5%), but few had conversations about same-sex sexual behaviors (21.3%), HIV testing (19.2%), or sexual orientation (29.2%). Speaking to a doctor about HIV testing had a large effect (odds ratio 25.29; confidence interval 15.91-41.16; P less then .001), with 75.4% who had such conversations having been tested, compared to only 10.8% of those who had not had such conversations. CONCLUSIONS Despite higher risk, few participants reported ever having received an HIV test. Data indicate pediatricians are an important, but largely untapped, source of testing and could be integral to achieving testing rates needed to end the epidemic. Copyright © 2020 by the American Academy of Pediatrics.Recently, there has been a significant increase in the use of noncombustible nicotine-containing products, including electronic cigarettes (e-cigarettes). Of increasing popularity are e-cigarettes that can deliver high doses of nicotine over short periods of time. These devices have led to a rise in nicotine addiction in adolescent users who were nonsmokers. Use of noncombustible nicotine products by pregnant mothers is also increasing and can expose the developing fetus to nicotine, a known teratogen. In addition, young children are frequently exposed to secondhand and thirdhand nicotine aerosols generated by e-cigarettes, with little understanding of the effects these exposures can have on health. With the advent of these new nicotine-delivery systems, many concerns have arisen regarding the short- and long-term health effects of nicotine on childhood health during all stages of development. Although health studies on nicotine exposure alone are limited, educating policy makers and health care providers on the potential health effects of noncombustible nicotine is needed because public acceptance of these products has become so widespread. Most studies evaluating the effects of nicotine on health have been undertaken in the context of smoke exposure. Nevertheless, in vitro and in vivo preclinical studies strongly indicate that nicotine exposure alone can adversely affect the nervous, respiratory, immune, and cardiovascular systems, particularly when exposure occurs during critical developmental periods. In this review, we have included both preclinical and clinical studies to identify age-related health effects of nicotine exposure alone, examining the mechanisms underlying these effects. Copyright © 2020 by the American Academy of Pediatrics.Endoplasmic reticulum (ER) stress-induced apoptosis is a primary cause and modifier of degeneration in a number of genetic disorders. Understanding how genetic variation influences the ER stress response and subsequent activation of apoptosis could improve individualized therapies and predictions of outcomes for patients. In this study, we find that the uncharacterized, membrane-bound metallopeptidase CG14516 in Drosophila melanogaster, which we rename as SUPpressor of ER stress-induced DEATH (superdeath), plays a role in modifying ER stress-induced apoptosis. We demonstrate that loss of superdeath reduces apoptosis and degeneration in the Rh1G69D model of ER stress through the JNK signaling cascade. This effect on apoptosis occurs without altering the activation of the unfolded protein response (IRE1 and PERK), suggesting that the beneficial pro-survival effects of this response are intact. Furthermore, we show that superdeath functions epistatically upstream of CDK5, a known JNK-activated pro-apoptotic factor in this model of ER stress. We demonstrate that superdeath is not only a modifier of this particular model, but affects the general tolerance to ER stress, including ER stress-induced apoptosis. Finally, we present evidence of Superdeath localization to the endoplasmic reticulum membrane. While similar in sequence to a number of human metallopeptidases found in the plasma membrane and ER membrane, its localization suggests that superdeath is orthologous to ERAP1/2 in humans. Together, this study provides evidence that superdeath is a link between stress in the ER and activation of cytosolic apoptotic pathways. Copyright © 2020, Genetics.Vitamin D is essential for several physiological functions and biological processes. Increasing levels of maternal vitamin D are required throughout pregnancy as a unique source of vitamin D for the fetus, and consequently maternal vitamin D deficiency may result in several adverse outcomes in newborns. However, the genetic regulation of vitamin D in pregnancy and at birth is not yet well understood. We performed genome-wide association studies of maternal mid-gestational serum-derived and neonatal bloodspot-derived total 25-hydroxyvitamin D from a case-control study of autism spectrum disorder (ASD). We identified one fetal locus (rs4588) significantly associated with neonatal vitamin D levels in the GC gene, encoding the binding protein for the transport and function of vitamin D. We also found suggestive cross-associated loci for neonatal and maternal vitamin D near immune genes, such as CXCL6-IL8 and ACKR1 We found no interactions with ASD. However, when including a set of cases with intellectual disability but not ASD (N=179), we observed a suggestive interaction between decreased levels of neonatal vitamin D and a specific maternal genotype near the PKN2 gene. Our results suggest that genetic variation influences total vitamin D levels during pregnancy and at birth via proteins in the vitamin D pathway, but also potentially via distinct mechanisms involving loci with known roles in immune function that might be involved in vitamin D pathophysiology in pregnancy. Copyright © 2020, Genetics.Norethisterone enanthate (NET-EN) and depot-medroxyprogesterone acetate (DMPA) are two forms of injectable progestin used for contraception. Whereas clinical research indicates that women using DMPA are more susceptible to HIV and other genital pathogens, causal relationships have not been determined. Providing an underlying mechanism for this connection, however, is recent work that showed DMPA weakens genital mucosal barrier function in mice and humans and respectively promotes susceptibility of wild-type and humanized mice to genital infection with HSV type 2 and HIV type 1. However, analogous effects of NET-EN treatment on antivirus immunity and host susceptibility to genital infection are much less explored. In this study, we show that compared with mice in estrus, treatment of mice with DMPA or NET-EN significantly decreased genital levels of the cell-cell adhesion molecule desmoglein-1 and increased genital mucosal permeability. These effects, however, were more pronounced in DMPA- versus NET-EN-treated mice. Likewise, we detected comparable mortality rates in DMPA- and NET-EN-treated wild-type and humanized mice after intravaginal infection with HSV type 2 or cell-associated HIV type 1, respectively, but NET-EN treatment was associated with slower onset of HSV-induced genital pathology and lower burden of systemic HIV disease. These findings reveal DMPA and NET-EN treatment of mice significantly reduces genital desmoglein-1 levels and increases genital mucosal permeability and susceptibility to genital pathogens while also implying that NET-EN generates less compromise of genital mucosal barrier function than DMPA. Copyright © 2020 The Authors.OBJECTIVE Faecal microbiota transplantation (FMT) has proved to be an extremely effective treatment for recurrent Clostridioides difficile infection, and there is interest in its potential application in other gastrointestinal and systemic diseases. However, the recent death and episode of septicaemia following FMT highlights the need for further appraisal and guidelines on donor evaluation, production standards, treatment facilities and acceptable clinical indications. DESIGN For these consensus statements, a 24-member multidisciplinary working group voted online and then convened in-person, using a modified Delphi approach to formulate and refine a series of recommendations based on best evidence and expert opinion. Invitations to participate were directed to Australian experts, with an international delegate assisting the development. The following issues regarding the use of FMT in clinical practice were addressed donor selection and screening, clinical indications, requirements of FMT centres and future directions. Evidence was rated using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. RESULTS Consensus was reached on 27 statements to provide guidance on best practice in FMT. These include (1) minimum standards for donor screening with recommended clinical selection criteria, blood and stool testing; (2) accepted routes of administration; (3) clinical indications; (4) minimum standards for FMT production and requirements for treatment facilities acknowledging distinction between single-site centres (eg, hospital-based) and stool banks; and (5) recommendations on future research and product development. CONCLUSIONS These FMT consensus statements provide comprehensive recommendations around the production and use of FMT in clinical practice with relevance to clinicians, researchers and policy makers. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.We describe the case of a 77-year-old woman, presenting with non-specific epigastric pain. Physical examination and subsequent imaging revealed the presence of a large mass in the right liver lobe. This was shown to be a leiomyosarcoma on biopsy histology. Further investigation confirmed this to be a primary hepatic leiomyosarcoma with no evidence of metastases. The patient underwent successful surgical resection. She is currently under imaging follow-up, with no evidence of disease recurrence. © BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.We present a case of a 68-year-old man with chronic hepatitis C infection, with no evidence of chronic liver disease during the first years of follow-up, diagnosed with a hepatocellular carcinoma (HCC) with 40 mm (α-fetoprotein (AFP) 205 ng/mL). He underwent segmental liver resection and pathology analysis was consistent with HCC and cirrhosis in the adjacent liver. Four months after surgery, AFP raised up to 126 661 ng/mL and abdominal MRI revealed a multinodular HCC. Patient rejected treatment with sorafenib and started megestrol and an herbal medicine, soursop (Annona muricata). Six months later, AFP markedly decreased (28 ng/mL) and abdominal MRI showed decreasing size and number of lesions. At 5 years of follow-up, he has no evidence of HCC. Spontaneous regression of HCC is a rare condition and the underlying mechanism is unclear. In this case there is a temporal relation between the start of megestrol and Annona muricata and HCC regression. © BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.A 71-year-old woman with metastatic squamous cell carcinoma of the lung and insulin-dependent type 2 diabetes mellitus presented with a necrotic lesion on her lower abdomen. Further history revealed that this was the site of repeat insulin injections with reuse of the same needles. On investigation, biopsy of the site was positive for broad, aseptate, right-angle branching fungal hyphae consistent with mucormycosis. Studies have shown that insulin needle reuse is a common practice among diabetics for several reasons, including cost and convenience. While the current American Diabetes Association guidelines suggest that this is an acceptable practice among the general population of diabetics, they advise against it in patients who are actively ill or immunocompromised. Discussion about insulin needle reuse should be of utmost importance among providers and their diabetic patients, especially for patients who are immunocompromised. © BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions.