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1.
Foodborne Pathog Dis ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38957999

RESUMO

Goats are often asymptomatic carriers of Campylobacter, including the foodborne pathogen Campylobacter jejuni. Infections can have significant and economically detrimental health outcomes in both humans and animals. The primary objective of this study was to estimate the prevalence of Campylobacter in U.S. goat herds. Campylobacter species were isolated from 106 of 3,959 individual animals and from 42 of 277 goat operations that participated in fecal sample collection as part of the National Animal Health Monitoring System Goat 2019 study. Weighted animal-level prevalence was 2.3% (SE = 0.5%) and operation prevalence was 13.0% (SE = 3.2%). Animal-level prevalence ranged widely from 0 to 70.0%, however, 52.4% of positive operations (22/42) had only a single isolate. C. jejuni was the most frequently isolated species (68.9%; 73/106), followed by C. coli (29.3%, 31/106). A total of 46.2% (36/78) of viable isolates were pan-susceptible to 8 antimicrobials. Resistance to tetracycline (TET) was observed in 44.9% (35/78) of isolates, while 12.8% (10/78) were resistant to ciprofloxacin (CIP) and nalidixic acid (NAL). Among all isolates, a single resistance profile CIP-NAL-TET was observed in 3.8% (3/78) of isolates. A total of 35 unique sequence types (STs) were identified, 11 of which are potentially new. Multiple C. jejuni STs were observed in 48.1% (13/27) of positive operations. Goats with access to surface water, operations reporting antibiotics in the feed or water (excluding ionophores and coccidiostats), and operations reporting abortions and without postabortion management tasks had significantly greater odds of being Campylobacter positive. This snapshot of the U.S. goat population enriches the limited pool of knowledge on Campylobacter species presence in U.S. goats.

2.
Hypertension ; 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38966986

RESUMO

BACKGROUND: Evidence suggests that increasing salt intake in pregnancy lowers blood pressure, protecting against preeclampsia. We hypothesized that sodium (Na+) evokes beneficial placental signals that are disrupted in preeclampsia. METHODS: Blood and urine were collected from nonpregnant women of reproductive age (n=26) and pregnant women with (n=50) and without (n=55) preeclampsia, along with placental biopsies. Human trophoblast cell lines and primary human trophoblasts were cultured with varying Na+ concentrations. RESULTS: Women with preeclampsia had reduced placental and urinary Na+ concentrations, yet increased urinary angiotensinogen and reduced active renin, aldosterone concentrations, and osmotic response signal TonEBP (tonicity-responsive enhancer binding protein) expression. In trophoblast cell cultures, TonEBP was consistently increased upon augmented Na+ exposure. Mechanistically, inhibiting Na+/K+-ATPase or adding mannitol evoked the TonEBP response, whereas inhibition of cytoskeletal signaling abolished it. CONCLUSIONS: Enhanced Na+ availability induced osmotic gradient-dependent cytoskeletal signals in trophoblasts, resulting in proangiogenic responses. As placental salt availability is compromised in preeclampsia, adverse systemic responses are thus conceivable.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38828012

RESUMO

Recent shifts in societal attitudes towards cannabis have led to a dramatic increase in consumption rates in many Western countries, particularly among young people. This trend has shed light on a significant link between cannabis use disorder (CUD) and pathological reactive aggression, a condition involving disproportionate aggressive and violent reactions to minor provocations. The discourse on the connection between cannabis use and aggression is frequently enmeshed in political and legal discussions, leading to a polarized understanding of the causative relationship between cannabis use and aggression. However, integrative analyses from both human and animal research indicate a complex, bidirectional interplay between cannabis misuse and pathological aggression. On the one hand, emerging research reveals a shared genetic and environmental predisposition for both cannabis use and aggression, suggesting a common underlying biological mechanism. On the other hand, there is evidence that cannabis consumption can lead to violent behaviors while also being used as a self-medication strategy to mitigate the negative emotions associated with pathological reactive aggression. This suggests that the coexistence of pathological aggression and CUD may result from overlapping vulnerabilities, potentially creating a self-perpetuating cycle where each condition exacerbates the other, escalating into externalizing and violent behaviors. This article aims to synthesize existing research on the intricate connections between these issues and propose a theoretical model to explain the neurobiological mechanisms underpinning this complex relationship.

4.
BMC Complement Med Ther ; 24(1): 210, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38831412

RESUMO

PURPOSE: In light of the mounting prevalence of stress in contemporary society and the growing interest in stress reduction methods, this review investigates the potential of taiji as a viable strategy for alleviating stress. METHODS: MEDLINE, EMBASE, the Cochrane Controlled Trials Register (CENTRAL), PsycINFO, and Web of Science were searched up to April 2023 to identify randomized controlled trials of taiji. Studies in both patients and healthy populations were considered. They had to provide a measure of perceived stress and include a no treatment or placebo control group. Data were extracted by two reviewers. Pooled standardized mean differences (SMD) were calculated for perceived stress, biological stress markers, anxiety, depression, and quality of life (QoL). Meta-regression analyses were performed to identify sources of heterogeneity. RESULTS: Eleven trials with a total of 1323 patients comparing taiji to no intervention met the inclusion criteria. The included studies varied strongly with regard to patient characteristics, taiji intervention, and methodological quality. The overall SMD for perceived stress was significant at -0.41 (95% confidence interval, CI, -0.63 to -0.19; I2 = 63%). Exclusion of studies with less than 100 participants yielded a diminished SMD at -0.26 (95% CI, -0.45 to -0.06). The SMD for perceived stress at follow-up was significant (-0.25, 95% CI -0.46 to -0.05). Secondary outcomes highlighted improvements in anxiety and physical QoL, while depression, mental QoL, and biological stress markers remained unchanged. CONCLUSIONS: Results underscore taiji's potential in mitigating perceived stress in both patients and healthy populations, paralleled by enhancements in depressive symptoms, anxiety levels, and physical QoL.


Assuntos
Estresse Psicológico , Tai Chi Chuan , Humanos , Estresse Psicológico/terapia , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Depressão/terapia , Ansiedade
5.
bioRxiv ; 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38915626

RESUMO

Tripartite resistance nodulation and cell division multidrug efflux pumps span the periplasm and are a major driver of multidrug resistance among Gram-negative bacteria. The periplasm provides a distinct environment between the inner and outer membranes of Gram-negative bacteria. Cations, such as Mg2+, become concentrated within the periplasm and, in contrast to the cytoplasm, its pH is sensitive to conditions outside the cell. Here, we reveal an interplay between Mg2+ and pH in modulating the dynamics of the periplasmic adaptor protein, AcrA, and its function within the prototypical AcrAB-TolC multidrug efflux pump from Escherichia coli. In the absence of Mg2+, AcrA becomes increasingly plastic within acidic conditions, but when Mg2+ is bound this is ameliorated, resulting in domain specific organisation in neutral to weakly acidic regimes. We establish a unique histidine residue directs these structural dynamics and is essential for sustaining pump efflux activity across acidic, neutral, and alkaline conditions. Overall, we propose Mg2+ conserves the structural mobility of AcrA to ensure optimal AcrAB-TolC function within rapid changing environments commonly faced by the periplasm during bacterial infection and colonization. This work highlights that Mg2+ is an important mechanistic component in this pump class and possibly across other periplasmic lipoproteins.

6.
bioRxiv ; 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38915482

RESUMO

Lysine Specific Demethylase 1 (KDM1A / LSD1) regulates mitochondrial respiration and stabilizes HIF-1A (hypoxia-inducible factor 1A). HIF-1A modulates reactive oxygen species (ROS) levels by increasing cellular glucose uptake, glycolysis, and endogenous antioxidants. The role of KDM1A in cellular ROS response has not previously been described. We determined the role of KDM1A in regulating the ROS response and the utility of KDM1A inhibitors in combination with ROS-inducing cancer therapies. Our results show that KDM1A inhibition sensitized cells to oxidative stress and increased total cellular ROS, which was mitigated by treatment with the antioxidant N-acetyl cysteine. KDM1A inhibition decreased basal mitochondrial respiration and impaired induction of HIF-1A after ROS exposure. Overexpression of HIF-1A salvaged cells from KDM1A inhibition enhanced sensitivity to ROS. Thus we found that increased sensitivity of ROS after KDM1A inhibition was mediated by HIF-1A and depletion of endogenous glutathione. We also show that KDM1A-specific inhibitor bizine synergized with antioxidant-depleting therapies, buthionine sulfoximine, and auranofin in rhabdomyosarcoma cell lines (Rh28 and Rh30). In this study, we describe a novel role for KDM1A in regulating HIF-1A functions under oxidative stress and found that dual targeting of KDM1A and antioxidant systems may serve as an effective combination anticancer strategy.

7.
Curr Protoc ; 4(6): e1087, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38896100

RESUMO

Fabry disease (FD) is a lysosomal storage disorder caused by variants in the GLA gene encoding α-galactosidase A, an enzyme required for catabolism of globotriaosylceramide (Gb3). Accumulation of Gb3 in patients' cells, tissues, and biological fluids causes clinical manifestations including ventricular hypertrophy, renal insufficiency, and strokes. This protocol describes a methodology to analyze urinary Gb3 and creatinine. Samples are diluted with an internal standard solution containing Gb3(C17:0) and creatinine-D3, centrifuged, and directly analyzed by ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS) using an 8.7-min method. Eight Gb3 isoforms [C16:0, C18:0, C20:0, C22:1, C22:0, C24:1, C24:0, and (C24:0)OH] are analyzed and the total is normalized to creatinine. Confirmation ions are monitored to detect potential interferences. The Gb3 limit of quantification is 0.023 µg/ml. Its interday coefficients of variation (3 concentrations measured) are ≤15.4%. This method minimizes matrix effects (≤6.5%) and prevents adsorption or precipitation of Gb3. Urine samples are stable (bias <15%) for 2 days at 21°C, 7 days at 4°C, and 4 freeze/thaw cycles, whereas prepared samples are stable for 5 days at 21°C, and 14 days at 4°C. The Gb3/creatinine age-related upper reference limits (mean + 2 standard deviations) are 29 mg/mol creatinine (<7 years) and 14 mg/mol creatinine (≥7 years). This simple, robust protocol has been fully validated (ISO 15189) and provides a valuable tool for diagnosis and monitoring of FD patients. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol: Analysis of urinary globotriaosylceramide (Gb3) and creatinine by UHPLC-MS/MS Support Protocol 1: Preparation of the urinary quality controls Support Protocol 2: Preparation of the urine matrix used for the Gb3 calibration curve Support Protocol 3: Preparation of the Gb3 calibrators Support Protocol 4: Preparation of the working solution containing the internal standards Support Protocol 5: Preparation of the creatinine calibrators Support Protocol 6: Preparation of the UHPLC solutions and mobile phases.


Assuntos
Doença de Fabry , Espectrometria de Massas em Tandem , Triexosilceramidas , Humanos , Espectrometria de Massas em Tandem/métodos , Triexosilceramidas/urina , Triexosilceramidas/metabolismo , Cromatografia Líquida de Alta Pressão/métodos , Doença de Fabry/urina , Doença de Fabry/diagnóstico , Creatinina/urina
8.
Br J Nutr ; : 1-26, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38826089

RESUMO

There are no high-quality data on dietary behavior of adolescents in India. This study aimed to assess the intake of energy (E), macronutrients and selected micronutrients in a sample of 11-13-year-old schoolchildren in Delhi, India. Participants from private schools (n=10) recorded dietary intake using a 3-day food diary. Information was entered into the dietary assessment tool, Intake24, to ascertain portion size and convert data into nutrient intake through integrated food tables. Of the 514 consenting participants, 393 (76.4%) (169 girls, 224 boys) aged 11.4 (± 1.8) years completed the study. The median (interquartile range (IQR) daily E intake was 2580 (2139.3-2989.8) kcal [10.8 (9.0 -12.5) MJ] for girls, and 2941.5 (2466.7- 3599.3) kcal [12.3 (10.3- 15.2) MJ] for boys. The median (IQR) daily nutrient intakes for girls and boys respectively were: protein 64.6 (54.8-79.3) g, 74.4 (61.4; 89.4) g; carbohydrate 336.5 (285.3- 393.6) g, 379.6 (317.8-461.8) g; and saturated fat 45.6 (34.8-58.3) g, 54.6 (41.9-69.5) g. There were no significant between-gender differences in percent E from protein (10.2 (9.2 - 11.4)), or carbohydrate (52.4 (48.7- 56.7)). Girls obtained less percent E from saturated fat (16.1 (11.0-18.2) compared with boys 16.3 (14.2 - 19.1) (P<0.05). E from saturated fat was above Food and Agriculture Organization recommendations in >74% participants. The EAR for iron was achieved by < 40% of girls. In conclusion, strategies to optimize dietary intake of adolescents in India should focus on preventing excess intakes of E and saturated fat, and improving iron intake in girls.

9.
N Engl J Med ; 391(1): 32-43, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38819658

RESUMO

BACKGROUND: Approved on-demand treatments for hereditary angioedema attacks need to be administered parenterally, a route of administration that is associated with delays in treatment or withholding of therapy. METHODS: In this phase 3, double-blind, three-way crossover trial, we randomly assigned participants at least 12 years of age with type 1 or type 2 hereditary angioedema to take up to two oral doses of sebetralstat (300 mg or 600 mg) or placebo for an angioedema attack. The primary end point, assessed in a time-to-event analysis, was the beginning of symptom relief, defined as a rating of "a little better" on the Patient Global Impression of Change scale (ratings range from "much worse" to "much better") at two or more consecutive time points within 12 hours after the first administration of the trial agent. Key secondary end points, assessed in a time-to-event analysis, were a reduction in attack severity (an improved rating on the Patient Global Impression of Severity [PGI-S] scale, with ratings ranging from "none" to "very severe") at two or more consecutive time points within 12 hours and complete attack resolution (a rating of "none" on the PGI-S scale) within 24 hours. RESULTS: A total of 136 participants were assigned to one of six trial sequences, with 110 treating 264 attacks. The time to the beginning of symptom relief with the 300-mg dose and the 600-mg dose was faster than with placebo (P<0.001 and P = 0.001 for the two comparisons, respectively), with median times of 1.61 hours (interquartile range, 0.78 to 7.04), 1.79 hours (1.02 to 3.79), and 6.72 hours (1.34 to >12), respectively. The time to reduction in the attack severity with the 300-mg dose and the 600-mg dose was faster than with placebo (P = 0.004 and P = 0.003), with median times of 9.27 hours (interquartile range, 1.53 to >12), 7.75 hours (2.19 to >12), and more than 12 hours (6.23 to >12). The time to complete resolution was faster with the 300-mg and 600-mg doses than with placebo (P = 0.002 and P<0.001). The percentage of attacks with complete resolution within 24 hours was 42.5% with the 300-mg dose, 49.5% with the 600-mg dose, and 27.4% with placebo. Sebetralstat and placebo had similar safety profiles; no serious adverse events related to the trial agents were reported. CONCLUSIONS: Oral sebetralstat provided faster times to the beginning of symptom relief, reduction in attack severity, and complete attack resolution than placebo. (Funded by KalVista Pharmaceuticals; KONFIDENT ClinicalTrials.gov number, NCT05259917; EudraCT number, 2021-001226-21.).


Assuntos
Estudos Cross-Over , Humanos , Feminino , Método Duplo-Cego , Masculino , Adulto , Administração Oral , Pessoa de Meia-Idade , Angioedemas Hereditários/tratamento farmacológico , Adolescente , Adulto Jovem , Idoso , Angioedema Hereditário Tipos I e II/tratamento farmacológico , Pirazóis
10.
Artigo em Inglês | MEDLINE | ID: mdl-38718950

RESUMO

BACKGROUND: Cockroach allergy contributes to morbidity among urban children with asthma. Few trials address the effect of subcutaneous immunotherapy (SCIT) with cockroach allergen among these at-risk children. OBJECTIVES: We sought to determine whether nasal allergen challenge (NAC) responses to cockroach allergen would improve following 1 year of SCIT. METHODS: Urban children with asthma, who were cockroach-sensitized and reactive on NAC, participated in a year-long randomized double-blind placebo-controlled SCIT trial using German cockroach extract. The primary endpoint was the change in mean Total Nasal Symptom Score (TNSS) during NAC after 12 months of SCIT. Changes in nasal transcriptomic responses during NAC, skin prick test wheal size, serum allergen-specific antibody production, and T-cell responses to cockroach allergen were assessed. RESULTS: Changes in mean NAC TNSS did not differ between SCIT-assigned (n = 28) versus placebo-assigned (n = 29) participants (P = .63). Nasal transcriptomic responses correlated with TNSS, but a treatment effect was not observed. Cockroach serum-specific IgE decreased to a similar extent in both groups, while decreased cockroach skin prick test wheal size was greater among SCIT participants (P = .04). A 200-fold increase in cockroach serum-specific IgG4 was observed among subjects receiving SCIT (P < .001) but was unchanged in the placebo group. T-cell IL-4 responses following cockroach allergen stimulation decreased to a greater extent among SCIT versus placebo (P = .002), while no effect was observed for IL-10 or IFN-γ. CONCLUSIONS: A year of SCIT failed to alter NAC TNSS and nasal transcriptome responses to cockroach allergen challenge despite systemic effects on allergen-specific skin tests, induction of serum-specific IgG4 serum production and down-modulation of allergen-stimulated T-cell responses.

12.
J Perinatol ; 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38796522

RESUMO

BACKGROUND: Fetal Centers use imaging studies to predict congenital diaphragmatic hernia (CDH) prognosis and the need for fetal therapy. Given improving CDH survival, we hypothesized that current fetal imaging severity predictions no longer reflect true outcomes and fail to justify the risks of fetal therapy. METHODS: We analyzed our single-center contemporary data in a left-sided CDH cohort (n = 58) by prognostic criteria determined by MRI observed-to-expected total fetal lung volumes: severe <25%, moderate 25-35%, and mild >35%. We compared contemporary survival to prior studies and the TOTAL trials. RESULTS: Contemporary survival was significantly higher than past studies for all prognostic classifications (mild 100% vs 80-94%, moderate 95% vs 59-75%, severe 79% vs 13-25%; P < 0.01), and to either control or fetal therapy arms of the TOTAL trials. CONCLUSIONS: Current fetal imaging criteria are overly pessimistic and may lead to unwarranted fetal intervention. Fetal therapies remain experimental. Future studies will require updated prognostic criteria.

13.
Matern Child Nutr ; : e13671, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38804267

RESUMO

Reducing free sugars intake is important for the prevention of dental caries and obesity in children. The study aimed to determine the amount and sources of free sugars known to contribute to dental caries, and identify sociodemographic determinants of intake by children aged 5 years in Australia. Cross-sectional analysis of dietary data from a cohort study, collected using a customized food frequency questionnaire were used to calculate free sugars intake as grams/day and percentage contribution to Estimated Energy Requirement (EER). The percent contribution of food sources to free sugars intake was derived. Sociodemographic determinants of achieving intakes within WHO thresholds (i.e., <5% and <10% Energy were explored with multinomial logistic regression. Complete data were available for 641 children (347 boys, 294 girls). Median (IQR) free sugars intake (g/day) was 31.6 (21.3-47.6) in boys and 28.1 (19.6-47.9) in girls. The median (IQR) percentage contribution to EER was 7.9 (5.4-12.7); 21% and 42% of children had intakes <5% EER and between 5% and <10%, respectively. The main sources of free sugars were: (1) Cakes, Biscuits and Cereal Bars; (2) Sweetened Milk Products (predominantly yoghurts) and (3) Desserts. Maternal university education, single-parent household, and maternal place of birth being Australia or New Zealand were associated with free sugars intake <5% EER. In conclusion, less than a quarter of 5-year-old children in the SMILE cohort achieved the WHO recommendations to limit free sugars to <5% EER. Strategies to lower free sugars intake could target priority populations such migrants, populations with lower levels of education or health literacy and identify areas for intervention in the wider food environments that children are exposed to.

14.
Blood Adv ; 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38815230

RESUMO

To address acute vaso-occlusive episodes (VOEs), the leading cause of Emergency Department (ED) visits among individuals with sickle cell disease (SCD), we conducted the clinical study, An Individualized Pain Plan with Patient and Provider Access for Emergency Department care of SCD (ALIGN), across eight sites. We hypothesized an improvement of 0.5 standard deviations in perceived quality of ED pain treatment of a VOE after implementing individualized pain plans (IPPs) accessible to both patients and providers. Patients with SCD were 18-45, owned a cell phone, and had an ED VOE visit within 90 days prior. Patients completed perceived quality of care surveys at baseline and within 96 hours after a VOE ED visit. Providers completed surveys regarding comfort managing VOEs at baseline and after managing an enrolled patient. Most of the 153 patients were African American (95.4%), female (64.7%) and had Hb SS/Sß0 genotype (71.9%). The perceived quality of ED pain treatment was high at both baseline and post implementation of IPPs; our primary outcome hypothesis was not met, as no statistically significant change in patient perceived quality ED treatment ocurred. A total of 135 providers completed baseline and follow-up surveys. On a scale of 1-7, with 7 being extremely comfortable managing VOEs, 60.5% reported a score ≥6 post IPP implementation vs. 57.8% at baseline. Almost all (97.6%) ordered the recommended medication, and 94.7% intend to use IPPs. In this implementation protocol, all sites successfully implemented IPPs . Patients and ED providers both endorsed the use of IPPs.

15.
J Allergy Clin Immunol Pract ; 12(6): 1614-1621, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38609017

RESUMO

BACKGROUND: Clinical trials investigating drugs for the acute treatment of hereditary angioedema attacks have assessed many different outcomes. This heterogeneity limits the comparability of trial results and may lead to selective outcome reporting bias and a high burden on trial participants. OBJECTIVE: To achieve consensus on a core outcome set composed of key outcomes that ideally should be used in all clinical efficacy trials involving the acute treatment of hereditary angioedema attacks. METHODS: We conducted a Delphi consensus study involving all relevant parties: patients with hereditary angioedema, hereditary angioedema expert clinicians and clinical researchers, pharmaceutical companies, and regulatory bodies. Two Internet-based survey rounds were conducted. In round 1, panelists indicated the importance of individual outcomes used in clinical trials on a 9-point Likert scale. Based on these results, a core outcome set was developed and voted on by panelists in round 2. RESULTS: A total of 58 worldwide panelists completed both rounds. The first round demonstrated high importance scores and substantial agreement among the panelists. In the second round, a consensus of 90% or greater was achieved on a core outcome set consisting of five key outcomes: change in overall symptom severity at one predetermined time point between 15 minutes and 4 hours after treatment, time to end of progression of all symptoms, the need for rescue medication during the entire attack, impairment of daily activities, and treatment satisfaction. CONCLUSIONS: This international study obtained a high level of consensus on a core outcome set for the acute treatment of hereditary angioedema attacks, consisting of five key outcomes.


Assuntos
Angioedemas Hereditários , Humanos , Angioedemas Hereditários/tratamento farmacológico , Resultado do Tratamento , Técnica Delphi , Inquéritos e Questionários , Ensaios Clínicos como Assunto , Consenso , Feminino , Avaliação de Resultados em Cuidados de Saúde
16.
Radiat Res ; 201(6): 628-646, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38616048

RESUMO

There have been a number of reported human exposures to high dose radiation, resulting from accidents at nuclear power plants (e.g., Chernobyl), atomic bombings (Hiroshima and Nagasaki), and mishaps in industrial and medical settings. If absorbed radiation doses are high enough, evolution of acute radiation syndromes (ARS) will likely impact both the bone marrow as well as the gastrointestinal (GI) tract. Damage incurred in the latter can lead to nutrient malabsorption, dehydration, electrolyte imbalance, altered microbiome and metabolites, and impaired barrier function, which can lead to septicemia and death. To prepare for a medical response should such an incident arise, the National Institute of Allergy and Infectious Diseases (NIAID) funds basic and translational research to address radiation-induced GI-ARS, which remains a critical and prioritized unmet need. Areas of interest include identification of targets for damage and mitigation, animal model development, and testing of medical countermeasures (MCMs) to address GI complications resulting from radiation exposure. To appropriately model expected human responses, it is helpful to study analogous disease states in the clinic that resemble GI-ARS, to inform on best practices for diagnosis and treatment, and translate them back to inform nonclinical drug efficacy models. For these reasons, the NIAID partnered with two other U.S. government agencies (the Biomedical Advanced Research and Development Authority, and the Food and Drug Administration), to explore models, biomarkers, and diagnostics to improve understanding of the complexities of GI-ARS and investigate promising treatment approaches. A two-day workshop was convened in August 2022 that comprised presentations from academia, industry, healthcare, and government, and highlighted talks from 26 subject matter experts across five scientific sessions. This report provides an overview of information that was presented during the conference, and important discussions surrounding a broad range of topics that are critical for the research, development, licensure, and use of MCMs for GI-ARS.


Assuntos
Síndrome Aguda da Radiação , Biomarcadores , Contramedidas Médicas , Síndrome Aguda da Radiação/etiologia , Humanos , Animais , Trato Gastrointestinal/efeitos da radiação , Gastroenteropatias/etiologia
18.
Biol Res Nurs ; : 10998004241250322, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38679469

RESUMO

Objective: Sickle cell disease (SCD), the most common inherited blood disorder in the United States, is associated with severe psychoneurological symptoms. While epigenetic age acceleration has been linked to psychoneurological symptom burden in other diseases, this connection is unexplored in SCD. This study aimed to assess the association between epigenetic age acceleration and psychoneurological symptom burden in SCD. Methods: In this cross-sectional study, emotional impact, pain impact, sleep impact, social functioning, and cognitive function were assessed in 87 adults living with SCD. DNA methylation data were generated from blood specimens and used to calculate epigenetic age using five clocks (Horvath, Hannum, PhenoAge, GrimAge, & DunedinPACE). Associations between epigenetic age acceleration and symptoms were assessed. Results: The sample (N = 87) had a mean (SD) chronologic age was 30.6 (8.1) years. Epigenetic age acceleration was associated with several symptom outcomes. GrimAge age acceleration (ß = -0.49, p = .03) and increased DunedinPACE (ß = -2.23, p = .004) were associated with worse emotional impact scores. PhenoAge (ß = -0.32, p = .04) and the GrimAge (ß = -0.48, p = .05) age acceleration were associated with worse pain impact scores. Increased DunedinPACE (ß = -2.07 p = .04) were associated with worse sleep impact scores. Increased DunedinPACE (ß = -2.87, p = .005) was associated with worse social functioning scores. We did not find associations between epigenetic age acceleration and cognitive function in this sample. Conclusion: Epigenetic age acceleration was associated with worse symptom experiences, suggesting the potential for epigenetic age acceleration as a biomarker to aid in risk stratification or targets for intervention to mitigate symptom burden in SCD.

19.
J Psychoactive Drugs ; : 1-11, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38646910

RESUMO

Stigma is a public health concern. Stigmatizing attitudes toward persons with substance use disorders (SUDs) can adversely impact clinical care and outcomes. Beliefs about SUD, prior experience and familiarity to persons with SUD, and educational curricula drive attitudes among health-care workers. In 2019, nursing and nursing assistant students were recruited through an online survey platform. Participants completed an SUD knowledge test and a survey assessing education, beliefs, personal experience, and confidence in recognizing the signs and symptoms of SUD. One hundred and ten health-care students (nursing students, n = 67 and nursing assistant students, n = 43) completed the survey. Among nursing assistant students, endorsing a disease model of addiction (F(2, 40) = 5.83, p < .001, R2 = .23), and personal familiarity with SUD (F(2, 40) = 4.46, p < .001, R2 = .18), were significantly positively predictive of positive regard toward working with persons with SUD. For nursing students, endorsing a disease model of addiction, educational curricula involving persons with SUD, and personal familiarity were significantly positively predictive of positive regard toward working with persons with SUDs (F(2, 61) = 11.52, p < .001, R2 = .36). Interventions to mitigate drug-related stigma among health-care students should center students with personal familiarity, promote the disease concept of addiction, and incorporate contact-based training.

20.
PLoS One ; 19(4): e0301285, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38564594

RESUMO

Increasing awareness of gender barriers and biases in academic institutions is an essential component of institutional change strategies to promote equity and inclusion. There is an established perception gap in recognizing gender inequities in the workplace, whereby men faculty under acknowledge the stressors, barriers, and biases faced by their women faculty colleagues. This study explored the gender gap in faculty perceptions of institutional diversity climate at a rural comprehensive regional university in the United States. In addition to gender, differences across academic discipline and time were explored using 2 (men and women) x 2 (STEM and other) x 2 (2017 and 2022) between-groups ANOVAs. Results revealed a gender gap that persisted across time and perceptions of stressors, diversity climate, student behavior, leadership, and fairness in promotion/tenure procedures, with marginalized (women) faculty consistently reporting greater barriers/concern for women faculty relative to the perceptions of their men faculty colleagues. These findings are largely consistent with the extant literature and are discussed both with regard to future research directions and recommendations for reducing the perception gap and addressing institutional barriers to gender equity.


Assuntos
Centros Médicos Acadêmicos , Docentes de Medicina , Masculino , Humanos , Feminino , Estados Unidos , Universidades , Fatores Sexuais , Faculdades de Medicina , Liderança , Mobilidade Ocupacional
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