Drug & alcohol use among LGBTS in the city of Leeds

Project A Representatives from seven drug and alcohol organisations in Leeds were interviewed about the services they provide and how accessible they believe those services to be to be for lesbian, gay,bisexual and transgender (LGBT) communities in the City of Leeds. Key findings: ● Only one of the groups had ever held an LGBT specific support group ● Only one of the groups were aware that they had LGB or, by implication, transgender clients, the rest were unsure as they do not ask such information of their clients ● Two of the groups had attended training sessions on LGBT specific issues ● None of the groups had any specific policies in place for treating/supporting LGBT clients ● Two of the groups had equality statements in their leaflets making LGBTs aware that they would be welcome ● Three of the support groups distributed their leaflets at LGBT support groups and venues Project B 101 participants completed a short questionnaire which asked about their use of alcohol and other substance, whether they had ever accessed any of the services in Leeds and had unprotected sex as a result of drug use. The main findings were as follows: ● 4% of the sample had no know history of substance use, including alcohol ● 21% of the sample reported using a Class ‘A’ substance, the most commonly cited was Ecstasy ● 4% of participants had attended a drug or alcohol support group in Leeds ● Of the 97 who had not accessed any of Leeds’ drug or alcohol services, 64 argued that they did not believe their alcohol/drug use to be a problem ● Of the 64, 20 scored highly on a standardised measure of drug and alcohol addiction risk ● 49% reported having had unsafe sex in the past year while under the influence of alcohol and/or other substances Recommendations The following recommendations are made: ● To increase awareness among drug and alcohol services of the specific needs of LGBTs ● To make drug and alcohol support services more accessible for LGBTs ● To increase awareness among LGBT communities of the existence and location of alcohol and drug services ● To increase awareness of the dangers associated with drug and alcohol us

Children of same-sex couples in the United Kingdom

To further develop an understanding of psychological and social functioning of children raised by lesbian couples, the current investigation compared 18 students ages 12 through 16 raised in families led by female same-sex couples who were identified from a large school-based survey with 18 matched students raised by opposite-sex couples, and the general student sample. Comparisons were made on factors including victimization, social support, and psychological functioning. Results indicated that those students raised by female same-sex couples did not differ significantly from those raised by opposite-sex couples, or the general student sample in terms of reports of victimization, psychological functioning, experience of common adolescent concerns, or prospective use of support outlets provided by family and peers. However, children of same-sex couples reported significantly less likelihood of using school-based support than children of opposite-sex couples, or the general student sample. Findings indicate the need for school administrators, teachers, and psychologists to be knowledgeable of and provide appropriate support and resources for these children. Additional implications for research and application are discussed

Observing bullying at school: The mental health implications of witness status

This study explores the impact of bullying on the mental health of students who witness it. A representative sample of 2,002 students aged 12 to 16 years attending 14 schools in the United Kingdom were surveyed using a questionnaire that included measures of bullying at school, substance abuse, and mental health risk. The results suggest that observing bullying at school predicted risks to mental health over and above that predicted for those students who were directly involved in bullying behavior as either a perpetrator or a victim. Observing others was also found to predict higher risk irrespective of whether students were or were not victims themselves. The results are discussed with reference to past research on bystander and witness behavior

“I h 8 u”: Findings from a five-year study of text and e-mail bullying

Copyright @ 2010 British Educational Research Association. The final version of this article is available at the link below.This study charts reports of nasty or threatening text and e-mail messages received by students in academic years 7 and 8 (11-13 years of age) attending 13 secondary schools in the North of England between 2002-2006. Annual surveys were undertaken on behalf of the local education authority (LEA) to monitor bullying. Results indicated that, over five years, the number of pupils receiving one or more nasty or threatening text messages or e-mails increased significantly, particularly among girls. However, receipt of frequent nasty or threatening text and e-mail messages remained relatively stable. For boys, being a victim of direct-physical bullying was associated with receiving nasty or threatening text and e-mail messages; for girls it was being unpopular among peers. Boys received more hate-related messages and girls were primarily the victims of name-calling, Findings are discussed with respect to theoretical and policy developments, and recommendations for future research are offered

Topical NSAIDs for acute pain: a meta-analysis

BACKGROUND: A previous systematic review reported that topical NSAIDs were effective in relieving pain in acute conditions like sprains and strains, with differences between individual drugs for efficacy. More trials, a better understanding of trial quality and bias, and a reclassification of certain drugs necessitate a new review. METHODS: Studies were identified by searching electronic databases and writing to manufacturers. We selected randomised double blind trials comparing topical NSAID with either placebo or another active treatment in adults with acute pain, and extracted dichotomous information approximating to a 50% reduction in pain at one week, together with details of adverse events and withdrawals. Relative benefit and number-needed-to-treat (NNT), and relative risk and number-needed-to-harm (NNH) were calculated, with sensitivity analyses where appropriate to investigate differences between individual drugs and aspects of trial design. RESULTS: Twenty-six double blind placebo controlled trials had information from 2,853 patients for evaluation of efficacy. Topical NSAID was significantly better than placebo in 19 of the 26 trials, with a pooled relative benefit of 1.6 (95% confidence interval 1.4 to 1.7), and NNT of 3.8 (95% confidence interval 3.4 to 4.4) compared with placebo for the outcome of half pain relief at seven days. Results were not affected by outcome reported, or condition treated, but smaller trials yielded a larger estimate of efficacy. Indirect comparisons of individual topical NSAIDs showed that ketoprofen was significantly better than all other topical NSAIDs, while indomethacin was barely distinguished from placebo. Three trials, with 433 patients, compared topical with oral NSAID (two trials compared the same drug, one compared different drugs) and found no difference in efficacy. Local adverse events, systemic adverse events, or withdrawals due to an adverse event were rare, and no different between topical NSAID and placebo. CONCLUSIONS: Topical NSAIDs were effective and safe in treating acute painful conditions for one week

Chikungunya Disease: Infection-Associated Markers from the Acute to the Chronic Phase of Arbovirus-Induced Arthralgia

At the end of 2005, an outbreak of fever associated with joint pain occurred in La Réunion. The causal agent, chikungunya virus (CHIKV), has been known for 50 years and could thus be readily identified. This arbovirus is present worldwide, particularly in India, but also in Europe, with new variants returning to Africa. In humans, it causes a disease characterized by a typical acute infection, sometimes followed by persistent arthralgia and myalgia lasting months or years. Investigations in the La Réunion cohort and studies in a macaque model of chikungunya implicated monocytes-macrophages in viral persistence. In this Review, we consider the relationship between CHIKV and the immune response and discuss predictive factors for chronic arthralgia and myalgia by providing an overview of current knowledge on chikungunya pathogenesis. Comparisons of data from animal models of the acute and chronic phases of infection, and data from clinical series, provide information about the mechanisms of CHIKV infection–associated inflammation, viral persistence in monocytes-macrophages, and their link to chronic signs

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

Background: We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods: We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results: No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions: Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old

Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

C. PRESL) at the transcriptional level.

This paper investigates differences in gene expression among the two Thlaspi caerulescens ecotypes La Calamine (LC) and Lellingen (LE) that have been shown to differ in metal tolerance and metal uptake. LC originates from a metalliferous soil and tolerates higher metal concentrations than LE which originates from a non-metalliferous soil. The two ecotypes were treated with different levels of zinc in solution culture, and differences in gene expression were assessed through application of a cDNA microarray consisting of 1,700 root and 2,700 shoot cDNAs. Hybridisation of root and shoot cDNA from the two ecotypes revealed a total of 257 differentially expressed genes. The regulation of selected genes was verified by quantitative reverse transcriptase polymerase chain reaction. Comparison of the expression profiles of the two ecotypes suggests that LC has a higher capacity to cope with reactive oxygen species and to avoid the formation of peroxynitrite. Furthermore, increased transcripts for the genes encoding for water channel proteins could explain the higher Zn tolerance of LC compared to LE. The higher Zn tolerance of LC was reflected by a lower expression of the genes involved in disease and defence mechanisms. The results of this study provide a valuable set of data that may help to improve our understanding of the mechanisms employed by plants to tolerate toxic concentrations of metal in the soil