PCB-Related Alteration of Thyroid Hormones and Thyroid Hormone Receptor Gene Expression in Free-Ranging Harbor Seals (Phoca vitulina)

Persistent organic pollutants are environmental contaminants that, because of their lipophilic properties and long half-lives, bioaccumulate within aquatic food webs and often reach high concentrations in marine mammals, such as harbor seals (Phoca vitulina). Exposure to these contaminants has been associated with developmental abnormalities, immunotoxicity, and reproductive impairment in marine mammals and other high-trophic-level wildlife, mediated via a disruption of endocrine processes. The highly conserved thyroid hormones (THs) represent one vulnerable endocrine end point that is critical for metabolism, growth, and development in vertebrates. We characterized the relationship between contaminants and specific TH receptor (TR ) gene expression in skin/blubber biopsy samples, as well as serum THs, from free-ranging harbor seal pups (n = 39) in British Columbia, Canada, and Washington State, USA. We observed a contaminant-related increase in blubber TR-α gene expression [total polychlorinated biphenyls (∑PCBs); r = 0.679; p < 0.001] and a concomitant decrease in circulating total thyroxine concentrations (∑PCBs; r = −0.711; p < 0.001). Consistent with results observed in carefully controlled laboratory and captive feeding studies, our findings suggest that the TH system in harbor seals is highly sensitive to disruption by environmental contaminants. Such a disruption not only may lead to adverse effects on growth and development but also could have important ramifications for lipid metabolism and energetics in marine mammals

Absent otoacoustic emissions predict otitis media in young Aboriginal children: A birth cohort study in Aboriginal and non-Aboriginal children in an arid zone of Western Australia

AbstractBackground: Otitis media (OM) is the most common paediatric illness for which antibiotics areprescribed. In Australian Aboriginal children OM is frequently asymptomatic and starts at a youngerage, is more common and more likely to result in hearing loss than in non-Aboriginal children.Absent transient evoked otoacoustic emissions (TEOAEs) may predict subsequent risk of OM.Methods: 100 Aboriginal and 180 non-Aboriginal children in a semi-arid zone of WesternAustralia were followed regularly from birth to age 2 years. Tympanometry was conducted atroutine field follow-up from age 3 months. Routine clinical examination by an ENT specialist wasto be done 3 times and hearing assessment by an audiologist twice. TEOAEs were measured at ages&lt;1 and 1–2 months. Cox proportional hazards model was used to investigate the associationbetween absent TEOAEs and subsequent risk of OM.Results: At routine ENT specialist clinics, OM was detected in 55% of 184 examinations inAboriginal children and 26% of 392 examinations in non-Aboriginal children; peak prevalence was72% at age 5–9 months in Aboriginal children and 40% at 10–14 months in non-Aboriginal children.Moderate-severe hearing loss was present in 32% of 47 Aboriginal children and 7% of 120 non-Aboriginal children aged 12 months or more.TEOAE responses were present in 90% (46/51) of Aboriginal children and 99% (120/121) of non-Aboriginal children aged &lt;1 month and in 62% (21/34) and 93% (108/116), respectively, inAboriginal and non-Aboriginal children at age 1–2 months. Aboriginal children who failed TEOAEat age 1–2 months were 2.6 times more likely to develop OM subsequently than those who passed.Overall prevalence of type B tympanograms at field follow-up was 50% (n = 78) in Aboriginalchildren and 20% (n = 95) in non-Aboriginal children

HIV infection and sexual risk among men who have sex with men and women (MSMW): A systematic review and meta-analysis

Objectives: To estimate the number of men who have sex with men and women who are HIV-positive in the United States, and to compare HIV prevalence rates between men who have sex with men and women, men who have sex with men only, and men who have sex with women exclusively. Methods: Following PRISMA guidelines, we conducted a systematic review and meta-analysis of reports referencing HIV prevalence and men who have sex with men and women. We searched PubMed and Ovid PsycINFO for peer-reviewed, U.S.-based articles reporting on HIV prevalence among men who have sex with men and women. We conducted event rate, effect size, moderation and sensitivity analyses. Results: We estimate that 1.0% of U.S. males are bisexually-behaving, and that 121,800 bisexually-behaving men are HIV-positive. Men who have sex with men and women are less than half as likely to be HIV-positive as men who have sex with men only (16.9% vs. 33.3%; OR = 0.41, 95% CI: 0.31, 0.54), but more than five times as likely to be HIV-positive as men who have sex with women exclusively (18.3% vs. 3.5%; OR = 5.71, 95% CI: 3.47, 9.39). They are less likely to engage in unprotected receptive anal intercourse than men who have sex with men only (15.9% vs. 35.0%; OR = 0.36, 95% CI: 0.28, 0.46). Men who have sex with men and women in samples with high racial/ethnic minority proportions had significantly higher HIV prevalence than their counterparts in low racial/ethnic minority samples. Conclusions: This represents the first meta-analysis of HIV prevalence in the U.S. between men who have sex with men and women and men who have sex with men only. Data collection, research, and HIV prevention and care delivery specifically tailored to men who have sex with men and women are necessary to better quantify and ameliorate this population's HIV burden. © 2014 Friedman et al

Molecular Mechanisms Generating and Stabilizing Terminal 22q13 Deletions in 44 Subjects with Phelan/McDermid Syndrome

In this study, we used deletions at 22q13, which represent a substantial source of human pathology (Phelan/McDermid syndrome), as a model for investigating the molecular mechanisms of terminal deletions that are currently poorly understood. We characterized at the molecular level the genomic rearrangement in 44 unrelated patients with 22q13 monosomy resulting from simple terminal deletions (72%), ring chromosomes (14%), and unbalanced translocations (7%). We also discovered interstitial deletions between 17–74 kb in 9% of the patients. Haploinsufficiency of the SHANK3 gene, confirmed in all rearrangements, is very likely the cause of the major neurological features associated with PMS. SHANK3 mutations can also result in language and/or social interaction disabilities. We determined the breakpoint junctions in 29 cases, providing a realistic snapshot of the variety of mechanisms driving non-recurrent deletion and repair at chromosome ends. De novo telomere synthesis and telomere capture are used to repair terminal deletions; non-homologous end-joining or microhomology-mediated break-induced replication is probably involved in ring 22 formation and translocations; non-homologous end-joining and fork stalling and template switching prevail in cases with interstitial 22q13.3. For the first time, we also demonstrated that distinct stabilizing events of the same terminal deletion can occur in different early embryonic cells, proving that terminal deletions can be repaired by multistep healing events and supporting the recent hypothesis that rare pathogenic germline rearrangements may have mitotic origin. Finally, the progressive clinical deterioration observed throughout the longitudinal medical history of three subjects over forty years supports the hypothesis of a role for SHANK3 haploinsufficiency in neurological deterioration, in addition to its involvement in the neurobehavioral phenotype of PMS

The Gaia-ESO Public Spectroscopic Survey: Motivation, implementation, GIRAFFE data processing, analysis, and final data products

The Gaia-ESO Public Spectroscopic Survey is an ambitious project designed to obtain astrophysical parameters and elemental abundances for 100,000 stars, including large representative samples of the stellar populations in the Galaxy, and a well-defined sample of 60 (plus 20 archive) open clusters. We provide internally consistent results calibrated on benchmark stars and star clusters, extending across a very wide range of abundances and ages. This provides a legacy data set of intrinsic value, and equally a large wide-ranging dataset that is of value for homogenisation of other and future stellar surveys and Gaia's astrophysical parameters. This article provides an overview of the survey methodology, the scientific aims, and the implementation, including a description of the data processing for the GIRAFFE spectra. A companion paper (arXiv:2206.02901) introduces the survey results. Gaia-ESO aspires to quantify both random and systematic contributions to measurement uncertainties. Thus all available spectroscopic analysis techniques are utilised, each spectrum being analysed by up to several different analysis pipelines, with considerable effort being made to homogenise and calibrate the resulting parameters. We describe here the sequence of activities up to delivery of processed data products to the ESO Science Archive Facility for open use. The Gaia-ESO Survey obtained 202,000 spectra of 115,000 stars using 340 allocated VLT nights between December 2011 and January 2018 from GIRAFFE and UVES. The full consistently reduced final data set of spectra was released through the ESO Science Archive Facility in late 2020, with the full astrophysical parameters sets following in 2022

SARS-CoV-2 lineage dynamics in England from September to November 2021: high diversity of Delta sub-lineages and increased transmissibility of AY.4.2

Background: Since the emergence of SARS-CoV-2, evolutionary pressure has driven large increases in the transmissibility of the virus. However, with increasing levels of immunity through vaccination and natural infection the evolutionary pressure will switch towards immune escape. Genomic surveillance in regions of high immunity is crucial in detecting emerging variants that can more successfully navigate the immune landscape. Methods: We present phylogenetic relationships and lineage dynamics within England (a country with high levels of immunity), as inferred from a random community sample of individuals who provided a self-administered throat and nose swab for rt-PCR testing as part of the REal-time Assessment of Community Transmission-1 (REACT-1) study. During round 14 (9 September–27 September 2021) and 15 (19 October–5 November 2021) lineages were determined for 1322 positive individuals, with 27.1% of those which reported their symptom status reporting no symptoms in the previous month. Results: We identified 44 unique lineages, all of which were Delta or Delta sub-lineages, and found a reduction in their mutation rate over the study period. The proportion of the Delta sub-lineage AY.4.2 was increasing, with a reproduction number 15% (95% CI 8–23%) greater than the most prevalent lineage, AY.4. Further, AY.4.2 was less associated with the most predictive COVID-19 symptoms (p = 0.029) and had a reduced mutation rate (p = 0.050). Both AY.4.2 and AY.4 were found to be geographically clustered in September but this was no longer the case by late October/early November, with only the lineage AY.6 exhibiting clustering towards the South of England. Conclusions: As SARS-CoV-2 moves towards endemicity and new variants emerge, genomic data obtained from random community samples can augment routine surveillance data without the potential biases introduced due to higher sampling rates of symptomatic individuals. © 2022, The Author(s)