Sex Differences in the Risk of Stroke Associated With Traditional and Non-Traditional Factors in a US Cohort of People With HIV Infection.

BACKGROUND AND OBJECTIVES: Although stroke risk associated with HIV may be greater for women than men, little is known about whether the impact of different factors on cerebrovascular risk varies by sex in people with HIV (PWH) and contributes to stroke risk disparities in this population. The primary objective of this study was to examine whether sex modifies the effect of demographics, cardiometabolic factors, health-related behaviors, and HIV-specific variables on stroke risk in PWH from the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort. METHODS: In this observational cohort study, we analyzed data from clinical encounters for PWH followed at 5 CNICS sites from approximately 2005 to 2020. All potential stroke events were adjudicated by neurologists. Patient-reported outcomes collected at clinic visits, including substance use and depression, were also available. We used Cox proportional hazards models to determine whether sex modified the association of predictors of interest with incident stroke. RESULTS: Among 13,573 PWH (19% female sex at birth, mean age 44 years, mean follow-up 5.6 years), female sex was associated with a higher risk of stroke only among individuals aged 50 years or younger (hazard ratio [HR] 2.01 at age 40 [1.25-3.21] vs HR 0.60 at age 60 [0.34-1.06]; p = 0.001 for the interaction). Younger female participants who developed a stroke were more likely to have treated hypertension, a higher cardiovascular risk score, and detectable HIV than younger male participants whereas these factors were comparable by sex among older participants who developed a stroke. Sex modified the effect of detectable HIV (HR 4.66 for female participants [2.48-8.74] vs HR 1.30 for male participants [0.83-2.03]; p = 0.001 for the interaction), methamphetamine use (HR 4.78 for female participants [1.47-15.56] vs HR 1.19 for male participants [0.62-2.29]; p = 0.04 for the interaction), and treated hypertension (HR 3.44 for female participants [1.74-6.81] vs HR 1.66 for male participants [1.14-2.41]; p = 0.06 for the interaction) on stroke risk. DISCUSSION: Younger female participants with HIV were at elevated cerebrovascular risk compared with younger male participants. Several risk factors had a greater adverse effect on stroke risk in female participants than in male participants, including HIV viremia, methamphetamine use, and treated hypertension. These findings underscore the importance of a personalized approach to predict and prevent cerebrovascular risk among PWH.

Evaluation of Long-Term Surgical and Patient-Reported Outcomes after Pediatric Facial Reanimation.

BACKGROUND: Outcomes of pediatric facial reanimation beyond 10 years are not known. This cross-sectional study evaluated long-term surgical and patient-reported outcomes of adults who underwent smile reconstruction as children with either a cross-face nerve graft (CFNG) or masseter nerve transfer at least 10 years previously. METHODS: Commissure excursion was quantified with FACE-Gram software at 3 time points: preoperatively, early postoperatively within 2 years, and at long-term follow-up. Patient-reported outcomes were evaluated with validated questionnaires (Facial Clinimetric Evaluation Scale, FACE-Q 1.0) and thematic analysis of semistructured interviews. Results are reported as median (interquartile range [IQR]). RESULTS: A total of 42 patients were included (26 women and 16 men). Median long-term follow-up was 19.3 years (IQR, 8.8 years) for CFNG and 17.6 years (IQR, 5.8 years) for masseter nerve transfer. For both groups, commissure excursion increased significantly from preoperative to early postoperative time points and remained stable at long-term follow-up (P < 0.0001). Commissure excursion at long-term follow-up between the 2 groups was not significantly different (CFNG, 5.0 mm [IQR, 9.4 mm]; masseter nerve transfer, 8.4 mm [IQR, 4.1 mm]); P > 0.05). For patient-reported outcomes, median Facial Clinimetric Evaluation Scale score was 72 of 100, and 95% of respondents agreed with the statement "I am pleased with the result" on the FACE-Q 1.0. Overall quality of life was rated at 7 of 10 or greater by 97% of participants, and all participants would recommend the surgery to other children. CONCLUSIONS: Pediatric facial reanimation with CFNG or masseter nerve transfer reliably improves commissure excursion with longevity beyond 10 years. Adult patients report overall high satisfaction and social functioning.

Comparison of Surgical Wait Times and Procedure Length in the Management of Postaxial Polydactyly Using Local or General Anesthesia.

Introduction: For infants with ulnar polydactyly, surgical removal of the supernumerary digit can be performed under general or local anesthetic. This study evaluated the wait times, surgical duration, and sedation times associated with performing the procedure under local versus general anesthetic in infants with ulnar polydactyly. Methods: The databases of three surgeons at our institution were reviewed for children less than 2 years of age who underwent surgery for non-syndromic ulnar polydactyly. Data collection included patient demographics, wait times, duration of surgery and sedation and complications. Results: The study included children (n = 55) who received treatment under local (n = 22) or general (n = 33) anesthesia. The wait times for the local anesthetic group were significantly shorter than the general anesthetic group (p < 0.05) for: referral to first consultation appointment; referral to surgery date, and decision date to surgery date. The duration of surgery (17.9 ± 6.9 vs 36.6 ± 20.2 min) and sedation time (26.3 ± 11.1 vs 74.8 ± 29.1 min) were significantly shorter in the local anaesthetic group (p < 0.05). There were no differences in complication rates between the groups. Conclusion: In this single-institution retrospective analysis, treatment of non-syndromic ulnar polydactyly with local anesthetic and bottle sedation was associated with shorter wait times, and duration of surgery and sedation. Level of Evidence: III, retrospective chart review and quality improvement initiative.

Introduction : Chez les nourrissons présentant une polydactylie cubitale, il est possible de procéder à l'ablation chirurgicale du doigt excédentaire sous anesthésie locale ou générale. La présente étude visait à évaluer les temps d'attente, la durée de l'opération et la durée de la sédation associés à l'intervention lorsqu'elle était effectuée sous anesthésie locale ou générale chez les nourrissons présentant une polydactylie cubitale. méthodes : Les chercheurs ont fouillé les bases de données de trois chirurgiens de leur établissement pour en extraire les cas d'enfants de moins de deux ans ayant subi une opération de la polydactylie cubitale non syndromique. La collecte de données incluait les caractéristiques des patients, les temps d'attente, la durée de l'opération et de la sédation et les complications. Résultats : La présente étude incluait des enfants (n=55) qui avaient été traités sous anesthésie locale (n=22) ou générale (n=33). Le temps d'attente du groupe sous anesthésie locale était beaucoup plus court que celui du groupe sous anesthésie générale (p<0,05) pour ce qui est de la période entre l'orientation et la première consultation, l'orientation et la date de l'opération, ainsi que la date de la décision et la date de l'opération. La durée de l'opération (17,9 ± 6,9 minutes par rapport à 36,6 ± 20,2 minutes) et de la sédation (26,3 ± 11,1 minutes par rapport à 74,8 ± 29,1 minutes) était beaucoup plus courte dans le groupe sous anesthésie locale (p<0,05). Il n'y avait pas de différence entre les groupes à l'égard des taux de complications. Conclusion : Dans cette analyse rétrospective mono-institutionnelle, le traitement de la polydactylie cubitale non syndromique accompagné d'une anesthésie locale et d'une sédation par bonbonne était associé à une diminution du temps d'attente ainsi que de la durée d'opération et de sédation.

Sentiment and semantic analysis: Urban quality inference using machine learning algorithms.

Sustainable urban transformation requires comprehensive knowledge about the built environment, including people's perceptions, use of sites, and wishes. Qualitative interviews are conducted to understand better people's opinions about a specific topic or location. This study explores the automatization of the interview coding process by investigating how state-of-the-art natural language processing techniques classify sentiment and semantic orientation from interviews transcribed in Swedish. For the sentiment analysis, the Swedish bidirectional encoder representations from transformers (BERT) model KB-BERT was used to perform a multi-class classification task on a text sentence level into three different classes: positive, negative, and neutral. Named entity recognition (NER) and string search were used for the semantic analysis to perform multi-label classification to match domain-related topics to the sentence. The models were trained and evaluated on partially annotated datasets. The results demonstrate that the implemented deep learning techniques are a possible and promising solution to achieve the stated goal.

Identification of biological signatures of cruciferous vegetable consumption utilizing machine learning-based global untargeted stable isotope traced metabolomics.

In recent years there has been increased interest in identifying biological signatures of food consumption for use as biomarkers. Traditional metabolomics-based biomarker discovery approaches rely on multivariate statistics which cannot differentiate between host- and food-derived compounds, thus novel approaches to biomarker discovery are required to advance the field. To this aim, we have developed a new method that combines global untargeted stable isotope traced metabolomics and a machine learning approach to identify biological signatures of cruciferous vegetable consumption. Participants consumed a single serving of broccoli (n = 16), alfalfa sprouts (n = 16) or collard greens (n = 26) which contained either control unlabeled metabolites, or that were grown in the presence of deuterium-labeled water to intrinsically label metabolites. Mass spectrometry analysis indicated 133 metabolites in broccoli sprouts and 139 metabolites in the alfalfa sprouts were labeled with deuterium isotopes. Urine and plasma were collected and analyzed using untargeted metabolomics on an AB SCIEX TripleTOF 5,600 mass spectrometer. Global untargeted stable isotope tracing was completed using openly available software and a novel random forest machine learning based classifier. Among participants who consumed labeled broccoli sprouts or collard greens, 13 deuterium-incorporated metabolomic features were detected in urine representing 8 urine metabolites. Plasma was analyzed among collard green consumers and 11 labeled features were detected representing 5 plasma metabolites. These deuterium-labeled metabolites represent potential biological signatures of cruciferous vegetables consumption. Isoleucine, indole-3-acetic acid-N-O-glucuronide, dihydrosinapic acid were annotated as labeled compounds but other labeled metabolites could not be annotated. This work presents a novel framework for identifying biological signatures of food consumption for biomarker discovery. Additionally, this work presents novel applications of metabolomics and machine learning in the life sciences.

B-cell-directed CAR T-cell therapy activates CD8+ cytotoxic CARneg bystander T cells in patients and nonhuman primates.

ABSTRACT: Chimeric antigen receptor (CAR) T cells hold promise as a therapy for B-cell-derived malignancies, and despite their impressive initial response rates, a significant proportion of patients ultimately experience relapse. Although recent studies have explored the mechanisms of in vivo CAR T-cell function, little is understood about the activation of surrounding CARneg bystander T cells and their potential to enhance tumor responses. We performed single-cell RNA sequencing on nonhuman primate (NHP) and patient-derived T cells to identify the phenotypic and transcriptomic hallmarks of bystander activation of CARneg T cells following B-cell-targeted CAR T-cell therapy. Using a highly translatable CD20 CAR NHP model, we observed a distinct population of activated CD8+ CARneg T cells emerging during CAR T-cell expansion. These bystander CD8+ CARneg T cells exhibited a unique transcriptional signature with upregulation of natural killer-cell markers (KIR3DL2, CD160, and KLRD1), chemokines, and chemokine receptors (CCL5, XCL1, and CCR9), and downregulation of naïve T-cell-associated genes (SELL and CD28). A transcriptionally similar population was identified in patients after a tisagenlecleucel infusion. Mechanistic studies revealed that interleukin-2 (IL-2) and IL-15 exposure induced bystander-like CD8+ T cells in a dose-dependent manner. In vitro activated and patient-derived T cells with a bystander phenotype efficiently killed leukemic cells through a T-cell receptor-independent mechanism. Collectively, to our knowledge, these data provide the first comprehensive identification and profiling of CARneg bystander CD8+ T cells following B-cell-targeting CAR T-cell therapy and suggest a novel mechanism through which CAR T-cell infusion might trigger enhanced antileukemic responses. Patient samples were obtained from the trial #NCT03369353, registered at www.ClinicalTrials.gov.

Using SCENTinel® to predict SARS-CoV-2 infection: insights from a community sample during dominance of Delta and Omicron variants.

Introduction: Based on a large body of previous research suggesting that smell loss was a predictor of COVID-19, we investigated the ability of SCENTinel®, a newly validated rapid olfactory test that assesses odor detection, intensity, and identification, to predict SARS-CoV-2 infection in a community sample. Methods: Between April 5, 2021, and July 5, 2022, 1,979 individuals took one SCENTinel® test, completed at least one physician-ordered SARS-CoV-2 PCR test, and endorsed a list of self-reported symptoms. Results: Among the of SCENTinel® subtests, the self-rated odor intensity score, especially when dichotomized using a previously established threshold, was the strongest predictor of SARS-CoV-2 infection. SCENTinel® had high specificity and negative predictive value, indicating that those who passed SCENTinel® likely did not have a SARS-CoV-2 infection. Predictability of the SCENTinel® performance was stronger when the SARS-CoV-2 Delta variant was dominant rather than when the SARS-CoV-2 Omicron variant was dominant. Additionally, SCENTinel® predicted SARS-CoV-2 positivity better than using a self-reported symptom checklist alone. Discussion: These results indicate that SCENTinel® is a rapid assessment tool that can be used for population-level screening to monitor abrupt changes in olfactory function, and to evaluate spread of viral infections like SARS-CoV-2 that often have smell loss as a symptom.

Prevalence and predictors of elbow flexion contractures during early childhood following brachial plexus birth injury.

BACKGROUND: Elbow flexion contracture development in school-age children with a brachial plexus birth injury (BPBI) is common. Reports indicate onset between 2 and 4 years; however, little is known about early childhood prevalence, development, and trajectory of these contractures. PURPOSE: To determine the prevalence and predictors of BPBI elbow flexion contractures during early childhood. STUDY DESIGN: A retrospective cross-sectional study. METHODS: Demographic, diagnostic, treatment, and elbow contracture data were collected for children with a BPBI <4 years between 2015 and 2019 from a prospectively collected database. Spinal root motor contributions and injury were determined using Active Movement Scale (AMS) scores at 6 weeks of age and used to predict contracture development. RESULTS: Of the 171 children that met inclusion criteria, 87% (n = 149) had upper plexus injuries. The mean age at the time of evaluation for an elbow contracture was 21.4 ± 12.7 months. The prevalence of elbow flexion contractures was 22% (n = 38), with mean onset at 13.4 ± 11.0 months. Mean contracture degree was -10.8 ± -6.9 degrees with 76% (n = 29) <-10 degrees. AMS shoulder abduction, flexion, and external rotation; elbow flexion; forearm supination; and wrist extension scores at a mean 2.3 ± 1.4 months were significantly lower in children who developed elbow flexion contractures (p < 0.001). Logistic regression found that low AMS elbow flexion with high elbow extension scores were a significant (p < 0.003) predictor of elbow contracture development. CONCLUSIONS: The prevalence of elbow flexion contractures in early childhood is greater than previously understood. These findings indicate that C5-C6 injury affecting elbow flexion with relative preservation of elbow extension is a predictor of contracture development. Further research is needed to investigate the nature and sequelae of C5-C6 injury and its effects on elbow flexion contracture development.

Gut enterotype-dependent modulation of gut microbiota and their metabolism in response to xanthohumol supplementation in healthy adults.

Xanthohumol (XN), a polyphenol found in the hop plant (Humulus lupulus), has antioxidant, anti-inflammatory, prebiotic, and anti-hyperlipidemic activity. Preclinical evidence suggests the gut microbiome is essential in mediating these bioactivities; however, relatively little is known about XN's impact on human gut microbiota in vivo. We conducted a randomized, triple-blinded, placebo-controlled clinical trial (ClinicalTrials.gov NCT03735420) to determine safety and tolerability of XN in healthy adults. Thirty healthy participants were randomized to 24 mg/day XN or placebo for 8 weeks. As secondary outcomes, quantification of bacterial metabolites and 16S rRNA gene sequencing were utilized to explore the relationships between XN supplementation, gut microbiota, and biomarkers of gut health. Although XN did not significantly change gut microbiota composition, it did re-shape individual taxa in an enterotype-dependent manner. High levels of inter-individual variation in metabolic profiles and bioavailability of XN metabolites were observed. Moreover, reductions in microbiota-derived bile acid metabolism were observed, which were specific to Prevotella and Ruminococcus enterotypes. These results suggest interactions between XN and gut microbiota in healthy adults are highly inter-individualized and potentially indicate that XN elicits effects on gut health in an enterotype-dependent manner.

Measuring Multidimensional Aspects of Health in the Oldest Old Using the NIH Toolbox: Results From the ARMADA Study.

OBJECTIVE: The percentage of older adults living into their 80s and beyond is expanding rapidly. Characterization of typical cognitive performance in this population is complicated by a dearth of normative data for the oldest old. Additionally, little attention has been paid to other aspects of health, such as motor, sensory, and emotional functioning, that may interact with cognitive changes to predict quality of life and well-being. The current study used the NIH Toolbox (NIHTB) to determine age group differences between persons aged 65-84 and 85+ with normal cognition. METHOD: Participants were recruited in two age bands (i.e., 65-84 and 85+). All participants completed the NIHTB Cognition, Motor, Sensation, and Emotion modules. Independent-samples t-tests determined age group differences with post-hoc adjustments using Bonferroni corrections. All subtest and composite scores were then regressed on age and other demographic covariates. RESULTS: The 65-84 group obtained significantly higher scores than the 85+ group across all cognitive measures except oral reading, all motor measures except gait speed, and all sensation measures except pain interference. Age remained a significant predictor after controlling for covariates. Age was not significantly associated with differences in emotion scores. CONCLUSIONS: Results support the use of the NIHTB in persons over 85 with normal cognition. As expected, fluid reasoning abilities and certain motor and sensory functions decreased with age in the oldest old. Inclusion of motor and sensation batteries is warranted when studying trajectories of aging in the oldest old to allow for multidimensional characterization of health.

Catalytic activity of OGG1 is impaired by Zinc deficiency.

Oxidative stress-induced DNA base modifications, if unrepaired, can increase mutagenesis and genomic instability, ultimately leading to cell death. Cells predominantly use the base excision repair (BER) pathway to repair oxidatively-induced non-helix distorting lesions. BER is initiated by DNA glycosylases, such as 8-oxoguanine DNA glycosylase (OGG1), which repairs oxidatively modified guanine bases, including 7,8-dihydro-8-oxoguanine (8-oxoG) and ring-opened formamidopyrimidine lesions, 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG). The OGG1 protein contains a C2H2 zinc (Zn) finger DNA binding domain. However, the impact of dietary Zn deficiency on OGG1 catalytic activity has not been extensively studied. Zn is a common nutrient of concern with increasing age, and the prevalence of oxidative DNA damage is also concurrently increased during aging. Thus, understanding the potential regulation of OGG1 activity by Zn is clinically relevant. The present study investigates the impact of a range of Zn statuses, varying from severe Zn deficiency to exogenous Zn-supplementation, in the context of young and aged animals to determine the impact of dietary Zn-status on OGG1 activity and oxidative DNA damage in mice. Our findings suggest that nutritional Zn deficiency impairs OGG1 activity and function, without altering gene expression, and that aging further exacerbates these effects. These results have important implications for nutritional management of Zn during aging to mitigate age-associated DNA damage.

Patient reported outcomes in brachial plexus birth injury: results from the iPLUTO world-wide consensus survey.

PURPOSE: Brachial plexus birth injuries (BPBI) can have lifelong effects on the development and functional use of the upper extremity. Currently there is no agreement with regards to what patient-reported outcome (PRO) measures should be used. Therefore, the ability to compare the effects of treatment between individuals and institutions is challenging. This study aimed to achieve consensus among clinicians on the use of PRO measures within this patient group to allow for improved comparison of treatments and outcomes in the future. MATERIALS AND METHODS: Online, a 3 round Delphi survey was completed by 35 international multi-disciplinary specialist centers. RESULTS: All respondents (100%) agreed that PRO measures are useful for clinical evaluation and patient treatment. None of the outcome measures scored >75% agreement for ability to assess responsiveness and current state in children with BPBI as most outcome measures were judged as not specific for BPBI. Additionally, participant centers were asked their perspective on the best available PRO option for each of the 3 categories: functional use of the upper limb, quality of life and pain. This resulted in endorsement by the participant centers of the Brachial Plexus Outcome Measure - Self-Evaluation, the Pediatric Quality of Life Inventory, and Visual Analogue Scale/Brief Pain Inventory respectively. CONCLUSION: International specialists in BPBI agree that PRO measures are important to use both clinically and in research in children aged 5 years and above.

Patient-reported outcome measures were judged as useful both in clinic and in research for brachial plexus birth injury (BPBI), according to a panel of specialized centers.Currently available outcome measures were judged as not specific for BPBI.The panel endorsed the following measures as best available: the Brachial Plexus Outcome Measure ­ Self-Evaluation scale for functional evaluation, the Pediatric Quality of Life Inventory for disease-related quality of life and the Faces Pain Scale - Revised/Visual Analogue Scale/Brief Pain Inventory for pain.

Evaluating the feasibility of implementing the Sup-ER protocol for infants with brachial plexus birth injury.

BACKGROUND: The Sup-ER protocol involves a repositioning program for infants with brachial plexus birth injury to position the shoulder in external rotation (ER) to address progressive loss in passive range of motion (PROM). The British Columbia Children's Hospital (BCCH) eligibility criteria for this protocol are infants aged 4-8 weeks with decreased shoulder ER PROM and/or Active Movement Scale (AMS) shoulder ER and/or supination scores ≤2. The resources needed to implement this protocol in large clinics have not been studied. PURPOSE: This study aims to evaluate the BCCH criteria that are used to identify appropriate candidates for the Sup-ER protocol. STUDY DESIGN: A retrospective cohort study was conducted to identify the percentage of infants who would have been recommended the Sup-ER protocol based on their PROM and AMS scores between 4 and 8 weeks of age. METHODS: A sensitivity and specificity evaluation was used to describe the BCCH criteria's ability to identify infants in this historical cohort who went on to have incomplete shoulder function (ie, true positive) vs infants who had functional shoulder outcome at 9 months of age (ie, false positive). RESULTS: At a mean of 5.8 weeks (95% confidence interval [CI] 5.3, 6.3), 46 of the 87 (53%) infants satisfied the BCCH Sup-ER protocol criteria. Forty-four (51%) were female, half (n = 45) were left side affected, and 88% had upper plexus injury. The BCCH Sup-ER protocol criteria had sensitivity of 100% and specificity of 71% to identify infants with incomplete shoulder function. Removing the AMS supination ≤2 score criterion from the criteria improves the specificity to 84%, while sensitivity remains high (97%). CONCLUSIONS: Modifying the BCCH criteria to all infants aged 4-8 weeks with AMS shoulder ER ≤2 and/or decreased shoulder ER PROM improves the precision of identifying infants who would benefit from the Sup-ER protocol.

Surgery for internal rotation contracture in infancy may obviate the need for brachial plexus nerve reconstruction: early experience.

BACKGROUND: Shoulder internal rotation contracture and subluxation in the first year of life has long been recognized in some patients with brachial plexus birth injury (BPBI). Surgical management of shoulder pathology has traditionally been undertaken following nerve reconstruction as necessary. In some patients; however, shoulder pathology may impair or obscure functional neuromuscular recovery of the upper extremity. As a proof of concept, we report a highly selected subset of patients with BPBI in whom shoulder surgery undertaken before one year of age obviated the need for neuroma resection and nerve grafting. METHODS: A retrospective review was performed of all patients with upper trunk BPBI who underwent shoulder surgery before one year of age from 2015 to 2018. Upper extremity motor function was evaluated with preoperative and postoperative Active Movement Scale scores, Cookie tests, and the requirement for subsequent neuroma resection and nerve grafting. RESULTS: Fifteen patients with BPBI meeting the inclusion criteria underwent shoulder surgery (including a subscapularis slide and tendon transfers of the teres major and latissimus dorsi muscles) before 1 year of age. Preoperatively, no patients of the appropriate age passed the Cookie test for elbow flexion. Thirteen patients either passed the Cookie test or scored Active Movement Scale score 7 for elbow flexion at or before the last available follow-up undertaken at a median age of 3.4 [1.4, 5.2] years. One of those 13 patients underwent single fascicular distal nerve transfer to improve elbow flexion before subsequently passing the Cookie test. Two patients did not have sufficient follow-up to assess elbow flexion. CONCLUSION: Although the exact role of shoulder surgery in infancy for BPBI remains to be defined, the findings from this study provide proof of concept that early, targeted surgical treatment of the shoulder may obviate the need for brachial plexus nerve reconstruction in a highly selected group of infants with BPBI.

Integrating Data Across Multiple Sites in the Northeastern United States to Examine Associations Between a Prenatal Metal Mixture and Child Cognition.

We applied a novel hierarchical Bayesian weighted quantile sum (HBWQS) regression to combine data across 3 study sites to examine associations between prenatal exposure to metals and cognitive functioning in childhood. Data from 326 mother-child dyads enrolled in an ongoing cohort study, the Programming of Intergenerational Stress Mechanisms (PRISM) Study, based in New York, New York (recruitment in 2013-2020) and Boston, Massachusetts (recruitment 2011-2013), and the First Thousand Days of Life (FTDL) cohort study (recruitment 2012-2019), based in northern Virginia, were used. Arsenic, cadmium, manganese, lead, and antimony were measured in urine collected during pregnancy. Cognitive functioning was assessed in children aged 3-11 years using the National Institutes of Health Toolbox Cognition Battery. The HBWQS regression showed a negative association between the urinary metal mixture and the Cognition Early Childhood Composite Score in the PRISM New York City (ß = -3.67, 95% credible interval (CrI): -7.61, -0.01) and FTDL (ß = -3.76, 95% CrI: -7.66, -0.24) samples, with a similar trend in the PRISM Boston sample (ß = -3.24, 95% CrI: -6.77, 0.144). We did not detect these associations in traditionally pooled models. HBWQS regression allowed us to account for site heterogeneity and detect associations between prenatal metal-mixture exposure and cognitive outcomes in childhood. Given the ubiquity of metals exposure, interventions aimed at reducing prenatal exposure may improve cognitive outcomes in children. This article is part of a Special Collection on Environmental Epidemiology.

Evaluation of the NIH Toolbox Odor Identification Test across normal cognition, amnestic mild cognitive impairment, and dementia due to Alzheimer's disease.

INTRODUCTION: Olfactory decline is associated with cognitive decline in aging, amnestic mild cognitive impairment (aMCI), and amnestic dementia associated with Alzheimer's disease neuropathology (ADd). The National Institutes of Health Toolbox Odor Identification Test (NIHTB-OIT) may distinguish between these clinical categories. METHODS: We compared NIHTB-OIT scores across normal cognition (NC), aMCI, and ADd participants (N = 389, ≥65 years) and between participants positive versus negative for AD biomarkers and the APOE ε4 allele. RESULTS: NIHTB-OIT scores decreased with age (p < 0.001) and were lower for aMCI (p < 0.001) and ADd (p < 0.001) compared to NC participants, correcting for age and sex. The NIHTB-OIT detects aMCI (ADd) versus NC participants with 49.4% (56.5%) sensitivity and 88.8% (89.5%) specificity. NIHTB-OIT scores were lower for participants with positive AD biomarkers (p < 0.005), but did not differ based on the APOE ε4 allele (p > 0.05). DISCUSSION: The NIHTB-OIT distinguishes clinically aMCI and ADd participants from NC participants. HIGHLIGHTS: National Institutes of Health Toolbox Odor Identification Test (NIHTB-OIT) discriminated normal controls from mild cognitive impairment. NIHTB-OIT discriminated normal controls from Alzheimer's disease dementia. Rate of olfactory decline with age was similar across all diagnostic categories. NIHTB-OIT scores were lower in participants with positive Alzheimer's biomarker tests. NIHTB-OIT scores did not differ based on APOE genotype.

Sulforaphane and Sulforaphane-Nitrile Metabolism in Humans Following Broccoli Sprout Consumption: Inter-individual Variation, Association with Gut Microbiome Composition, and Differential Bioactivity.

SCOPE: The glucosinolate glucoraphanin from broccoli is converted to sulforaphane (SFN) or sulforaphane-nitrile (SFN-NIT) by plant enzymes or the gut microbiome. Human feeding studies typically observe high inter-individual variation in absorption and excretion of SFN, however, the source of this variation is not fully known. To address this, a human feeding trial to comprehensively evaluate inter-individual variation in the absorption and excretion of all known SFN metabolites in urine, plasma, and stool, and tested the hypothesis that gut microbiome composition influences inter-individual variation in total SFN excretion has been conducted. METHODS AND RESULTS: Participants (n = 55) consumed a single serving of broccoli or alfalfa sprouts and plasma, stool, and total urine are collected over 72 h for quantification of SFN metabolites and gut microbiome profiling using 16S gene sequencing. SFN-NIT excretion is markedly slower than SFN excretion (72 h vs 24 h). Members of genus Bifidobacterium, Dorea, and Ruminococcus torques are positively associated with SFN metabolite excretion while members of genus Alistipes and Blautia has a negative association. CONCLUSION: This is the first report of SFN-NIT metabolite levels in human plasma, urine, and stool following consumption of broccoli sprouts. The results help explain factors driving inter-individual variation in SFN metabolism and are relevant for precision nutrition.

Mental health and psychosocial support for children with upper limb musculoskeletal conditions.

This study describes mental health and psychosocial screening processes, access to care and interventions provided to children with upper limb musculoskeletal conditions. A cross-sectional e-survey study was conducted of 107 healthcare professionals who work with children with congenital hand and upper limb differences and brachial plexus birth injuries. Of them, 41 (38%) reported that they routinely screen for mental health and psychosocial concerns. Few (12%) reported the use of standardized outcome measures. In total, 51 (48%) healthcare professionals reported that there was a waiting list for mental health services at their institution. Collectively, healthcare professionals were unsatisfied with the staffing, access to care and types of interventions available. Reported barriers to care included the growing need for mental health support, lack of resources and poor continuity of care after referrals. Future research should focus on identifying and validating a mental health screening tool and investigating the processes affecting access to mental health care.Level of evidence: IV.

Advancing nutrition science to meet evolving global health needs.

Populations in crisis!A global overview of health challenges and policy efforts within the scope of current nutrition issues, from persistent forms of undernutrition, including micronutrient deficiency, to diet-related chronic diseases. Nutrition science has evolved from a therapeutic and prevention emphasis to include a focus on diets and food systems. Working and consensus definitions are needed, as well as guidance related to healthy diets and the emerging issues that require further research and consensus building. Between nutrient deficiency and chronic disease, nutrition has evolved from focusing exclusively on the extremes of overt nutrient deficiency and chronic disease prevention, to equipping bodies with the ability to cope with physiologic, metabolic, and psychological stress. Just what is 'optimal nutrition', is that a valid public health goal, and what terminology is being provided by the nutrition science community? Nutrition research on 'healthspan', resilience, and intrinsic capacity may provide evidence to support optimal nutrition. Finally, experts provide views on ongoing challenges of achieving consensus or acceptance of the various definitions and interventions for health promotion, and how these can inform government health policies.Nutrition topics that receive particular focus in these proceedings include choline, NAD-replenishment in neurodegenerative diseases, and xanthophyll carotenoids. Choline is a crucial nutrient essential for cellular metabolism, requiring consumption from foods or supplements due to inadequate endogenous synthesis. Maternal choline intake is vital for fetal and infant development to prevent neural tube defects. Neurodegenerative diseases pose a growing health challenge, lacking effective therapies. Nutrition, including NAD-replenishing nutrients, might aid prevention. Emerging research indicates xanthophyll carotenoids enhance vision and cognition, potentially impacting age-related diseases.

Sulforaphane Bioavailability in Healthy Subjects Fed a Single Serving of Fresh Broccoli Microgreens.

Cruciferous vegetable consumption is associated with numerous health benefits attributed to the phytochemical sulforaphane (SFN) that exerts antioxidant and chemopreventive properties, among other bioactive compounds. Broccoli sprouts, rich in SFN precursor glucoraphanin (GRN), have been investigated in numerous clinical trials. Broccoli microgreens are similarly rich in GRN but have remained largely unexplored. The goal of this study was to examine SFN bioavailability and the microbiome profile in subjects fed a single serving of fresh broccoli microgreens. Eleven subjects participated in a broccoli microgreens feeding study. Broccoli microgreens GRN and SFN contents and stability were measured. Urine and stool SFN metabolite profiles and microbiome composition were examined. Broccoli microgreens had similar GRN content to values previously reported for broccoli sprouts, which was stable over time. Urine SFN metabolite profiles in broccoli microgreens-fed subjects were similar to those reported previously in broccoli sprouts-fed subjects, including the detection of SFN-nitriles. We also reported the detection of SFN metabolites in stool samples for the first time. A single serving of broccoli microgreens did not significantly alter microbiome composition. We showed in this study that broccoli microgreens are a significant source of SFN. Our work provides the foundation for future studies to establish the health benefits of broccoli microgreens consumption.