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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

Language problems can be associated with specific genetic syndromes, such as Klinefelter syndrome and fragile X syndrome, even in the absence of intellectual and developmental disabilities. Turner syndrome, a relatively common genetic disorder, is caused by the complete or partial absence of 1 of the 2 X chromosomes typically present in women. The syndrome is characterized by a distinct profile of physical and neuropsychological characteristics. The language characteristics of Turner syndrome have received considerably less attention than other cognitive domains, such as executive function and visual spatial ability. The present article focuses on describing the language and literacy characteristics associated with Turner syndrome, which are generally considered to be areas of relative strength. Related cognitive skills, such as executive function, and clinical implications are also discussed. [ABSTRACT FROM AUTHOR]

The American Society of Electroneurodiagnostic Technologists, Inc. (ASET) presents this document to provide national criteria for evaluating the competencies needed by technologists to perform Polysomnography Studies (PSG). These national competencies were established following the analysis of survey data collected in the fall of 2005. The tabulation was completed by ASET staff and the PSG Task Force, according to nationally recognized and accepted criteria. ASET also recognizes the review by and valued input from the Board of Registered Polysomnographic Technologists (BRPT). [ABSTRACT FROM AUTHOR]

C-reactive protein (CRP) has been proposed as an independent risk factor for cardiovascular disease. In this study we sought to investigate the association between several nutritional and lifestyle factors and serum CRP concentration in a population-based study. We studied 359 individuals (172 women, 187 men; age range 18-75 years) randomly selected from the town hall's registers and assessed their daily dietary intake using a 3-day estimated-food record. The median serum CRP concentration was 1.40 mg/I (range <0.10-47.48 mg/L; geometric mean 1.20 mg/L). We noted significant and independent direct associations between CRP and age, body-mass index, female sex, and serum triglyceride concentration. Bivariate analysis showed a significant inverse association between CRP and many nutrients (e.g., carbohydrates, proteins, lipids, thiamine, pyridoxine, tocopherol, and folate), but multiple-regression analysis indicated that only the effect of dietary folate intake was not dependent on other factors. Differences in folate intake did not produce changes in plasma homocysteine concentration, and we detected no negative correlation between dietary folate intake and log homocysteine (r = .02, P = .711). Strong positive correlations between the intake of folate and numerous other nutrients were found. This population-based study shows that a higher folate intake, in addition to other known constitutive and lifestyle factors, is significantly associated with a lower serum CRP concentration. [ABSTRACT FROM AUTHOR]

Mental retardation is typically associated with substantial delays in language. Researchers have been interested in the possible differences in the extent or nature of these delays across genetic syndromes, such as fragile X, Down, and Williams syndromes. This article addresses how genetic factors and environmental characteristics interact to produce specific language outcomes. We suggest that episodes of joint attention provide a means by which genetic anomalies can have indirect effects on some facets of language development. In doing so, we explain the nature of indirect effects and their influence on development; illustrate the link between joint attention and later language ability; discuss how joint attention may account for the characteristics associated with genetic syndromes, with special attention on fragile X syndrome; and consider implications for intervention. [ABSTRACT FROM AUTHOR]

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]

Purpose: Glutamatergic neuron-glioma synaptogenesis and peritumoral hyperexcitability promote glioma growth in a positive feedback loop. The objective of this study was to evaluate the feasibility and estimated effect sizes of the targeted AMPA receptor antagonist perampanel on peritumoral hyperexcitability., Experimental Design: An open-label trial was performed comparing perampanel with standard of care (SOC) in patients undergoing resection of newly diagnosed radiologic high-grade glioma. Perampanel was administered as a preoperative loading dose followed by maintenance therapy until progressive disease or up to 12 months. SOC treatment involved levetiracetam for 7 days or as clinically indicated. The primary outcome of hyperexcitability was defined by intraoperative electrocorticography high-frequency oscillation (HFO) rates. Seizure freedom and overall survival were estimated by the Kaplan-Meier method. Tissue concentrations of perampanel, levetiracetam, and correlative biomarkers were measured by mass spectrometry., Results: HFO rates were similar between patients treated with perampanel and levetiracetam. The trial was terminated early after a planned interim analysis, and outcomes assessed in 11 patients (seven perampanel treated; four treated with SOC). Over a median 281 days of postenrollment follow-up, 27% of patients had seizures, including 14% maintained on perampanel and 50% treated with SOC. Overall survival in perampanel-treated patients was similar to that in a glioblastoma reference cohort. Glutamate concentrations in surface biopsies were positively correlated with HFO rates in adjacent electrode contacts and were not significantly associated with treatment assignment or drug concentrations., Conclusions: Glioma peritumoral glutamate concentrations correlated with high-gamma oscillation rates. Targeting glutamatergic activity with perampanel achieved similar electrocorticographic hyperexcitability levels as in levetiracetam-treated patients., (©2024 American Association for Cancer Research.)

High-impact genetic variants associated with neurodevelopmental disorders provide biologically-defined entry points for mechanistic investigation. The 3q29 deletion (3q29Del) is one such variant, conferring a 40-100-fold increased risk for schizophrenia, as well as high risk for autism and intellectual disability. However, the mechanisms leading to neurodevelopmental disability remain largely unknown. Here, we report the first in vivo quantitative neuroimaging study in individuals with 3q29Del (N = 24) and neurotypical controls (N = 1608) using structural MRI. Given prior radiology reports of posterior fossa abnormalities in 3q29Del, we focused our investigation on the cerebellum and its tissue-types and lobules. Additionally, we compared the prevalence of cystic/cyst-like malformations of the posterior fossa between 3q29Del and controls and examined the association between neuroanatomical findings and quantitative traits to probe gene-brain-behavior relationships. 3q29Del participants had smaller cerebellar cortex volumes than controls, before and after correction for intracranial volume (ICV). An anterior-posterior gradient emerged in finer grained lobule-based and voxel-wise analyses. 3q29Del participants also had larger cerebellar white matter volumes than controls following ICV-correction and displayed elevated rates of posterior fossa arachnoid cysts and mega cisterna magna findings independent of cerebellar volume. Cerebellar white matter and subregional gray matter volumes were associated with visual-perception and visual-motor integration skills as well as IQ, while cystic/cyst-like malformations yielded no behavioral link. In summary, we find that abnormal development of cerebellar structures may represent neuroimaging-based biomarkers of cognitive and sensorimotor function in 3q29Del, adding to the growing evidence identifying cerebellar pathology as an intersection point between syndromic and idiopathic forms of neurodevelopmental disabilities., (© 2024. The Author(s).)

Background: 3q29 deletion syndrome (3q29del) is a rare (~1:30 000) genomic disorder associated with a wide array of neurodevelopmental and psychiatric phenotypes. Prior work by our team identified clinically significant executive function (EF) deficits in 47% of individuals with 3q29del; however, the nuances of EF in this population have not been described., Methods: We used the Behavior Rating Inventory of Executive Function (BRIEF) to perform the first in-depth assessment of real-world EF in a cohort of 32 individuals with 3q29del (62.5% male, mean age = 14.5 ± 8.3 years). All participants were also evaluated with gold-standard neuropsychiatric and cognitive assessments. High-resolution structural magnetic resonance imaging was performed on a subset of participants ( n = 24)., Results: We found global deficits in EF; individuals with 3q29del scored higher than the population mean on the BRIEF global executive composite (GEC) and all subscales. In total, 81.3% of study subjects ( n = 26) scored in the clinical range on at least one BRIEF subscale. BRIEF GEC T scores were higher among 3q29del participants with a diagnosis of attention deficit/hyperactivity disorder (ADHD), and BRIEF GEC T scores were associated with schizophrenia spectrum symptoms as measured by the Structured Interview for Psychosis-Risk Syndromes. BRIEF GEC T scores were not associated with cognitive ability. The BRIEF-2 ADHD form accurately (sensitivity = 86.7%) classified individuals with 3q29del based on ADHD diagnosis status. BRIEF GEC T scores were correlated with cerebellar white matter and subregional cerebellar cortex volumes., Conclusions: Together, these data expand our understanding of the phenotypic spectrum of 3q29del and identify EF as a core feature linked to both psychiatric and neuroanatomical features of the syndrome.

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.)

Background: Folate and cobalamin status, although essential for pregnancy, are not routinely monitored in prenatal care., Objectives: To investigate folate and cobalamin status and determinants throughout pregnancy, in the absence of mandatory folic acid (FA) fortification., Methods: In a cohort study of 831 mothers recruited at <12 gestational weeks (GW), plasma folate, total homocysteine (tHcy), cobalamin, holotranscobalamin (holoTC), methylmalonic acid (MMA), red blood cell folate (RBCF), and the combined cobalamin status indicator (cB12) were determined at ≤12, 15, 24-27, 34 GW, labor and in the cord. Single nucleotide polymorphisms affecting folate and cobalamin status were determined. FA, cobalamin, micronutrient supplement use, and dietary folate and cobalamin intake (food frequency questionnaire) were recorded. Folate and cobalamin status predictors were assessed by multiple linear regression analysis., Results: Only 36.1% of the participants took FA preconceptionally and 47.4% and 7.3% had suboptimal RBCF (<906 nmol/L) and plasma cobalamin status (≤221 pmol/L), respectively, at ≤12 GW. RBCF determinants included planned pregnancy, FA supplementation, plasma cobalamin, and methylenetetrahydrofolate (MTHFR) 677C>T genotype. Cobalamin supplementation was positively associated with plasma cobalamin and early holoTC. Smoking and BMI were inversely associated with plasma cobalamin and early holoTC, but none were associated with MMA. Only participants with the MTHFR 677TT genotype, exceeding FA supplement recommendations, improved their folate status (interaction term: B (95% CI):0.15 (0.01, 0.29), P = 0.032). Smoking was inversely associated with plasma cobalamin status in participants with the methionine synthase reductase (MTRR) 524CC genotype only (interaction term:0.07 (0.01, 0.04), P = 0.014). Mothers with low early pregnancy cobalamin status and also those with bigger newborns, had lower cobalamin status at labor., Conclusions: Suboptimal early pregnancy folate or cobalamin status affected 47.4% and 7.3% of the participants, respectively. The MTHFR 677TT genotype predicted folate status throughout pregnancy. Smoking and BMI were negatively associated with cobalamin status throughout pregnancy. Clinical Trial Registry number and website where it was obtained: NCT01778205. www., Clinicaltrials: gov., Competing Interests: Conflict of interest The authors have no conflict of interest to disclose., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

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).)

3q29 deletion syndrome (3q29del) is associated with neuropsychiatric and neurodevelopmental phenotypes. We previously reported that graphomotor weakness is present in up to 78% of individuals with 3q29del. We have now explored nuances of the graphomotor phenotype and its association with other comorbidities in this population. Participants were recruited from the online 3q29 registry (3q29deletion.org) for two days of deep phenotyping. 32 individuals with 3q29del (62.5% male) were evaluated with the Beery-Buktenica Developmental Test of Visual-Motor Integration (VMI) to assess visual-motor integration. Participants were also evaluated with measures of cognitive ability, executive function, adaptive behavior, and school function. Males with 3q29del performed significantly worse than females on the VMI and Motor Coordination subtest. VMI performance was significantly associated with ADHD diagnosis and cognitive ability. Compared to published data from individuals with 22q11.2 deletion syndrome, individuals with 3q29del showed significantly more impairment. The 3q29 deletion is associated with substantial deficits in visual-motor integration, Visual Perception, and Motor Coordination. Our data suggests that 3q29del may qualify as a nonverbal learning disability. Future studies should assess whether individuals with 3q29del would benefit from early interventions, including occupational therapy., (© 2023. 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.)

Small Island Developing States (SIDS) include 37 UN member countries sharing economic, environmental, and social vulnerabilities and intractable health challenges. In over 80% of SIDS, more than one in six adults die prematurely from a non-communicable disease (NCD), with poor diet being a major factor. Complex upstream food system determinants include marginalised local food production and reliance on low nutritional quality food imports. These drivers need to be seen against colonial and post-colonial political-economic legacies as well as the environmental and climate crises that challenge local production systems. A range of policy commitments (eg, the 2023 Bridgetown Declaration on NCDs and Mental Health) highlight these complex interdependencies and call for cross-sectoral food system policies to improve food security, food sovereignty, and nutrition, including integrating measures for climate change adaptation and mitigation. Although addressing these intersecting challenges will also depend on global efforts, the unique approach of SIDS can inform other settings., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Published by Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

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.

The 3q29 deletion (3q29Del) is a copy number variant (CNV) with one of the highest effect sizes for psychosis-risk (>40-fold). Systematic research offers avenues for elucidating mechanism; however, compared to CNVs like 22q11.2Del, 3q29Del remains understudied. Emerging findings indicate that posterior fossa abnormalities are common among carriers, but their clinical relevance is unclear. We report the first in-depth evaluation of psychotic symptoms in participants with 3q29Del (N=23), using the Structured Interview for Psychosis-Risk Syndromes, and compare this profile to 22q11.2Del (N=31) and healthy controls (N=279). We also explore correlations between psychotic symptoms and posterior fossa abnormalities. Cumulatively, 48% of the 3q29Del sample exhibited a psychotic disorder or attenuated positive symptoms, with a subset meeting criteria for clinical high-risk. 3q29Del had more severe ratings than controls on all domains and only exhibited less severe ratings than 22q11.2Del in negative symptoms; ratings demonstrated select sex differences but no domain-wise correlations with IQ. An inverse relationship was identified between positive symptoms and cerebellar cortex volume in 3q29Del, documenting the first clinically-relevant neuroanatomical connection in this syndrome. Our findings characterize the profile of psychotic symptoms in the largest 3q29Del sample reported to date, contrast with another high-impact CNV, and highlight cerebellar involvement in psychosis-risk., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Over the last decade, EEG resting-state microstate analysis has evolved from a niche existence to a widely used and well-accepted methodology. The rapidly increasing body of empirical findings started to yield overarching patterns of associations of biological and psychological states and traits with specific microstate classes. However, currently, this cross-referencing among apparently similar microstate classes of different studies is typically done by "eyeballing" of printed template maps by the individual authors, lacking a systematic procedure. To improve the reliability and validity of future findings, we present a tool to systematically collect the actual data of template maps from as many published studies as possible and present them in their entirety as a matrix of spatial similarity. The tool also allows importing novel template maps and systematically extracting the findings associated with specific microstate maps from ongoing or published studies. The tool also allows importing novel template maps and systematically extracting the findings associated with specific microstate maps in the literature. The analysis of 40 included sets of template maps indicated that: (i) there is a high degree of similarity of template maps across studies, (ii) similar template maps were associated with converging empirical findings, and (iii) representative meta-microstates can be extracted from the individual studies. We hope that this tool will be useful in coming to a more comprehensive, objective, and overarching representation of microstate findings., (© 2023. The Author(s).)

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.)

Background: Telomeres are essential for the integrity of chromosome ends during cell division and their involvement in different processes linked to aging has been established. These chromosome components are involved in spermatogenesis and seem to play an important role in fertilization and embryo development. Telomere length is shortened with each cell division. Recently, short sperm telomere length has been proposed as a potential biomarker of male infertility., Objectives: To conduct a systematic review and meta-analysis of studies exploring the association between spermatozoa and/or leukocyte telomere length with sperm quality parameters and different infertility conditions., Material and Methods: A systematic review and meta-analysis was conducted with studies from Medline-PUBMED and Cochrane Library databases until May 2022. Eligible studies included cohort, cross-sectional and case-control studies, and telomere length in spermatozoa and/or leukocytes cells was defined as the exposure. Semen quality parameters or infertility conditions (e.g., oligozoospermia, asthenozoospermia, teratozoospermia, or other spermatogenic impairment combinations) were defined as the outcomes., Results: Twenty-three observational studies were included. In the qualitative analysis, high heterogeneity was observed between studies regarding the associations between telomere length and semen parameters in different normozoospermic/fertile and oligozoospermic/infertile populations. In the meta-analysis, spermatozoa and leukocyte telomere length were shorter in infertile individuals than in fertile individuals (mean difference [95% confidence interval]: -1.43 [-1.66 to -1.21], p-value <0.001 and -1.67 [-2.02 to -1.31], p-value <0.001, respectively). Moreover, in terms of sperm telomere length, these differences were also significant between individuals with a normal seminogram and individuals with a low quantity of spermatozoa in the ejaculate (-0.97 [-1.32, -0.61], p-value <0.001)., Conclusion: The current systematic review and meta-analysis suggests the potential role of spermatozoa or leukocyte telomere length as a reliable biomarker of semen quality, which may help distinguish between infertility conditions beyond the routine semen analysis., (© 2023 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.)

Background: 3q29 deletion syndrome (3q29del) is associated with a significantly increased risk for neurodevelopmental and neuropsychiatric phenotypes. Mild to moderate intellectual disability (ID) is common in this population, and previous work by our team identified substantial deficits in adaptive behaviour. However, the full profile of adaptive function in 3q29del has not been described nor has it been compared with other genomic syndromes associated with elevated risk for neurodevelopmental and neuropsychiatric phenotypes., Methods: Individuals with 3q29del (n = 32, 62.5% male) were evaluated using the Vineland Adaptive Behaviour Scales, Third Edition, Comprehensive Parent/Caregiver Form (Vineland-3). We explored the relationship between adaptive behaviour and cognitive function, executive function, and neurodevelopmental and neuropsychiatric comorbidities in our 3q29del study sample, and we compared subjects with 3q29del with published data on fragile X syndrome, 22q11.2 deletion syndrome and 16p11.2 deletion and duplication syndromes., Results: Individuals with 3q29del had global deficits in adaptive behaviour that were not driven by specific weaknesses in any given domain. Individual neurodevelopmental and neuropsychiatric diagnoses had a small effect on adaptive behaviour, and the cumulative number of comorbid diagnoses was significantly negatively associated with Vineland-3 performance. Both cognitive ability and executive function were significantly associated with adaptive behaviour, and executive function was a better predictor of Vineland-3 performance than cognitive ability. Finally, the severity of adaptive behaviour deficits in 3q29del was distinct from previously published data on comparable genomic disorders., Conclusions: Individuals with 3q29del have significant deficits in adaptive behaviour, affecting all domains assessed by the Vineland-3. Executive function is a better predictor of adaptive behaviour than cognitive ability in this population and suggests that interventions targeting executive function may be an effective therapeutic strategy., (© 2023 The Authors. Journal of Intellectual Disability Research published by MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.)

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.)

Serendipity berry plant (Dioscoreophyllum cumminsii (Stapf) Diels) is the source of a naturally sweet protein referred to as monellin. The safety of serendipity berry sweet protein (SBSP) containing single polypeptide monellin (MON) expressed in Komagataella phaffii (formerly Pichia pastoris) and produced via precision fermentation was examined comprehensively through assessments of in vitro and in silico protein digestion, in silico allergenicity, in vitro genotoxicity (reverse mutation and mammalian micronucleus assays), and 14-day and 90-day oral (dietary) toxicity studies in rats. There was no indication of allergenicity for SBSP in the in silico analyses. Results from both in vitro and in silico protein digestibility assessments indicated that SBSP is digested upon ingestion and would therefore be unlikely to pose a toxigenic or allergenic risk to consumers. SBSP was non-genotoxic in in vitro assays and showed no adverse effects in the 14-day or 90-day toxicity studies up to the highest dose tested. The 90-day toxicity study supports a NOAEL for SBSP of 1954 mg/kg bw/day, which corresponds to a NOAEL for MON of 408 mg/kg bw/day., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The author(s) declared potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Tina Wang and Jason Ryder are employees of Oobli, Inc. Elaine Freeman, Rachel Ward, and Mary Murphy are employees of Exponent, Inc. Oobli, Inc. is a client of Exponent, Inc., (Copyright © 2024 The Authors. Published by Elsevier Inc. 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.)

3q29 deletion syndrome (3q29del) is associated with a significantly increased risk for neurodevelopmental and neuropsychiatric disorders. However, the full spectrum of behavioral phenotypes associated with 3q29del is still evolving. Individuals with 3q29del (n = 96, 60.42% male) or their guardian completed the Achenbach Child or Adult Behavior Checklist (CBCL/ABCL) via the online 3q29 registry (3q29deletion.org). Typically developing controls (n = 57, 49.12% male) were ascertained as a comparison group. We analyzed mean performance on the CBCL/ABCL for individuals with 3q29del and controls across composite, DSM-keyed, and developmental scales; and the relationship between CBCL/ABCL performance and clinical and developmental phenotypes for individuals with 3q29del. Individuals with 3q29del showed significantly elevated behavioral and developmental impairment relative to controls across CBCL/ABCL domains. A substantial proportion of study participants with 3q29del scored in the Borderline or Clinical range for composite and DSM-keyed scales, indicating significant behavioral problems that may require clinical evaluation. We found that the preschool CBCL DSM-keyed autism spectrum problems scale is a potential screening tool for autism spectrum disorder (ASD) for individuals with 3q29del; CBCL/ABCL DSM-keyed scales were not accurate screeners for anxiety disorders or attention-deficit/hyperactivity disorder (ADHD) in our study sample. We identified a high degree of psychiatric comorbidity in individuals with 3q29del, with 60.42% (n = 58) of individuals with 3q29del scoring in the Borderline or Clinical range on two or more DSM-keyed CBCL/ABCL scales. Finally, we found that the degree of developmental delay in participants with 3q29del does not explain the increased behavioral problems observed on the CBCL/ABCL. The CBCL/ABCL can be used as screening tools in populations such as 3q29del, even in the presence of substantial psychiatric comorbidity. These results expand our understanding of the phenotypic spectrum of 3q29del and demonstrate an effective method for recruiting and phenotyping a large sample of individuals with a rare genetic disorder., (© 2024. The Author(s).)

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.)

The bone marrow contains peripheral nerves that promote haematopoietic regeneration after irradiation or chemotherapy (myeloablation), but little is known about how this is regulated. Here we found that nerve growth factor (NGF) produced by leptin receptor-expressing (LepR + ) stromal cells is required to maintain nerve fibres in adult bone marrow. In nerveless bone marrow, steady-state haematopoiesis was normal but haematopoietic and vascular regeneration were impaired after myeloablation. LepR + cells, and the adipocytes they gave rise to, increased NGF production after myeloablation, promoting nerve sprouting in the bone marrow and haematopoietic and vascular regeneration. Nerves promoted regeneration by activating β2 and β3 adrenergic receptor signalling in LepR + cells, and potentially in adipocytes, increasing their production of multiple haematopoietic and vascular regeneration growth factors. Peripheral nerves and LepR + cells thus promote bone marrow regeneration through a reciprocal relationship in which LepR + cells sustain nerves by synthesizing NGF and nerves increase regeneration by promoting the production of growth factors by LepR + cells., (© 2023. The Author(s).)

3q29 deletion syndrome (3q29del) is a rare genomic disorder caused by a 1.6 Mb deletion (hg19, chr3:195725000-197350000). 3q29del is associated with neurodevelopmental and psychiatric phenotypes, including an astonishing >40-fold increased risk for schizophrenia, but medical phenotypes are less well-described. We used the online 3q29 registry of 206 individuals (3q29deletion.org) to recruit 57 individuals with 3q29del (56.14% male) and requested information about musculoskeletal phenotypes with a custom questionnaire. 85.96% of participants with 3q29del reported at least one musculoskeletal phenotype. Congenital anomalies were most common (70.18%), with pes planus (40.35%), pectus excavatum (22.81%), and pectus carinatum (5.26%) significantly elevated relative to the pediatric general population. 49.12% of participants reported fatigue after 30 min or less of activity. Bone fractures (8.77%) were significantly elevated relative to the pediatric general population. Participants commonly report receiving medical care for musculoskeletal complaints (71.93%), indicating that these phenotypes impact quality of life for individuals with 3q29del. This is the most comprehensive description of musculoskeletal phenotypes in 3q29del to date, suggests ideas for clinical evaluation, and expands our understanding of the phenotypic spectrum of this syndrome., (© 2023 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)

Systems thinking can reveal surprising, counterintuitive or unintended reactions to population health interventions (PHIs), yet this lens has rarely been applied to sugar-sweetened beverage (SSB) taxation. Using a systematic scoping review approach, we identified 329 papers concerning SSB taxation, of which 45 considered influences and impacts of SSB taxation jointly, involving methodological approaches that may prove promising for operationalizing a systems informed approach to PHI evaluation. Influences and impacts concerning SSB taxation may be cyclically linked, and studies that consider both enable us to identify implications beyond a predicted linear effect. Only three studies explicitly used systems thinking informed methods. Finally, we developed an illustrative, feedback-oriented conceptual framework, emphasizing the processes that could result in an SSB tax being increased, maintained, eroded or repealed over time. Such a framework could be used to synthesize evidence from non-systems informed evaluations, leading to novel research questions and further policy development., (© 2023. The Author(s).)

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.)

Suboptimal status of folate and/or interrelated B vitamins (B 12 , B 6 and riboflavin) can perturb one-carbon metabolism and adversely affect brain development in early life and brain function in later life. Human studies show that maternal folate status during pregnancy is associated with cognitive development in the child, whilst optimal B vitamin status may help to prevent cognitive dysfunction in later life. The biological mechanisms explaining these relationships are not clear but may involve folate-related DNA methylation of epigenetically controlled genes related to brain development and function. A better understanding of the mechanisms linking these B vitamins and the epigenome with brain health at critical stages of the lifecycle is necessary to support evidence-based health improvement strategies. The EpiBrain project, a transnational collaboration involving partners in the United Kingdom, Canada and Spain, is investigating the nutrition-epigenome-brain relationship, particularly focussing on folate-related epigenetic effects in relation to brain health outcomes. We are conducting new epigenetics analysis on bio-banked samples from existing well-characterised cohorts and randomised trials conducted in pregnancy and later life. Dietary, nutrient biomarker and epigenetic data will be linked with brain outcomes in children and older adults. In addition, we will investigate the nutrition-epigenome-brain relationship in B vitamin intervention trial participants using magnetoencephalography, a state-of-the-art neuroimaging modality to assess neuronal functioning. The project outcomes will provide an improved understanding of the role of folate and related B vitamins in brain health, and the epigenetic mechanisms involved. The results are expected to provide scientific substantiation to support nutritional strategies for better brain health across the lifecycle., (© 2023 The Authors. Nutrition Bulletin published by John Wiley & Sons Ltd on behalf of British Nutrition Foundation.)

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.