Healyjohannessen0633

RESULTS The Finnish patients harboured compound heterozygous loss-of-function variants (c.1165_1166dup p.(Gln390Phefs*32), and c.2151del p.(Lys717Asnfs*29)) in TBC1D32; the Pakistani proband carried a known pathogenic homozygous TBC1D32 splice-site variant c.1372+1G>A p.(Arg411_Gly458del), as did a fetus with cleft lip and partial intestinal malrotation from a terminated pregnancy within the same pedigree. TBC1D32 was expressed in the developing hypothalamus, Rathke's pouch and areas of the hindbrain. TBC1D32 interacted with proteins implicated in cilium assembly, Shh signaling, and brain development. CONCLUSIONS Biallelic TBC1D32 variants underlie syndromic hypopituitarism, and the underlying mechanism may be via disrupted Shh signaling. © Endocrine Society 2020.Bone loss in aging is linked with chronic low-grade inflammation and the accumulation of marrowfat in animals and humans. Peroxisome proliferator-activated receptor gamma (PPARγ), an adipogenic regulator, plays key roles in these biological processes. However, studies of the roles of PPARγ in age-related bone loss and inflammation are lacking. We hypothesized that deletion of PPARγ in bone marrow mesenchymal lineage cells would reduce bone loss with aging, potentially through a reduction in fat-generated inflammatory responses and an increase in osteoblastic activity. In the present study, we show that mice deficient of PPARγ in Dermo1-expressing mesenchymal lineage cells (Dermo1-CrePPARγfl/fl) have reduced fat mass and increased cortical bone thickness, but that deficiency of PPARγ had limited effect on protection of trabecular bone with aging as demonstrated by DXA, µ-CT, and histomorphometric analyses. Conditional knockout of PPARγ reduced serum concentrations of adipokines including adiponectin, resistin and leptin and reduced marrow stromal cell expression levels of inflammation-related genes. Inflammation genes involved in the interferon (IFN) signaling pathway were reduced the most. These results demonstrate that disruption of the master adipogenic regulator, PPARγ, has a certain protective effect on aging-induced bone loss, suggesting that regulation of adipose function and modulation of IFN signaling are among the key mechanisms by which PPARγ regulates bone homeostasis during aging process. © The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.BACKGROUND The association between high selenium (Se) intake and metabolic disorders such as type 2 diabetes has raised great concern, but the underlying mechanism remains unclear. OBJECTIVE Through targeted metabolomics analysis, we examined the liver sugar and acylcarnitine metabolism responses to supranutritional selenomethionine (SeMet) supplementation in pigs. METHODS Thirty-six castrated male pigs (Duroc-Landrace-Yorkshire, 62.0 ± 3.3 kg) were fed SeMet adequate (Se-A, 0.25 mg Se/kg) or SeMet supranutritional (Se-S, 2.5 mg Se/kg) diets for 60 d. The Se concentration, biochemical, gene expression, enzyme activity, and energy-targeted metabolite profiles were analyzed. RESULTS The Se-S group had greater fasting serum concentrations of glucose (1.9-fold), insulin (1.4-fold), and free fatty acids (FFAs,1.3-fold) relative to the Se-A group (P less then  0.05). The liver total Se concentration was 4.2-fold that of the Se-A group in the Se-S group (P less then  0.05), but expression of most selenoprotein gensugar metabolism and elevation of lipid synthesis in pig livers. Our research provides novel insights into high SeMet intake-induced type 2 diabetes. Copyright © The Author(s) 2020.INTRODUCTION eScreening is a mobile health technology resource for veterans and staff to support Veterans Health Administration initiatives such as early identification of health problems, shared decision-making, and measurement-based care. METHODS We conducted an exploratory mixed methods retrospective study with newly enrolling post-9/11 veterans to (1) understand eScreening user experience and obtain practical feedback on the technology to guide improvements, (2) assess veteran satisfaction with eScreening following improvements to the technology, and (3) examine veteran characteristics associated with eScreening satisfaction. Focus group data were collected on user experience with eScreening from a sample of veterans who participated in an eScreening pilot. Guided by a user-centered design approach, findings informed improvements to the technology. Survey data were subsequently collected from a large cohort of veterans to assess satisfaction with the improved program. Questionnaire data were also collectey significant, though not clinically meaningful relationships between health-related characteristics and satisfaction with eScreening. However, millennials showed significantly higher satisfaction ratings compared with non-millennials. CONCLUSIONS These findings support the use of patient experiences and feedback to aide product development. In addition, post-9/11 veterans support the use of eScreening to assist health screening. However, evaluating the eScreening program in more diverse veteran groups and Veterans Affairs settings is needed to improve the generalizability of these findings to the larger veteran population. © Association of Military Surgeons of the United States 2020. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.BACKGROUND Environmental distractions have been shown to affect eating patterns. OBJECTIVE The purpose of this study was to determine the effects of a cognitive distraction on amount, preference, and memory of food consumed and perceptions of fullness, hunger, and enjoyment of food in a healthy young-adult population. METHODS A randomized controlled crossover study of 119 healthy adults (20.2 ± 1.4 y; 57% women; 48% white) assigned participants to begin under either the distracted (DIS, n = 55) or control (CON, n = 64) conditions. DIS participants consumed a meal of quiche while completing a Rapid Visual Information Processing (RVIP) for 15 min. CON participants ate without any task assignment. After a 30-min rest period, participants were offered a snack and given 5 min to eat ad libitum. Participants completed a survey assessing fullness, hunger, and enjoyment of the meal using 100 mm visual analogue scales. One week later, participants completed the opposite condition. Data were analyzed using ANOVA. RESULTS Those in DIS consumed 13 g less of the meal (P  less then  0.001), even when comparing by initial condition (P  less then  0.001) and adjusting for sex (P  less then  0.001). A carryover effect of initial condition was found (P  less then  0.001), such that participants first assigned to DIS condition consumed less (95.2 ± 61.7 g) when distracted compared to all other condition combinations (127-133 g). Those in DIS had decreased accuracy for both memory of quiche received (absolute difference, 1.1 ± 1.6 compared with 0.7 ± 1.2 for CON, P  less then  0.001) and memory of quiche consumed (0.8 ± 1.1 for DIS compared with 0.7 ± 1.2 for CON, P = 0.007). CONCLUSIONS When distracted, healthy young adults consumed significantly less food and their memory of the meal was dampened. These findings underscore the potential importance of cognitive distraction in affecting food intake. This trial was registered at clinicaltrials.gov as NCT04078607. Copyright © The Author(s) 2020.INTRODUCTION The past decade has seen both an increase in use and research into ways in which psychological therapy might be delivered remotely. Remote access therapy uses technology to deliver talking therapies. It is important to understand how remote technologies are being used as part of the therapeutic process and consider what effect this has on the success of therapeutic interventions. This review discusses what is currently known about the use of remote access therapy with a veteran population. Moreover, the review summarizes potential benefits and barriers to conducting therapy remotely. MATERIALS AND METHODS This review was conducted to explore the use of remote access therapies with veterans. All available literature identified for this review focused on veteran cohorts from the US and UK. To meet search criteria, studies had to include veteran participants engaging with any form of talking therapy delivered remotely. A total of 15 studies met the inclusion criteria two from the UK and 13 from the arent cost effectiveness of delivering therapy remotely needs to be further investigated, particularly in relation to costs involved in enabling remote access technologies in locations where poor infrastructure exists. CONCLUSIONS Overall, studies reported largely positive outcomes for veterans undergoing remote access therapy and in general participants did not find the therapeutic process compromised by remote delivery. Studies showed that remote access therapy is being conducted successfully in both the US and UK. There is, however, a need for more research into the use of remote access therapies to treat a wider range of psychological difficulties in veterans. © The Author(s) 2020. Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.The perspective summarizes the presentations and discussions at the International Symposium on Synthetic Biology in Photosynthesis Research, which was held in Shanghai in 2018. Leveraging the current advanced understanding of photosynthetic systems, the symposium brain stormed about the redesign and engineering photosynthetic systems for translational goals and evaluated available new technologies/tools for synthetic biology as well as technological obstacles and new tools that would be needed to overcome them. Four major research areas for redesigning photosynthesis were identified i) mining natural variations of photosynthesis, ii) coordinating photosynthesis with pathways utilizing photosynthate, iii) reconstruction of highly efficient photosynthetic systems in non-host species, and iv) development of new photosynthetic systems that do not exist in nature. To expedite photosynthesis synthetic biology research, an array of new technologies and community resources need to be developed, which include expanded modelling capacities, molecular engineering toolboxes, model species, and phenotyping tools. © The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Experimental Biology.CONTEXT Mutations in Cytochrome P450 oxidoreductase (POR) cause a form of congenital adrenal hyperplasia (CAH). We are reporting a novel R550W mutation in POR identified in a 46, XX patient with signs of aromatase deficiency. OBJECTIVE Analysis of aromatase deficiency from R550W mutation in POR. DESIGN, SETTING, AND PATIENT Both the child and the mother had signs of virilization. Ultrasound revealed the presence of uterus and ovaries. No defects in CYP19A1 were found, but further analysis with a targeted Disorders of Sexual Development NGS panel (DSDSeq.V1, 111 genes) on a NextSeq (Illumina) platform in Madrid and Barcelona, Spain, revealed compound heterozygous mutations c.73_74delCT/p.L25FfsTer93 and c.1648C>T/p.R550W in POR. selleck products WT and R550W POR were produced as recombinant proteins and tested with multiple cytochrome P450 enzymes at University Children's Hospital, Bern, Switzerland. MAIN OUTCOME MEASURE AND RESULTS R550W POR showed 41% of the WT activity in cytochrome c and 7.7% activity for reduction of MTT.