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1.
J Sch Health ; 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39117586

RESUMEN

BACKGROUND: Youth mental health rates of depression and anxiety continue to climb. Schools have a role to play to support youth mental health but often struggle to navigate community expectations. METHODS: Focus groups (n = 17) were conducted with over 100 participants to understand community perceptions on the role of schools. RESULTS: Three themes emerged around what schools should be doing: (1) provide accurate education about mental health, (2) create mental health promoting environments that positively supports young people, and (3) act as a common space to bring community members and organizations together for their young people. IMPLICATIONS FOR SCHOOL HEALTH POLICY, PRACTICE, AND EQUITY: School professionals and systems should be equipped to adequately address youth mental health. The current US institutional response to this crisis is underdeveloped and exacerbates equity issues and health outcome disparities. Schools need institutional support for addressing mental health in ways that incorporate building a shared understanding with families and providing efforts to prevent and detect rather than just treat mental health. CONCLUSIONS: Schools should work with their communities to promote shared understanding and accountability for all to engage in building rich protective environments that promote mental well-being for kids in their care.

2.
J Sch Health ; 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38962928

RESUMEN

BACKGROUND: The school climate concept has been promising, but has long-standing critiques that have not been adequately addressed to date. The School as a Protective Factor approach represents one attempt to offer a new approach that builds on and extends beyond the concept of school climate while addressing previously identified limitations. CONTRIBUTIONS TO THEORY: The School as a Protective Factor approach offers a new framework for conceptualizing, measuring, and establishing protective school social and learning environments that co-promote academic achievement and student health in schools, especially student mental health and substance use/abuse prevention. This new framework includes clear definitions, explicit goals, firmly established constructs, validated measures, and an intentionally parsimonious approach that prioritizes the implementation of well-established, high-impact constructs. CONCLUSIONS AND IMPLICATIONS FOR SCHOOL HEALTH POLICY, PRACTICE, AND EQUITY: The School as a Protective Factor approach presents a simple, easy-to-use means of ensuring a school social environment that meets the developmental, academic, and health needs of all children and adolescents while maximizing protection across a range of desired outcomes. Perhaps most importantly, it does so in a manner that is manageable and easily integrated into every aspect of schooling, resonates with the practical experience of school personnel, and includes brief, effective, and free measurement tools.

3.
JCO Oncol Pract ; : OP2400425, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39008799

RESUMEN

Discussing the less recognized financial toxicities of cancer care, including mental health and dental care.

4.
J Adolesc ; 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39051139

RESUMEN

INTRODUCTION: Caffeine is a psychostimulant possessing arousal, motor activation, and reinforcing properties, which is consumed daily by most adolescents aged 12-19 years. Although current understanding of the implications of adolescent caffeine consumption for school behaviors remains incomplete, studies have shown that in addition to acute effects of the drug, in common with other habit-forming psychoactive substances, regular use leads to physical dependence, evidenced by recurring negative withdrawal symptoms. METHODS: Employing two waves of longitudinal data, we tested the prospective association between daily caffeine use and homeroom teacher-observed self-control and problem behavior in a sample of middle-school students in 20 schools in West Virginia in the United States. Caffeine was operationalized with two dichotomized variables, daily consumption of <100 mg, and daily consumption of >100 mg, versus no daily use. Gender, mother's education, family financial status, social support by primary caregiver and adults in school, and school climate, were applied as covariates in linear mixed models. RESULTS: Daily caffeine use of >100 mg was robustly and inversely associated with self-control and positively associated with problem behavior. CONCLUSIONS: Caffeine consumption and associated withdrawal symptoms may be an important factor in problematic school behavior among adolescents. Recent advent of highly concentrated caffeine products (e.g., caffeine "shots") commonly marketed directly at youth, should give rise to concerns including consideration about limiting caffeine consumption among children and youth.

5.
Brain Lang ; 255: 105448, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39083998

RESUMEN

The corpus callosum, the largest white matter inter-hemispheric pathway, is involved in language and communication. In a cohort of 15 children and adolescents (8-15 years) with developmental absence of the corpus callosum (AgCC), this study aimed to describe language and everyday communication functioning, and explored the role of anatomical factors, social risk, and non-verbal IQ in these outcomes. Standardised measures of language and everyday communication functioning, intellectual ability and social risk were used. AgCC classification and anterior commissure volume, a potential alternative pathway, were extracted from T1-weighted images. Participants with AgCC showed reduced receptive and expressive language compared with test norms, and high rates of language and communication impairments. Complete AgCC, higher social risk and lower non-verbal IQ were associated with communication difficulties. Anterior commissure volume was not associated with language and communication. Recognising heterogeneity in language and communication functioning enhances our understanding and suggests specific focuses for potential interventions.


Asunto(s)
Agenesia del Cuerpo Calloso , Humanos , Adolescente , Niño , Masculino , Femenino , Agenesia del Cuerpo Calloso/fisiopatología , Agenesia del Cuerpo Calloso/diagnóstico por imagen , Agenesia del Cuerpo Calloso/complicaciones , Agenesia del Cuerpo Calloso/patología , Cuerpo Calloso/diagnóstico por imagen , Cuerpo Calloso/fisiopatología , Cuerpo Calloso/patología , Comunicación , Imagen por Resonancia Magnética , Lenguaje , Trastornos de la Comunicación/fisiopatología , Trastornos de la Comunicación/etiología , Inteligencia/fisiología
6.
Hernia ; 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38890182

RESUMEN

PURPOSE: Although intraoperative music is purported to mitigate postoperative pain after some procedures, its application has never been explored in abdominal wall reconstruction (AWR). We sought to determine whether intraoperative music would decrease early postoperative pain following AWR. METHODS: We conducted a placebo-controlled, patient-, surgeon-, and assessor-blinded, randomized controlled trial at a single center between June 2022 and July 2023 including 321 adult patients undergoing open AWR with retromuscular mesh. Patients received noise-canceling headphones and were randomized 1:1 to patient-selected music or silence after induction, stratified by preoperative chronic opioid use. All patients received multimodal pain control. The primary outcome was pain (NRS-11) at 24 ± 3 h. The primary outcome was analyzed by linear regression with pre-specified covariates (chronic opioid use, hernia width, operative time, myofascial release, anxiety disorder diagnosis, and preoperative STAI-6 score). RESULTS: 178 patients were randomized to music, 164 of which were analyzed. 177 were randomized to silence, 157 of which were analyzed. At 24 ± 3 h postoperatively, there was no difference in the primary outcome of NRS-11 scores (5.18 ± 2.62 vs 5.27 ± 2.46, p = 0.75). After adjusting for prespecified covariates, the difference of NRS-11 scores at 24 ± 3 h between the music and silence groups remained insignificant (p = 0.83). There was no difference in NRS-11 or STAI-6 scores at 48 ± 3 and 72 ± 3 h, intraoperative sedation, or postoperative narcotic usage. CONCLUSION: For patients undergoing AWR, there was no benefit of intraoperative music over routine multimodal pain control for early postoperative pain reduction. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05374096.

7.
J Sch Health ; 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38937967

RESUMEN

BACKGROUND: The conceptual framework for School as a Protective Factor approach was presented in a companion article in this issue of the journal. The current article describes the validation of the School as a Protective Factor-Brief (SPF-Brief), a 13-item survey measuring the 3 core constructs and 13 defining characteristics of this framework. METHODS: The SPF-Brief was validated through 2 studies. The developmental study used a longitudinal design including 1349 participants who completed surveys over 5 semesters, while the validation study used a cross-sectional design with 2775 participants. Both studies included middle and high school students. Factor analysis, growth model analysis, criterion-related validation, and outcome analysis were employed. RESULTS: Analyses provided strong evidence supporting the reliability and validity of the instrument and conceptual framework. Higher SPF-Brief scores were associated with higher math grades, English grades, and quality of life, as well as lower rates of anxiety, depression, conduct disorder, alcohol, e-cigarette, tobacco, and cannabis use. Effect size estimates ranged from moderate to strong. CONCLUSIONS: These findings suggest the utility of the SPF-Brief instrument and the School as a Protective Factor framework. Together, they may offer advantages to the traditional school climate approach.

8.
Cureus ; 16(5): e60038, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38854284

RESUMEN

Several treatments and preventive measures for SARS-CoV-2 were studied during the pandemic, but few focused on the neonatal gut microbiome and its role in the setting of COVID-19. This case report is unique because it describes the gut microbiomes of a mother and her newborn, who both contracted COVID-19 shortly after the baby's birth. In this prospective study, on day 11 postpartum, both the newborn and mother (38 years old), of white race/ethnicity, were exposed to a COVID-19-positive person. After exposure, the mother received a 40,000 IU bolus of vitamin D orally and started a five-day course of high-dose vitamin C (10,000 mg daily), after which she continued her daily combination of vitamins C, D, and zinc pill with probiotic skyr yogurt and manuka honey. Stool specimens and DNA were extracted, quantitated, and normalized from the mother and the newborn for downstream library fabrication utilizing shotgun methodology. Baseline Bifidobacteria level for the mother was 1.5% which increased to 19% on day 15 postpartum after testing positive for COVID-19 and taking vitamin C. Neonatal Bifidobacteriasteadily increased regardless of COVID-19 infection. We propose that the disease course was altered by maternal supplementation of vitamins C and D and zinc, which may have increased Bifidobacterium levels and led to improved outcomes for both patients.

9.
J Hosp Med ; 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38837594

RESUMEN

BACKGROUND AND OBJECTIVES: With a growing interest in screening for food insecurity (FI) during pediatric hospitalization, there is a parallel need to develop interventions. With input from caregivers experiencing FI, we sought to identify interventions to assist with short-term FI after discharge and evaluate their feasibility, acceptability, and appropriateness. METHODS: We first employed qualitative methods to identify potential interventions. Next, we conducted a pilot study of selected interventions for families experiencing FI. Seven days postdischarge, caregivers rated the intervention's feasibility, acceptability, and appropriateness. We also assessed for ongoing FI. We summarized the median and proportion of "completely agree" responses to feasibility, acceptability, and appropriateness questions, and we compared in-hospital and postdischarge FI using McNemar's test. RESULTS: In the qualitative stage, 14 caregivers prioritized three interventions: grocery store gift cards, grocery delivery/pick-up, and frozen meals. In the pilot study, 53 caregivers (25% of those screened) endorsed FI during their child's hospitalization and received one or more of the interventions. Every caregiver selected the grocery gift card option; 37 families (69.8%) also received frozen meals. Seven days after discharge, most caregivers rated the intervention as "completely" feasible (76%), acceptable (90%), and appropriate (88%). There was a significant decrease in caregivers who reported FI after discharge compared to during the hospitalization (p < .001). CONCLUSIONS: This study demonstrates the feasibility, acceptability, and appropriateness of inpatient interventions to address FI, particularly at the time of pediatric hospital discharge and transition home. Randomized trials are needed to further evaluate the efficacy of interventions employed during hospitalization.

10.
Eval Program Plann ; 106: 102451, 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38879919

RESUMEN

The Icelandic Prevention Model (IPM) follows a systematic but flexible process of community capacity building, data collection, analysis, dissemination, and community-engaged decision-making to guide the data-informed selection, prioritization, and implementation of intervention strategies in preventing adolescent substance use. This paper describes two new evaluation tools intended to assess the: 1) integrity of IPM implementation, and 2) unique aspects of IPM implementation in different community contexts. These evaluation tools include a: 1) five-phase IPM Evaluation Framework for Assessing Value Across Communities, Cultures, and Outcomes (IPM-EF); and 2) 10-Step IPM Implementation Integrity and Consistency Assessment (IPM-IICA) that utilizes both quantitative (scored) and qualitative (narrative) data elements to characterize implementation integrity and consistency at both community coalition and school community levels. The IPM-EF includes five phases. Phase 1: Describe the Intervention Context; Phase 2a: Document the Extent to Which the 10 Steps of the IPM were Implemented (using the IPM-IICA scored); Phase 2b: Document the Unique Community-Specific Methods Used within the 10 Steps of the IPM to Tailor Local Intervention Delivery (using the IPM-IICA narrative); Phase 3: Measure Changes in Community Risk and Protective Factors; Phase 4: Measure the Outcomes Associated with the IPM; and Phase 5: Investigate Multiple Full Cycles Over Time.

11.
Sci Rep ; 14(1): 14065, 2024 06 18.
Artículo en Inglés | MEDLINE | ID: mdl-38890384

RESUMEN

Difficulties in executive functioning (EF) can result in impulsivity, forgetfulness, and inattention. Children living in remote/regional communities are particularly at risk of impairment in these cognitive skills due to reduced educational engagement and poorer access to interventions. This vulnerability has been exacerbated by the COVID-19 pandemic and strategies are needed to mitigate long-term negative impacts on EF. Here we propose a pilot trial investigating the benefits, feasibility, and acceptability of a school-based EF intervention for primary school students (6-8 years) living in regional, developmentally vulnerable, and socio-economically disadvantaged communities. Students were randomised to a digital intervention or teaching as usual, for 7 weeks. Children completed measures of EF and parents/educators completed ratings of everyday EF and social/emotional wellbeing at pre-intervention, post-intervention, and 3-month follow-up. Change in EFs (primary outcome), everyday EF, and social/emotional wellbeing (secondary outcomes) from pre- to post-intervention and pre-intervention to 3-month follow-up were examined. Feasibility and acceptability of the intervention was assessed through educator feedback and intervention adherence.Protocol Registration: The stage 1 protocol for this Registered Report was accepted in principle on 20 April 2023. The protocol, as accepted by the journal, can be found at: https://doi.org/10.17605/OSF.IO/WT3S2 . The approved Stage 1 protocol is available here: https://osf.io/kzfwn .


Asunto(s)
COVID-19 , Cognición , Humanos , Niño , COVID-19/psicología , COVID-19/epidemiología , Proyectos Piloto , Masculino , Femenino , Función Ejecutiva , Pandemias , SARS-CoV-2 , Instituciones Académicas , Estudiantes/psicología
12.
Cancer Med ; 13(10): e7254, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38785177

RESUMEN

OBJECTIVE: Primary care practitioners are crucial to engaging people in Australia's national cervical screening program. From July 2022, practitioners have been able to offer all screen-eligible people the choice to collect their own self-collected sample; an option introduced to increase equity. This study explored how practitioners are intending to incorporate universal access to self-collection into their clinical care. METHODS: Semi-structed interviews with 27 general practitioners, nurses, and practice managers from 10 practices in Victoria, Australia conducted between May and August 2022. Interviews were deductively coded, informed by the Consolidated Framework for Implementation Research. The Diffusion of Innovations theory was used to categorise intention to provide self-collection. RESULTS: Participants were supportive of universal access to self-collection, citing benefits for screen-eligible people and that it overcame the limited adaptability of the previous policy. Most participants' practices (n = 7, 70%) had implemented or had plans to offer the option for self-collection to all. Participants deliberating whether to provide universal access to self-collection held concerns about the correct performance of the self-test and the perceived loss of opportunity to perform a pelvic examination. Limited time to change practice-level processes and competing demands within consultations were anticipated as implementation barriers. CONCLUSIONS: The extent to which self-collection can promote equity within the program will be limited without wide-spread adoption by practitioners. Communication and education that addresses concerns of practitioners, along with targeted implementation support, will be critical to ensuring that self-collection can increase participation and Australia's progression towards elimination of cervical cancer.


Asunto(s)
Detección Precoz del Cáncer , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/diagnóstico , Detección Precoz del Cáncer/métodos , Australia , Actitud del Personal de Salud , Adulto , Persona de Mediana Edad , Manejo de Especímenes/métodos , Victoria , Tamizaje Masivo/métodos , Intención
13.
Am Surg ; : 31348241256064, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38776896

RESUMEN

At Cleveland clinic, an incorrect surgical count triggers Code Rust; a protocol that mandates an intraoperative patient X-ray, staff radiology read, and discussion with the surgeon before the incision is closed. Code Rust calls from November 2014 to December 2022 were retrospectively reviewed. Realtime workflow and operative details of Code Rust cases were analyzed.1277 Code Rusts were identified. Average time from ordering the X-ray to final radiology report was 50 minutes, totalling $2,362,450.00 spent on operating room time. Code Rust was called twice as frequently during urgent or emergent cases, compared to elective. There were more staff in Code Rust rooms compared to non-Code Rust rooms. A foreign body on X-ray was identified in 42/1277 (3.3%) cases. Code Rust is a resource intensive process that is more common in emergent cases that involve multiple staff. While retained foreign bodies are identified in a small percentage of cases, the current system should be revisited to reduce operating time and expense.

14.
Geroscience ; 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38773057

RESUMEN

The naked mole-rat (Heterocephalus glaber) is a mouse-sized rodent species, notable for its eusociality and long lifespan. Previously, we reported that demographic aging, i.e., the exponential increase of mortality hazard that accompanies advancing age in mammals and other organisms, does not occur in naked mole-rats (Ruby et al., 2018), a finding that has potential implications for human healthy aging. The demographic data supporting that conclusion had taken over three decades to accumulate, starting with the original rearing of H. glaber in captivity. This finding was controversial since many of the animals in that study were relatively young. In the 5 years following that study, we have doubled our quantity of demographic data. Here, we re-evaluated our prior conclusions in light of these new data and found them to be not only supported but indeed strengthened. We additionally provided insight into the social dynamics of captive H. glaber with data and analyses of body weight and colony size versus mortality. Finally, we provide a phylogenetically proximal comparator in the form of lifespan data from our Damaraland mole-rat (Fukomys damarensis) colony and demographic meta-analysis of those data along with published data from Ansell's mole-rat (Fukomys anselli). We found Fukomys mortality hazard to increase gradually with age, an observation with inferences on the evolution of exceptional lifespan among mole-rats and the ecological factors that may have accompanied that evolution.

15.
Genetics ; 227(4)2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-38805070

RESUMEN

Detecting introgression between closely related populations or species is a fundamental objective in evolutionary biology. Existing methods for detecting migration and inferring migration rates from population genetic data often assume a neutral model of evolution. Growing evidence of the pervasive impact of selection on large portions of the genome across diverse taxa suggests that this assumption is unrealistic in most empirical systems. Further, ignoring selection has previously been shown to negatively impact demographic inferences (e.g. of population size histories). However, the impacts of biologically realistic selection on inferences of migration remain poorly explored. Here, we simulate data under models of background selection, selective sweeps, balancing selection, and adaptive introgression. We show that ignoring selection sometimes leads to false inferences of migration in popularly used methods that rely on the site frequency spectrum. Specifically, balancing selection and some models of background selection result in the rejection of isolation-only models in favor of isolation-with-migration models and lead to elevated estimates of migration rates. BPP, a method that analyzes sequence data directly, showed false positives for all conditions at recent divergence times, but balancing selection also led to false positives at medium-divergence times. Our results suggest that such methods may be unreliable in some empirical systems, such that new methods that are robust to selection need to be developed.


Asunto(s)
Modelos Genéticos , Selección Genética , Introgresión Genética , Genética de Población/métodos , Evolución Molecular , Animales
16.
Mol Phylogenet Evol ; 196: 108066, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38565358

RESUMEN

Machine learning has increasingly been applied to a wide range of questions in phylogenetic inference. Supervised machine learning approaches that rely on simulated training data have been used to infer tree topologies and branch lengths, to select substitution models, and to perform downstream inferences of introgression and diversification. Here, we review how researchers have used several promising machine learning approaches to make phylogenetic inferences. Despite the promise of these methods, several barriers prevent supervised machine learning from reaching its full potential in phylogenetics. We discuss these barriers and potential paths forward. In the future, we expect that the application of careful network designs and data encodings will allow supervised machine learning to accommodate the complex processes that continue to confound traditional phylogenetic methods.


Asunto(s)
Aprendizaje Automático , Filogenia , Aprendizaje Automático Supervisado , Modelos Genéticos
17.
Nat Commun ; 15(1): 3145, 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38605005

RESUMEN

Naked mole-rats (NMRs) are best known for their extreme longevity and cancer resistance, suggesting that their immune system might have evolved to facilitate these phenotypes. Natural killer (NK) and T cells have evolved to detect and destroy cells infected with pathogens and to provide an early response to malignancies. While it is known that NMRs lack NK cells, likely lost during evolution, little is known about their T-cell subsets in terms of the evolution of the genes that regulate their function, their clonotypic diversity, and the thymus where they mature. Here we find, using single-cell transcriptomics, that NMRs have a large circulating population of γδT cells, which in mice and humans mostly reside in peripheral tissues and induce anti-cancer cytotoxicity. Using single-cell-T-cell-receptor sequencing, we find that a cytotoxic γδT-cell subset of NMRs harbors a dominant clonotype, and that their conventional CD8 αßT cells exhibit modest clonotypic diversity. Consistently, perinatal NMR thymuses are considerably smaller than those of mice yet follow similar involution progression. Our findings suggest that NMRs have evolved under a relaxed intracellular pathogenic selective pressure that may have allowed cancer resistance and longevity to become stronger targets of selection to which the immune system has responded by utilizing γδT cells.


Asunto(s)
Longevidad , Neoplasias , Humanos , Animales , Ratones , Longevidad/fisiología , Neoplasias/genética , Subgrupos de Linfocitos T , Células Asesinas Naturales , Ratas Topo/fisiología
18.
Drug Alcohol Rev ; 43(5): 1235-1246, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38623042

RESUMEN

INTRODUCTION: Alcohol is a leading cause of morbidity and mortality in the United States and people who are unstably housed are disproportionately impacted by adverse alcohol-related health outcomes. Addressing the needs of unstably housed people with high-intensity alcohol use (i.e., heavy episodic use or binge drinking), including those whose goal is not abstinence, is critical to reducing harms among this population. This study explores the alcohol-related treatment and support needs among unstably housed people who use alcohol. METHODS: Data collection included participant observation and semi-structured interviews (n = 25) with unstably housed people with high-intensity alcohol use. Data were analysed thematically, with attention to structural vulnerability and social-structural forces at shaping perceptions of and experiences with alcohol treatment. RESULTS: Participants underscored how housing instability was critical in precipitating and maintaining heavy alcohol use, with alcohol often used to manage the stress and anxiety related to housing instability. While participants regularly engaged with alcohol treatment programs, program design and barriers to access undermined the effectiveness of these services for participants. Participants described the need for a range of program and service options across a continuum of care to be implemented to support participants in meeting their diverse needs and identified goals regarding alcohol use. DISCUSSION AND CONCLUSIONS: Alcohol treatment and supports need to be modified so that they include a range of harm reduction and abstinence-based models to better meet people's diverse needs. Furthermore, treatment must be paired with permanent and affordable housing to address underlying drivers of alcohol-related harm for unstably housed people.


Asunto(s)
Personas con Mala Vivienda , Humanos , Femenino , Masculino , Adulto , Persona de Mediana Edad , Personas con Mala Vivienda/psicología , Rhode Island/epidemiología , Alcoholismo/terapia , Alcoholismo/psicología , Consumo de Bebidas Alcohólicas/psicología , Consumo de Bebidas Alcohólicas/epidemiología , Consumo de Bebidas Alcohólicas/terapia , Adulto Joven , Necesidades y Demandas de Servicios de Salud , Vivienda
19.
Sci Rep ; 14(1): 7567, 2024 03 30.
Artículo en Inglés | MEDLINE | ID: mdl-38555297

RESUMEN

Mounting evidence suggests that environmentally induced epigenetic inheritance occurs in mammals and that traits in the progeny can be shaped by parental environmental experiences. Epidemiological studies link parental exposure to environmental toxicants, such as the pesticide DDT, to health phenotypes in the progeny, including low birth and increased risk of chronic diseases later in life. Here, we show that the progeny of male mice exposed to DDT in the pre-conception period are born smaller and exhibit sexual dimorphism in metabolic function, with male, but not female, offspring developing severe glucose intolerance compared to controls. These phenotypes in DDT offspring were linked to reduced fetal growth and placenta size as well as placenta-specific reduction of glycogen levels and the nutrient sensor and epigenetic regulator OGT, with more pronounced phenotypes observed in male placentas. However, placenta-specific genetic reduction of OGT only partially replicates the metabolic phenotype observed in offspring of DDT-exposed males. Our findings reveal a role for paternal pre-conception environmental experiences in shaping placenta development and in fetal growth restriction. While many questions remain, our data raise the tantalizing possibility that placenta programming could be a mediator of environmentally induced intergenerational epigenetic inheritance of phenotypes and needs to be further evaluated.


Asunto(s)
DDT , Efectos Tardíos de la Exposición Prenatal , Humanos , Femenino , Masculino , Ratones , Animales , DDT/toxicidad , Efectos Tardíos de la Exposición Prenatal/metabolismo , Desarrollo Fetal , Exposición Paterna/efectos adversos , Fenotipo , Mamíferos
20.
Thromb Res ; 236: 144-154, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38447421

RESUMEN

BACKGROUND: Impaired endogenous fibrinolysis is adverse cardiovascular risk factor in acute coronary syndrome (ACS) patients. Addition of very low dose rivaroxaban (VLDR) to dual antiplatelet therapy (DAPT) reduces cardiovascular events but increases bleeding. OBJECTIVE: We aimed to assess whether addition of VLDR to DAPT can enhance endogenous fibrinolysis. METHODS: In a prospective, open-label trial, we assessed endogenous fibrinolysis in whole blood, in 549 patients with ACS using the Global Thrombosis Test (GTT) and Thromboelastography (TEG). Patients (n = 180) who demonstrated impaired endogenous fibrinolysis (lysis time [LT] >2000s with the GTT) were randomised 1:1:1 to (i) clopidogrel 75 mg daily; (ii) clopidogrel 75 mg daily plus rivaroxaban 2.5 mg twice daily; or (iii) ticagrelor 90 mg twice daily, for 30 days, in addition to aspirin. Fibrinolytic status was assessed at 0, 2, 4 and 8 weeks. The primary outcome was the change in LT from admission to week 4. We also measured thrombotic occlusion time (OT) at high shear, and rivaroxaban level. RESULTS: There was no difference between the groups with respect to LT or clot lysis with TEG, and no change in these parameters compared to baseline during study drug allocation. In the rivaroxaban plus clopidogrel group, OT was prolonged compared to the other groups, although rivaroxaban levels were low, suggesting non-compliance. CONCLUSION: Addition of rivaroxaban 2.5 mg twice daily to DAPT does not affect endogenous fibrinolysis of thrombus formed at either high or low shear. Further studies are needed to determine whether higher doses of rivaroxaban can favourably modulate fibrinolysis. CONDENSED ABSTRACT: Impaired endogenous fibrinolysis is a strong risk factor in ACS. We aimed to assess whether adding very low dose rivaroxaban (VLDR) to DAPT can enhance fibrinolysis. Fibrin and clot lysis were assessed in whole blood. ACS patients with impaired fibrinolysis were randomised 1:1:1 to clopidogrel 75 mg daily; clopidogrel 75 mg plus VLDR; or ticagrelor 90 mg twice daily, in addition to aspirin. At 30-days, there was no difference in lysis time between the groups, nor change from baseline. VLDR does not improve fibrinolysis at high or low shear. Further studies are needed to determine whether alternative antithrombotic regimens can enhance endogenous fibrinolysis.


Asunto(s)
Síndrome Coronario Agudo , Trombosis , Humanos , Inhibidores de Agregación Plaquetaria/farmacología , Inhibidores de Agregación Plaquetaria/uso terapéutico , Rivaroxabán/farmacología , Rivaroxabán/uso terapéutico , Clopidogrel/uso terapéutico , Fibrinólisis , Ticagrelor/uso terapéutico , Síndrome Coronario Agudo/tratamiento farmacológico , Estudios Prospectivos , Aspirina/farmacología , Aspirina/uso terapéutico
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