Transgender healthcare is a rapidly evolving interdisciplinary field. In the last decade, there has been an unprecedented increase in the number and visibility of transgender and gender diverse (TGD) ...people seeking support and gender-affirming medical treatment in parallel with a significant rise in the scientific literature in this area. The World Professional Association for Transgender Health (WPATH) is an international, multidisciplinary, professional association whose mission is to promote evidence-based care, education, research, public policy, and respect in transgender health. One of the main functions of WPATH is to promote the highest standards of health care for TGD people through the Standards of Care (SOC). The SOC was initially developed in 1979 and the last version (SOC-7) was published in 2012. In view of the increasing scientific evidence, WPATH commissioned a new version of the Standards of Care, the SOC-8.
The overall goal of SOC-8 is to provide health care professionals (HCPs) with clinical guidance to assist TGD people in accessing safe and effective pathways to achieving lasting personal comfort with their gendered selves with the aim of optimizing their overall physical health, psychological well-being, and self-fulfillment.
The SOC-8 is based on the best available science and expert professional consensus in transgender health. International professionals and stakeholders were selected to serve on the SOC-8 committee. Recommendation statements were developed based on data derived from independent systematic literature reviews, where available, background reviews and expert opinions. Grading of recommendations was based on the available evidence supporting interventions, a discussion of risks and harms, as well as the feasibility and acceptability within different contexts and country settings.
A total of 18 chapters were developed as part of the SOC-8. They contain recommendations for health care professionals who provide care and treatment for TGD people. Each of the recommendations is followed by explanatory text with relevant references. General areas related to transgender health are covered in the chapters Terminology, Global Applicability, Population Estimates, and Education. The chapters developed for the diverse population of TGD people include Assessment of Adults, Adolescents, Children, Nonbinary, Eunuchs, and Intersex Individuals, and people living in Institutional Environments. Finally, the chapters related to gender-affirming treatment are Hormone Therapy, Surgery and Postoperative Care, Voice and Communication, Primary Care, Reproductive Health, Sexual Health, and Mental Health.
The SOC-8 guidelines are intended to be flexible to meet the diverse health care needs of TGD people globally. While adaptable, they offer standards for promoting optimal health care and guidance for the treatment of people experiencing gender incongruence. As in all previous versions of the SOC, the criteria set forth in this document for gender-affirming medical interventions are clinical guidelines; individual health care professionals and programs may modify these in consultation with the TGD person.
We compared the rates of detection of respiratory viruses by reverse-transcription polymerase chain reaction (RT-PCR) and by conventional viral culture in 668 combined nasal and throat samples from a ...prospective, multicenter, populationbased study of acute respiratory tract infections among hospitalized children aged <5 years. RT-PCR increased the yield of viral identification by 2-fold, compared with that of culture alone. The increased sensitivity of viral detection by RT-PCR will yield better estimates of the population burden of viral respiratory infections.
Recent studies have associated human metapneu-movirus (HMPV) infection in children with respiratory disease of similar severity as respiratory syncytial virus (RSV) infection. We studied 668 banked ...swab specimens (one per admission) collected from a population-based, prospective study of acute respiratory illness among inpatient children from two U.S. cities. Specimens were tested for HMPV, RSV, influenza, and parainfluenza viruses by reverse transcription-polymerase chain reaction assays. Twenty-six (3.9%) were positive for HMPV; 125 (18.7%) for RSV; 45 (6.7%) for parainfluenza 1, 2, or 3; and 23 (3.4%) for influenza. HMPV-positive children were significantly older than RSV-positive children. HMPV-positive children required medical intensive care and received supplemental oxygen in similar frequencies to RSV-positive children. Among children hospitalized with respiratory illness, the incidence of HMPV infection was less than RSV, but clinical disease severity mirrored that of RSV infection. Further investigations to better characterize HMPV infection and its clinical effect are needed.
Respiratory syncytial virus (RSV), influenza virus, and parainfluenza viruses (PIV) cause significant morbidity in young children. Although only influenza virus infection and illness is currently ...vaccine-preventable, vaccines are under development for RSV and PIV. We established a prospective, active population-based surveillance network to provide precise estimates of hospitalization rates for viral acute respiratory illness (ARI) in young children and to measure the potential impact of enhanced vaccine usage on these rates.
Prospective, active population-based surveillance was conducted in young children who were hospitalized for ARI from October 1, 2000, to September 30, 2001, in Monroe County, New York (Rochester area) and Davidson County, Tennessee (Nashville area). Eligible children younger than 5 years were those who resided in surveillance counties and were hospitalized for febrile or acute respiratory illness. Viral culture and polymerase chain reaction identified viruses from nasal and throat samples obtained from all surveillance children. We measured population-based rates of hospitalization for RSV, influenza virus, and PIV as well as demographic, clinical, and risk factor assessment for each virus.
Of 812 eligible hospital admissions, 592 (73%) children were enrolled. Of the enrolled children, RSV was identified in 20%, influenza in 3%, PIV in 7%, other respiratory viruses in 36%, and no detectable virus in 39%. Population-based rates of ARI hospitalizations in children younger than 5 years were 18 per 1000. Virus-positive hospitalization rates per 1000 children were 3.5 for RSV, 1.2 for PIV, and 0.6 for influenza virus. Younger age (particularly <1 year), black and Hispanic race/ethnicity, male gender, and presence of chronic underlying illness were associated with higher hospitalization rates.
This study confirms that children younger than 5 years and particularly children younger than 1 year have a high burden of hospitalization from RSV, influenza, and PIV. The enhanced use of influenza vaccine and the development of RSV and PIV vaccines have the potential to reduce markedly the pediatric morbidity from ARIs.
This two-volume collection, supported by an in-depth introduction that addresses origins, actuality, endgame and afterlife, brings together for the first time contemporary documentation and more ...recent scholarship to give a broad picture of Japan's Treaty Ports and their inhabitants at work and play in the second half of the nineteenth century.
We present a post-hoc analysis of the safety and efficacy of duloxetine, a selective serotonin/norepinephrine reuptake inhibitor, for treatment of diabetic peripheral neuropathic pain (DPNP) in older ...patients.
Data from three double-blind, placebo-controlled trials in adult patients with DPNP were pooled and stratified by age (<65, >or=65 years). Patients were randomized to duloxetine (DLX) 60 mg once-daily, 60 mg twice-daily, or placebo for 12 weeks, followed by a 52-week extension phase (re-randomization to routine care or DLX 120 mg/day). Intent-to-treat analyses were used for safety and efficacy assessment.
In the acute phase, overall TEAE rates did not differ significantly by age. A greater percentage of older patients discontinued due to TEAEs (P<0.001), regardless of treatment group. Duloxetine improved weekly mean 24-hour average pain scores versus placebo in both age groups (P<0.01). In the extension phase, a significant therapy-by-age interaction (P<0.05) was observed in overall TEAE rate; with routine care, 86.6% of older patients had >or=1 TEAE versus 74.6% of younger patients.
Although TEAEs more frequently lead to discontinuation in older patients, duloxetine was well tolerated and efficacious for treatment of DPNP regardless of age. These data suggest duloxetine may be beneficial for treatment of DPNP in patients>or=65.
Combinations of anti-cancer drugs can overcome resistance and provide new treatments
. The number of possible drug combinations vastly exceeds what could be tested clinically. Efforts to ...systematically identify active combinations and the tissues and molecular contexts in which they are most effective could accelerate the development of combination treatments. Here we evaluate the potency and efficacy of 2,025 clinically relevant two-drug combinations, generating a dataset encompassing 125 molecularly characterized breast, colorectal and pancreatic cancer cell lines. We show that synergy between drugs is rare and highly context-dependent, and that combinations of targeted agents are most likely to be synergistic. We incorporate multi-omic molecular features to identify combination biomarkers and specify synergistic drug combinations and their active contexts, including in basal-like breast cancer, and microsatellite-stable or KRAS-mutant colon cancer. Our results show that irinotecan and CHEK1 inhibition have synergistic effects in microsatellite-stable or KRAS-TP53 double-mutant colon cancer cells, leading to apoptosis and suppression of tumour xenograft growth. This study identifies clinically relevant effective drug combinations in distinct molecular subpopulations and is a resource to guide rational efforts to develop combinatorial drug treatments.
Some bacterial species are able to utilize extracellular mineral forms of iron and manganese as respiratory electron acceptors. In Shewanella oneidensis this involves decaheme cytochromes that are ...located on the bacterial cell surface at the termini of trans-outer-membrane electron transfer conduits. The cell surface cytochromes can potentially play multiple roles in mediating electron transfer directly to insoluble electron sinks, catalyzing electron exchange with flavin electron shuttles or participating in extracellular intercytochrome electron exchange along "nanowire" appendages. We present a 3.2-à crystal structure of one of these decaheme cytochromes, MtrF, that allows the spatial organization of the 10 hemes to be visualized for the first time. The hemes are organized across four domains in a unique crossed conformation, in which a staggered 65-à octaheme chain transects the length of the protein and is bisected by a planar 45-à tetraheme chain that connects two extended Greek key split β-barrel domains. The structure provides molecular insight into how reduction of insoluble substrate (e.g., minerals), soluble substrates (e.g., flavins), and cytochrome redox partners might be possible in tandem at different termini of a trifurcated electron transport chain on the cell surface.
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