Muellerabernathy0922

After having one of the most restrictive abortion laws worldwide, Ireland legalised abortion in January 2019. We examine how legalisation impacted on demand for online telemedicine outside the jurisdiction.

We analysed anonymised data from 534 people from Ireland seeking online telemedicine abortion prior to legalisation (January-March and October-December 2018) and in the first 3 months following legalisation (January-March 2019). Numbers, characteristics and reasons for seeking the service before and after legalisation were compared. Content analysis of emails from people seeking the service following legalisation explored reasons for seeking care.

Half as many people contacted Women on Web in the 3 months immediately after legalisation as compared with contacts 12 months prior (103 vs 221). Of these, the proportion receiving the service reduced, from 72% prior to legalisation to 26% after legalisation (p≤0.001). After legalisation, access related reasons for seeking online telemedicine featured less ns of coercive control or abuse including the role of telemedicine in the local model of care. Abortion provided through online telemedicine continues to be an important part of providing safe, accessible abortion even after legalisation.

To explore how women and their partners navigate (pre)conception healthcare and the role of Natural Cycles fertility awareness technology in this process.

In-depth interviews with 24 cisgender women aged 24-43 years who had used Natural Cycles' 'Plan a Pregnancy' mode, and six partners of Natural Cycles users, all cisgender men aged 30-39 years. Participants were recruited via direct messaging in the Natural Cycles app, social media and, for partners, snowball sampling. Purposive sampling was conducted to ensure diversity among participants. Interviews were audio-recorded and transcribed verbatim. An iterative, inductive approach was adopted for thematic data analysis.

Natural Cycles helped most users better understand their menstrual cycles and fertility. Fertility awareness and preconception counselling with healthcare providers were uncommon. Women felt discussions about planning pregnancy in healthcare settings were often fraught with difficulties. They described not wanting to be an extra burden to overworked staff, being concerned that their worries about trying for pregnancy would be dismissed, or feeling staff did not have expertise in fertility awareness. Some women had shared their Natural Cycles data with healthcare professionals to demonstrate their menstrual cycle data or time of conception. However, it was not always clear to those not accessing services when they should seek further advice, for example, those using the app for longer time periods who had not yet conceived.

Digital technologies can provide information and support for those wanting to conceive. They should, however, complement care in statutory services, and be accompanied by greater investment in fertility awareness and preconception support.

Digital technologies can provide information and support for those wanting to conceive. They should, however, complement care in statutory services, and be accompanied by greater investment in fertility awareness and preconception support.Reduced expression of brain-derived neurotrophic factor (BDNF) and impaired activation of the BDNF receptor, tropomyosin receptor kinase B (TrkB; also known as Ntrk2), are thought to contribute significantly to the pathophysiology of Rett syndrome (RTT), a severe neurodevelopmental disorder caused by loss-of-function mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (MeCP2). Previous studies from this and other laboratories have shown that enhancing BDNF expression and/or TrkB activation in Mecp2-deficient mouse models of RTT can ameliorate or reverse abnormal neurological phenotypes that mimic human RTT symptoms. The present study reports on the preclinical efficacy of a novel, small-molecule, non-peptide TrkB partial agonist, PTX-BD4-3, in heterozygous female Mecp2 mutant mice, a well-established RTT model that recapitulates the genetic mosaicism of the human disease. PTX-BD4-3 exhibited specificity for TrkB in cell-based assays of neurotrophin receptor activation and neuronal cell survival and in in vitro receptor binding assays. PTX-BD4-3 also activated TrkB following systemic administration to wild-type and Mecp2 mutant mice and was rapidly cleared from the brain and plasma with a half-life of ∼2 h. Chronic intermittent treatment of Mecp2 mutants with a low dose of PTX-BD4-3 (5 mg/kg, intraperitoneally, once every 3 days for 8 weeks) reversed deficits in two core RTT symptom domains - respiration and motor control - and symptom rescue was maintained for at least 24 h after the last dose. Together, these data indicate that significant clinically relevant benefit can be achieved in a mouse model of RTT with a chronic intermittent, low-dose treatment paradigm targeting the neurotrophin receptor TrkB.Immunoglobulin G (IgG) antibodies are crucial for protection against invading pathogens. A highly conserved N-linked glycan within the IgG-Fc tail, which is essential for IgG function, shows variable composition in humans. Afucosylated IgG variants are already used in anticancer therapeutic antibodies for their increased activity through Fc receptors (FcγRIIIa). Here, we report that afucosylated IgG (approximately 6% of total IgG in humans) are specifically formed against enveloped viruses but generally not against other antigens. This mediates stronger FcγRIIIa responses but also amplifies brewing cytokine storms and immune-mediated pathologies. Critically ill COVID-19 patients, but not those with mild symptoms, had high concentrations of afucosylated IgG antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), amplifying proinflammatory cytokine release and acute phase responses. Thus, antibody glycosylation plays a critical role in immune responses to enveloped viruses, including COVID-19.Biosynthetic gene clusters (BGCs) are operonic sets of microbial genes that synthesize specialized metabolites with diverse functions, including siderophores and antibiotics, which often require export to the extracellular environment. LY2228820 For this reason, genes for transport across cellular membranes are essential for the production of specialized metabolites and are often genomically colocalized with BGCs. Here, we conducted a comprehensive computational analysis of transporters associated with characterized BGCs. In addition to known exporters, in BGCs we found many importer-specific transmembrane domains that co-occur with substrate binding proteins possibly for uptake of siderophores or metabolic precursors. Machine learning models using transporter gene frequencies were predictive of known siderophore activity, molecular weights, and a measure of lipophilicity (log P) for corresponding BGC-synthesized metabolites. Transporter genes associated with BGCs were often equally or more predictive of metabolite features than biosynthetic genes.