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.
Background
There is a clear association between hyperglycaemia and surgical‐site infection (SSI). Intensive glucose control may involve a risk of hypoglycaemia, which in turn results in potentially ...severe complications. A systematic review was undertaken of studies comparing intensive versus conventional glucose control protocols in relation to reduction of SSI and other outcomes, including hypoglycaemia, mortality and stroke.
Methods
PubMed, Embase, CENTRAL, CINAHL and WHO databases from 1 January 1990 to 1 August 2015 were searched. Inclusion criteria were RCTs comparing intensive with conventional glucose control protocols, and reporting on the incidence of SSI. Meta‐analyses were performed with a random‐effects model, and meta‐regression was subsequently undertaken. Targeted blood glucose levels, achieved blood glucose levels, and important adverse events were summarized.
Results
Fifteen RCTs were included. The summary estimate showed a significant benefit for an intensive compared with a conventional glucose control protocol in reducing SSI (odds ratio (OR) 0·43, 95 per cent c.i. 0·29 to 0·64; P < 0·001). A significantly higher risk of hypoglycaemic events was found for the intensive group compared with the conventional group (OR 5·55, 2·58 to 11·96), with no increased risk of death (OR 0·74, 0·45 to 1·23) or stroke (OR 1·37, 0·26 to 7·20). These results were consistent both in patients with and those without diabetes, and in studies with moderately strict and very strict glucose control.
Conclusion
Stricter and lower blood glucose target levels of less than 150 mg/dl (8·3 mmol/l), using an intensive protocol in the perioperative period, reduce SSI with an inherent risk of hypoglycaemic events but without a significant increase in serious adverse events.
Low glucose prevents surgical‐site infection
WM injury is associated with different disabilities that children born prematurely may experience during their lives. The aim of this study was to use TBSS to test the hypothesis that WM ...microstructure at TEA in preterm infants is correlated with cognitive and motor outcome at 2-year corrected age.
Sixty-three preterm infants, born at a mean gestational age of 28.7 weeks, underwent MR imaging and DTI at TEA. Neurodevelopmental performance was assessed by using the BSITD-III. Voxelwise analysis of the DTI data was performed by using TBSS to assess the relationship among FA, AD, and RD at TEA, and cognitive, fine-motor, and gross-motor scores at 2-year corrected age.
Cognitive scores were correlated with FA values in the CC. Fine-motor scores were correlated with FA and RD throughout the WM. Gross-motor scores were associated with RD in the CC, fornix, and internal and external capsule.
WM microstructure in preterm infants at TEA was associated with cognitive, fine-motor, and gross-motor performance at 2-year corrected age. This study suggests that TBSS of DTI data at TEA has the potential to be used as a biomarker for subsequent neurodevelopment.
We present the open source Astrophysical Multi-purpose Software Environment (AMUSE), a component library for performing astrophysical simulations involving different physical domains and scales. It ...couples existing codes within a Python framework based on a communication layer using MPI. The interfaces are standardized for each domain and their implementation based on MPI guarantees that the whole framework is well-suited for distributed computation. It includes facilities for unit handling and data storage. Currently it includes codes for gravitational dynamics, stellar evolution, hydrodynamics and radiative transfer. Within each domain the interfaces to the codes are as similar as possible. We describe the design and implementation of AMUSE, as well as the main components and community codes currently supported and we discuss the code interactions facilitated by the framework. Additionally, we demonstrate how AMUSE can be used to resolve complex astrophysical problems by presenting example applications.
Abstract
Background
Janus kinases (JAKs) mediate cytokine signaling involved in inflammatory bowel disease. The pan-JAK inhibitor tofacitinib has shown efficacy in the treatment of ulcerative ...colitis. However, concerns regarding adverse events due to their wide spectrum inhibition fueled efforts to develop selective JAK inhibitors. Given the crucial role of myeloid cells in intestinal immune homeostasis, we evaluated the effect of pan-JAK and selective JAK inhibitors on pro- and anti-inflammatory macrophage polarization and function (M1/M2) and in experimental colitis.
Methods
Murine bone marrow-derived macrophages or human monocytes were treated using JAK1 and JAK3 selective inhibitors (JAK1i;JAK3i) and tofacitinib and were evaluated by transcriptional, functional, and metabolic analyses. In vivo, oral administration of JAK1i and tofacitinib (10 or 30 mg/kg) was tested in both acute and acute rescue dextran sodium sulfate (DSS) colitis.
Results
Both tofacitinib and JAK1i but not JAK3i effectively inhibited STAT1 phosphorylation and interferon gamma-induced transcripts in M1 polarized macrophages. Strikingly, transcriptional profiling suggested a switch from M1 to M2 type macrophages, which was supported by increased protein expression of M2-associated markers. In addition, both inhibitors enhanced oxidative phosphorylation rates. In vivo, JAK1i and tofacitinib did not protect mice from acute DSS-induced colitis but ameliorated recovery from weight loss and disease activity during acute rescue DSS-induced colitis at the highest dose.
Conclusion
JAK1i and tofacitinib but not JAK3i induce phenotypical and functional characteristics of anti-inflammatory macrophages, suggesting JAK1 as the main effector pathway for tofacitinib in these cells. In vivo, JAK1i and tofacitinib modestly affect acute rescue DSS-induced colitis.
Outcome of full-term infants with neonatal encephalopathy of hypoxic-ischemic origin is often assessed in infancy or early childhood and data on outcome in childhood and adolescence is limited. MRI ...performed in the neonatal period has made a huge contribution to recognition of different patterns of injury. These different patterns of injury are related to the severity of later motor and cognitive disabilities. Long-term follow-up shows that cognitive and memory difficulties may follow even in children without motor deficits. It is therefore recommended to perform follow-up assessment into childhood in children with and without adverse neurological outcome in early infancy.
The HLA locus is the strongest risk factor for anti-citrullinated protein antibody (ACPA)(+) rheumatoid arthritis (RA). Despite considerable efforts in the last 35 years, this association is poorly ...understood. Here we identify (citrullinated) vinculin, present in the joints of ACPA(+) RA patients, as an autoantigen targeted by ACPA and CD4(+) T cells. These T cells recognize an epitope with the core sequence DERAA, which is also found in many microbes and in protective HLA-DRB1*13 molecules, presented by predisposing HLA-DQ molecules. Moreover, these T cells crossreact with vinculin-derived and microbial-derived DERAA epitopes. Intriguingly, DERAA-directed T cells are not detected in HLA-DRB1*13(+) donors, indicating that the DERAA epitope from HLA-DRB1*13 mediates (thymic) tolerance in these donors and explaining the protective effects associated with HLA-DRB1*13. Together our data indicate the involvement of pathogen-induced DERAA-directed T cells in the HLA-RA association and provide a molecular basis for the contribution of protective/predisposing HLA alleles.
Brain oxygen consumption reflects neuronal activity and can therefore be used to investigate brain development or neuronal injury in neonates. In this paper we present the first results of a ...non-invasive MRI method to evaluate whole brain oxygen consumption in neonates.
For this study 51 neonates were included. The T1 and T2 of blood in the sagittal sinus were fitted using the ‘T2 prepared tissue relaxation inversion recovery’ pulse sequence (T2-TRIR). From the T1 and the T2 of blood, the venous oxygenation and the oxygen extraction fraction (OEF) were calculated. The cerebral metabolic rate of oxygen (CMRO2) was the resultant of the venous oxygenation and arterial spin labeling whole brain cerebral blood flow (CBF) measurements.
Venous oxygenation was 59±14% (mean±sd), OEF was 40±14%, CBF was 14±5ml/100g/min and CMRO2 was 30±12μmol/100g/min. The OEF in preterms at term-equivalent age was higher than in the preterms and in the infants with hypoxic–ischemic encephalopathy (p<0.01). The OEF, CBF and CMRO2 increased (p<0.01, <0.05 and <0.01, respectively) with postnatal age.
We presented an MRI technique to evaluate whole-brain oxygen consumption in neonates non-invasively. The measured values are in line with reference values found by invasive measurement techniques. Preterms and infants with HIE demonstrated significant lower oxygen extraction fraction than the preterms at term-equivalent age. This could be due to decreased neuronal activity as a reflection of brain development or as a result of tissue damage, increased cerebral blood flow due to immature or impaired autoregulation, or could be caused by differences in postnatal age.
•We present a non-invasive method which evaluates the brain oxygen metabolism.•The results are in agreement with reference values found by invasive techniques.•We were able to detect differences related to postnatal age and disease state.
Objective
Isolated agenesis of the corpus callosum on fetal ultrasound has a varied prognosis. Microarray and exome sequencing (ES) might aid in prenatal counseling.
Method
This study includes 25 ...fetuses with apparently isolated complete corpus callosum (cACC) on ultrasound. All cases were offered single nucleotide polymorphism array. Complementary ES was offered postnatally in selected cases. Clinical physical and neurodevelopmental follow‐up was collected.
Results
Eighteen cases opted for single nucleotide polymorphism array testing, which detected a causal anomaly in 2/18 (11.1%; 95% CI 2.0%‐31%). Among ongoing pregnancies without a causal anomaly on microarray, 30% (95% CI 8.5%‐60%) showed intellectual disability. Postnatal magnetic resonance imaging and physical examination often (64%; 95% CI 38%‐85%, and 64%; 95% CI 38%‐85%, respectively) revealed additional physical anomalies in cases without a causal anomaly on microarray. Two cases appeared truly isolated after birth. Postnatal sequencing in 4 of 16 cases without a causal anomaly on microarray but with intellectual disability and/or additional postnatal physical anomalies revealed 2 single‐gene disorders. Therefore, the estimated diagnostic yield of ES in chromosomally normal cACC fetuses is between 2/4 (50%; 95% CI 11%‐89%) and 2/16 (13.3%; 95% CI 2.4%‐36%).
Conclusion
In accordance with current guidelines, we conclude that microarray should be offered in case of isolated cACC on ultrasound. ES is likely to be informative for prenatal counseling and should be offered if microarray is normal.
What's already known about this topic?
Agenesis of the corpus callosum is associated with a varied fetal prognosis. The presence of a genetic syndrome is an important determinant in the fetal prognosis.
What does this study add?
Single nucleotide polymorphism array and exome sequencing can be informative for prenatal counseling in fetuses with isolated complete ACC on prenatal ultrasound.
PDF
