B in terms of differences in area of tissue affected and number and size of granulomas observed in tissues. P-rAg85B microparticles appeared to be effective in boosting a primary BCG immunization against MTB infection, as indicated by histopathology and morphometric analysis. These encouraging observations are relevant to boosting adults previously immunized with BCG or exposed to MTB, commonly the case in the developing world, and should be followed by further assessment of an appropriate immunization protocol for maximum protection

Sheep and Goat BSE Propagate More Efficiently than Cattle BSE in Human PrP Transgenic Mice

A new variant of Creutzfeldt Jacob Disease (vCJD) was identified in humans and linked to the consumption of Bovine Spongiform Encephalopathy (BSE)-infected meat products. Recycling of ruminant tissue in meat and bone meal (MBM) has been proposed as origin of the BSE epidemic. During this epidemic, sheep and goats have been exposed to BSE-contaminated MBM. It is well known that sheep can be experimentally infected with BSE and two field BSE-like cases have been reported in goats. In this work we evaluated the human susceptibility to small ruminants-passaged BSE prions by inoculating two different transgenic mouse lines expressing the methionine (Met) allele of human PrP at codon 129 (tg650 and tg340) with several sheep and goat BSE isolates and compared their transmission characteristics with those of cattle BSE. While the molecular and neuropathological transmission features were undistinguishable and similar to those obtained after transmission of vCJD in both transgenic mouse lines, sheep and goat BSE isolates showed higher transmission efficiency on serial passaging compared to cattle BSE. We found that this higher transmission efficiency was strongly influenced by the ovine PrP sequence, rather than by other host species-specific factors. Although extrapolation of results from prion transmission studies by using transgenic mice has to be done very carefully, especially when human susceptibility to prions is analyzed, our results clearly indicate that Met129 homozygous individuals might be susceptible to a sheep or goat BSE agent at a higher degree than to cattle BSE, and that these agents might transmit with molecular and neuropathological properties indistinguishable from those of vCJD. Our results suggest that the possibility of a small ruminant BSE prion as vCJD causal agent could not be ruled out, and that the risk for humans of a potential goat and/or sheep BSE agent should not be underestimated

Mechanism of KMT5B haploinsufficiency in neurodevelopment in humans and mice.

Pathogenic variants in KMT5B, a lysine methyltransferase, are associated with global developmental delay, macrocephaly, autism, and congenital anomalies (OMIM# 617788). Given the relatively recent discovery of this disorder, it has not been fully characterized. Deep phenotyping of the largest (n = 43) patient cohort to date identified that hypotonia and congenital heart defects are prominent features that were previously not associated with this syndrome. Both missense variants and putative loss-of-function variants resulted in slow growth in patient-derived cell lines. KMT5B homozygous knockout mice were smaller in size than their wild-type littermates but did not have significantly smaller brains, suggesting relative macrocephaly, also noted as a prominent clinical feature. RNA sequencing of patient lymphoblasts and Kmt5b haploinsufficient mouse brains identified differentially expressed pathways associated with nervous system development and function including axon guidance signaling. Overall, we identified additional pathogenic variants and clinical features in KMT5B-related neurodevelopmental disorder and provide insights into the molecular mechanisms of the disorder using multiple model systems