Risk of low energy availability, eating disorders and food insecurity amongst development female rugby league players.

BACKGROUND: There have been several published studies on the prevalence of low energy availability (LEA) risk amongst North American and European endurance athletes. Yet the prevalence and risk factors amongst rugby league players are less well understood. This study assessed the prevalence of low energy availability risk, eating disorder risk, and food security amongst players from a female National Rugby League squad in Australia. METHODS: Players from one Australian professional rugby league club volunteered to participate in the study. An online questionnaire was conducted to determine the prevalence of low energy availability (Low Energy Availability in Females Questionnaire [LEAF-Q]), eating disorder risk (Eating Disorders Inventory [EDI-3]), and food security. RESULTS: Differences between those "at risk" and "not at risk" based on their total LEAF-Q score were determined. Of the 28 players, 64% (N.=18) were at risk of LEA. Raw scores for the EDI-3 subscales, body dissatisfaction (P=0.043), bulimia (P=0.002), composite score (P=0.038), were significantly higher for those at risk and not at risk of LEA. Forty percent of players had some level of food insecurity. CONCLUSIONS: The results suggest LEA risk is similar to other populations and those at risk of LEA are more likely to have an elevated clinical risk of eating disorders. Food security is also an issue in this population and could contribute to LEA risk for some. Future research is needed amongst team sports athletes to understand interplay between eating disorder risk and food insecurity with LEA risk.

Retroperitoneal venous malformation mimics paraganglioma on triple imaging modalities.

Here, we report a case of a woman in her 50s who was referred for an incidentally discovered lesion anterior to the origin of inferior vena cava suspicious for a paraganglioma following a CT scan for vaginal bleeding. A follow-up 68Ga-DOTATATE PET-CT and MRI of the abdomen reinforced the radiological impression of an extra-adrenal paraganglioma (EAP). The EAP was deemed non-functional given normal urine biogenic amine, supine plasma fractionated metanephrines and chromogranin A levels. The mass was resected laparoscopically without perioperative blockade. Histological examination revealed a venous malformation. Extrahepatic abdominal venous malformations are rare and can be indistinguishable from an EAP on imaging preoperatively. Although benign, the lesion nevertheless warrants excision as it is associated with a risk of haemorrhage.

Risk of low energy availability and nutrition knowledge among female team sport athletes.

BACKGROUND: Nutrition knowledge influences adequate dietary intake in athletes. Inadequate dietary intakes can result in low energy availability (LEA) which can lead to relative energy deficiency in sport (RED-S). To date, there is little information on the relationship between nutrition knowledge and the risk of LEA in female team sport athletes. This study investigates if general and sports nutrition knowledge are associated with the risk of LEA in female team athletes. METHODS: A cross-sectional design was used. Female athletes (>16 years) who participate in team sports in New Zealand were asked to complete an online questionnaire. The LEA in Females Questionnaire and the Abridged Sport Nutrition Knowledge Questionnaire were included. LEA risk and general/sports nutrition knowledge were assessed. The relationship between LEA risk and knowledge was analyzed using the Kruskal-Wallis Test of independent variables and χ2 tests. RESULTS: Among 100 female athletes, 53% were at-risk for LEA, and 70% (N.=67) had poor nutrition knowledge. Athletes who were "at-risk' for LEA and those who were "not at-risk' for LEA did not differ statistically in terms of age (P=0.350) or BMI (P=0.576). Of those "not at risk' 54% had an A-NSK score between 50 and 60% (i.e., average knowledge), whereas 54% of the athletes who were "at risk' for LEA had poor nutrition knowledge. There was no statistical difference between the groups (P=0.273). CONCLUSIONS: The poor nutrition knowledge and the high rates of those "at risk' of LEA among team sports athletes indicates the need for more nutrition education in this population.

Comparing subtotal parathyroidectomy and total parathyroidectomy with autotransplantation in renal transplant recipients.

Background: Both subtotal parathyroidectomy (SPTX) and total parathyroidectomy with autotransplantation (TPTX + AT) are considered acceptable surgical approaches for renal patients. It is common that parathyroid surgery is performed in patients before they undergo kidney transplantation and there is currently no evidence considering the best surgical approach in this subset of patients. Methods: Two cohorts were identified of consecutive patients who underwent parathyroidectomy for renal hyperparathyroidism by two surgeons at a single institution over equivalent time periods (SPTX and TPTX + AT). A retrospective chart review was performed to assess these techniques, including outcomes following kidney transplantation. Results: There were 125 patients analysed, with 56 patients who underwent SPTX and 69 who underwent TPTX + AT. Both cohorts effectively reduced PTH post operatively. There were 22 patients in the SPTX cohort and 26 in the TPTX + AT cohort that subsequently received kidney transplants. There were no cases of recurrent hyperparathyroidism and one of hypoparathyroidism (4.5%) in the SPTX patients post-transplant. There was one case of recurrent hyperparathyroidism (3.8%) and four of persistent hypoparathyroidism (15.4%) in the TPTX + AT patients post-transplant. Conclusions: Surgery for renal hyperparathyroidism requires a careful balance of the extent of parathyroid resection to prevent persistent/recurrent disease and avoid permanent hypoparathyroidism. SPTX may be a more appropriate option in kidney transplant candidates in order to minimise the risk of long-term hypoparathyroidism.

Optimization of an Allysine-Targeted PET Probe for Quantifying Fibrogenesis in a Mouse Model of Pulmonary Fibrosis.

PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a destructive lung disease with a poor prognosis, an unpredictable clinical course, and inadequate therapies. There are currently no measures of disease activity to guide clinicians making treatment decisions. The aim of this study was to develop a PET probe to identify lung fibrogenesis using a pre-clinical model of pulmonary fibrosis, with potential for translation into clinical use to predict disease progression and inform treatment decisions. METHODS: Eight novel allysine-targeting chelators, PIF-1, PIF-2, …, PIF-8, with different aldehyde-reactive moieties were designed, synthesized, and radiolabeled with gallium-68 or copper-64. PET probe performance was assessed in C57BL/6J male mice 2 weeks after intratracheal bleomycin challenge and in naïve mice by dynamic PET/MR imaging and with biodistribution at 90 min post injection. Lung hydroxyproline and allysine were quantified ex vivo and histological staining for fibrosis and aldehyde was performed. RESULTS: In vivo screening of probes identified 68GaPIF-3 and 68GaPIF-7 as probes with high uptake in injured lung, high uptake in injured lung versus normal lung, and high uptake in injured lung versus adjacent liver and heart tissue. A crossover, intra-animal PET/MR imaging study of 68GaPIF-3 and 68GaPIF-7 confirmed 68GaPIF-7 as the superior probe. Specificity for fibrogenesis was confirmed in a crossover, intra-animal PET/MR imaging study with 68GaPIF-7 and a non-binding control compound, 68GaPIF-Ctrl. Substituting copper-64 for gallium-68 did not affect lung uptake or specificity indicating that either isotope could be used. CONCLUSION: A series of allysine-reactive PET probes with variations in the aldehyde-reactive moiety were evaluated in a pre-clinical model of lung fibrosis. The hydrazine-bearing probe, 68GaPIF-7, exhibited the highest uptake in fibrogenic lung, low uptake in surrounding liver or heart tissue, and low lung uptake in healthy mice and should be considered for further clinical translation.

Listeria monocytogenes GlmR Is an Accessory Uridyltransferase Essential for Cytosolic Survival and Virulence.

The cytosol of eukaryotic host cells is an intrinsically hostile environment for bacteria. Understanding how cytosolic pathogens adapt to and survive in the cytosol is critical to developing novel therapeutic interventions against these pathogens. The cytosolic pathogen Listeria monocytogenes requires glmR (previously known as yvcK), a gene of unknown function, for resistance to cell-wall stress, cytosolic survival, inflammasome avoidance, and, ultimately, virulence in vivo. In this study, a genetic suppressor screen revealed that blocking utilization of UDP N-acetylglucosamine (UDP-GlcNAc) by a nonessential wall teichoic acid decoration pathway restored resistance to lysozyme and partially restored virulence of ΔglmR mutants. In parallel, metabolomic analysis revealed that ΔglmR mutants are impaired in the production of UDP-GlcNAc, an essential peptidoglycan and wall teichoic acid (WTA) precursor. We next demonstrated that purified GlmR can directly catalyze the synthesis of UDP-GlcNAc from GlcNAc-1P and UTP, suggesting that it is an accessory uridyltransferase. Biochemical analysis of GlmR orthologues suggests that uridyltransferase activity is conserved. Finally, mutational analysis resulting in a GlmR mutant with impaired catalytic activity demonstrated that uridyltransferase activity was essential to facilitate cell-wall stress responses and virulence in vivo. Taken together, these studies indicate that GlmR is an evolutionary conserved accessory uridyltransferase required for cytosolic survival and virulence of L. monocytogenes. IMPORTANCE Bacterial pathogens must adapt to their host environment in order to cause disease. The cytosolic bacterial pathogen Listeria monocytogenes requires a highly conserved protein of unknown function, GlmR (previously known as YvcK), to survive in the host cytosol. GlmR is important for resistance to some cell-wall stresses and is essential for virulence. The ΔglmR mutant is deficient in production of an essential cell-wall metabolite, UDP-GlcNAc, and suppressors that increase metabolite levels also restore virulence. Purified GlmR can directly catalyze the synthesis of UDP-GlcNAc, and this enzymatic activity is conserved in both Bacillus subtilis and Staphylococcus aureus. These results highlight the importance of accessory cell wall metabolism enzymes in responding to cell-wall stress in a variety of Gram-positive bacteria.

A 0.1% L-Menthol Mouth Swill in Elite Male Rugby Players Has Different Effects in Forwards and Backs.

PURPOSE: Menthol mouth swills can improve endurance performance in the heat, which is attributed to attenuations in nonthermally derived thermal sensation (TS) and perception of effort. However, research in elite team-sport athletes is absent. Therefore, this study investigated the performance and TS responses to a 0.1% menthol mouth rinse (MR) or placebo (PLA) among elite male rugby union players. METHOD: Twenty-seven (15 Forwards and 12 Backs) elite male Super Rugby players completed two 3-minute 15-a-side rugby-specific conditioning blocks, with MR or PLA provided at the start of training (baseline), at the start of each 3-minute block (swill 1 [S1] and swill 2 [S2]), and at the end of training (swill 3 [S3]). TS was assessed using the American Society of Heating, Refrigerating and Air-Conditioning Engineers 9-point Analog Sensation Scale after each swill and at baseline (preconditioning block). Acceptability was measured after baseline swill and S3 using a 5-question Likert scale. Physical performance was measured throughout training using global positioning system metrics. RESULTS: MR attenuated TS from baseline to S1 (P = .003, SD = 1.01) and S2 (P = .002, SD = 1.09) in Forwards only, compared with PLA. Acceptability was higher only for Forwards in MR versus PLA at baseline (P = .003, SD = 1.3) and S3 (P = .004, SD = 0.75). MR had no effect on physical performance metrics (P > .05). CONCLUSION: MR attenuated the rise in TS with higher acceptability at S1 and S3 (in Forwards only) with no effect on selected physical performance metrics. Longer-duration exercise (eg, a match) in hot-humid conditions eliciting markedly increased body temperatures could theoretically allow favorable changes in TS to enhance performance-these postulations warrant experimental investigation.

Dietary energy intake across the menstrual cycle: a narrative review.

Females are often underrepresented in the scientific literature, but awareness of the need for female-specific research is increasing. Review articles have been published on the effects of the menstrual cycle on aspects of exercise performance and physiology, yet to date no research has reviewed the effect of menstrual cycle phase on dietary energy intake. Fluctuations in endogenous sex hormones across the menstrual cycle influence a range of physiological processes, including those involved in nutritional status. Observational research typically quantifies female athletes' nutritional intakes at a single time point; however, this may provide inaccurate information if dietary intake fluctuates across the menstrual cycle. Similarly, this may have implications for interventional research, where dietary intake is often poorly controlled or monitored. This review aimed to synthesize the published literature on dietary energy intakes of naturally menstruating females in various phases of the menstrual cycle. The review critiques the relevant literature in light of recent publications on good practice for female research, explores the impact of the menstrual cycle on energy intake, identifies gaps within the evidence base, and informs future research. Overall, energy intake appears to be lower in the follicular phase compared with the luteal phase, with a particular decrease in the days leading up to and including ovulation. The magnitude of these fluctuations is not yet clearly quantifiable and most likely varies, both between individuals, and from cycle to cycle. This review notes the lack of high-quality research investigating the energy intakes of females across the menstrual cycle, and the very limited data available for female athletes and others who undertake large amounts of physical activity. It also highlights the need for researchers to take into consideration anovulatory cycles and the potential effects of premenstrual disorders on dietary intake.

Pediatric CYP2D6 metabolizer status and post-tonsillectomy nausea and vomiting after ondansetron.

The goal of this study was to determine whether CYP2D6 metabolizer status within the ondansetron-treated pediatric tonsillectomy population is associated with risk of postoperative nausea and vomiting (PONV) in the post-anesthesia care unit. We conducted a retrospective cohort study of pediatric patients (<18 years) who underwent tonsillectomy and received ondansetron on the day of the procedure. Data were obtained from BioVU, an institutional biobank that links DNA to de-identified electronic health record data. Subjects were tested for 10 CYP2D6 allelic variants and copy number variation, and genotype data translated into CYP2D6 metabolizer status. The cohort included 652 individuals, 105 (16.1%) of whom had PONV. Rates of PONV were similar across groups: ultrarapid metabolizers (UMs), 1 of 9 (11.1%); normal metabolizers (NMs), 64 of 354 (18.1%); intermediate metabolizers (IMs), 33 of 234 (14.1%); poor metabolizers (PMs), 6 of 39 (15.4%); and ambiguous phenotypes, 1 of 16 (6.3%). In multivariable analysis adjusted for age, sex, and time under anesthesia, CYP2D6 metabolizer status was not associated with PONV, with an odds ratio of 1.37 (95% confidence interval 0.9, 2.1) when comparing PM/IM versus NM/UM. In this large pediatric population, no significant differences were detected for PONV based on CYP2D6 metabolizer status. Further investigation is needed to determine mechanisms for ondansetron inefficacy in children.

The development and validation of a questionnaire to assess relative energy deficiency in sport (RED-S) knowledge.

OBJECTIVES: The aim of this study was to develop and validate a questionnaire assessing knowledge of signs and symptoms of relative energy deficiency in sport among healthcareprofessionals and physically active individuals. DESIGN: Cross-sectional study. METHODS: The questionnaire was created in two phases: 1)Item development was established through a literature review, expert review (n = 4), and pre-testing among healthcare professionals, dietetic students, and the general population (n = 35). 2) Validity (item analysis, construct validity) and internal reliability were assessed by administrating the questionnaire to healthcare professionals (n = 97) and physically active individuals who engaged in moderate to intense physical activity (n=77). The questionnaire was re-administered in a subset of the same groups (n = 88) for test-retest reliability. RESULTS: The expert responses showed >80% acceptability and pretesting through interviews indicated good content and face validity. Item response analysis resulted in removal of 6 items due to low discrimination ability. Significantly higher knowledge scores in health professionals compared with non-health professionals (mean difference (95% CI) = 2.8 (1.9, 3.7)) confirmed construct validity. Internal consistency, assessed using Cronbach's alpha (α = 0.79), and test-retest reliability using intra-class correlation coefficients (intra-class correlation coefficients = 0.80; Spearman's correlation = 0.84, p < 0.001) were good. The final questionnaire had 18 items assessing knowledge of signs and symptoms of Relative Energy Deficiency in Sport. CONCLUSIONS: The questionnaire provides a valid and reliable tool to assess knowledge of signs and symptoms of Relative Energy Deficiency in Sport among health professionals and physically active individuals, which could guide future education requirements by assessing current knowledge.

Pediatric Liver Transplant Survival in Alagille Syndrome Is Comparable to Biliary Atresia-A Linked Database Analysis.

OBJECTIVES: This study aims to report liver transplantation (LT) outcomes and cardiac disease manifestations in children with Alagille Syndrome (ALGS) in a contemporary cohort. METHODS: This project used a novel linkage between the Scientific Registry of Transplant Recipients and Pediatric Health Information System databases. All children ≤21 years undergoing a first LT were identified (2002-2018). The presence of ALGS was identified using Scientific Registry of Transplant Recipients diagnosis coding. Subjects with ALGS were age-matched 1:2 to LT recipients with biliary atresia (BA). The Kaplan-Meier method and log-rank test were used to compare patient and graft survival between groups. RESULTS: A total of 156 LT recipients with ALGS were identified and matched to a control group of 312 LT recipients with BA. Children with ALGS were more likely to have an associated diagnosis of congenital heart disease (80.7% vs 16.4%; P = 0.001) compared with children with BA with 40 (25.6%) children with AGS requiring cardiac intervention (catheter or surgical) either before or after LT. Those patients with ALGS had a higher creatinine, laboratory MELD, and PELD scores before LT. No difference was observed regarding patient or graft survival between children with ALGS and children with BA ( P = 0.08 and P = 0.27, respectively). CONCLUSIONS: Despite increased rate of congenital heart defects and cardiac interventions, higher creatinine, and higher laboratory MELD/PELD scores at time of transplant, this study demonstrates that there is no difference in either patient or graft survival between patients with ALGS and BA.

Sulfur Availability Impacts Accumulation of the 2-Thiouridine tRNA Modification in Bacillus subtilis.

Posttranscriptional modifications to tRNA are critical elements for the folding and functionality of these adaptor molecules. Sulfur modifications in tRNA are installed by specialized enzymes that act on cognate tRNA substrates at specific locations. Most studied organisms contain a general cysteine desulfurase to mobilize sulfur for the synthesis of S-tRNA and other thio-cofactors. Bacillus subtilis and other Gram-positive bacteria encode multiple cysteine desulfurases that partner with specific sulfur acceptors in the biosynthesis of thio-cofactors. This metabolic layout suggests an alternate mode of regulation in these biosynthetic pathways. In this study, tRNA modifications were exploited as a readout for the functionality of pathways involving cysteine desulfurases. These analyses showed that the relative abundance of 2-thiouridine-modified tRNA (s2U) responds to sulfur availability in the growth medium in a dose-dependent manner. This study found that low sulfur concentrations lead to decreased levels of the s2U cysteine desulfurase YrvO and thiouridylase MnmA, without altering the levels of other cysteine desulfurases, SufS, NifS, and NifZ. Analysis of pathway metabolites that depend on the activity of cysteine desulfurases indicates that sulfur nutrient availability specifically impacts s2U accumulation while having no effect on the levels of other S-modified tRNA or activity levels of Fe-S enzymes. Collectively, these results support a model in which s2U tRNA serves as a marker for sulfur availability in B. subtilis. IMPORTANCE The 2-thiouridine (s2U) tRNA modification is found ubiquitously across all domains of life. YrvO and MnmA, the enzymes involved in this modification, are essential in B. subtilis, confirming the well-established role of s2U in maintaining translational efficiency and, consequently, cellular viability. Herein, we show that in the model Gram-positive organism Bacillus subtilis, the levels of s2U are responsive to sulfur availability. Downregulation of the s2U biosynthetic components leads to lower s2U levels, which may serve as a signal for the slowing of the translational apparatus during cellular nutrient insufficiency. Our findings provide the basis for the identification of a potential bacterial mode of regulation during S-metabolite depletion that may use s2U as a marker of suboptimal metabolic status.

Selective laryngoscopy before thyroidectomy: a risk assessment.

BACKGROUND: Patients presenting for thyroidectomy may have an unrecognized pre-existing vocal cord palsy (VCP). This raises the danger of bilateral VCP if a patient sustains an injury to the RLN on the sole functioning side. Part of the rationale for routine preoperative laryngoscopy is to eliminate such a risk. This paper endeavours to quantify the relevant potential risk. METHODS: Patients who underwent laryngoscopy prior to thyroid or parathyroid surgery in an endocrine surgical unit over a 5 year period were identified. Literature review revealed four papers in which VCP prevalence in patients without risk factors was reported. Using our data, combined with that of these other authors, the background rate of pre-existing VCP was ascertained, and the subsequent risk of bilateral VCP estimated. RESULTS: Of our 632 patients who underwent preoperative laryngoscopy, there were four patients (0.63%) who were found to have a unilateral VCP, but all had voice symptoms or previous neck surgery. When patients with these risk factors are excluded, our data combined with the published data provides a pre-existing VCP rate of 0.2%. Calculations estimate that if preoperative laryngoscopy is omitted in patients with no risk factors, the risk of bilateral VCP, due to the nerve on the sole functioning side being injured, would be between 1/50000 and 1/150000, depending on an individual surgeon's level of experience. CONCLUSION: Selective use of laryngoscopy prior to thyroidectomy would result in an acceptably low statistical risk of bilateral VCP. Routine laryngoscopy for all patients is not necessary.

Best Practices for Probiotic Research in Athletic and Physically Active Populations: Guidance for Future Randomized Controlled Trials.

Probiotic supplementation, traditionally used for the prevention or treatment of a variety of disease indications, is now recognized in a variety of population groups including athletes and those physically active for improving general health and performance. However, experimental and clinical trials with probiotics commonly suffer from design flaws and different outcome measures, making comparison and synthesis of conclusions difficult. Here we review current randomized controlled trials (RCTs) using probiotics for performance improvement, prevention of common illnesses, or general health, in a specific target population (athletes and those physically active). Future RCTs should address the key elements of (1) properly defining and characterizing a probiotic intervention, (2) study design factors, (3) study population characteristics, and (4) outcome measures, that will allow valid conclusions to be drawn. Careful evaluation and implementation of these elements should yield improved trials, which will better facilitate the generation of evidence-based probiotic supplementation recommendations for athletes and physically active individuals.

Epidemiology of Pediatric Foreign Body Ingestions Amidst the Coronavirus 2019 Pandemic at a Tertiary Care Children's Hospital.

OBJECTIVES: The coronavirus disease (COVID) 2019 pandemic and resultant stay-at-home orders altered caregivers' responsibilities and children's daily environments. We aimed to compare the epidemiology and morbidity of foreign body ingestions (FBIs) during the COVID pandemic and the prior year. METHODS: We performed a retrospective review of children cared for at our tertiary care children's hospital for FBI from March to July 2019 (pre-COVID) and March to July 2020 (COVID). Cases were identified via a search of all diagnoses of foreign bodies (FBs) in the alimentary tract. Charts were reviewed to determine the types of FBs ingested and the patients' clinical courses. RESULTS: A total of 71 encounters were identified. Thirty ingestions occurred in the pre-COVID cohort and 42 in the COVID cohort. One patient ingested 2 different FBs. There was a significantly higher rate of FBIs per day in May 2020 (COVID) compared with May 2019 (pre-COVID; 0.387 versus 0.161; P = 0.046). The median age at presentation was not significantly different between the two groups (pre-COVID, 63.8 months; COVID, 62.5 months; P = 0.78). FBs were located in the esophagus less frequently in the COVID cohort than in the pre-COVID cohort (P < 0.01). Endoscopies were less frequently performed in the COVID cohort (52.4% versus 70.0%; odds ratio, 0.47; 95% CI, 0.15-1.40). CONCLUSIONS: The frequency of FBIs trended higher in the COVID cohort, with significantly more FBIs in May 2020 when compared with May 2019. Patients in the COVID cohort more frequently had FBs located beyond the esophagus, indicating later presentation and a lesser need for urgent endoscopic removal.

Endothelial-Specific Loss of Sphingosine-1-Phosphate Receptor 1 Increases Vascular Permeability and Exacerbates Bleomycin-induced Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive disease which leads to significant morbidity and mortality from respiratory failure. The two drugs currently approved for clinical use slow the rate of decline in lung function but have not been shown to halt disease progression or reverse established fibrosis. Thus, new therapeutic targets are needed. Endothelial injury and the resultant vascular permeability are critical components in the response to tissue injury and are present in patients with IPF. However, it remains unclear how vascular permeability affects lung repair and fibrosis following injury. Lipid mediators such as sphingosine-1-phosphate (S1P) are known to regulate multiple homeostatic processes in the lung including vascular permeability. We demonstrate that endothelial cell-(EC) specific deletion of the S1P receptor 1 (S1PR1) in mice (EC-S1pr1-/-) results in increased lung vascular permeability at baseline. Following a low-dose intratracheal bleomycin challenge, EC-S1pr1-/- mice had increased and persistent vascular permeability compared with wild-type mice, which was strongly correlated with the amount and localization of resulting pulmonary fibrosis. EC-S1pr1-/- mice also had increased immune cell infiltration and activation of the coagulation cascade within the lung. However, increased circulating S1P ligand in ApoM-overexpressing mice was insufficient to protect against bleomycin-induced pulmonary fibrosis. Overall, these data demonstrate that endothelial cell S1PR1 controls vascular permeability in the lung, is associated with changes in immune cell infiltration and extravascular coagulation, and modulates the fibrotic response to lung injury.

Growth of Mycobacterium tuberculosis at acidic pH depends on lipid assimilation and is accompanied by reduced GAPDH activity.

Acidic pH arrests the growth of Mycobacterium tuberculosis in vitro (pH < 5.8) and is thought to significantly contribute to the ability of macrophages to control M. tuberculosis replication. However, this pathogen has been shown to survive and even slowly replicate within macrophage phagolysosomes (pH 4.5 to 5) [M. S. Gomes et al., Infect. Immun. 67, 3199-3206 (1999)] [S. Levitte et al., Cell Host Microbe 20, 250-258 (2016)]. Here, we demonstrate that M. tuberculosis can grow at acidic pH, as low as pH 4.5, in the presence of host-relevant lipids. We show that lack of phosphoenolpyruvate carboxykinase and isocitrate lyase, two enzymes necessary for lipid assimilation, is cidal to M. tuberculosis in the presence of oleic acid at acidic pH. Metabolomic analysis revealed that M. tuberculosis responds to acidic pH by altering its metabolism to preferentially assimilate lipids such as oleic acid over carbohydrates such as glycerol. We show that the activity of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is impaired in acid-exposed M. tuberculosis likely contributing to a reduction in glycolytic flux. The generation of endogenous reactive oxygen species at acidic pH is consistent with the inhibition of GAPDH, an enzyme well-known to be sensitive to oxidation. This work shows that M. tuberculosis alters its carbon diet in response to pH and provides a greater understanding of the physiology of this pathogen during acid stress.

Social jetlag is associated with obesity-related outcomes in 9-11-year-old children, independent of other sleep characteristics.

INTRODUCTION: Social jetlag has been reported to predict obesity-related indices, independent of sleep duration, with associations in female adolescents but not males. However, such sex-specific relationships have not been investigated in pre-adolescents. OBJECTIVES: To examine: (i) the relationships between sleep characteristics, including social jetlag, and obesity-related outcomes during childhood, and (ii) whether these relationships are moderated by sex. METHODS: This cross-sectional study included 381 children aged 9-11 years (49.6% female). Average sleep duration, social jetlag, and physical activity were assessed via wrist-worn accelerometry. Sleep disturbances were quantified from the Children's Sleep Habits Questionnaire. Obesity-related outcomes included age-specific body mass index Z-scores (zBMI) and waist-to-height ratio. Additionally % fat, total fat mass, and fat mass index were assessed via bioelectrical impedance analysis. Linear mixed models that nested children within schools were used to identify relationships among sleep characteristics and obesity-related outcomes. RESULTS: Positive associations between social jetlag with zBMI, % fat, and fat mass index were seen in univariable and unadjusted multivariable analyses. Following adjustments for known confounders, social jetlag remained significantly associated with zBMI (ß = 0.12, p = 0.013). Simple slopes suggested a positive association in girls (ß = 0.19, p = 0.006) but not in boys (ß = 0.03, p = 0.703). CONCLUSIONS: Obesity prevention efforts, particularly in girls, may benefit from targeted approaches to improving the consistency of sleep timing in youth.

Metabolic bifunctionality of Rv0812 couples folate and peptidoglycan biosynthesis in Mycobacterium tuberculosis.

Comparative sequence analysis has enabled the annotation of millions of genes from organisms across the evolutionary tree. However, this approach has inherently biased the annotation of phylogenetically ubiquitous, rather than species-specific, functions. The ecologically unusual pathogen Mycobacterium tuberculosis (Mtb) has evolved in humans as its sole reservoir and emerged as the leading bacterial cause of death worldwide. However, the physiological factors that define Mtb's pathogenicity are poorly understood. Here, we report the structure and function of a protein that is required for optimal in vitro fitness and bears homology to two distinct enzymes, Rv0812. Despite diversification of related orthologues into biochemically distinct enzyme families, rv0812 encodes a single active site with aminodeoxychorismate lyase and D-amino acid transaminase activities. The mutual exclusivity of substrate occupancy in this active site mediates coupling between nucleic acid and cell wall biosynthesis, prioritizing PABA over D-Ala/D-Glu biosynthesis. This bifunctionality reveals a novel, enzymatically encoded fail-safe mechanism that may help Mtb and other bacteria couple replication and division.

Seasonal thaw and landscape position determine foliar functional traits and whole-plant water use in tall shrubs on the low arctic tundra.

Climate warming is driving tundra shrub expansion with implications for ecosystem function and regional climate. Understanding associations between shrub ecophysiological function, distribution and environment is necessary for predicting consequences of expansion. We evaluated the role of topographic gradients on upland shrub productivity to understand potential constraints on shrub expansion. At a low arctic tundra site near Inuvik, Northwest Territories, Canada, we measured sap flow, stem water potential and productivity-related functional traits in green alder, and environmental predictors (water and nutrient availability and seasonal thaw depth) across a toposequence in alder patches. Seasonal thaw reduced stem sap flow whereas topographic position predicted stem water potential and productivity-related functional traits. Upslope shrubs were more water-limited than those downslope. Shrubs in drainage channels had traits associated with greater productivity than those on the tops of slopes. The effect of thaw depth on sap flow has implications for seasonal water-use patterns and warming impacts on tundra ecohydrology. Topographic variation in functional traits corresponds with observed spatial patterns of tundra shrub expansion along floodplains and concave hillslopes rather than in upland areas. Green alder is expanding rapidly across the low arctic tundra in northwestern North America; thus, anticipating the implications of its expansion is essential for predicting tundra function.