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Background and Objectives: Cervical flexion-induced myelopathy, also known as Hirayama disease (HD), is a lower motor neuron disorder seen mainly in adolescents and young adults, affecting the C7–T1 myotomes, presenting as asymmetric weakness with wasting of one or both the distal upper limbs. We aimed to describe the clinical features, electrophysiology, and radiologic features of HD in a tertiary care institute in northern India. Methods: One hundred and forty patients between 2017 and 2022 with clinical and imaging features consistent with HD were retrospectively reviewed from the All India Institute of Medical Sciences-Comprehensive Neuromuscular Diseases center database. Results: Majority were males with the mean age of onset of illness being 17.8 years. The median duration of the symptoms was 3 (1.5–4) years. Sixty-nine (49%) patients had unilateral involvement, and the disease was actively progressing in 88 (63%) patients at presentation. Two families had history of HD in two (1.4%) siblings. Electromyography showed abnormal findings in the clinically involved limb in all the patients and in the clinically uninvolved limb in 17/50 (34%) patients. Flexion magnetic resonance imaging (MRI) demonstrated forward dural displacement in 134 (96%) patients and asymmetric cord flattening in 124 (88.5%) patients. Disability was graded as mild, moderate, and severe; 12 (13%) had severe disability. The majority were managed conservatively, and four underwent surgery for HD. Conclusion: A high index of suspicion of HD needs to be kept in a young male presenting with distal upper limb weakness and atrophy. Dynamic MRI of the cervical spine in young adults presenting with hand wasting is inevitable. This disease needs to be managed aggressively and early to prevent serious dysfunction and loss of productivity.

Abstract Epigenetic modifications control gene expression and are essential for turning genes on and off to regulate and maintain differentiated cell types. Epigenetics are also modified by a multitude of environmental exposures, including diet and pollutants, allowing an individual’s environment to influence gene expression and resultant phenotypes and clinical outcomes. These epigenetic modifications due to gene–environment interactions can also be transmitted across generations, raising the possibility that environmental influences that occurred in one generation may be transmitted beyond the second generation, exerting a long-lasting effect. In this review, we cover the known mechanisms of epigenetic modification acquisition, reprogramming and persistence, animal models and human studies used to understand multigenerational epigenetic transmission, and examples of environmentally induced epigenetic change and its transmission across generations. We highlight the importance of environmental health not only on the current population but also on future generations that will experience health outcomes transmitted through epigenetic inheritance.

Abstract The gut microbiome is implicated in the pathogenesis of colorectal cancer (CRC), but the full scope of this dialogue is unknown. Here we aimed to define the scale and membership of the body of CRC- and health-associated gut bacteria in global populations. We performed a microbiome-CRC correlation analysis of published ultra-deep shotgun metagenomic sequencing data from global microbiome surveys, utilizing a de novo (reference-agnostic) gene-level clustering approach to identify protein-coding co-abundant gene (CAGs) clusters. We link an unprecedented ~ 23–40% of gut bacteria to CRC or health, split nearly evenly as CRC- or health-associated. These microbes encode 2319 CAGs encompassing 427,261 bacterial genes significantly enriched or depleted in CRC. We identified many microbes that had not previously been linked to CRC, thus expanding the scope of “known unknowns” of CRC-associated microbes. We performed an agnostic CAG-based screen of bacterial isolates and validated predicted effects of previously unimplicated bacteria in preclinical models, in which we observed differential induction of precancerous adenomas and field effects. Single-cell RNA sequencing disclosed microbiome-induced senescence-associated gene expression signatures in discrete colonic populations including fibroblasts. In organoid co-cultures, primary colon fibroblasts from mice with microbiomes promoted significantly greater growth than fibroblasts from microbiome-depleted mice. These results offer proof-of-principle for gene-level metagenomic analysis enabling discovery of microbiome links to health and demonstrate that the microbiome can drive precancer states, thereby potentially revealing novel cancer prevention opportunities.

Abstract Individuals with mental illness are at higher risk of severe COVID-19 outcomes. However, previous studies on the uptake of COVID-19 vaccination in this population have reported conflicting results. Using data from seven cohort studies (N = 325,298) included in the multinational COVIDMENT consortium, and the Swedish registers (N = 8,080,234), this study investigates the association between mental illness (defined using self-report measures, clinical diagnosis and prescription data) and COVID-19 vaccination uptake. Results from the COVIDMENT cohort studies were pooled using meta-analyses, the majority of which showed no significant association between mental illness and vaccination uptake. In the Swedish register study population, we observed a very small reduction in the uptake of both the first and second dose of a COVID-19 vaccine among individuals with vs. without mental illness; the reduction was however greater among those not using psychiatric medication. Here we show that uptake of the COVID-19 vaccine is generally high among individuals both with and without mental illness, however the lower levels of vaccination uptake observed among subgroups of individuals with unmedicated mental illness warrants further attention.

Abstract Background This study aimed to compare the marginal adaptation of a single customized gutta percha cone with calcium silicate-based sealer versus mineral trioxide aggregate (MTA) and Biodentine apical plugs in simulated immature permanent teeth. Methods Thirty-nine extracted human maxillary anterior teeth were selected, prepared to simulate immature permanent teeth with an apical diameter 1.1 mm, placed in moist foam and divided into three groups. Group 1: Obturation with a single customized gutta percha cone and calcium silicate sealer. Group 2: MTA apical plug. Group 3: Biodentine apical plug. After incubation, teeth were horizontally sectioned at 1 mm and 3 mm from the apex and marginal adaptation was evaluated using scanning electron microscope (SEM). Results Biodentine showed the least mean gap size at both 1 and 3 mm from the apex with no statistically significant differences compared to MTA (p > 0.05). The single customized cone with calcium silicate based sealer showed the greatest mean gap size at both 1 and 3 mm from the apex with a statistically significant difference compared to the other groups (p

Start Strong, a 4-week culinary nutrition education and obesity prevention program designed for rural family care providers in low-income areas of Minnesota, was initially an in-person training program and was recently adapted into a virtual version. Using a quasi-experimental design, this study examined within-group and between-group (in-person versus virtual) changes in culinary skill confidence and familiarity with food assistance programs after Start Strong participation. Additionally, we examined post-program participant experiences. The in-person program (n = 12, mean age of 45 years, September 2019) took place at community locations. The virtual program (n = 27, mean age of 41 years, Fall 2021–Winter 2022) used online learning and videoconferencing. Following data collection pre- and post-program, we used t-tests to examine within-group changes after Start Strong participation, repeated measures analysis of variance tests to compare outcomes between the in-person and virtual implementations, and Fisher’s exact test to compare post-survey outcomes. The in-person and virtual programs demonstrated similar improvements in cooking skill confidence and familiarity with food assistance programs. Compared to the virtual program, in-person participants reported significantly greater connection with other providers. This evaluation is relevant to addressing disparities in obesity prevention and provides an initial model for public health and community partnerships with ECE providers.

Abstract Robust diagnostic tools and surveillance are crucial for malaria control and elimination efforts. Malaria caused by neglected Plasmodium parasites is often underestimated due to the lack of rapid diagnostic tools that can accurately detect these species. While nucleic-acid amplification technologies stand out as the most sensitive methods for detecting and confirming Plasmodium species, their implementation in resource-constrained settings poses significant challenges. Here, we present a Pan Plasmodium recombinase polymerase amplification lateral flow (RPA–LF) assay, capable of detecting all six human infecting Plasmodium species in low resource settings. The Pan Plasmodium RPA-LF assay successfully detected low density clinical infections with a preliminary limit of detection between 10–100 fg/µl for P. falciparum. When combined with crude nucleic acid extraction, the assay can serve as a point-of-need tool for molecular xenomonitoring. This utility was demonstrated by screening laboratory-reared Anopheles stephensi mosquitoes fed with Plasmodium-infected blood, as well as field samples of An. funestus s.l. and An. gambiae s.l. collected from central Africa. Overall, our proof-of-concept Pan Plasmodium diagnostic tool has the potential to be applied for clinical and xenomonitoring field surveillance, and after further evaluation, could become an essential tool to assist malaria control and elimination.

Introduction Among women at risk for alcohol-exposed pregnancies (AEP), smoking tobacco may be associated with increased severity of alcohol use, and risk for tobacco-exposed and other substance-exposed pregnancies (TEPs/SEPs). Our secondary data analysis of the ‘CHOICES Plus’ intervention trial explored AEP and SEP risk by smoking status. Material and Methods Eligible women (N=261) were recruited from 12 primary care clinics in a public healthcare system, not pregnant, aged 18–44 years, drinking >3 drinks/ day or >7 drinks/week, sexually active, and not using effective contraception. We compared women who did and did not smoke tobacco on alcohol and drug severity, and psychological distress (e.g. anxiety) at baseline. Results Participants were primarily Hispanic (47.1%) or non-Hispanic Black (41.8%) and reported incomes

Abstract Background Magnetic resonance imaging (MRI) quantification of intramuscular fat accumulation is a responsive biomarker in neuromuscular diseases. Despite emergence of automated methods, manual muscle segmentation remains an essential foundation. We aimed to develop a training programme for new observers to demonstrate competence in lower limb muscle segmentation and establish reliability benchmarks for future human observers and machine learning segmentation packages. Methods The learning phase of the training programme comprised a training manual, direct instruction, and eight lower limb MRI scans with reference standard large and small regions of interest (ROIs). The assessment phase used test–retest scans from two patients and two healthy controls. Interscan and interobserver reliability metrics were calculated to identify underperforming outliers and to determine competency benchmarks. Results Three experienced observers undertook the assessment phase, whilst eight new observers completed the full training programme. Two of the new observers were identified as underperforming outliers, relating to variation in size or consistency of segmentations; six had interscan and interobserver reliability equivalent to those of experienced observers. The calculated benchmark for the Sørensen-Dice similarity coefficient between observers was greater than 0.87 and 0.92 for individual thigh and calf muscles, respectively. Interscan and interobserver reliability were significantly higher for large than small ROIs (all p

Abstract Efficiency of evidence accumulation (EEA), an individual’s ability to selectively gather goal-relevant information to make adaptive choices, is thought to be a key neurocomputational mechanism associated with cognitive functioning and transdiagnostic risk for psychopathology. However, the neural basis of individual differences in EEA is poorly understood, especially regarding the role of largescale brain network dynamics. We leverage data from 5198 participants from the Human Connectome Project and Adolescent Brain Cognitive Development Study to demonstrate a strong association between EEA and flexible adaptation to cognitive demand in the “task-positive” frontoparietal and dorsal attention networks. Notably, individuals with higher EEA displayed divergent task-positive network activation across n-back task conditions: higher activation under high cognitive demand (2-back) and lower activation under low demand (0-back). These findings suggest that brain networks’ flexible adaptation to cognitive demands is a key neural underpinning of EEA.

Abstract The transforming growth factor-beta (TGF-β) signaling pathway is a vital regulator of cell proliferation, differentiation, apoptosis, and extracellular matrix production. It functions through canonical SMAD-mediated processes and noncanonical pathways involving MAPK cascades, PI3K/AKT, Rho-like GTPases, and NF-κB signaling. This intricate signaling system is finely tuned by interactions between canonical and noncanonical pathways and plays key roles in both physiologic and pathologic conditions including tissue homeostasis, fibrosis, and cancer progression. TGF-β signaling is known to have paradoxical actions. Under normal physiologic conditions, TGF-β signaling promotes cell quiescence and apoptosis, acting as a tumor suppressor. In contrast, in pathological states such as inflammation and cancer, it triggers processes that facilitate cancer progression and tissue remodeling, thus promoting tumor development and fibrosis. Here, we detail the role that TGF-β plays in cancer and fibrosis and highlight the potential for future theranostics targeting this pathway.

Abstract People with lower extremity peripheral artery disease (PAD) have increased oxidative stress, impaired mitochondrial activity, and poor walking performance. NAD+ reduces oxidative stress and is an essential cofactor for mitochondrial respiration. Oral nicotinamide riboside (NR) increases bioavailability of NAD+ in humans. Among 90 people with PAD, this randomized double-blind clinical trial assessed whether 6-months of NR, with and without resveratrol, improves 6-min walk distance, compared to placebo, at 6-month follow-up. At 6-month follow-up, compared to placebo, NR significantly improved 6-min walk (+7.0 vs. −10.6 meters, between group difference: +17.6 (90% CI: + 1.8,+∞). Among participants who took at least 75% of study pills, compared to placebo, NR improved 6-min walk by 31.0 meters and NR + resveratrol improved 6-min walk by 26.9 meters. In this work, NR meaningfully improved 6-min walk, and resveratrol did not add benefit to NR alone in PAD. A larger clinical trial to confirm these findings is needed. Clinical Trials.gov registration: NCT03743636.

Anthropogenic activities have left a legacy of contaminated vacant land, which disproportionately affects lower income communities and can have detrimental impacts on human health, particularly children. A management solution is needed to address this widespread lead contamination in urban soils of vacant lots. In this study, high-Fe biosolids incinerator ash (BIA) was evaluated for its ability to sequester soil Pb. Five blends were created using BIA and different amount of other products (dredge, biosolids compost, and yard waste compost) to determine the most effective treatment to reduce Pb bioaccessibility in the soil. The sorption capacity of the BIA for Pb was evaluated by mixing the BIA with Pb(NO3)2 at 1000 to 100,000 ​mg ​Pb/kg BIA. The contaminated soil from Cleveland, OH was treated with five BIA-based blends at a 1:1 (w/w) ratio, and Pb bioaccessibility was evaluated using USEPA Method 1340 ​at pH 2.5 and the Physiologically Based Extraction Test (PBET) at pH 2.5. BIA was a strong sorbent for Pb, sorbing ∼100% of the Pb from solution at 10,000 ​mg/L with only 41% bioaccessibility based on Method 1340 ​at pH 2.5. The blend containing 4.5%, 10%, or 19% BIA reduced the Pb bioaccessibility by 48% from the control based on both bioaccessibility methods. The bioaccessible Pb determined by PBET was less than that by USEPA Method 1340 ​at pH 2.5. However, similar reductions in bioaccessible Pb between blend-treated soils and the unamended soil were observed for all bioaccessibility methods. Plant growth assays showed the blends to have little to no significant impact on clover growth, mortality, or flower production, with the blend containing 10% BIA showing greater biomass yield. Results showed BIA-based blends were able to reduce bioaccessible Pb in the soil. This remediation approach may improve the urban living environment and protects public health.

Gonoderma lucidum (G. lucidum) and Cordyceps militaris (C. militaris) are among the many mushrooms known for their long history of use in traditional medicine. Wildcrafted sources of mushrooms including G. lucidum and C. militaris can be limited from a scarcity and quality perspective, but solid fermentation processes in cultivation settings can provide an efficient way to deliver whole mushroom preparations of a consistent composition. Despite the historical use of these mushrooms, few published reports have explored their potential subchronic oral toxicity or genotoxicity, either from specific components or whole mushroom preparations. The purpose of this study was to assess the potential for acute toxicity, subchronic toxicity, and genotoxicity of powders produced from G. lucidum mycelial biomass and fruiting body (“Organic Reishi M2-102-02 powder”) cultured on oats, and C. militaris mycelial biomass, stroma, and fruiting body (“Organic Cordyceps M2-116-04 powder”) cultured on oats. Results of the testing demonstrate that both Organic Reishi M2-102-02 powder and Organic Cordyceps M2-116-04 powder were not acutely toxic, did not exhibit subchronic oral toxicity in rats at doses up to the highest dose tested of 2,000 mg/kg bw/day, and did not have genotoxic potential based on in vitro and in vivo genotoxicity assays.

ABSTRACT Introduction The term “Mediterranean lifestyle” has gained increasing prominence in recent years, yet a specific definition remains elusive. In response, the Mediterranean Lifestyle Medicine Institute Board of Directors convened a multidisciplinary panel comprising international experts and leaders in lifestyle medicine. Their goal was to review existing literature and formulate a consensus definition of the “traditional Mediterranean lifestyle (tMedL),” referring to the historical way of living of the people in the Mediterranean region. This paper presents the agreed consensus statement and a comprehensive holistic definition of the term “traditional Mediterranean lifestyle.” Methods Major medical and social sciences electronic databases from inception to February 2023 were searched, employing keywords relevant to the Mediterranean lifestyle and its constituent elements (diet, physical activity, sleep, stress, socialization). Subsequently, definitions for each pillar were created and synthesized to derive a comprehensive definition of the “traditional Mediterranean lifestyle.” Results This proposed definition received ratification from the Mediterranean Lifestyle Medicine Institute's expert working group during the First International Mediterranean Lifestyle Medicine Conference held in June 2023 on the island of Leros, Greece. “The traditional Mediterranean lifestyle is characterized by its diverse and adaptable nature. Key facets encompass conviviality, lifelong social connectedness, purposeful living, strong community and familial bonds, harmony with nature and the environment, profound spirituality, adherence to religious practices, preservation of local customs, resilience cultivated through adversity, and a commitment to moderation across all spheres of life.” Conclusions This definition comprehensively outlines the primary lifestyle factors ingrained in Mediterranean inhabitants across generations. Its holistic nature furnishes a crucial conceptual framework for directing lifestyle medicine practitioners in assisting patients to mitigate diseases, promote overall well‐being, devise research initiatives to investigate the health ramifications of this lifestyle, and inform curriculum development.

IntroductionThe Implementation Research Logic Model (IRLM) aids users in combining, organizing, and specifying the relationships between important constructs in implementation research. The goal of the IRLM is to improve the rigor, reproducibility, and transparency of implementation research projects. The article describing the IRLM was published September 25, 2020 (Implement Sci, Vol 15); it has since been highly cited and included as a required element in multiple funding opportunity announcements from federal agencies. The proliferation of IRLM use across dissemination and implementation research projects and practice provides an excellent opportunity to examine applications across a variety of different contexts. This protocol will result in a description of the impact of the IRLM on the field of dissemination and implementation science and guidance on refinements to the IRLM to increase its utility and impact through (1) a citation analysis, (2) a scoping review, and (3) user surveys and interviews.Methods and analysisThis protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping review reporting guidelines (PRISMA-ScR). We plan to conduct a citation search and analysis of the Smith et al. 2020 article and a scoping review. The review search will be conducted in Medline, Embase, CINAHL Complete, Cochrane Library, APA PsycINFO4, ProQuest Dissertations & Theses Global, Scopus and Web of Science Core Collection., and grey literature will be searched to identify studies that use alternative logic models for implementation research. A survey will be developed from the findings of the scoping review and administered to individuals who used the IRLM. Semi-structured interviews will then be conducted with a sample of survey respondents to provide an opportunity for sequential mixed-methods analysis to achieve a deeper understanding of needed IRLM refinements and recommendations.Ethics and disseminationEthics approval for the scoping review and citation analysis is not applicable as only data from published literature will be used and no original data will be collected. For the survey, IRB will be completed once items are developed from the results of the scoping review and citation analysis. Results will be disseminated through peer-reviewed publications, conference presentations, and via online tools. Registration detailsThis protocol was registered with OSF, https://osf.io/y94bj (1).

Summary: Background: Almost all acquired severe aplastic anaemia is immune mediated and characterised by hypocellular bone marrow and ≥2 affected haematopoietic lineages. The optimal preparartive regimen for unrelated donor transplantation remains to be established. We aimed to study long-term outcomes after unrelated donor transplantation for severe aplastic anaemia with de-escalation of cyclophosphamide (Cy) dose in steps of 50 mg/kg (150, 100, 50, 0 mg/kg) in combination with total body irradiation (TBI) 2 Gy, anti-thymocyte globulin (ATG) and fludarabine. Methods: Ninety-six patients with severe aplastic anaemia aged ≤65 years with adequate organ function enrolled on a trial of human leukocyte antigen (HLA)-matched or 1 HLA-locus mismatched unrelated donor marrow transplantation conducted between 02/2006 and 12/2013 in the United States (NCT00326417). Exclusion criteria were Karnofsky performance status of less than 60, clonal cytogenetic abnormalities and inherited marrow failure syndormes. The primary outcome was day-100 engraftment (achievement of absolute neutrophil recovery to at least 0.5 × 109/L without subsequent decline) and day-100 survival. The trial determined the lowest effective Cy dose as 50 mg/kg (n = 38) for day-100 engraftment and survival. Cy dose 100 mg/kg (n = 41) was also acceptable. Accrual to Cy doses 150 mg/kg (n = 15) and 0 mg/kg (n = 3) was terminated early for toxicities. The current study is an extended follow up of patients enrolled on the trial (NCT00326477) and includes 76 of 96 patients alive ≥1 year after transplantation. There were 20 deaths in the first year after transplantation (Cy 0 mg/kg [n = 2], Cy 50 mg/kg [n = 1], Cy 100 mg/kg [n = 10], Cy 150 mg/kg [n = 7]). Patients were followed prospectively from transplantation and data reported using standardized data collection forms until death, loss to follow up or last contact through November 2023. The incidence of graft failure was calculated using the cumulative incidence estimator and the probability of survival using the Kaplan–Meier estimator. Findings: The median follow up of the cohort is 8.02 (IQR) 5.16–10.12) years. With Cy 50 mg/kg, there was one graft failure and five deaths ≥1 year after transplantation. With Cy 100 mg/kg there was only one late death and no graft failure. The 8-year probabilities of survival were 85.0% (95% CI 67.3–93.5) and 75.6% (95% CI 59.4–86.1) after Cy 50 mg/kg and 100 mg/kg, respectively, P = 0.31. With Cy 0 mg/kg and 150 mg/kg, there were no graft failures or death ≥1 year after transplantation. Regardless of Cy dose 12 of 15 patients aged ≥50 years died. Interpretation: Cy 50 mg/kg or 100 mg/kg with TBI 2 Gy, ATG and fludarabine are effective conditioning regimens for unrelated donor marrow transplants for aplastic anaemia. Identification of an optimized transplantation approach for patients aged ≥50 years is needed. Funding: US National Institutes of Health.

No prospective data have been described to inform guidelines on antibiotic prophylaxis for partial vulvectomies. Thus, we conducted a single-center, pilot, double-blind randomized controlled trial to assess the effectiveness of prophylactic antibiotics to prevent wound complications after partial vulvectomies. Patients were randomly assigned 1:1 to preoperative antibiotics or no preoperative antibiotics. The primary outcome of 30-day postoperative wound complications occurred in 31 (62 %) of all patients, with no differences between groups. The most common wound complications were superficial separation (54.2 % antibiotic prophylaxis vs. 65.3 % no prophylaxis, p = 0.37) and surgical site infection (0 % antibiotic prophylaxis vs 7.7 % no prophylaxis, p = 0.49). However, this study was limited by differences in patient characteristics between the groups. This study provides data to perform power calculations for a trial examining the effect of preoperative antibiotics on surgical site infection.

Theological reflection that employs themes including the dignity of the person, solidarity with the vulnerable, participation in the common good, and the principle of subsidiarity, all through an antiracist and anti-misogynist lens, yields a framework for reproductive justice that better captures lived experiences of reproductive oppression and points toward the kinds of practices and policies that actually support women and children. This essay focuses on the shameful rates of maternal and infant morbidity and mortality for Black woman and children in the United States. Any adequate ethic of reproductive justice from a Catholic perspective must take its lead from the experiences and advocacy of women of color. Working for intersectional reproductive justice must take the form of lending support and solidarity to the innovative grassroots work of Black women.

In this theo-ethical roundtable, scholars from the Philippines, USA, and Nigeria describe threats to women’s flourishing in their contexts and highlight how a framework of reproductive justice can provide meaningful categories for social action.

Background:. Limited studies have detailed the risk of mastectomy with immediate breast reconstruction among women who previously received mantle field radiation. Methods:. A single institution retrospective review from 2010 to 2020 of patients previously treated with mantle field radiation (MF-RT) and subsequent mastectomy with immediate breast reconstruction was performed. Patients with prior whole breast irradiation (WBI) were also included as a reference group. Demographic, comorbidity, and surgical factors were collected. The primary outcome was major complications, defined as those requiring reoperation, intravenous antibiotics, or debridement. Results:. Fourteen patients with prior MF-RT (27 breasts) and 129 with prior WBI (132 breasts) underwent mastectomy with immediate reconstruction. Prior MF-RT patients were significantly younger (43.8 versus 57.5, P

Abstract Legacy phosphorus (P) is a reservoir of sparingly available P, and its recovery could enhance sustainable use of nonrenewable mineral fertilizers. Domestication has affected P acquisition, but it is unknown if subsequent breeding efforts, like the Green Revolution (GR), had a similar effect. We examined how domestication and breeding events altered P acquisition by growing wild, traditional (pre-GR), and modern (post-GR) tomato in soil with legacy P but low bioavailable P. Wild tomatoes, particularly accession LA0716 (Solanum pennellii), heavily cultured rhizosphere P solubilizers, suggesting reliance on microbial associations to acquire P. Wild tomato also had a greater abundance of other putatively beneficial bacteria, including those that produce chelating agents and antibiotic compounds. Although wild tomatoes had a high abundance of these P solubilizers, they had lower relative biomass and greater P stress factor than traditional or modern tomato. Compared to wild tomato, domesticated tomato was more tolerant to P deficiency, and both cultivated groups had a similar rhizosphere bacterial community composition. Ultimately, this study suggests that while domestication changed tomato P recovery by reducing microbial associations, subsequent breeding processes have not further impacted microbial P acquisition mechanisms. Selecting microbial P-related traits that diminished with domestication may therefore increase legacy P solubilization.

Abstract Background Substance use-related emergency department (ED) visits have increased substantially in North America. Screening for substance use in EDs is recommended; best approaches are unclear. This systematic review synthesizes evidence on diagnostic accuracy of ED screening tools to detect harmful substance use. Methods We included derivation or validation studies, with or without comparator, that included adult (≥ 18 years) ED patients and evaluated screening tools to identify general or specific substance use disorders or harmful use. Our search strategy combined concepts Emergency Department AND Screening AND Substance Use. Trained reviewers assessed title/abstracts and full-text articles for inclusion, extracted data, and assessed risk of bias (QUADAS-2) independently and in duplicate. Reviewers resolved disagreements by discussion. Primary investigators adjudicated if necessary. Heterogeneity precluded meta-analysis. We descriptively summarized results. Results Our search strategy yielded 2696 studies; we included 33. Twenty-one (64%) evaluated a North American population. Fourteen (42%) applied screening among general ED patients. Screening tools were administered by research staff (n = 21), self-administered by patients (n = 10), or non-research healthcare providers (n = 1). Most studies evaluated alcohol use screens (n = 26), most commonly the Alcohol Use Disorders Identification Test (AUDIT; n = 14), Cut down/Annoyed/Guilty/Eye-opener (CAGE; n = 13), and Rapid Alcohol Problems Screen (RAPS/RAPS4/RAPS4-QF; n = 12). Four studies assessing six tools and screening thresholds for alcohol abuse/dependence in North American patients (AUDIT ≥ 8; CAGE ≥ 2; Diagnostic and Statistical Manual of Mental Disorders, 4th Edition [DSM-IV-2] ≥ 1; RAPS ≥ 1; National Institute on Alcohol Abuse and Alcoholism [NIAAA]; Tolerance/Worry/Eye-opener/Amnesia/K-Cut down [TWEAK] ≥ 3) reported both sensitivities and specificities ≥ 83%. Two studies evaluating a single alcohol screening question (SASQ) (When was the last time you had more than X drinks in 1 day?, X = 4 for women; X = 5 for men) reported sensitivities 82–85% and specificities 70–77%. Five evaluated screening tools for general substance abuse/dependence (Relax/Alone/Friends/Family/Trouble [RAFFT] ≥ 3, Drug Abuse Screening Test [DAST] ≥ 4, single drug screening question, Alcohol, Smoking and Substance Involvement Screening Test [ASSIST] ≥ 42/18), reporting sensitivities 64%-90% and specificities 61%-100%. Studies’ risk of bias were mostly high or uncertain. Conclusions Six screening tools demonstrated both sensitivities and specificities ≥ 83% for detecting alcohol abuse/dependence in EDs. Tools with the highest sensitivities (AUDIT ≥ 8; RAPS ≥ 1) and that prioritize simplicity and efficiency (SASQ) should be prioritized.

Abstract Objective With potential therapies for many forms of Charcot‐Marie‐Tooth disease (CMT), responsive outcome measures are urgently needed for clinical trials. Quantitative lower limb MRI demonstrated progressive calf intramuscular fat accumulation in the commonest form, CMT1A with large responsiveness. In this study, we evaluated the responsiveness and validity in the three other common forms, due to variants in GJB1 (CMTX1), MPZ (CMT1B) and MFN2 (CMT2A). Methods 22 CMTX1, 21 CMT1B and 21 CMT2A patients and matched controls were assessed at a 1‐year interval. Intramuscular fat fraction (FF) was evaluated using three‐point Dixon MRI at thigh and calf level along with clinical measures including CMT examination score, clinical strength assessment, CMT‐HI and plasma neurofilament light chain. Results All patient groups had elevated muscle fat fraction at thigh and calf levels, with highest thigh FF and atrophy in CMT2A. There was moderate correlation between calf muscle FF and clinical measures (CMTESv2 rho = 0.405; p = 0.001, ankle MRC strength rho = −0.481; p

Residing in poverty-impacted Ugandan communities and raising children with disruptive behavior disorders (DBDs) is associated with above heightened parenting stress. An evidence-based intervention designed to help parents tailor their parenting style to effectively manage children with DBDs was implemented in Uganda between 2017 and 2023. At the end of the intervention, caregivers displayed lower levels of parenting stress than controls, however the mechanisms by which stress reduction occurred is unknown. We investigated whether the intervention's effect on parenting stress was mediated by parenting practices, family cohesion, or mental health.Mediation was assessed using Mitchell and Maxwell's cross-lagged auto-regressive approach. Each mediation model regressed the outcome parenting stress score at each time point onto intervention group assignment (0 = Control; 1 = Multiple Family Group (MFG) intervention) and parenting stress score at the preceding time point. Each mediator was investigated one at a time and regressed onto intervention group assignment and the mediator score at the preceding time point. Parenting stress score was also regressed onto the preceding time point mediator score. The residuals for mediators and parenting stress were allowed to correlate at each time point. We included regression pathways from each covariate to the mediators and outcomes at subsequent waves and were included in the model as random variables.The findings show that the intervention had a significant direct effect on parenting stress at 16 weeks post intervention initiation and was partially mediated by parenting practices, caregiver mental health, and parenting stress at 8 weeks, but we found no evidence it was mediated by family cohesion, supporting two of our hypotheses.Equipping caregivers with parenting skills and strategies to improve mental health can go a long way in reducing overall parenting stress among caregivers with DBDs. Our findings could be leveraged to enhance stress reduction among caregivers of children with DBDs in the long-term.

ABSTRACTThe ability of bacteria to sense and respond to mechanical forces has important implications for pathogens during infection, as they experience wide fluid shear fluctuations in the host. However, little is known about how mechanical forces encountered in the infected host drive microbial pathogenesis. Herein, we combined mathematical modeling with hydrodynamic bacterial culture to profile transcriptomic and pathogenesis-related phenotypes of multidrug resistant S. Typhimurium (ST313 D23580) under different fluid shear conditions relevant to its transition from the intestinal tract to the bloodstream. We report that D23580 exhibited incremental changes in transcriptomic profiles that correlated with its pathogenic phenotypes in response to these progressive increases in fluid shear. This is the first demonstration that incremental changes in fluid shear forces alter stress responses and gene expression in any ST313 strain and offers mechanistic insight into how forces encountered by bacteria during infection might impact their disease-causing ability in unexpected ways.

Background: Exercise during pregnancy is beneficial to both the pregnant woman and the foetus. Midwifery educators play a crucial role in ensuring that midwifery students receive the knowledge and training needed to demonstrate antenatal exercises. To ensure that their students understand and deliver adequate antenatal care, midwifery educators should be highly knowledgeable in pregnancy-related exercises. Objectives: The study was conducted to determine the knowledge of midwifery educators about antenatal exercise. Method: A descriptive cross-sectional study was conducted of the knowledge about antenatal exercises by midwifery educators. A purposive total population of 54 midwifery educators from three midwifery schools in Cross River State, Nigeria, was included in the study. Questionnaires were used for data collection, and Statistical Package for Social Sciences (SPSS) version 27 was used for data analysis. Ethical issues and rigour were maintained. Results: The study revealed that antenatal exercises are included in the midwifery curriculum and exercise demonstration were mainly done by midwifery educators and clinical instructors. The majority (n = 34, 66.7%) of the respondents were knowledgeable about World Health Organization (WHO) guidelines for exercise during pregnancy and had an average knowledge of the ideal antenatal exercises. Conclusion: Midwifery educators have average knowledge of the ideal antenatal exercises, which prompts the development of an exercise programme to guide midwifery training and practice. Midwifery educators should collaborate with exercise specialists to teach and demonstrate antenatal exercises. Contribution: The study highlighted the need for midwifery educators to obtain more information on antenatal exercises to adequately prepare midwifery students for evidence-based exercise care for pregnant women.

BackgroundThe electrophysiological mechanism connecting mitral valve prolapse (MVP), premature ventricular complexes and life-threatening ventricular arrhythmia is unknown. A common hypothesis is that stretch activated channels (SACs) play a significant role. SACs can trigger depolarizations or shorten repolarization times in response to myocardial stretch. Through these mechanisms, pathological traction of the papillary muscle (PM), as has been observed in patients with MVP, may induce irregular electrical activity and result in reentrant arrhythmia.MethodsBased on a patient with MVP and mitral annulus disjunction, we modeled the effect of excessive PM traction in a detailed medical image-derived ventricular model by activating SACs in the PM insertion region. By systematically varying the onset of SAC activation following sinus pacing, we identified vulnerability windows for reentry with 1 ms resolution. We explored how reentry was affected by the SAC reversal potential (ESAC) and the size of the region with simulated stretch (SAC region). Finally, the effect of global or focal fibrosis, modeled as reduction in tissue conductivity or mesh splitting (fibrotic microstructure), was investigated.ResultsIn models with healthy tissue or fibrosis modeled solely as CV slowing, we observed two vulnerable periods of reentry: For ESAC of −10 and −30 mV, SAC activated during the T-wave could cause depolarization of the SAC region which lead to reentry. For ESAC of −40 and −70 mV, SAC activated during the QRS complex could result in early repolarization of the SAC region and subsequent reentry. In models with fibrotic microstructure in the SAC region, we observed micro-reentries and a larger variability in which times of SAC activation triggered reentry. In these models, 86% of reentries were triggered during the QRS complex or T-wave. We only observed reentry for sufficiently large SAC regions (>= 8 mm radius in models with healthy tissue).ConclusionStretch of the PM insertion region following sinus activation may initiate ventricular reentry in patients with MVP, with or without fibrosis. Depending on the SAC reversal potential and timing of stretch, reentry may be triggered by ectopy due to SAC-induced depolarizations or by early repolarization within the SAC region.

Abstract Introduction Pharmacy‐delivered HIV prevention services might create more options for pregnant women to use HIV prevention tools earlier and more consistently during pregnancy. We quantified preferences for attributes of potential HIV prevention services among women of childbearing age in Western Kenya. Methods From June to November 2023, we administered a face‐to‐face discrete choice experiment survey to women aged 15–44 in Kenya's Homa Bay, Kisumu and Siaya counties. The survey evaluated preferences for HIV prevention services, described by seven attributes: service location, travel time, type of HIV test, sexually transmitted infection (STI) testing, partner HIV testing, pre‐exposure prophylaxis (PrEP) and service fee. Participants answered a series of 12‐choice questions. Each question asked them to select one of two service options or no services—an opt‐out option. We used hierarchical Bayesian modelling levels to estimate each attribute level's coefficient and understand how attributes influenced service choice. Results Overall, 599 participants completed the survey, among whom the median age was 23 years (IQR: 18–27); 33% were married, 20% had a job and worked regularly, and 52% had been pregnant before. Participants, on average, strongly preferred having any HIV prevention service option over none (opt‐out preference weight: −5.84 [95% CI: −5.97, −5.72]). The most important attributes were the availability of PrEP (relative importance 27.04% [95% CI: 25.98%, 28.11%]), followed by STI testing (relative importance 20.26% [95% CI: 19.52%, 21.01%]) and partner HIV testing (relative importance: 16.35% [95% CI: 15.79%, 16.90%]). While, on average, participants preferred obtaining services at the clinic more than pharmacies, women prioritized the availability of PrEP, STI testing and partner HIV testing more than the location or cost. Conclusions These findings suggest the importance of providing comprehensive HIV prevention services and ensuring PrEP, STI testing and partner HIV testing are available. If pharmacies can offer these services, women are likely to access those services at pharmacies even if they prefer clinics.

IntroductionDisease susceptibility of chronic axonal polyneuropathy is not fully explained by clinical risk factors. Therefore, we determined the contribution of common genetic variants in chronic axonal polyneuropathy in the general population.MethodsThis study was performed in two population-based studies. Polyneuropathy diagnosis was based on screening in the Rotterdam Study and on ICD-10 codes in the UK Biobank. We determined the heritability of the sural nerve amplitude and performed genome-wide association studies of chronic axonal polyneuropathy and sural sensory nerve amplitude. Furthermore, we zoomed in on variants in and surrounding 100 autosomal genes known to cause polyneuropathy based on literature and expert knowledge (candidate genes), and we performed a gene-based analysis. Analyses were adjusted for age, sex and population stratification.ResultsChronic axonal polyneuropathy was present in 2,357 of the 458,567 participants and 54.3% of the total population was female. Heritability of sural nerve amplitude was 0.49 (p = 0.067) (N = 1,153). No variants (p

The role of stressors, insect bites, and infections on disease relapse of ANCA vasculitis has yet to be entirely explored, with limited retrospective studies focused on disease onset from small participant cohorts. Our study analyzes longitudinal survey data from 2011–2022 to evaluate this perspective from a large ANCA vasculitis cohort. We collected surveys every three to six months to obtain information on self-reported psychological stressors and significant life events, insect bites, and infections throughout clinical disease. We defined cohorts as those who relapsed (Relapse Cohort) and controls as those who did not relapse (Remission Cohort) during the study period. Survey responses were retrospectively reviewed during a 15-month timeframe prior to relapse or during 15 months of remission and categorized by type of stress event, insect bite, and infections at every available 3-month interval. There were no significant differences in stress and insect bites between the relapse and remission cohorts. Patients who relapsed reported more frequent upper respiratory infections and other infections, such as those affecting the skin and eyes, but there were no significant differences in the incidence of pulmonary or urinary infections compared to the remission cohort. There was a significant difference in reported upper respiratory infections 9 to 15 months prior to the relapse date, indicating a remote history of infections as a potentially significant physical stressor that may contribute to disease relapse. More frequent patient-reported infections, specifically upper respiratory infections, may contribute to patient vulnerability to relapse. Counseling and close monitoring of patients after infectious symptoms could aid in earlier detection of disease flares. Future studies are essential to further understand the importance of distal risk factors and how they impact relapse.

Summary: During COVID-19 in the US, social determinants of health (SDH) have driven health disparities. However, the use of SDH in COVID-19 vaccine modeling is unclear. This review aimed to summarize the current landscape of incorporating SDH into COVID-19 vaccine transmission modeling in the US. Medline and Embase were searched up to October 2022. We included studies that used transmission modeling to assess the effects of COVID-19 vaccine strategies in the US. Studies’ characteristics, factors incorporated into models, and approaches to incorporate these factors were extracted. Ninety-two studies were included. Of these, 11 studies incorporated SDH factors (alone or combined with demographic factors). Various sets of SDH factors were integrated, with occupation being the most common (8 studies), followed by geographical location (5 studies). The results show that few studies incorporate SDHs into their models, highlighting the need for research on SDH impact and approaches to incorporating SDH into modeling. Funding: This research was funded by the Centers for Disease Control and Prevention (CDC).

IntroductionHistorically, secular and seasonal trend analyses have been examined using self-report measures of intake. Rarely are objective measures and known determinants of dietary intake used in these analyses. Our objective was to quantify the seasonal and secular differences in an objective ad libitum intake paradigm while considering the contribution of determinants, such as fat-free mass (FFM) index and spontaneous physical activity (SPA) limited to the restricted space of a whole-room calorimeter.MethodsFor this study, recruitment of N = 292 healthy, diabetes free, adults occurred from 1999 to 2020. Assessment during their 10-day stay included body composition (by DXA), SPA (by an approximately 24-h stay in whole-room calorimetry), and ad libitum intake (by a vending machine for 3 days). This secondary analysis used general linear models (GLM) to investigate secular and seasonal differences while adjusting for sex, age, FFM index, FM (fat mass) index, SPA, and race/ethnicity.ResultsFFM index and SPA were positively associated with all intake measures (p < 0.05). In all adjusted seasonal models, season did not affect intake. Adjusted secular trends models (kcals/year) demonstrated a decrease in total kcals (β = −55), intake as percent weight maintaining energy needs (β = −2), protein kcals (β = −10), fat kcals (β = −27), and carbohydrates kcals (β = −22) (all p < 0.05). After further adjustment for SPA, significance remained in all intake measures (p < 0.05). Secular trends in body composition revealed no changes in weight, BMI, and percent body fat (all p > 0.20).DiscussionOur results indicate that over time, ad libitum intake decreased in this controlled research setting and remained significant even after accounting for positive determinants of intake. A significant ad libitum decrease, coupled with no change in body composition, may highlight a participant bias toward calorie restriction in a controlled setting over time and deserves further investigation.

IntroductionSandwiches are commonly consumed in the United States. This study summarizes contributions of beef sandwiches to energy and select nutrient intakes.MethodsBeef 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.ResultsOn 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 B12 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 B12, 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.DiscussionBeef sandwiches are an important source of energy, protein, vitamin B12, 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.

A preclinical model of cue exposure therapy, cue extinction, reduces cue-induced cocaine seeking that is goal-directed but not habit-like. Goal-directed and habitual behaviors differentially rely on the dorsomedial striatum (DMS) and dorsolateral striatum (DLS), but the effects of cue extinction on dorsal striatal responses to cue-induced drug seeking are unknown. We used fiber photometry in rats trained to self-administer cocaine paired with an audiovisual cue to examine how dorsal striatal intracellular calcium and extracellular dopamine activity differs between goal-directed and habit-like cue-induced cocaine seeking and how it is impacted by cue extinction. After minimal fixed-ratio training, rats showed enhanced DMS and DLS calcium responses to cue-reinforced compared to unreinforced lever presses. After rats were trained on goal-promoting fixed ratio schedules or habit-promoting second-order schedules of reinforcement, different patterns of dorsal striatal calcium and dopamine responses to cue-reinforced lever presses emerged. Rats trained on habit-promoting second-order schedules showed reduced DMS calcium responses and enhanced DLS dopamine responses to cue-reinforced lever presses. Cue extinction reduced calcium responses during subsequent drug seeking in the DMS, but not in the DLS. Therefore, cue extinction may reduce goal-directed behavior through its effects on the DMS, whereas habit-like behavior and the DLS are unaffected.

Abstract Background Androgens are important sex hormones in both men and women and are supplemented when endogenous levels are low, for gender transitioning, or to increase libido. Androgens also circulate at higher levels in women with polycystic ovarian syndrome, a condition that increases the risk for cardiovascular diseases including hypertension and arterial stiffness. Since our previous work shows an important role for the G protein-coupled estrogen receptor (GPER) in arterial stiffness, we hypothesized that other hormones including androgens may impact arterial stiffness in female mice via downregulation of GPER. Methods The impact of the non-aromatizable androgen dihydrotestosterone (DHT), the glucocorticoid dexamethasone, and the progestin medroxyprogesterone acetate (all 100 nM for 24 h) on GPER and ERα expression was assessed in cultured vascular smooth muscle cells using droplet digital PCR (ddPCR). To assess the in vivo impact of the DHT-induced downregulation of GPER, female ovary-intact C57Bl/6 mice at 15–16 weeks of age were treated with silastic capsules containing DHT for 4 weeks, one with a dosage expected to mimic human male DHT levels and another to double the expected human concentration (n = 8–9/group). Results In cultured vascular smooth muscle cells, GPER mRNA was decreased by DHT (P = 0.001) but was not impacted by dexamethasone or medroxyprogesterone. In contrast, ERα expression in cultured cells was significantly suppressed by all three hormones (P

Abstract Purpose Evaluate the behavior of lung nodules occurring in areas of pulmonary fibrosis and compare them to pulmonary nodules occurring in the non-fibrotic lung parenchyma. Methods This retrospective review of chest CT scans and electronic medical records received expedited IRB approval and a waiver of informed consent. 4500 consecutive patients with a chest CT scan report containing the word fibrosis or a specific type of fibrosis were identified using the system M*Model Catalyst (Maplewood, Minnesota, U.S.). The largest nodule was measured in the longest dimension and re-evaluated, in the same way, on the follow-up exam if multiple time points were available. The nodule doubling time was calculated. If the patient developed cancer, the histologic diagnosis was documented. Results Six hundred and nine patients were found to have at least one pulmonary nodule on either the first or the second CT scan. 274 of the largest pulmonary nodules were in the fibrotic tissue and 335 were in the non-fibrotic lung parenchyma. Pathology proven cancer was more common in nodules occurring in areas of pulmonary fibrosis compared to nodules occurring in areas of non-fibrotic lung (34% vs 15%, p

Abstract Background Chest Computed tomography (CT) scans detect lung nodules and assess pulmonary fibrosis. While pulmonary fibrosis indicates increased lung cancer risk, current clinical practice characterizes nodule risk of malignancy based on nodule size and smoking history; little consideration is given to the fibrotic microenvironment. Purpose To evaluate the effect of incorporating fibrotic microenvironment into classifying malignancy of lung nodules in chest CT images using deep learning techniques. Materials and methods We developed a visualizable 3D classification model trained with in-house CT dataset for the nodule malignancy classification task. Three slightly-modified datasets were created: (1) nodule alone (microenvironment removed); (2) nodule with surrounding lung microenvironment; and (3) nodule in microenvironment with semantic fibrosis metadata. For each of the models, tenfold cross-validation was performed. Results were evaluated using quantitative measures, such as accuracy, sensitivity, specificity, and area-under-curve (AUC), as well as qualitative assessments, such as attention maps and class activation maps (CAM). Results The classification model trained with nodule alone achieved 75.61% accuracy, 50.00% sensitivity, 88.46% specificity, and 0.78 AUC; the model trained with nodule and microenvironment achieved 79.03% accuracy, 65.46% sensitivity, 85.86% specificity, and 0.84 AUC. The model trained with additional semantic fibrosis metadata achieved 80.84% accuracy, 74.67% sensitivity, 84.95% specificity, and 0.89 AUC. Our visual evaluation of attention maps and CAM suggested that both the nodules and the microenvironment contributed to the task. Conclusion The nodule malignancy classification performance was found to be improving with microenvironment data. Further improvement was found when incorporating semantic fibrosis information.

Background: Few data on maternal-infant hair cortisol are available from HIV high-burden settings. We evaluated maternal hair cortisol and its relationship with infant hair cortisol, perinatal stressors, and pregnancy outcomes in Kenya. Materials and Methods: We analyzed data from an HIV prevention trial (NCT03070600). Pregnant women without HIV were enrolled and followed through 9 months postpartum. We utilized hair samples collected at 6 weeks postpartum from mother-infant pairs to quantify hair cortisol concentrations (HCC) reflecting cortisol levels over the prior ?3 months. HCC was measured by enzyme immunoassay. We tested whether mean maternal HCC was associated with infant HCC, stressors, and/or birth outcomes using linear regression. Results: Overall, 153 women had HCC available at 6 weeks postpartum. Median maternal age was 25 years (Interquartile range [IQR] 22?30), median completed education was 12 years (IQR: 8?12), and 95% were married. Median birthweight was 3.4 kilograms (IQR: 3.1?3.7), 13% of women experienced preterm birth (PTB), and 2% of infants had low birthweight (LBW); 11% were small-for-gestational age (SGA). Median maternal HCC was 12.0?pg/mg (IQR: 6.3?20.4); and median infant HCC was 10.4?pg/mg (IQR: 5.5?23.7). Infant HCC was correlated with maternal HCC (r?=?0.498, p?0.001). Stressors associated with maternal HCC (p?

Abstract Background College students who experience the negative impact of poverty, such as food, financial, and housing insecurity, are at higher risk for poor academic performance. One recent study examined grief in a college student sample and found students with a diverse racial or ethnic background were more likely to experience prolonged grief disorder, however, did not examine poverty in their sample. To date, no known reviews have examined poverty by racial and ethnic identity and the experience of grief due to the death of a family member or friend, and no reviews have examined how these three factors relate to interventions designed to support student academic performance and degree completion. Methods Our aim is to map the primary literature reporting on college students of any age who identify or are identified as non-white racial or ethnic groups who experience poverty and grief due to the death of a family member or friend. The mapping strategy includes extracting the various types of interventional support of academic performance and degree completion delivered from campus or community services in any geographic setting worldwide. We will conduct our scoping review with guidance from the latest version of the JBI Manual for Evidence Synthesis. Utilizing the framework as outlined by Arksey and O’Malley, we will conduct our scoping review with Arksey’s five stages: (1) identifying the research question, (2) identifying relevant studies, (3) study selection, (4) charting the data, and (5) collating, summarizing, and reporting the results. For transparency and reproducibility, we will adhere to the PRISMA reporting guidelines. Discussion The purpose of this scoping review is to map the primary literature reporting college students, regardless of their age, who belong to non-white racial or ethnic groups and face poverty and grief resulting from the loss of a family member or friend. This analysis includes mapping the various types of intervention and support available both on and off campus, in any global setting, with the aim of enhancing academic performance and facilitating degree completion. The results of this review may inform the further research needed in this area to help prevent poor academic performance and dropout for many vulnerable college students. The results may be of value, particularly to college administrators developing prevention and interventional programs to support college student success. Systematic review registration Open Science Framework ( https://osf.io/enuwt ).

The risk-factor-based prediction of atherosclerotic coronary artery disease (CAD) remains suboptimal, particularly in the absence of any of the standard modifiable cardiovascular risk factors (SMuRFs), making the discovery of biomarkers that correlate with atherosclerosis burden critically important. We hypothesized that cytokines and receptors associated with inflammation in CAD—tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), interleukin-18 (IL-18), and osteoprotegerin (OPG)—would be independently associated with CAD. To determine this, we measured the serum biomarker levels of 993 participants from the BioHEART study who had CT coronary angiograms that were scored for severity of stenosis and plaque composition. We found that the quartiles of TRAIL, OPG, and IL-18 were significantly associated with disease scores, and that the IL-18/TRAIL and OPG/TRAIL ratios demonstrated significant differences between no CAD vs. STEMI whereas only the OPG/TRAIL ratio showed differences between no CAD and obstructive CAD (stenosis > 50%). However, these associations did not persist after adjustment for age, sex, SMuRFs, and a family history of CAD. In conclusion, TRAIL, IL-18, and OPG and the derived ratios of IL-18/TRAIL and OPG/TRAIL demonstrate significant associations with raw disease scores and risk factors, but these markers are not discriminatory biomarkers for the prediction of CAD when incorporated into multi-variable risk models.

Promoting access to and excellence in hematopoietic cell transplantation (HCT) by collecting and disseminating data on global HCT activities is one of the principal activities of the Worldwide Network for Blood and Marrow Transplantation, a non-Governmental organization in working relations with the World Health Organization. HCT activities are recorded annually by member societies, national registries and individual centers including indication, donor type (allogeneic/autologous), donor match and stem cell source (bone marrow/peripheral blood stem cells/cord blood). In 2018, 1,768 HCT teams in 89 countries (six WHO regions) reported 93,105 (48,680 autologous and 44,425 allogeneic) HCT. Major indications were plasma cell disorders and lymphoma for autologous, and acute leukemias and MDS/MPN for allogeneic HCT. HCT number increased from 48,709 in 2007. Notable increases were seen for autoimmune diseases in autologous and hemoglobinopathies in allogeneic HCT. The number of allogeneic HCT more than doubled with significant changes in donor match. While HCT from HLA identical siblings has seen only limited growth, HCT from non-identical related donors showed significant increase worldwide. Strongest correlation between economic growth indicator of gross national income/capita and HCT activity/ten million population was observed for autologous HCT (r=0.79). HCT from unrelated donors showed strong correlation (r=0.68), but only moderate correlation (r=0.51) was detected from related donors. The use of HCT doubled in about a decade worldwide at different speed and with significant changes regarding donor match as a sign of improved access to HCT worldwide. Although narrowing, significant gaps remain between developing and non-developing countries.

ObjectivesThis study investigated the influence of long-term talker familiarity on speech-in-speech recognition in school-age children, with a specific emphasis on the role of familiarity with the mother’s voice as either the target or masker speech.DesignOpen-set sentence recognition was measured adaptively in a two-talker masker. Target and masker sentences were recorded by the adult mothers of the child participants. Each child heard sentences spoken by three adult female voices during testing; their own mother’s voice (familiar voice) and two unfamiliar adult female voices.Study sampleTwenty-four school age children (8–13 years) with normal hearing.ResultsWhen the target speech was spoken by a familiar talker (the mother), speech recognition was significantly better compared to when the target was unfamiliar. When the masker was spoken by the familiar talker, there was no difference in performance relative to the unfamiliar masker condition. Across all conditions, younger children required a more favorable signal-to-noise ratio than older children.ConclusionImplicit long-term familiarity with a talker consistently improves children’s speech-in-speech recognition across the age range tested, specifically when the target talker is familiar. However, performance remains unaffected by masker talker familiarity. Additionally, while target familiarity is advantageous, it does not entirely eliminate children’s increased susceptibility to competing speech.

Background Schools are critical venues for supporting LGBTQ+ youth well-being. Implementing LGBTQ-supportive practices can decrease experiences of stigmatization, discrimination, and victimization that lead to adverse mental health outcomes like anxiety, depression, and suicidality. However, schools are also subject to a wide range of outer-context pressures that may influence their priorities and implementation of LGBTQ-supportive practices. We assessed the role of emergent outer-context determinants in the context of a 5-year cluster randomized controlled trial to study the implementation of LGBTQ-supportive evidence-informed practices (EIPs) in New Mexico high schools. Method Using an iterative coding approach, we analyzed qualitative data from annual interviews with school professionals involved in EIP implementation efforts. Results The analysis yielded three categories of outer-context determinants that created challenges and opportunities for implementation: (a) social barriers related to heterocentrism, cisgenderism, and religious conservatism; (b) local, state, and national policy and political discourse; and (c) crisis events. Conclusions By exploring the implications of outer-context determinants for the uptake of LGBTQ-supportive practices, we demonstrate that these elements are dynamic—not simply reducible to barriers or facilitators—and that assessing outer-context determinants shaping implementation environments is crucial for addressing LGBTQ health equity.

A major aim in the field of synthetic biology is developing tools capable of responding to user-defined inputs by activating therapeutically relevant cellular functions. Gene transcription and regulation in response to external stimuli are some of the most powerful and versatile of these cellular functions being explored. Motivated by the success of chimeric antigen receptor (CAR) T-cell therapies, transmembrane receptor-based platforms have been embraced for their ability to sense extracellular ligands and to subsequently activate intracellular signal transduction. The integration of transmembrane receptors with transcriptional activation platforms has not yet achieved its full potential. Transient expression of plasmid DNA is often used to explore gene regulation platforms in vitro. However, applications capable of targeting therapeutically relevant endogenous or stably integrated genes are more clinically relevant. Gene regulation may allow for engineered cells to traffic into tissues of interest and secrete functional proteins into the extracellular space or to differentiate into functional cells. Transmembrane receptors that regulate transcription have the potential to revolutionize cell therapies in a myriad of applications, including cancer treatment and regenerative medicine. In this review, we will examine current engineering approaches to control transcription in mammalian cells with an emphasis on systems that can be selectively activated in response to extracellular signals. We will also speculate on the potential therapeutic applications of these technologies and examine promising approaches to expand their capabilities and tighten the control of gene regulation in cellular therapies.

Posterior cortical atrophy (PCA) and dementia with Lewy bodies (DLB) show distinct atrophy and overlapping hypometabolism profiles, but it is unknown how disruptions in structural and functional connectivity compare between these disorders and whether breakdowns in connectivity relate to either atrophy or hypometabolism.Thirty amyloid-positive PCA patients, 24 amyloid-negative DLB patients and 30 amyloid-negative cognitively unimpaired (CU) healthy individuals were recruited at Mayo Clinic, Rochester, MN, and underwent a 3T head MRI, including structural MRI, resting state functional MRI (rsfMRI) and diffusion tensor imaging (DTI) sequences, as well as [18F] fluorodeoxyglucose (FDG) PET. We assessed functional connectivity within and between 12 brain networks using rsfMRI and the CONN functional connectivity toolbox and calculated regional DTI metrics using the Johns Hopkins atlas. Multivariate linear-regression models corrected for multiple comparisons and adjusted for age and sex compared DTI metrics and within-network and between-network functional connectivity across groups. Regional gray-matter volumes and FDG-PET standard uptake value ratios (SUVRs) were calculated and analyzed at the voxel-level using SPM12. We used univariate linear-regression models to investigate the relationship between connectivity measures, gray-matter volume, and FDG-PET SUVR.On DTI, PCA showed degeneration in occipito-parietal white matter, posterior thalamic radiations, splenium of the corpus collosum and sagittal stratum compared to DLB and CU, with greater degeneration in the temporal white matter and the fornix compared to CU. We observed no white-matter degeneration in DLB compared to CU. On rsfMRI, reduced within-network connectivity was present in dorsal and ventral default mode networks (DMN) and the dorsal-attention network in PCA compared to DLB and CU, with reduced within-network connectivity in the visual and sensorimotor networks compared to CU. DLB showed reduced connectivity in the cerebellar network compared to CU. Between-network analysis showed increased connectivity in both cerebellar-to-sensorimotor and cerebellar-to-dorsal attention network connectivity in PCA and DLB. PCA showed reduced anterior DMN-to-cerebellar and dorsal attention-to-sensorimotor connectivity, while DLB showed reduced posterior DMN-to-sensorimotor connectivity compared to CU. PCA showed reduced dorsal DMN-to-visual connectivity compared to DLB. The multimodal analysis revealed weak associations between functional connectivity and volume in PCA, and between functional connectivity and metabolism in DLB.These findings suggest that PCA and DLB have unique connectivity alterations, with PCA showing more widespread disruptions in both structural and functional connectivity; yet some overlap was observed with both disorders showing increased connectivity from the cerebellum.

Introduction: Patients with non-ischemic cardiomyopathy (NICM) are at risk for ventricular arrhythmias, but diagnosis and treatment planning remain a serious clinical challenge. Although computational modeling has provided valuable insight into arrhythmic mechanisms, the optimal method for simulating reentry in NICM patients with structural disease is unknown.Methods: Here, we compare the effects of fibrotic representation on both reentry initiation and reentry morphology in patient-specific cardiac models. We investigate models with heterogeneous networks of non-conducting structures (cleft models) and models where fibrosis is represented as a dense core with a surrounding border zone (non-cleft models). Using segmented cardiac magnetic resonance with late gadolinium enhancement (LGE) of five NICM patients, we created 185 3D ventricular electrophysiological models with different fibrotic representations (clefts, reduced conductivity and ionic remodeling).Results: Reentry was induced by electrical pacing in 647 out of 3,145 simulations. Both cleft and non-cleft models can give rise to double-loop reentries meandering through fibrotic regions (Type 1-reentry). When accounting for fibrotic volume, the initiation sites of these reentries are associated with high local fibrotic density (mean LGE in cleft models: p< 0.001, core volume in non-cleft models: p = 0.018, negative binomial regression). In non-cleft models, Type 1-reentries required slow conduction in core tissue (non-cleftsc models) as opposed to total conduction block. Incorporating ionic remodeling in fibrotic regions can give rise to single- or double-loop rotors close to healthy-fibrotic interfaces (Type 2-reentry). Increasing the cleft density or core-to-border zone ratio in cleft and non-cleftc models, respectively, leads to increased inducibility and a change in reentry morphology from Type 2 to Type 1.Conclusions: By demonstrating how fibrotic representation affects reentry morphology and location, our findings can aid model selection for simulating arrhythmogenesis in NICM.

Controlled release fertilizers (CRFs) mitigate negative effects of high nitrogen (N) fertilization rates, such as N toxicity and soil N loss. However, it is unknown if potentially toxic rates of CRF and quick release fertilizer differentially affect soil bacterial communities. To examine potential N toxicity effects on soil microbial communities, we grew tomato (Solanum lycopersicum “Rutgers”) for eight weeks in soils that were fertilized with high levels of quick release or controlled release urea and in soils with either low or high initial microbial N competitor populations. In both soils, we observed N toxicity in urea-fertilized tomatoes, but toxicity was ameliorated with CRF application. Controlled release fertilization increased soil N retention, thereby reducing soil N loss. While N toxicity symptoms manifested in the plant, the soil microbiome was only minorly affected. There were subtle differences in soil bacterial populations, in which nitrifying bacteria accumulated in soils fertilized at high N rates, regardless of the type of N fertilizer used. Ultimately, CRF reduced plant N toxicity symptoms but did not change the soil microbiome compared to quick release urea. These results show that while there are clear benefits of CRF regarding N toxicity tolerance on crops, the soil microbiome is resilient to this abiotic stressor.

Abstract Substance use in adolescence is a known risk factor for the development of neuropsychiatric and substance use disorders in adulthood. This is in part due to the fact that critical aspects of brain development occur during adolescence, which can be altered by drug use. Despite concerted efforts to educate youth about the potential negative consequences of substance use, initiation remains common amongst adolescents world-wide. Additionally, though there has been substantial research on the topic, many questions remain about the predictors and the consequences of adolescent drug use. In the following review, we will highlight some of the most recent literature on the neurobiological and behavioral effects of adolescent drug use in rodents, non-human primates, and humans, with a specific focus on alcohol, cannabis, nicotine, and the interactions between these substances. Overall, consumption of these substances during adolescence can produce long-lasting changes across a variety of structures and networks which can have enduring effects on behavior, emotion, and cognition.

When plant-available phosphorus (P) is lost from a soil solution, it often accumulates in the soil as a pool of unavailable legacy P. To acquire legacy P, plants employ recovery strategies, such as forming associations with soil microbes. However, the degree to which plants rely on microbial associations for this purpose varies with crop domestication and subsequent breeding. Here, by generating microbial co-occurrence networks, we sought to explore rhizosphere bacterial interactions in low-P conditions and how they change with tomato domestication and breeding. We grew wild tomato, traditional tomato (developed circa 1900), and modern tomato (developed circa 2020) in high-P and low-P soil throughout their vegetative developmental stage. Co-occurrence network analysis revealed that as the tomatoes progressed along the stages of domestication, the rhizosphere microbiome increased in complexity in a P deficit. However, with the addition of P fertilizer, the wild tomato group became more complex, surpassing the complexity of traditional and modern tomato, suggesting a high degree of responsiveness in the rhizosphere microbiome to P fertilizer by wild tomato relatives. By illustrating these changing patterns of network complexity in the tomato rhizosphere microbiome, we can further understand how plant domestication and breeding have shaped plant–microbe interactions.