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Paula Michele Lashley,1 Natasha P Sobers,2 Michael H Campbell,1 Maisha K Emmanuel,1 Natalie Greaves,1 Marquita Gittens-St Hilaire,1 Madhuvanti M Murphy,1 Md Anwarul Azim Majumder1 1Faculty of Medical Sciences, The University of the West Indies, Cave Hill Campus, Bridgetown, Barbados; 2George Alleyne Chronic Diseases Research Centre (GA CDRC), The University of the West Indies, Bridgetown, BarbadosCorrespondence: Md Anwarul Azim Majumder, Faculty of Medical Sciences, The University of the West Indies, Cave Hill Campus, Bridgetown, Barbados, Tel +1 246 8228160, Fax +1 246 438 9170, Email azim.majumder@cavehill.uwi.eduPurpose: The COVID-19 pandemic has caused significant disruption to medical education and clinical training and resulted in stressors that impede student learning. This study aimed to assess student satisfaction and self-efficacy in a novel online clinical clerkship curriculum delivered during the COVID-19 pandemic.Methods: Fourth- and fifth-year medical students completed an online survey in January 2021 covering the following areas: student satisfaction, self-efficacy, and perceived effectiveness of online versus face-to-face learning.Results: Just over half of students (51%) were satisfied with online clerkship delivery. However, fewer than half of students (46%) believed online learning effectively increased their knowledge, compared to 56% of students who believed face-to-face learning was effective. The perception of the effectiveness of online learning and face-to-face teaching for clinical skills was 18% and 89%, respectively (p < 0.0001). Few students perceived online teaching to be effective for developing social competencies (27%) compared to face-to-face instruction (67%) (p < 0.001). In addition, mean self-efficacy scores were higher for persons who perceived online teaching to be effective for increasing knowledge, improving clinical skills, and developing social competencies. Overall, students’ perception of online learning was strongly associated with online self-efficacy.Conclusion: Student satisfaction and perceived self-efficacy in online learning were higher than reported acceptance of online clerkship curriculum.Keywords: online learning, face-to-face learning, clinical knowledge and skills, online curriculum, social competencies, medical education

Mary M Murphy,1 Nicolas Stettler,1,2 Kimberly M Smith,1 Richard Reiss3 1Exponent, Inc., Center for Chemical Regulation and Food Safety, Washington, DC, USA; 2The Lewin Group, Falls Church, VA, USA; 3Exponent, Inc., Center for Chemical Regulation and Food Safety, Alexandria, VA, USA Abstract: Maternal nutrition is recognized as one of the determinants of fetal growth. Consumption of fruits and vegetables is promoted as part of a healthful diet; however, intakes are typically lower than recommended levels. The purpose of this study was to systematically review results from studies examining the relationship between maternal consumption of fruits and vegetables during pregnancy with infant birth weight or risk for delivering a small for gestational age baby. A comprehensive search of PubMed and EMBASE was conducted and abstracts were screened using predefined criteria. Eleven relevant studies were identified and systematically reviewed, including six prospective cohort studies, three retrospective cohort studies, and two case–control studies. Seven studies were conducted in cohorts from highly developed countries. One prospective study from a highly developed area reported increased risk for small for gestational age birth by women with low vegetable intakes (odds ratio 3.1; 95% confidence interval 1.4–6.9; P=0.01); another large prospective study reported a 10.4 g increase in birth weight per quintile increase in fruit intake (95% confidence interval 6.9–3.9; P

Nicolas Stettler,1 Mary M Murphy,1 Leila M Barraj,1 Kimberly M Smith,2 Rexford S Ahima3 1Exponent Inc, Washington, DC, USA; 2Exponent Inc, Derby, United Kingdom; 3Translational Research Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA Abstract: Globally, both the incidence of type 2 diabetes and the consumption of meat, in particular pork meat, have increased, concurrently. Processed meats have been associated with an increased risk for diabetes in observational studies. Therefore, it is important to understand the possible mechanisms of this association and the impact of meats from different species. The goal of this systematic review was to assess experimental human studies of the impact of pork intake compared with other protein sources on early markers for the development of diabetes, ie, insulin resistance, glucose intolerance, and the components of the metabolic syndrome. A systematic review was conducted searching PubMed and EMBASE and using the Cochrane and PRISMA guidelines. Eight studies were eligible and critically reviewed. Five studies were based on a single meal or single day exposure to pork, as compared with other sources of protein. The glucose-insulin response following the pork meals did not differ compared with beef, shrimp, or mixed sources of proteins. However, compared with eggs, ham (processed meat) led to a larger insulin response in nonobese subjects. Compared with whey, ham led to a smaller insulin response and a larger glucose response. These findings suggest possible mechanisms for the association between processed meat and the development of diabetes. Nonprocessed pork meats were not compared with eggs or whey. The three longer interventions (11 days to 6 months) did not show a significant impact of pork on the components of the metabolic syndrome, with the exception of a possible benefit on waist circumference and high-density lipoprotein cholesterol (one study each with significant limitations). Most of the findings are weak and there is a lack of solid evidence. The literature on the topic is limited and important research gaps are identified. Considering recent trends and projections for diabetes and pork intake, this is an important global public health question that requires more attention in order to provide improved evidence-based dietary recommendations. Keywords: blood glucose, high-density lipoprotein cholesterol, insulin resistance, meat, triglycerides, waist circumference

BACKGROUND: Fasting plasma total homocysteine (tHcy) decreases during pregnancy. Previous reports suggested that this is due to folic acid supplementation, hemodilution, or a decrease in albumin. However, these hypotheses have not been tested in a longitudinal study. OBJECTIVE: We investigated the relation between pregnancy-related physiologic changes and tHcy in a group of healthy women who were either unsupplemented or supplemented with folic acid. DESIGN: In a longitudinal study from preconception throughout pregnancy, we studied 54 unsupplemented women and 39 women who were supplemented with folic acid during the second or third trimester of pregnancy. tHcy, hematocrit, and serum albumin were determined preconceptionally and at 8, 20, and 32 wk of pregnancy. RESULTS: For the entire group, geometric mean tHcy concentrations at preconception (8.2 micro mol/L) were significantly greater (P < 0.001) than those at 8 wk of pregnancy (6.4 micro mol/L). When the unsupplemented and supplemented groups were regarded separately, geometric mean tHcy concentrations at preconception were significantly greater than those at 20 (5.22 and 4.18 micro mol/L, respectively) and 32 (5.16 and 4.42 micro mol/L, respectively) wk of pregnancy (P < 0.001 for both). Mean reductions from preconception concentrations at 8, 20, and 32 wk of pregnancy were significantly greater (P < 0.001) for tHcy (-11.5%, -25.5%, and -24.5%, respectively) than for hematocrit (-1.9%, -4.2%, and -4.3%, respectively) or serum albumin (-1.1%, -9.8%, and -13.4%, respectively). There was no correlation between changes in either hematocrit or serum albumin and changes in tHcy. CONCLUSIONS: This study refutes the previous explanations for the reduction in plasma tHcy known to occur in pregnancy, namely, folic acid supplementation, hemodilution, and a decrease in serum albumin. We suggest that the changes may be endocrine-based. Copyright © 2002 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (AMR), known as the "silent pandemic," is exacerbated by pathogenic bacteria's ability to form biofilms. Marine compounds hold promise for novel antibacterial drug discovery. Two isolates from preliminary saltwater environment screening demonstrated antimicrobial activity and were subsequently identified as Bacillus subtilis MTUA2 and Bacillus velezensis MTUC2. Minimum inhibitory concentrations (MICs), minimum biofilm inhibition concentrations (MBICs) and minimum biofilm eradication concentrations (MBECs) required to prevent and/or disrupt bacterial growth and biofilm formation were established for MRSA, Staphylococcus aureus, Acinetobacter baumannii and Escherichia coli. The metabolic activity within biofilms was determined by the 2,3,5-triphenyltetrazolium chloride assay. Both Bacillus species exhibited unique antimicrobial effects, reducing MRSA and S. aureus planktonic cell growth by 50% and sessile cell growth for S. aureus and E. coli by 50% and 90%, respectively. No effect was observed against A. baumannii. Significant MBIC and MBEC values were achieved, with 99% inhibition and 90% reduction in MRSA and S. aureus biofilms. Additionally, 90% and 50% inhibition was observed in E. coli and A. baumannii biofilms, respectively, with a 50% reduction in E. coli biofilm. These findings suggest that the mode of action employed by B. subtilis MTUA2 and B. velezensis MTUC2 metabolites should be further characterized and could be beneficial if used independently or in combination with other treatments., (© 2024 The Author(s). Environmental Microbiology Reports published by John Wiley & Sons Ltd.)

Transmission spectroscopy has been a workhorse technique used over the past two decades to constrain the physical and chemical properties of exoplanet atmospheres 1-5 . One of its classical key assumptions is that the portion of the atmosphere it probes-the terminator region-is homogeneous. Several works from the past decade, however, have put this into question for highly irradiated, hot (T eq  ≳ 1,000 K) gas giant exoplanets, both empirically 6-10 and through three-dimensional modelling 11-17 . While models have predicted clear differences between the evening (day-to-night) and morning (night-to-day) terminators, direct morning and evening transmission spectra in a wide wavelength range have not been reported for an exoplanet so far. Under the assumption of precise and accurate orbital parameters for the exoplanet WASP-39 b, here we report the detection of inhomogeneous terminators on WASP-39 b, which has allowed us to retrieve its morning and evening transmission spectra in the near-infrared (2-5 μm) using the James Webb Space Telescope. We have observed larger transit depths in the evening, which are, on average, 405 ± 88 ppm larger than the morning ones, and also have qualitatively larger features than the morning spectrum. The spectra are best explained by models in which the evening terminator is hotter than the morning terminator by 17 7 - 57 + 65  K, with both terminators having C/O ratios consistent with solar. General circulation models predict temperature differences broadly consistent with the above value and point towards a cloudy morning terminator and a clearer evening terminator., (© 2024. The Author(s).)

Introduction: Sandwiches are commonly consumed in the United States. This study summarizes contributions of beef sandwiches to energy and select nutrient intakes., Methods: Beef sandwiches were categorized as beef burger sandwiches (hamburgers or cheeseburgers) and non-burger beef sandwiches. Per capita and per user consumption of beef sandwiches (total and by type) and contributions to total nutrient intakes from beef and non-beef sandwich components were estimated for the population ages ≥2 years ( n  = 15,984) participating in WWEIA/NHANES, 2013-2016., Results: On any given day, 21.4% of the population consumed a beef sandwich. Among all Americans, beef sandwiches provided 6.3% of mean energy intake and accounted for approximately 10% of the population's mean intake of vitamin B 12 and saturated fat, 9% of protein and sodium, 7% of iron, 6% of choline, and 5% of potassium. Among beef sandwich consumers, beef sandwiches accounted for 26.2% of mean energy intake on a day of consumption. The beef component of sandwiches accounted for the majority of vitamin B 12 , choline, and protein, non-beef components accounted for the majority of sodium, iron, and potassium, and beef and non-beef components made similar contributions to saturated fat. Hamburgers provided consumers the lowest energy, sodium, and saturated fat intake, while non-burger sandwiches provided the highest intake of these nutrients., Discussion: Beef sandwiches are an important source of energy, protein, vitamin B 12, iron, and choline, and like other sandwiches, are also a source of sodium and saturated fat. Americans could enhance nutrient contributions from sandwiches by selecting lean meat and limiting use of saturated fat- or sodium-rich non-beef components., Competing Interests: MM, MA, and XB were employees of Exponent, Inc. when the analysis was completed. Exponent, Inc. provides scientific consulting to the food and beverage industry., (Copyright © 2024 Murphy, Anderson and Bi.)

Background: Little attention has been given to prenatal cobalamin insufficiency in settings where dietary cobalamin intake is presumed adequate, such as populations with habitual intake of foods from animal sources., Results: However, low cobalamin status in women of fertile age has been reported in Europe, United States, and Canada. In India, where cobalamin deficiency is highly prevalent, it has been associated with an increased risk of miscarriage, intrauterine growth retardation, as well as insulin resistance and lower neurodevelopment scores in the offspring. Low cobalamin status in pregnancy has been associated with similar outcomes as those reported in the Indian studies although the evidence is scant and conflicting., Conclusions: Consideration should be given to maternal cobalamin status in the context of prevention of adverse pregnancy outcomes as well as cobalamin insufficiency both in the mother and the offspring during lactation. Further attention is now justified with the increasing tendency toward plant-based diets. Reference intervals for cobalamin status during each trimester of pregnancy are needed and further investigation of the long-term conse-quences of low cobalamin status during pregnancy for health and development in the offspring is warranted., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

A functional role has been ascribed to the human dihydrofolate reductase 2 (DHFR2) gene based on the enzymatic activity of recombinant versions of the predicted translated protein. However, the in vivo function is still unclear. The high amino acid sequence identity (92%) between DHFR2 and its parental homolog, DHFR, makes analysis of the endogenous protein challenging. This paper describes a targeted mass spectrometry proteomics approach in several human cell lines and tissue types to identify DHFR2-specific peptides as evidence of its translation. We show definitive evidence that the DHFR2 activity in the mitochondria is in fact mediated by DHFR, and not DHFR2. Analysis of Ribo-seq data and an experimental assessment of ribosome association using a sucrose cushion showed that the two main Ensembl annotated mRNA isoforms of DHFR2, 201 and 202, are differentially associated with the ribosome. This indicates a functional role at both the RNA and protein level. However, we were unable to detect DHFR2 protein at a detectable level in most cell types examined despite various RNA isoforms of DHFR2 being relatively abundant. We did detect a DHFR2-specific peptide in embryonic heart, indicating that the protein may have a specific role during embryogenesis. We propose that the main functionality of the DHFR2 gene in adult cells is likely to arise at the RNA level., Competing Interests: Conflict of interest The authors declare no competing interests., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

Spermidine is a polyamine consumed in the diet, endogenously biosynthesized in most cells, and produced by the intestinal microbiome. A variety of foods contribute to intake of spermidine along with other polyamines. Spermidine trihydrochloride (spermidine-3HCl) of high purity can be produced using an engineered strain of Saccharomyces cerevisiae. Spermidine has a demonstrated history of safe use in the diet; however, limited information is available in the public literature to assess the potential toxicity of spermidine-3HCl. To support a safety assessment for this spermidine-3HCl as a dietary source of spermidine, authoritative guideline and good laboratory practice (GLP) compliant in vitro genotoxicity assays (bacterial reverse mutation and mammalian micronucleus assays) and a 90-day oral (dietary) toxicity study in rats were conducted with spermidine-3HCl. Spermidine-3HCl was non-genotoxic in the in vitro assays, and no adverse effects were reported in the 90-day oral toxicity study up to the highest dose tested, 12500 ppm, equivalent to 728 mg/kg bw/day for males and 829 mg/kg bw/day for females. The subchronic no observed adverse effect level (NOAEL) is 728 mg/kg bw/day., Competing Interests: Declaration of competing interest Patrick Keohane and Rui Pereria are employees of Chrysea Labs Lda, which sponsored the studies presented in this paper. Paola P. Chrysostomou, Elaine L. Freeman, and Mary M. Murphy are employees of Exponent, Inc.; Chrysea Labs Lda is a client of Exponent, Inc. David J. Esdaile is an employee of Charles River Laboratories Hungary, Kft. where the study was conducted; Chrysea Labs Lda is a client of Charles River Laboratories. Sprevive® is a registered trademark of Chrysea Labs Lda., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Study Question: Is ultra-processed food (UPF) consumption associated with semen quality parameters?, Summary Answer: Higher UPF consumption was inversely associated with total sperm count, sperm concentration, and total motility in men of reproductive age., What Is Known Already: The consumption of UPF, which has been rising during the last decades, has been demonstrated to be positively associated with several chronic diseases such as diabetes or cardiovascular diseases. However, the scientific evidence on its potential impact on semen quality remains notably limited., Study Design Size Duration: A cross-sectional analysis was conducted using data from 200 healthy men (mean age 28.4 ± 5.5 years) enrolled in the Led-Fertyl (Lifestyle and Environmental Determinants of Seminogram and Other Male Fertility-Related Parameters) study between February 2021 and April 2023., Participants/materials Setting Methods: UPF consumption (% of energy from UPF) was estimated according to the NOVA classification system using a validated 143-item semi-quantitative food frequency questionnaire. Total sperm count, sperm concentration, sperm vitality, total motility, progressive motility, and normal sperm forms were set as the main outcomes. Microscopic parameters were analyzed using a phase-contrast microscope and a computer-assisted sperm analysis (CASA) system. Semen samples were collected and tested according to World Health Organization 2010 standards. Multivariable linear regression models were fitted to estimate the associations between UPF tertile and semen quality parameters., Main Results and the Role of Chance: Sperm concentration ( β : -1.42 × 10 6 spz./ml; 95% CI: -2.72 to -0.12) and motility ( β : -7.83%; 95% CI: -15.16 to -0.51) were lower in participants in the highest tertile of UPF compared to the lowest. A similar association was observed for sperm count when UPF was analyzed per 10% increment of energy from UPF consumption ( β : -1.50 × 10 6 spz.; 95% CI: -2.83 to -0.17). Theoretically replacing 10% of energy from UPF consumption with 10% of energy from unprocessed or minimally processed food consumption was associated with a higher total sperm count, sperm concentration, total motility, progressive motility, and normal sperm forms., Limitations Reasons for Caution: Cross-sectional studies do not permit the drawing of causal inferences. Measurement errors and reporting bias cannot be entirely ruled out., Wider Implications of the Findings: This work suggests that consumption of UPF may have an impact on certain semen quality parameters. Furthermore, opting for unprocessed or minimally processed foods instead of UPFs could potentially benefit semen quality. If these results are replicated in future epidemiological studies with different long-term designs, these novel findings could provide valuable insights for updating or even designing preventive and interventional programs to address infertility among men of reproductive age., Study Funding/competing Interests: This study was supported by the Spanish government's official funding agency for biomedical research, ISCIII, through the Fondo de Investigación para la Salud (FIS), the European Union ERDF/ESF, 'A way to make Europe'/'Investing in your future' [PI21/01447], and the Diputació de Tarragona (2021/11-No.Exp. 8004330008-2021-0022642). J.S.-S. gratefully acknowledges the financial support of ICREA under the ICREA Academia program. C.V.-H. received a predoctoral grant from the Generalitat de Catalunya (2022 FI&#95;B100108). M.Á.M. was supported by the Sara Borrell postdoctoral fellowship (CD21/00045-Instituto de Salud Carlos III (ISCIII)). M.F.d.l.P. was supported by a predoctoral grant from the Rovira i Virgili University and Diputació de Tarragona (2020-PMF-PIPF-8). All authors have no conflict of interest to declare., Trial Registration Number: N/A., Competing Interests: All authors have no conflict of interest to declare., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Introduction: Evidence exploring the relationship between COVID-19 mitigation measures and mental health has primarily been from quantitative studies in large, developed countries. A qualitative study to explore the knowledge, attitudes and behaviors of young people living in Trinidad and Tobago was conducted to engage and collaborate with youth on matters affecting them during the pandemic., Methods: Ten virtual focus groups were conducted with 64 participants aged 18 to 24 in 2021 when partial lockdown measures were in effect for COVID-19 prevention. Groups were stratified by geographic location and socioeconomic status. The recordings were transcribed and analyzed to explore themes of importance to youth., Results: Negative impacts on mental health emerged as a strong theme. Lack of timelines for restrictions led to wide ranging mental health impacts, conflict and tension existed in home environments, longer restrictions led to erosion of the social culture, and young people experienced stress about the changing face of education and job security due to the pandemic., Discussion: Measures taken to address one serious public health concern, COVID-19, led to the aggravation of another serious public health concern, mental ill-health. Mental health initiatives to help young people navigate issues specific to their generation must be developed. In low resourced Small Island Developing States settings. The increased need for mental health services during and because of the COVID-19 pandemic highlights the need for strengthening the capacity and resilience of these to respond to environmental and health emergencies. Building the resilience of educational and employment services is also needed., Competing Interests: CP was employed by QURE Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Murphy, Pemberton, Wheeler, Gulston, Kerr-Layne, John, Baksh, Thomas and Allen.)

Consuming too few fruits and vegetables and excess fat can increase the risk of childhood obesity. Interventions which target mediators such as caregivers' dietary intake, parenting strategies, and the family meal context can improve children's diets. A quasi-experimental, pre-post intervention with four conditions (healthcare (HC-only), public health (PH-only), HC + PH, and control) was implemented to assess the effects of the interventions and the effects of the mediators. HC (implemented with the Obesity Care Model) and PH interventions entailed capacity building; policy, system, and environment changes; and a small-scale media campaign to promote healthy eating. Linear mixed models were used to assess intervention effects and the mediation analysis was performed. Predominantly Hispanic/Latino children and caregivers from rural communities in Imperial County, California, were measured at baseline (N = 1186 children/848 caregivers) and 12 months post-baseline (N = 985/706, respectively). Children who were overweight/obese in the HC-only condition (M = 1.32) consumed more cups of fruits at the 12-month follow-up than those in the control condition (M = 1.09; p = 0.04). No significant mediation was observed. Children in the PH-only condition consumed a significantly higher percentage of energy from fat (M = 36.01) at the follow-up than those in the control condition (M = 34.94, p < 0.01). An obesity intervention delivered through healthcare settings slightly improved fruit intake among at-risk children, but the mechanisms of effect remain unclear.

Globalized food systems are a major driver of climate change, biodiversity loss, environmental degradation, and the increasing prevalence of overweight and obesity in society. Small Island Developing States (SIDS) are particularly sensitive to the negative effects of rapid environmental change, with many also exhibiting a heavy reliance on food imports and high burdens of nutrition-related disease, resulting in calls to (re)localize their food systems. Such a transition represents a complex challenge, with adaptation interventions in one part of the food system contingent on the success of interventions in other parts. To help address this challenge, we used group model-building techniques from the science of system dynamics to engage food system stakeholders in Caribbean and Pacific SIDS. Our aim was to understand the drivers of unhealthy and unsustainable food systems in SIDS, and the potential role that increased local food production could play in transformative adaptation. We present two causal loop diagrams (CLDs) considered helpful in designing resilience-enhancing interventions in local food systems. These CLDs represent 'dynamic hypotheses' and provide starting points that can be adapted to local contexts for identifying food system factors, understanding the interactions between them, and co-creating and implementing adaptation interventions, particularly in SIDS. The results can help guide understanding of complexity, assist in the co-creation of interventions, and reduce the risk of maladaptive consequences., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Guariguata et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Intentional cranial modification has a long history, being a ubiquitous practice in many cultures around the world for millennia. The crania excavated at the Hirota site on Tanegashima Island, Kagoshima Prefecture, Japan, has been previously noted to have a marked tendency toward a short head and a flattened occipital bone, which has been suggested to be the result of artificial cranial deformation. However, whether this deformation was intentional or caused by unintentional habits remains unclear. This study aimed to investigate the characteristics of the cranial shape of the Hirota site to clarify whether the crania were intentionally modified. In the examination of Hirota crania, Kyushu Island Jomon and Doigahama Yayoi crania were added as comparative data and contrasted with three-dimensional (3D) surface scan imaging and two-dimensional outline-based geometric morphometric analysis, combined with objective assessments of potential cranial modification. The results showcased Hirota's short and flattened cranial morphology, indicating clear alignment with our hypothesis that Hirota samples are morphologically different from Doigahama and Jomon samples. No sex-based differences were found. Morphological abnormalities in cranial sutures were visually assessed utilizing novel 3D visualization methods of cranial outer surfaces. Based on a comprehensive review of the results, we concluded that Hirota site crania were intentionally modified. Although the motivation of the practice is unclear, the Hirota people may have deformed their crania to preserve group identity and possibly aid in the long-distance trade of shellfish, as seen archaeologically., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Seguchi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

We previously reported that exercise training drives enhanced agonist-stimulated hydrogen peroxide (H 2 O 2 ) levels and restores endothelium-dependent dilation via an increased reliance on H 2 O 2 in arterioles isolated from ischemic porcine hearts. In this study, we tested the hypothesis that exercise training would correct impaired H 2 O 2 -mediated dilation in coronary arterioles isolated from ischemic myocardium through increases in protein kinase G (PKG) and protein kinase A (PKA) activation and subsequent colocalization with sarcolemmal K + channels. Female adult Yucatan miniature swine were surgically instrumented with an ameroid constrictor around the proximal left circumflex coronary artery, gradually inducing a collateral-dependent vascular bed. Arterioles (∼125 µm) supplied by the left anterior descending artery served as nonoccluded control vessels. Pigs were separated into exercise (treadmill; 5 days/wk for 14 wk) and sedentary groups. Collateral-dependent arterioles isolated from sedentary pigs were significantly less sensitive to H 2 O 2 -induced dilation compared with nonoccluded arterioles, whereas exercise training reversed the impaired sensitivity. Large conductance calcium-activated potassium (BK Ca ) channels and 4AP-sensitive voltage-gated (K v ) channels contributed significantly to dilation in nonoccluded and collateral-dependent arterioles of exercise-trained but not sedentary pigs. Exercise training significantly increased H 2 O 2 -stimulated colocalization of BK Ca channels and PKA, but not PKG, in smooth muscle cells of collateral-dependent arterioles compared with other treatment groups. Taken together, our studies suggest that with exercise training, nonoccluded and collateral-dependent coronary arterioles better use H 2 O 2 as a vasodilator through increased coupling with BK Ca and 4AP-sensitive K v channels; changes that are mediated in part by enhanced colocalization of PKA with BK Ca channels. NEW & NOTEWORTHY The current study reveals that coronary arterioles distal to stenosis display attenuated dilation responses to H 2 O 2 that are restored with endurance exercise training. Enhanced H 2 O 2 dilation after exercise is dependent on K v and BK Ca channels and at least in part on in colocalization of BK Ca channel and PKA and independent of PKA dimerization. These findings expand our earlier studies which demonstrated that exercise training drives beneficial adaptive responses of reactive oxygen species in the microvasculature of the ischemic heart.

Mammalian hematopoietic stem cells (HSCs) colonize the bone marrow during late fetal development, and this becomes the major site of hematopoiesis after birth. However, little is known about the early postnatal bone marrow niche. We performed single-cell RNA sequencing of mouse bone marrow stromal cells at 4 days, 14 days, and 8 weeks after birth. Leptin-receptor-expressing (LepR + ) stromal cells and endothelial cells increased in frequency during this period and changed their properties. At all postnatal stages, LepR + cells and endothelial cells expressed the highest stem cell factor (Scf) levels in the bone marrow. LepR + cells expressed the highest Cxcl12 levels. In early postnatal bone marrow, SCF from LepR + /Prx1 + stromal cells promoted myeloid and erythroid progenitor maintenance, while SCF from endothelial cells promoted HSC maintenance. Membrane-bound SCF in endothelial cells contributed to HSC maintenance. LepR + cells and endothelial cells are thus important niche components in early postnatal bone marrow., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Inadequate pregnancy cobalamin status has been associated with adverse offspring metabolic health in Indian and Nepalese studies. Studies of pregnancy cobalamin status and mid-childhood health outside of Asia are scarce., Methods: Associations between pregnancy fasting plasma total homocysteine (tHcy), cobalamin status (plasma cobalamin, holotranscobalamin (holoTC), methylmalonic acid (MMA)) and mid-childhood metabolic score (MetSco) ((including fat mass index (zFMI), homeostatic model assessment of insulin resistance (zHOMA-IR) and dyslipidemia (zTG - zHDLc)/2) z-scores)) were investigated in a prospective study of 293 mother-child dyads., Results: Highest versus low-mid pregnancy tHcy tertile was associated with higher mid-childhood MetSco, specifically with higher child zFMI. Stratifying by sex, the maternal tHcy-child MetSco association was limited to boys and confirmed for zFMI and zHOMA-IR. The maternal tHcy-child zFMI association was not mediated by birth weight z-score. First trimester plasma cobalamin was not associated with child outcomes, but other indicators of cobalamin status were. Lowest versus mid-high plasma holoTC tertile was associated with MetSco (specifically zFMI and zHOMA-IR) and highest versus low-mid plasma MMA tertile with higher MetSco and dyslipidemia in boys., Conclusions: Moderately elevated pregnancy tHcy and low cobalamin status were associated with mid-childhood metabolic score in boys. The pregnancy tHcy-child zFMI association was not mediated by birth weight., Impact: Fasting plasma total homocysteine (tHcy) during pregnancy and low cobalamin status during early pregnancy are associated with mid-childhood metabolic score and its components in the offspring. These findings were only significant in male offspring. The study provides new evidence that impaired one carbon metabolism during pregnancy is associated with negative health outcomes in the offspring, in a population with low prevalence of cobalamin deficiency. The maternal-offspring associations were observed in the functional markers of cobalamin status (holotranscobalamin and methylmalonic acid) and tHcy, not with plasma cobalamin concentration. Screening for low pregnancy cobalamin status should be considered., (© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Objective: To describe how using a supine arm cycle ergometer can safely reduce deconditioning experienced by patients with spinal cord injury or disorder (SCI/D) during their four to six weeks of complete bed rest after surgery to close a stage 4 pressure injury., Design: This pilot project used a newly designed arm cycle ergometer (known as the M-PACE) that extends over the bed, allowing a patient to lie completely supine while exercising., Setting: The M-PACE was designed and built at the Minneapolis Veterans Affairs Health Care System (MVAHCS) and pilot tested at the MVAHCS SCI/D Center., Participants: Patients with SCI/D, recovering from flap surgery and deemed appropriate to use the arm cycle ergometer were enrolled in the pilot study ( n  = 47)., Outcome Measures: A pre-post six-minute arm test (6MAT), a proxy for conditioning, was conducted on a subset ( n  = 15) of participants before and after the supine cycling exercise training program. Participants' rating of perceived exertion (RPE) scores were collected at cessation of each 6MAT. Participants gave feedback on their perception of using the M-PACE., Results/conclusions: The 6MAT RPE was significantly reduced after training with the M-PACE while on bed rest ( P  = 0.003). Also, significantly more rotations were performed after completing the training program ( P  = 0.02). Further, study participants who accessed the M-PACE found using it helped offset the tedium of laying supine during flap surgery recovery. The differences in the 6MAT pre- to post measures indicate the M-PACE should be further studied for offsetting the normal deconditioning that occurs with extended bedrest.

Background: The 1.6 Mb 3q29 deletion is associated with neurodevelopmental and neuropsychiatric phenotypes, including a 19-fold increased risk for autism spectrum disorder (ASD). Previous work by our team identified elevated social disability in this population via parent-report questionnaires. However, clinical features of ASD in this population have not been explored in detail., Methods: Thirty-one individuals with 3q29 deletion syndrome (3q29del, 61.3% male) were evaluated using two gold-standard clinical ASD evaluations: the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2), and the Autism Diagnostic Interview, Revised (ADI-R). Four matched comparators for each subject were ascertained from the National Database for Autism Research. Item-level scores on the ADOS-2 and ADI-R were compared between subjects with 3q29del and matched comparators., Results: Subjects with 3q29del and no ASD (3q29del-ASD) had greater evidence of social disability compared to typically developing (TD) comparison subjects across the ADOS-2. Subjects with 3q29del and ASD (3q29del + ASD) were largely indistinguishable from non-syndromic ASD (nsASD) subjects on the ADOS-2. 3q29del + ASD performed significantly better on social communication on the ADI-R than nsASD (3q29 + ASD mean = 11.36; nsASD mean = 15.70; p = 0.01), and this was driven by reduced deficits in nonverbal communication (3q29 + ASD mean = 1.73; nsASD mean = 3.63; p = 0.03). 3q29del + ASD reported significantly later age at the first two-word phrase compared to nsASD (3q29del + ASD mean = 43.89 months; nsASD mean = 37.86 months; p = 0.01). However, speech delay was not related to improved nonverbal communication in 3q29del + ASD., Limitations: There were not enough TD comparators with ADI-R data in NDAR to include in the present analysis. Additionally, our relatively small sample size made it difficult to assess race and ethnicity effects., Conclusions: 3q29del is associated with significant social disability, irrespective of ASD diagnosis. 3q29del + ASD have similar levels of social disability to nsASD, while 3q29del-ASD have significantly increased social disability compared to TD individuals. However, social communication is reasonably well preserved in 3q29del + ASD relative to nsASD. It is critical that verbal ability and social disability be examined separately in this population to ensure equal access to ASD and social skills evaluations and services., (© 2022. The Author(s).)

Small island developing states (SIDS) have a high burden of nutrition-related disease associated with nutrient-poor, energy-dense diets. In response to these issues, we assessed the effectiveness of nutrition-based interventions on nutritional status (under-nutrition) and metabolic health (over-nutrition) among persons in SIDS. We included SIDS-based nutrition studies with change in nutrition status (e.g., markers of anaemia) or metabolic status (e.g., markers of glycaemia) as outcomes. The PRISMA framework was applied and MEDLINE, Embase, CINAHL, OARE library, Web of Science, Scopus, ASSIA, EconLit, AGORA, AGRICOLA, AGRIS, WHO-EMRO, and LILACS were searched (2000−2020). Cochrane risk of bias (ROB) and Cochrane ROBINS-I tools assessed ROB for randomised and non-randomised studies, respectively. PROSPERO registration (CRD42021236396) was undertaken. We included 50 eligible interventions, involving 37,591 participants: 14 trials reported on nutritional status, 36 on metabolic health. Effective interventions, evaluated at the individual level, took a multifaceted approach for metabolic outcomes; while nutrition outcomes utilised supplements. Most intervention types were suitable for issues related to ‘over’ nutrition versus ‘under’ nutrition. Twenty-six studies (nutrition status (six); metabolic health (twenty)) were effective (p < 0.05). With the current rise of nutrition-related public health challenges, there is a need for further development and evaluation of these and related interventions at the population level., Competing Interests: The authors declare no conflict of interest. This publication will be used as a chapter of a PhD Thesis.

Objective: To describe features of nutritional interventions implemented in Small Island Developing States (SIDS) in the past 20 years., Methods: A rapid scoping review was conducted by searching PubMed and Web of Science databases for interventions conducted in SIDS that sought to improve the nutrition of their populations between 2000 and 2019 inclusive. The Noncommunicable diseases progress monitor 2020 was also examined to assess nutritional policies in SIDS., Results: A total of 174 interventions were implemented in 49 of the 58 SIDS. The greatest proportion were conducted in the Caribbean (75 interventions; 43%), with the Pacific region, and the Atlantic, Indian Ocean, Mediterranean and South China Sea region each implementing about 30% of interventions. Using the NOURISHING framework, most interventions (67%) were implemented at the community and national or policy level, using multiple components of the framework. The greatest proportion of interventions (35%) were educational and awareness raising. Restrictions on physical availability of and increased taxation on alcohol were the most commonly reported policies that were partially or fully achieved; restrictions on fats were the least commonly reported. These findings were generally consistent across the SIDS regions., Conclusions: There is a paucity of nutritional policies in SIDS; the reasons may be linked to their social, economic, and environmental vulnerabilities. Interventions should be expanded beyond education to encompass multiple components of the NOURISHING framework, with multisectoral inclusion to ensure stronger stakeholder collaboration and buy-in. A systematic review is warranted using a fuller range of sources to assess the effectiveness of interventions.

Background: Dietary patterns developed by the USDA provide modest levels of protein (14-18% energy) within the Acceptable Macronutrient Distribution Range (AMDR) of 10-35% for adults, though diets providing a higher percentage of energy may be beneficial for some individuals. The purpose of this study was to determine if it is feasible to modify the Healthy U.S.-Style Eating Pattern ("HEP") to provide a higher percentage of energy from protein., Methods: Using the framework implemented by the USDA in developing the HEP, energy from protein was set at 20%, 25%, and 30%. Amounts of protein foods were proportionally increased while amounts of other foods were adjusted iteratively within specified parameters. The models also disaggregated total meat/poultry into fresh and processed forms to develop patterns maintaining current proportions, current levels, reduced, or no processed meat/poultry. Nutrient intakes were compared with nutrient goals for representative U.S. populations with 2,000 kcal needs (females 19-30 years, males 51-70 years), with 90% of the Recommended Dietary Allowance or Adequate Intake regarded as sufficient., Results: Dietary patterns with 20% energy from protein were constructed with minor deviations from the current 2,000 kcal HEP. Dietary patterns with 25% energy from protein were constructed for all levels of processed meat/poultry excluding the current proportion model, though relative to the current HEP the constructed patterns reflect substantial reductions in amounts of refined grains and starchy vegetables, and substantial increases in protein foods consumed as beans and peas, seafood, and soy products. It was not possible to develop a pattern with 30% energy from protein without reducing the percentage of energy from carbohydrate below the AMDR or non-compliance with other modeling constraints. Stepwise reductions in processed meat/poultry reduced sodium intake., Conclusions: It is feasible to develop dietary patterns in a 2,000 kcal diet while mirroring the HEP that meet recommended intakes of nutrients with 20% or 25% energy from protein, though the pattern with 25% energy from protein may be more idealistic than realistic. Reduced levels of processed meat/poultry may translate to lower sodium intake., (© 2022. The Author(s).)

Bilaterally fixed and dilated pupils (BFDP) in traumatic acute subdural haematoma (ASDH) patients represent an ominous sign that portends irreversible brainstem injury and death. Whether patients with spontaneous ASDH and BFDP follow similar outcomes is unknown. We present a mid-60s man, found unconscious, with a Glasgow Coma Scale (GCS) of 4 following 8 days of headaches. Emergency CT imaging demonstrated a large right ASDH and the patient exhibited BFDP for >3 hours despite sedation and mannitol. Neurological improvement and spontaneously reduced SDH thickness were observed 10 hours postadmission, and he was later transferred for craniotomy and ASDH evacuation. His long-term outcomes were good: achieving independence in his activities of daily living and a GCS of 15. To the best of our knowledge, this is the first reported patient with a spontaneous, regressing ASDH and prolonged BFDP who clinically improved. This case raises important questions regarding factors used to determine prognosis and surgical viability for ASDH., Competing Interests: Competing interests: As the supervising author I can confirm that all authors have met BMJ criteria for authorship and contribution and have no conflict of interest to disclose., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The Barbados Diabetes Remission Study-2 reported that a low-calorie diet for weight loss and diabetes remission implemented within the community and supported by trained community health advocates was both an acceptable implementation strategy and a clinically effective intervention. This study aimed to examine the adaptability of the face-to-face protocol into an online modality., Methods: The Iterative Decision-making for Evaluation of Adaptations (IDEA) framework guides researchers in examining the necessity of the adaptation and the preservation of core intervention elements during the adaptation process. Adaptation outcomes were documented using the Framework for Reporting Adaptations and Modifications to Evidence-Based Implementation Strategies (FRAME-IS). Implementation outcome was determined by fidelity to core elements. Intervention effectiveness was determined from the analysis of clinical data., Results: We decided that an adaptation was needed as COVID-19 control measures prohibited in-person interactions. The core elements-i.e. 12-week intervention duration, daily 840-kcal allowance, and weekly monitoring of weight and blood glucose-could be preserved during the adaptation process. Adaptations were made to the following: (1) the context in which data were collected-participants self-measured at home instead of following the original implementation strategy which involved being measured by community health advocates (CHA) at a community site; (2) the context in which data were entered-participants posted their measurements to a mobile application site which was accessible by CHAs. As with the original protocol, CHAs then entered the measurements into an online database; (3) the formulation of the low-calorie diet-participants substituted the liquid formulation for a solid meal plan of equivalent caloric content. There was non-inferiority in fidelity to attendance with the online format (97.5% visit rate), as compared to the face-to-face modality (95% visit rate). One participant deviated from the calorie allowances citing difficulty in estimating non-exact portion sizes and financial difficulty in procuring meals. Weight change ranged from - 14.3 to 0.4 kg over the 12-week period, and all group members achieved induction of diabetes remission as determined by a FBG of < 7mmol/l and an A1C of < 6.5%., Conclusion: The results suggest that this adapted online protocol-which includes changes to both the implementation strategy and the evidence-based practice-is clinically effective whilst maintaining fidelity to key elements. Utilization of the IDEA and FRAME-IS adaptation frameworks add scientific rigour to the research., Trial Registration: ClinicalTrials.gov NCT03536377 . Registered on 24 May 2018., (© 2022. The Author(s).)

Background: Only three of twenty Caribbean Community (CARCICOM) countries have mandatory school nutrition policies despite one third of the region's children being overweight or obese. In Barbados, there are nutrition guidelines which lack the legal mandate of a formal policy. We aim to assess the comprehensiveness of current national nutrition guidelines and to understand the factors operating in the inner and outer school setting that may influence the implementation of a mandatory school nutrition policy from the perspectives of school administrators., Methods: A documentary analysis of existing nutritional guidelines was conducted along with qualitative semi-structured interviews in primary (elementary) and secondary (high) schools in Barbados. We purposively sampled six primary and four secondary school administrators (principals, deputy principals or senior teachers) to explore their knowledge and views on the National School Nutrition Guidelines. The deterministic implementation paradigm, Consolidated Framework for Implementation (CFIR), was used to explore the complexities within the inner and outer settings of schools. Documentary analysis used a theory-based framework informed by the Wellness School Assessment Tool-school policy analysis questionnaire. Interview transcripts were team coded using thematic analysis with constant comparison facilitated by NVIVO software version12., Results: School administrators were unaware of the existing National School Nutrition Guidelines which documentary analysis found to be restrictive and weak for implementation. Administrators envisioned a government-led (outer setting), whole of society approach as the most effective strategy for the development and implementation of a proposed mandatory school nutrition policy. School administrators identified lack of financial and human resources as barriers to nutrition policy implementation. Formal and informal food vendors are institutionalized in schools and are influential determinants of the school food environment. Schools have individually reached into the outer setting to work with civil society organizations and private individuals to provide financial support and nutrition expertise to their institutions. Mass media campaigns in the outer setting may influence child and parental food choices., Conclusion: School administrators describe that government-led, CSO supported policy development using a whole-of-society approach has implications for improving nutrition policy implementation. Our findings demonstrate the use of a deterministic implementation framework in the pre-implementation phase of school nutrition policy development., (© 2021. The Author(s).)

Background: Sodium intake in the USA exceeds recommendations. The replacement of added sodium chloride (NaCl) with potassium chloride (KCl) provides a potential strategy to reduce sodium intake., Objective: The purpose of this study was to quantitatively estimate changes in intakes of sodium and potassium by the US population assuming use of potassium-based NaCl replacers in top dietary sodium sources., Methods: Data collected in the What We Eat in America (WWEIA) component of the 2015-2016 and 2009-2010 NHANES were used to identify top-ranking sources of dietary sodium among the population aged 2 y and older based on contributions from food categories aligning with the FDA draft guidance for voluntary sodium reduction. Predicted nutrient intakes were estimated in models assuming total and feasible and practical (F&P) replacement of added NaCl with KCl in foods and ingredients within the top food sources of sodium. An expert elicitation was conducted to collect information on the F&P KCl replacement of added NaCl., Results: Using 2015-2016 consumption data, the total replacement of added NaCl with KCl in the 18 top-ranking sources of dietary sodium results in a predicted sodium intake of 2004 mg/d from the replacement of 1406 mg/d sodium with 1870 mg/d potassium as KCl. Modeled F&P replacement predicted sodium intakes of 3117 mg/d (range of 2953 to 3255 mg/d) from the replacement of 294 mg/d sodium (155 to 457 mg/d) with 390 mg/d potassium (206 to 608 mg/d). Similar results are seen with 2009-2010 data., Conclusions: The F&P replacement of NaCl with KCl in top-ranking sources of dietary sodium modeled in this study can result in decreased sodium to a level consistent with the short-term intake goal targeted by the FDA of 3000 mg/d, with the mean potassium intake remaining in the range recommended for the apparently healthy population., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Across the United States, the number of staff scientists (master's- or doctoral-level professionals working in nonfaculty roles) has grown by 35% since 2010, and they play an increasingly important role in research efforts. However, few targeted resources are available, which potentially limits the effectiveness of this group. Launched in 2016, the staff scientist path at Emory has tripled in size over 4 y to 138 staff. The present case study evaluated the perceptions of staff scientists related to onboarding experiences and professional development needs, including those needs arising from coronavirus disease 2019 (COVID-19) impacts in the workplace. A survey of Emory staff scientists was conducted from May to June 2019 as part of a program evaluation initiative to assess perceptions of onboarding and professional development opportunities. Interviews with a subset of scientists informed the survey development and identified COVID-19-related impacts on daily work. Results indicated the need for targeted orientation resources specific to staff scientists, accurate and timely information and resources to support scientists' supervisors, and professional development for scientists in leadership and management-related skills. Remote work associated with COVID-19 accentuated the need for managerial skills, including team development in digital work environments. Findings from this case study can inform policies and practices at Emory and other institutions that employ a similar staff scientist model., (© Association of Biomolecular Resource Facilities.)

Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Purpose: To understand the consequences of the 3q29 deletion on medical, neurodevelopmental, psychiatric, brain structural, and neurological sequalae by systematic evaluation of affected individuals. To develop evidence-based recommendations using these data for effective clinical care., Methods: Thirty-two individuals with the 3q29 deletion were evaluated using a defined phenotyping protocol and standardized data collection instruments., Results: Medical manifestations were varied and reported across nearly every organ system. The most severe manifestations were congenital heart defects (25%) and the most common were gastrointestinal symptoms (81%). Physical examination revealed a high proportion of musculoskeletal findings (81%). Neurodevelopmental phenotypes represent a significant burden and include intellectual disability (34%), autism spectrum disorder (38%), executive function deficits (46%), and graphomotor weakness (78%). Psychiatric illness manifests across the lifespan with psychosis prodrome (15%), psychosis (20%), anxiety disorders (40%), and attention deficit-hyperactivity disorder (ADHD) (63%). Neuroimaging revealed structural anomalies of the posterior fossa, but on neurological exam study subjects displayed only mild or moderate motor vulnerabilities., Conclusion: By direct evaluation of 3q29 deletion study subjects, we document common features of the syndrome, including a high burden of neurodevelopmental and neuropsychiatric phenotypes. Evidence-based recommendations for evaluation, referral, and management are provided to help guide clinicians in the care of 3q29 deletion patients.

Stromal cells in adult bone marrow that express leptin receptor (LEPR) are a critical source of growth factors, including stem cell factor (SCF), for the maintenance of haematopoietic stem cells and early restricted progenitors 1-6 . LEPR + cells are heterogeneous, including skeletal stem cells and osteogenic and adipogenic progenitors 7-12 , although few markers have been available to distinguish these subsets or to compare their functions. Here we show that expression of an osteogenic growth factor, osteolectin 13,14 , distinguishes peri-arteriolar LEPR + cells poised to undergo osteogenesis from peri-sinusoidal LEPR + cells poised to undergo adipogenesis (but retaining osteogenic potential). Peri-arteriolar LEPR + osteolectin + cells are rapidly dividing, short-lived osteogenic progenitors that increase in number after fracture and are depleted during ageing. Deletion of Scf from adult osteolectin + cells did not affect the maintenance of haematopoietic stem cells or most restricted progenitors but depleted common lymphoid progenitors, impairing lymphopoiesis, bacterial clearance, and survival after acute bacterial infection. Peri-arteriolar osteolectin + cell maintenance required mechanical stimulation. Voluntary running increased, whereas hindlimb unloading decreased, the frequencies of peri-arteriolar osteolectin + cells and common lymphoid progenitors. Deletion of the mechanosensitive ion channel PIEZO1 from osteolectin + cells depleted osteolectin + cells and common lymphoid progenitors. These results show that a peri-arteriolar niche for osteogenesis and lymphopoiesis in bone marrow is maintained by mechanical stimulation and depleted during ageing.

Limited information is available on protein intake and adequacy of protein intake among pregnant women. Using data from a sample of 528 pregnant women in the National Health and Nutrition Examination Surveys (NHANES) 2003-2012, usual intake of protein (g/day and g/kg body weight (bw)/day) and prevalence of intake below the Estimated Average Requirement (EAR) by trimester of pregnancy were calculated using the National Cancer Institute method. Percent contributions to protein intake by source (i.e., plant and animal, including type of animal source) were also calculated. Mean usual intake of protein was 88 ± 4.3, 82 ± 3.1, and 82 ± 2.9 g/day among women in trimester 1, 2, and 3 of pregnancy, respectively, or 1.30 ± 0.10, 1.35 ± 0.06, and 1.35 ± 0.05 g/kg bw/day, respectively. An estimated 4.5% of women in the first trimester of pregnancy consumed less protein than the EAR of 0.66 g/kg bw/day; among women in the second and third trimesters of pregnancy, 12.1% and 12.8% of women, respectively, consumed less protein than the EAR of 0.88 g/kg bw/day. Animal sources of protein accounted for approximately 66% of total protein. Findings from this study show that one in eight women in the second and third trimesters of pregnancy have inadequate intake of protein. Pregnant women should be encouraged to consume sufficient levels of protein from a variety of sources.

Little is known about the potential health economic impact of increasing the proportion of total grains consumed as whole grains to align with Dietary Guidelines for Americans (DGA) recommendations. Health economic analysis estimating difference in costs developed using (1) relative risk (RR) estimates between whole grains consumption and outcomes of cardiovascular disease (CVD) and a selected component (coronary heart disease, CHD); (2) estimates of total and whole grains consumption among US adults; and (3) annual direct and indirect medical costs associated with CVD. Using reported RR estimates and assuming a linear relationship, risk reductions per serving of whole grains were calculated and cost savings were estimated from proportional reductions by health outcome. With a 4% reduction in CVD incidence per serving and a daily increase of 2.24 oz-eq of whole grains, one-year direct medical cost savings were estimated at US$21.9 billion (B) (range, US$5.5B to US$38.4B). With this same increase in whole grains and a 5% reduction in CHD incidence per serving, one-year direct medical cost savings were estimated at US$14.0B (US$8.4B to US$22.4B). A modest increase in whole grains of 0.25 oz-eq per day was associated with one-year CVD-related savings of $2.4B (US$0.6B to US$4.3B) and CHD-related savings of US$1.6B (US$0.9B to US$2.5B). Increasing whole grains consumption among US adults to align more closely with DGA recommendations has the potential for substantial healthcare cost savings.

Evidence linking fasting plasma total homocysteine (tHcy) and methylenetetrahydrofolate reductase ( MTHFR ) 677C>T genotype with hypertension is inconsistent. Differences in B vitamin status, other lifestyle factors or their consideration in analyses might explain this. We investigated these associations in the absence of mandatory fortification with folic acid and B vitamin supplement use. A cross-sectional study was conducted in 788 adults, aged 18-75 years, randomly selected from three Catalonian town population registers. Fasting plasma folate, cobalamin, tHcy, erythrocyte folate, erythrocyte glutathione reductase activation coefficient (EGRAC, functional riboflavin status indicator; increasing EGRAC indicates worsening riboflavin status), MTHFR 677C>T and solute carrier family 1 ( SLC19A1 ) 80 G>A genotypes were determined. Medical history and lifestyle habits were recorded. Principal tHcy determinants differed between women (age, plasma folate, plasma cobalamin, cigarettes/d) and men ( MTHFR 677TT genotype, plasma folate, plasma cobalamin and CT genotype). The MTHFR 677C>T polymorphism-tHcy association ( β standardised regression coefficients) was stronger in male smokers (0·52, P < 0·001) compared with non-smokers (0·21, P = 0·001) and weaker in participants aged >50 years (0·19, P = 0·007) compared with ≤50 years (0·31, P < 0·001). Hypertension was more probable in the third tHcy tertile compared with other tertiles (OR 1·9; 95 % CI 1·2, 3·0), and in participants aged ≤50 years, for the MTHFR 677TT genotype compared with the CC genotype (OR 4·1; 95 % CI 1·0, 16·9). EGRAC was associated with increased probability of hypertension in participants aged >50 years (OR 6·2; 95 % CI 1·0, 38·7). In conclusion, moderately elevated tHcy and the MTHFR 677CT genotype were associated with hypertension. The MTHFR 677C>T genotype-hypertension association was confined to adults aged ≤50 years.

Background: 3q29 deletion syndrome is associated with a range of medical, neurodevelopmental, and psychiatric phenotypes. The deletion is usually de novo but cases have been reported where the deletion is inherited from apparently unaffected parents. The presence of these unaffected or mildly affected individuals suggests there may be an ascertainment bias for severely affected cases of 3q29 deletion syndrome, thus the more deleterious consequence of the 3q29 deletion may be overestimated. However, a substantial fraction of 3q29 deletion syndrome morbidity is due to psychiatric illness. In many case reports, probands and transmitting parents are not systematically evaluated for psychiatric traits. Here we report results from a systematic phenotyping protocol for neurodevelopmental and neuropsychiatric traits applied to all 3q29 deletion carriers in a multiplex family., Case Presentation: Through the 3q29 registry at Emory University, a multiplex family was identified where three offspring had a paternally inherited 3q29 deletion. We evaluated all 4 3q29 deletion family members using our previously described standardized, systematic phenotyping protocol. The transmitting parent reported no psychiatric history, however upon evaluation he was discovered to meet criteria for multiple psychiatric diagnoses including previously undiagnosed schizoaffective disorder. All four 3q29 deletion individuals in the pedigree had multiple psychiatric diagnoses that interfered with quality of life and prohibited successful academic and occupational functioning. Cognitive ability for all individuals was average or below average, but within the normal range., Conclusions: This is the first case report of inherited 3q29 deletion syndrome where all affected individuals in the pedigree have been comprehensively and systematically evaluated for neurodevelopmental and psychiatric symptoms, using a standard battery of normed instruments administered by expert clinicians. Our investigation reveals that individuals with 3q29 deletion syndrome may have psychiatric morbidity that is debilitating, but only apparent through specialized evaluation by an expert. In the absence of appropriate evaluation, individuals with 3q29 deletion syndrome may suffer from psychiatric illness but lack avenues for access to care. The individuals evaluated here all have cognition in the normal range alongside multiple psychiatric diagnoses each, suggesting that cognitive ability alone is not a representative proxy for 3q29 deletion-associated disability. These results require replication in a larger cohort of individuals with 3q29 deletion syndrome.

Many Small Island Developing States of the Caribbean experience a triple burden of malnutrition with high rates of obesity, undernutrition in children, and iron deficiency anemia in women of reproductive age, driven by an inadequate, unhealthy diet. This study aimed to map the complex dynamic systems driving unhealthy eating and to identify potential points for intervention in three dissimilar countries. Stakeholders from across the food system in Jamaica (n = 16), St. Kitts and Nevis (n = 19), and St. Vincent and the Grenadines (n = 6) engaged with researchers in two group model building (GMB) workshops in 2018. Participants described and mapped the system driving unhealthy eating, identified points of intervention, and created a prioritized list of intervention strategies. Stakeholders were also interviewed before and after the workshops to provide their perspectives on the utility of this approach. Stakeholders described similar underlying systems driving unhealthy eating across the three countries, with a series of dominant feedback loops identified at multiple levels. Participants emphasized the importance of the relative availability and price of unhealthy foods, shifting cultural norms on eating, and aggressive advertising from the food industry as dominant drivers. They saw opportunities for governments to better regulate advertising, disincentivize unhealthy food options, and bolster the local agricultural sector to promote food sovereignty. They also identified the need for better coordinated policy making across multiple sectors at national and regional levels to deliver more integrated approaches to improving nutrition. GMB proved to be an effective tool for engaging a highly diverse group of stakeholders in better collective understanding of a complex problem and potential interventions.

Background: The purpose of this study is to estimate the impact on health care costs if United States (US) adults increased their dairy consumption to meet Dietary Guidelines for Americans (DGA) recommendations., Methods: Risk estimates from recent meta-analyses quantifying the association between dairy consumption and health outcomes were combined with the increase in dairy consumption under two scenarios where population mean dairy intakes from the 2015-2016 What We Eat in America were increased to meet the DGA recommendations: (1) according to proportions by type as specified in US Department of Agriculture Food Intake Patterns and (2) assuming the consumption of a single dairy type. The resulting change in risk was combined with published data on annual health care costs to estimate impact on costs. Health care costs were adjusted to account for potential double counting due to overlapping comorbidities of the health outcomes included., Results: Total dairy consumption among adults in the US was 1.49 cup-equivalents per day (c-eq/day), requiring an increase of 1.51 c-eq/day to meet the DGA recommendation. Annual cost savings of $12.5 billion (B) (range of $2.0B to $25.6B) were estimated based on total dairy consumption resulting from a reduction in stroke, hypertension, type 2 diabetes, and colorectal cancer and an increased risk of Parkinson's disease and prostate cancer. Similar annual cost savings were estimated for an increase in low-fat dairy consumption ($14.1B; range of $0.8B to $27.9B). Among dairy sub-types, an increase of approximately 0.5 c-eq/day of yogurt consumption alone to help meet the DGA recommendations resulted in the highest annual cost savings of $32.5B (range of $16.5B to $52.8B), mostly driven by a reduction in type 2 diabetes., Conclusions: Adoption of a dietary pattern with increased dairy consumption among adults in the US to meet DGA recommendations has the potential to provide billions of dollars in savings.

Metastasis requires cancer cells to undergo metabolic changes that are poorly understood 1-3 . Here we show that metabolic differences among melanoma cells confer differences in metastatic potential as a result of differences in the function of the MCT1 transporter. In vivo isotope tracing analysis in patient-derived xenografts revealed differences in nutrient handling between efficiently and inefficiently metastasizing melanomas, with circulating lactate being a more prominent source of tumour lactate in efficient metastasizers. Efficient metastasizers had higher levels of MCT1, and inhibition of MCT1 reduced lactate uptake. MCT1 inhibition had little effect on the growth of primary subcutaneous tumours, but resulted in depletion of circulating melanoma cells and reduced the metastatic disease burden in patient-derived xenografts and in mouse melanomas. In addition, inhibition of MCT1 suppressed the oxidative pentose phosphate pathway and increased levels of reactive oxygen species. Antioxidants blocked the effects of MCT1 inhibition on metastasis. MCT1 high and MCT1 -/low cells from the same melanomas had similar capacities to form subcutaneous tumours, but MCT1 high cells formed more metastases after intravenous injection. Metabolic differences among cancer cells thus confer differences in metastatic potential as metastasizing cells depend on MCT1 to manage oxidative stress.

Background: The 1.6 Mb 3q29 deletion is associated with neurodevelopmental and psychiatric phenotypes, including increased risk for autism spectrum disorder (ASD) and a 20 to 40-fold increased risk for schizophrenia. However, the phenotypic spectrum of the deletion, particularly with respect to ASD, remains poorly described., Methods: We ascertained individuals with 3q29 deletion syndrome (3q29Del, "cases," n  = 93, 58.1% male) and typically developing controls ( n  = 64, 51.6% male) through the 3q29 registry (https://3q29deletion.patientcrossroads.org). Self-report of neuropsychiatric illness was evaluated for 93 cases. Subsets of participants were evaluated with the Social Responsiveness Scale (SRS, n  = 48 cases, 56 controls), Social Communication Questionnaire ( n  = 33 cases, 46 controls), Autism Spectrum Screening Questionnaire ( n  = 24 cases, 35 controls), and Achenbach Behavior Checklists ( n  = 48 cases, 57 controls)., Results: 3q29Del cases report a higher prevalence of autism diagnoses versus the general population (29.0% vs. 1.47%, p  < 2.2E- 16). Notably, 3q29 deletion confers a greater influence on risk for ASD in females (OR = 41.8, p  = 4.78E- 05) than in males (OR = 24.6, p  = 6.06E- 09); this is aligned with the reduced male:female bias from 4:1 in the general population to 2:1 in our study sample. Although 71% of cases do not report a diagnosis of ASD, there is evidence of significant social disability (3q29Del SRS T-score = 71.8, control SRS T-score = 45.9, p  = 2.16E- 13). Cases also report increased frequency of generalized anxiety disorder compared to controls (28.0% vs. 6.2%, p  = 0.001), which is mirrored by elevated mean scores on the Achenbach diagnostic and statistical manual-oriented sub-scales ( p  < 0.001). Finally, cases show a distinct constellation of ASD features on the SRS as compared to idiopathic ASD, with substantially elevated Restricted Interests and Repetitive Behaviors, but only mild impairment in Social Motivation., Conclusions: Our sample of 3q29Del is significantly enriched for ASD diagnosis, especially among females, and features of autism may be present even when an ASD diagnosis is not reported. Further, the constellation of ASD features in this population is distinct from idiopathic ASD, with substantially less impaired social motivation. Our study implies that ASD evaluation should be the standard of care for individuals with 3q29Del. From a research perspective, the distinct ASD subtype present in 3q29Del is an ideal entry point for expanding understanding of ASD., Competing Interests: Competing interestsCAS reports receiving royalties from Pearson Clinical for the Vineland-3. The other authors declare that they have no competing interests.