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Microneedle array patches (MAPs) are extensively studied for transdermal drug delivery. Additive manufacturing enables precise control over MAP customization and rapid fabrication. However, the scope of 3D-printable, bioresorbable materials is limited. Dexamethasone (DXM) is widely used to manage inflammation and pain, but its application is limited by systemic side effects. Thus, it is crucial to achieve high local drug concentrations while maintaining low serum levels. Here, poly(propylene fumarate-co-propylene succinate) oligomers are fabricated into DXM-loaded, bioresorbable MAPs via continuous liquid interface production 3D printing. Thiol-ene click chemistry yields MAPs with tailorable mechanical and degradation properties. DXM-loaded MAPs exhibit controlled elution of drug in vitro. Transdermal application of DXM-loaded MAPs in a murine tibial fracture model leads to substantial relief of postoperative pain. Pharmacokinetic analysis shows that MAP administration is able to control pain at a significantly lower dose than intravenous administration. This work expands the material properties of 3D-printed poly(propylene fumarate-co-propylene succinate) copolyesters and their use in drug delivery applications.
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The versatility of metal-organic frameworks (MOFs) has led to groundbreaking applications in a wide variety of fields, especially in the areas of energy, environment, and sustainability. For example, MOFs can be designed for high uptake of toxic gases and pollutants, such as CO2, NH3, and SO2, but designing a single MOF that shows tangible uptake for all of these gases is challenging due to the differences in the chemical and physical properties of these molecules. To this end, integrating multiple MOFs onto textile fibers and crafting various structures have emerged as pivotal developments, enhancing framework durability and usability. MOF composites prepared on readily available textile fibers offer the flexibility essential for critical applications, including heterogeneous catalysis, chemical sensing, toxic gas adsorption, and drug delivery, while preserving the unique characteristics of MOFs. This study introduces a scalable and adaptable method for seamlessly embedding multiple high-performing MOFs onto a single textile fiber using a dip-coating method. We explored the uptake capacity of these multi-MOF composites for CO2, NH3, and SO2 and observed a performance similar to that of traditional powdered materials. Along with harmful gas adsorption, we also have evaluated the permeation and reactivity of these MOF/textile composites toward chemical warfare agents (CWAs) like GD (soman), HD (mustard gas), and VX. In combination, these results demonstrate a fundamental advancement toward establishing a consistent strategy for the hydrolysis of nerve agents in real-world scenarios. This approach can substantially increase the protection toward CWAs and enhance the effectiveness of protective equipment such as fabrics for protective garments. This dip-coating method for the integration of multiple MOFs on a single textile fiber unlocks a wealth of possibilities and paves the way for future innovations in the deployment of MOF-based composites.
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The National Comprehensive Cancer Network guidelines provide evidence-based consensus for optimal individual site- and stage-specific treatments. This is a cohort study of 11,121 late-stage oral cancer patients in the National Cancer Database from 2010 to 2016. We hypothesized that patient travel distance may affect treatment choices and impact outcome. We split travel distance (miles) into quartiles (D1-4) and assessed treatment choices, type of facility, and survival outcome in relation to distance traveled. Univariate and multivariate analyses addressed contributions of specific variables. White patients were most likely to travel farthest (D4) for treatment compared to Black patients (D1). Urban area patients traveled shorter distances than those from rural areas. Greater travel distance was associated with patients undergoing surgical-based therapies and treatment at academic centers. Patients in D1 had the lowest median survival of all distance quartiles. Surgery-based multimodality treatment (surgery and radiation) had a median survival significantly greater than for non-surgical therapy. Several factors including travel distance and treatment facility were associated with survival outcomes for late-stage oral cavity cancers. Consideration of these factors may help improve the outcome for this patient population.
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Insomnia and suicidal ideation (SI) are common in schizophrenia, including in individuals at clinical high-risk for psychosis (CHR-P). Previous studies have found associations between sleep disturbance, SI, and psychopathology in schizophrenia. We explored these associations in a CHR-P cohort. We leveraged data from CHR-P individuals in the North American Prodrome Longitudinal Studies (NAPLS-3) (n = 688) cohort. We investigated relationships between sleep disturbance (Scale of Prodromal Symptoms [SOPS]; Calgary Depression Scale for Schizophrenia [CDSS], and the Pittsburgh Sleep Quality Index [PSQI]), suicidal ideation (CDSS), and psychosis-risk symptoms. The prevalence of terminal insomnia, sleep disturbance, and SI in NAPLS3 was 25 %, 69 %, and 29 %, respectively. After controlling for potential confounders, multiple indices of sleep disturbance (SOPS, PSQI: OR = 1.05-1.40) were significant indicators of concurrent SI. Terminal insomnia was not associated with conversion to psychosis. Multiple indices of sleep problems were associated with higher total and subscale psychosis-risk symptom scores (ß = 0.09-0.39). Sleep problems are prevalent and associated with SI and more severe psychosis-risk symptoms in CHR-P individuals. These findings underscore the importance of designing longitudinal intervention studies to investigate whether the treatment of sleep disturbances may reduce suicidality and symptoms in this population.
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Síntomas Prodrómicos , Trastornos Psicóticos , Trastornos del Sueño-Vigilia , Ideación Suicida , Humanos , Trastornos Psicóticos/epidemiología , Trastornos Psicóticos/psicología , Masculino , Femenino , Adulto Joven , Adulto , Estudios Longitudinales , Adolescente , Trastornos del Sueño-Vigilia/epidemiología , Trastornos del Inicio y del Mantenimiento del Sueño/epidemiología , Trastornos del Inicio y del Mantenimiento del Sueño/psicología , Esquizofrenia/epidemiología , Esquizofrenia/complicacionesRESUMEN
Introduction: Time spent in nature provides myriad physical and mental health benefits for both adults and children. Despite these benefits, most people spend too little time in nature to realize the maximal effect. Different types of childhood experiences may have differential influence on adult time in nature. This study assessed the influences of different kinds of childhood outdoor experiences on time spent in nature as an adult. The first aim was to utilize 20 childhood nature experience items to construct summative scales. The second aim was to examine the influence of each scale and other factors on adult time in nature. Methods: A 2-factor scale measuring wild and domesticated childhood nature experiences was developed using principal and confirmatory factor analyses. An online study of 2,109 American adults was conducted. Multiple linear regression examined the influences of the 2 childhood nature experiences scales, attitude and self-efficacy scales, and sex and age covariates on adult time spent in nature. Results: Significant predictors of adult time in nature were wild childhood nature experiences (ß=0.279, p<0.001), positive attitudes about nature (ß=0.12, p<0.05), negative attitudes about nature (ß= -0.23, p<0.001), and self-efficacy (ß=0.71, p<0.001). Conclusions: Wild childhood nature experiences (e.g., camping, hiking, and fishing) that include skill building, that are immersive and engaging, and that involve opportunity for social interaction may translate better into adult nature activities. Programs that introduce and support wild experiences may increase lifelong time spent in nature.
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Natural bioactives possess a wide range of chemical structures that can exert a plethora of pharmacological and toxicological actions, resulting in neuroprotection or neurotoxicity. These pharmacodynamic properties can positively or negatively impact human and animal global healthcare. Remarkably, Ayurvedic botanical Cannabis has been used worldwide by different ethnicities and religions for spiritual, commercial, recreational, nutraceutical, cosmeceutical, and medicinal purposes for centuries. Cannabis-based congeners have been approved by the United States of America's (USA) Food & Drug Administration (FDA) and other global law agencies for various therapeutic purposes. Surprisingly, the strict laws associated with possessing cannabis products have been mitigated in multiple states in the USA and across the globe for recreational use. This has consequently led to a radical escalation of exposure to cannabis-related substances of abuse. However, there is a lacuna in the literature on the acute and chronic effects of Cannabis and its congeners on various neuropathologies. Moreover, in the post-COVID era, there has been a drastic increase in the incidence and prevalence of numerous neuropathologies, leading to increased morbidity and mortality. There is an impending necessity for a safe, economically viable, multipotent, natural bioactive to prevent and treat various neuropathologies. The ayurvedic herb, Cannabis is one of the oldest botanicals known to humans and has been widely used. However, the comprehensive effect of Cannabis on various neuropathologies is not well established. Hence, this review presents effects of Cannabis on various neuropathologies.
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Metal-organic frameworks (MOFs) have garnered substantial attention for their unique properties, such as high porosity and tunable structures, making them versatile for various applications. This paper constructs photoactive titanium-organic frameworks by combining Ti(IV) clusters and a bipyridine linker. The MOF is synthesized in situ through imine condensation, resulting in NU-2300. Subsequent ex situ nickel salt complexation results in NU-2300-Ni, which is then used for light-mediated carbon-heteroatom cross-couplings. The photophysical properties of the metallaphotocatalyst were investigated by UV-vis and EPR analyses, and both the Ti cluster and the bipyridine linker were found to contribute to successful catalysis, making it a tandem catalyst. The heterogeneous material retained its performance through five cycles of thioetherification. This work contributes not only to MOF synthetic strategies but also to expanding MOF applications as recyclable, tandem metallaphotocatalysts.
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PURPOSE: Urodynamic testing (UDS) is an important tool in the management of pediatric lower urinary tract conditions. There have been notable efforts to standardize pediatric UDS nomenclature and technique, but no formal guidelines exist on essential elements to include in a clinical report. We sought to identify ideal structure and elements of a pediatric UDS assessment based on expert consensus. MATERIALS AND METHODS: Pediatric urologists regularly performing UDS were queried using a Delphi process. Participants were invited representing varied geographic, experience, and societal involvement. Participants underwent 3 rounds of questionnaires between November 2022 and August 2023 focusing on report organization, elements, definitions, and automated electronic health record clinical decision support. Professional billing requirements were also considered. Consensus was defined as 80% agreeing either in favor of or against a topic. Elements without consensus were discussed in subsequent rounds. RESULTS: A diverse sample of 30 providers, representing 27 institutions across 21 US states; Washington, District of Columbia; and Canada completed the study. Participants reported interpreting an average number of 5 UDS reports per week (range 1-22). The finalized consensus report identifies 93 elements that should be included in a pediatric UDS report based on applicable study conditions and findings. CONCLUSIONS: This consensus report details the key elements and structure agreed upon by an expert panel of pediatric urologists. Further standardization of documentation should aid collaboration and research for patients undergoing UDS. Based on this information, development of a standardized UDS report template using electronic health record implementation principles is underway, which will be openly available for pediatric urologists.
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Consenso , Técnica Delphi , Urodinámica , Humanos , Niño , Urología/normas , Pediatría/normas , Masculino , Encuestas y CuestionariosRESUMEN
BACKGROUND: ChatGPT is a conversational artificial intelligence technology that has shown application in various facets of healthcare. With the increased use of AI, it is imperative to assess the accuracy and comprehensibility of AI platforms. OBJECTIVE: This pilot project aimed to assess the understandability, readability, and accuracy of ChatGPT as a source of medication-related patient education as compared with an evidence-based medicine tertiary reference resource, LexiComp®. METHODS: Patient education materials (PEMs) were obtained from ChatGPT and LexiComp® for 8 common medications (albuterol, apixaban, atorvastatin, hydrocodone/acetaminophen, insulin glargine, levofloxacin, omeprazole, and sacubitril/valsartan). PEMs were extracted, blinded, and assessed by 2 investigators independently. The primary outcome was a comparison of the Patient Education Materials Assessment Tool-printable (PEMAT-P). Secondary outcomes included Flesch reading ease, Flesch Kincaid grade level, percent passive sentences, word count, and accuracy. A 7-item accuracy checklist for each medication was generated by expert consensus among pharmacist investigators, with LexiComp® PEMs serving as the control. PEMAT-P interrater reliability was determined via intraclass correlation coefficient (ICC). Flesch reading ease, Flesch Kincaid grade level, percent passive sentences, and word count were calculated by Microsoft® Word®. Continuous data were assessed using the Student's t-test via SPSS (version 20.0). RESULTS: No difference was found in the PEMAT-P understandability score of PEMs produced by ChatGPT versus LexiComp® [77.9% (11.0) vs. 72.5% (2.4), P=0.193]. Reading level was higher with ChatGPT [8.6 (1.2) vs. 5.6 (0.3), P < 0.001). ChatGPT PEMs had a lower percentage of passive sentences and lower word count. The average accuracy score of ChatGPT PEMs was 4.25/7 (61%), with scores ranging from 29% to 86%. CONCLUSION: Despite comparable PEMAT-P scores, ChatGPT PEMs did not meet grade level targets. Lower word count and passive text with ChatGPT PEMs could benefit patients, but the variable accuracy scores prevent routine use of ChatGPT to produce medication-related PEMs at this time.
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Patient-triggered modes of ventilation are currently the standard of practice in the care of term and preterm infants. Maintaining spontaneous breathing during mechanical ventilation promotes earlier weaning and possibly reduces ventilator-induced diaphragmatic dysfunction. A further development of assisted ventilation provides support in proportion to the respiratory effort and enables the patient to have full control of their ventilatory cycle. In this paper we will review the literature on two of these modes of ventilation: neurally adjusted ventilatory assist (NAVA) and proportional assist ventilation (PAV), propose future studies and suggest clinical applications of these modes.
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Soporte Ventilatorio Interactivo , Humanos , Recién Nacido , Recien Nacido Prematuro , Respiración Artificial , Diafragma , Volumen de Ventilación PulmonarRESUMEN
BACKGROUND: Observing trends in research publications helps to identify the quantity and quality of research produced, as well as reveal evidence gaps. No comprehensive review of the quality and quantity of physical activity intervention trials has been conducted. OBJECTIVE: We aimed to investigate i) the volume and quality (and changes in these over time) of randomized controlled trials evaluating physical activity interventions, and ii) the association between journal ranking and trial quality. METHODS: We searched the Physiotherapy Evidence Database (PEDro) for trials investigating physical activity interventions (no restrictions for population, comparison, or language). Descriptive statistics were used to describe the volume and quality of trials. The association between journal ranking (Journal Impact Factor) and trial quality (PEDro Scale) was examined using Spearman's rho correlation. RESULTS: We identified 1779 trials, of which 40% (n = 710) were published between 2016 and 2020. The mean (SD) total PEDro score was 5.3 (1.5) points out of 10, increasing over time from 2.5 (0.7) points in 1975-1980 to 5.6 (1.4) points in 2016-2020. Quality criteria that were least reported included blinding of intervention deliverers (therapists) (n = 3, 0.2%), participants (n = 21, 1.2%), or assessors (n = 541, 31%); concealed allocation to groups (n = 526, 30%); and intention to treat analysis (n = 764, 43%). There was a small correlation between trial quality and Journal Impact Factor (0.21, p < 0.001). CONCLUSION: A large volume of trials has investigated physical activity interventions. The quality of these trial reports is suboptimal but improving over time. Journal ranking should not be used for selecting high quality trials.
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Ejercicio Físico , Humanos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
PURPOSE: To assess Black women's exposure to and appraisal of racism-related stress during the postpartum period and to distinguish its impact on three indicators of postpartum mood and anxiety disorders (PMADs) symptoms. METHODS: Data from the Black Mothers' Mental Wellness Study (N = 231) and linear regression models estimated the associations between racism-related stress and the PMAD indicators: 3-item Edinburgh Postnatal Depression Scale (EPDS-3), 8-item Patient Health Questionnaire (PHQ-8), and PHQ-15. RESULTS: The majority of participants (80.5%, N = 186) experienced racism a few times a year or more, of which 37.1% (N = 69) were bothered somewhat and 19.3% (N = 36) a lot. Racism-related stress, income, level of education, and history of mental health diagnosis explained greater variance in PMAD symptoms as measured by the PHQ-8 score (R2 = 0.58, p = < 0.001) compared to the EPDS-3 (R2 = 0.46, p = < 0.001) or the PHQ-15 (R2 = 0.14, p = 0.035). CONCLUSIONS: Racism is a stressor for Black women living in Los Angeles County, California. Racism-related stress and emotional expression of PMAD symptoms were salient to the postpartum mental health of the Black women in this study. Findings from this study suggest that the PHQ-8 should be used to assess how racism impacts Black women's postpartum mental health.
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Trastornos de Ansiedad , Negro o Afroamericano , Salud Mental , Periodo Posparto , Racismo , Estrés Psicológico , Humanos , Femenino , Adulto , Racismo/psicología , Racismo/etnología , Negro o Afroamericano/psicología , Negro o Afroamericano/estadística & datos numéricos , Estrés Psicológico/etnología , Estrés Psicológico/psicología , Periodo Posparto/psicología , Periodo Posparto/etnología , Trastornos de Ansiedad/etnología , Trastornos de Ansiedad/psicología , Trastornos de Ansiedad/diagnóstico , Los Angeles , Depresión Posparto/etnología , Depresión Posparto/psicología , Depresión Posparto/diagnóstico , Madres/psicología , Encuestas y Cuestionarios , Escalas de Valoración Psiquiátrica , Adulto Joven , Tamizaje MasivoRESUMEN
Wastewater treatment wetlands are cost-effective strategies for remediating trace metals in industrial effluent. However, biogeochemical exchange between wastewater treatment wetlands and adjacent environments provides opportunities for trace metals to cycle in surrounding ecosystems. The transfer of trace metals to wildlife inhabiting treatment wetlands must be considered when evaluating wetland success. Using passerine birds as bioindicators, we conducted a multi-tissue analysis to investigate the mobilization of zinc, copper, and lead derived from wastewater to terrestrial wildlife in treatment wetlands and surrounding habitat. In addition, we evaluate the strength of relationships between metal concentrations in non-lethal (blood and feathers) and lethal (muscle and liver) sample types for estimation of toxicity risk. From July 2020 to August 2021, 177 passerines of seven species were captured at two wetlands constructed to treat industrial wastewater and two reference wetlands in the coastal plain of South Carolina. Feather, blood, liver, and muscle samples from each bird were analyzed for fourteen metals using inductively coupled plasma mass spectrometry and direct mercury analysis. Passerines inhabiting wastewater treatment wetlands accumulated higher concentrations of zinc in liver, copper in blood, and lead in feathers than passerines in reference wetlands, but neither blood nor feather concentrations were correlated with internal tissue concentrations. Of all the detected metals, only mercury in the blood showed a strong predictive relationship with mercury in internal tissues. This study indicates that trace metals derived from wastewater are bioavailable and exported to terrestrial wildlife and that passerine biomonitoring is a valuable tool for assessing metal transfer from treatment wetlands. Regular blood sampling can reveal proximate trace metal exposure but cannot predict internal body burdens for most metals.
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Monitoreo del Ambiente , Aguas Residuales , Contaminantes Químicos del Agua , Humedales , Animales , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/metabolismo , Aguas Residuales/química , Eliminación de Residuos Líquidos/métodos , Metales/análisis , Passeriformes/metabolismoRESUMEN
Ecological forecasts are becoming increasingly valuable tools for conservation and management. However, there are few examples of near-real-time forecasting systems that account for the wide range of ecological complexities. We developed a new coral disease ecological forecasting system that explores a suite of ecological relationships and their uncertainty and investigates how forecast skill changes with shorter lead times. The Multi-Factor Coral Disease Risk product introduced here uses a combination of ecological and marine environmental conditions to predict the risk of white syndromes and growth anomalies across reefs in the central and western Pacific and along the east coast of Australia and is available through the US National Oceanic and Atmospheric Administration Coral Reef Watch program. This product produces weekly forecasts for a moving window of 6 months at a resolution of ~5 km based on quantile regression forests. The forecasts show superior skill at predicting disease risk on withheld survey data from 2012 to 2020 compared with predecessor forecast systems, with the biggest improvements shown for predicting disease risk at mid- to high-disease levels. Most of the prediction uncertainty arises from model uncertainty, so prediction accuracy and precision do not improve substantially with shorter lead times. This result arises because many predictor variables cannot be accurately forecasted, which is a common challenge across ecosystems. Weekly forecasts and scenarios can be explored through an online decision support tool and data explorer, co-developed with end-user groups to improve use and understanding of ecological forecasts. The models provide near-real-time disease risk assessments and allow users to refine predictions and assess intervention scenarios. This work advances the field of ecological forecasting with real-world complexities and, in doing so, better supports near-term decision making for coral reef ecosystem managers and stakeholders. Secondarily, we identify clear needs and provide recommendations to further enhance our ability to forecast coral disease risk.
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Antozoos , Arrecifes de Coral , Animales , Medición de Riesgo/métodos , Predicción , Conservación de los Recursos Naturales/métodos , Australia , Monitoreo del Ambiente/métodos , Modelos BiológicosRESUMEN
Awareness of racial health care inequities is one prerequisite to eliminating them. Although extant research has described awareness of racial health care inequities in the United States, the health impacts of such awareness on communities that are most impacted by these inequities remains unknown. Therefore, we examined associations between awareness of Black-White racial health care inequities and self-rated health for Black and White adults in the United States. We used survey data from non-Hispanic Black and White participants (N = 6,449) who responded to the national American Health Values Survey (2015-2016) to test associations between awareness of Black-White inequities in health care and self-rated health. Accurate awareness of health care inequities was associated with 47% higher odds of poorer self-rated health for Black individuals. Inaccurate awareness was associated with 36% higher odds of poorer self-rated health for White individuals. Accurate awareness may be adaptive, yet place an additional burden on Black individuals. Inaccurate awareness may harm White individuals' health. Health care system changes and alleviation of racism-related stress may be preventive supports for the health of Black individuals. Accurate awareness should be a goal for White individuals, not only to prevent health risks, but to also facilitate structural change for racial equity. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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Aim: To understand awareness, knowledge and preferences regarding genetic testing among the USA general public. Methods: A cross-sectional online survey using a Qualtrics Panel. Results: Among 1600 respondents, 545 (34%) were White, 411 (26%) Black, 412 (26%) Hispanic or Latin(x) and 232 (15%) Asian. Most had heard of ancestry testing (87%) and genetic health risk testing (69%), but a third thought inherited genes were only a little or not at all responsible for obesity (36%) and mental health (33%). The majority preferred pre-emptive pharmacogenetic testing (n = 74%) compared with reactive testing. Statistically significant differences between racial/ethnic groups and rural-urban respondents were observed. Conclusion: Most preferred pre-emptive pharmacogenetic testing; however, about one-quarter preferred reactive testing. Preferences should be discussed during patient-clinician interactions.
What is this study about? This study presents a large online survey among the USA general public to understand their awareness, knowledge and preferences about genetic testing and how this may vary by racial/ethnic group and rural/urban status.What were the results? Most survey respondents had heard of ancestry testing (87%) and genetic health risk testing (69%). However, over a third of respondents thought that inherited genes may be only a little or not at all responsible for obesity (36%) and mental health (33%). When asked about preferences for pre-emptive compared with reactive pharmacogenetic testing, the majority preferred pre-emptive testing (n = 74%). Statistically significant differences between racial/ethnic groups as well as rural-urban respondents were seen.What do the results mean? The US general public may have a different understanding of genetic testing for different diseases, and have different preferences when it comes to the timing of testing. Appropriate educational content targeting the link between genetics and specific diseases should be prepared, and preferences for pre-emptive or reactive testing should be discussed during visits with healthcare providers.
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Pruebas Genéticas , Conocimientos, Actitudes y Práctica en Salud , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Concienciación , Estudios Transversales , Etnicidad/genética , Pruebas Genéticas/métodos , Prioridad del Paciente , Pruebas de Farmacogenómica , Encuestas y Cuestionarios , Estados Unidos , Blanco , Negro o Afroamericano , Hispánicos o Latinos , AsiáticoRESUMEN
Ceftriaxone is an antibiotic that increases central nervous system (CNS) protein expression of the glutamate transporters GLT-1 and xCT and ameliorates pathological behaviors in rodent models of neurological disease and substance use disorder. However, little ceftriaxone passes through the blood-brain barrier, the CNS binding partner of ceftriaxone is unknown, and ceftriaxone does not consistently upregulate GLT-1 and xCT in cell culture. Ceftriaxone alters the gut microbiome composition in rodents and humans, and the microbiome-gut-brain axis regulates drug-seeking. Thus, here we test the hypothesis that ceftriaxone reduces alcohol intake while ameliorating alcohol-induced disruption of the gut microbiome composition. Male and female Sprague-Dawley rats received intermittent access to alcohol (IAA) while controls received access to only water. Following 17 IAA sessions, ceftriaxone/vehicle treatment was given for 5 days. Analysis of the gut microbiome composition was assessed by 16S rRNA gene amplicon sequencing conducted on fecal pellets collected prior to and after alcohol consumption and following ceftriaxone treatment. Male rats displayed escalated alcohol intake and preference over the course of the 17 sessions; however, total alcohol intake did not differ between the sexes. Ceftriaxone reduced alcohol intake and preference in male and female rats. While alcohol affected a diverse set of amplicon sequencing variants (ASV), ceftriaxone markedly reduced the diversity of microbial communities reflected by a blooming of the Enterococcaceae family. The remaining effects of ceftriaxone, however, encompassed families both affected and unaffected by prior alcohol drinking and highlight the Ruminococcaceae and Muribaculaceae families as bidirectionally modulated by alcohol and ceftriaxone. Altogether, our study confirms that ceftriaxone reduces alcohol intake in rats and partially reverses alcohol-induced dysbiosis.
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Consumo de Bebidas Alcohólicas , Ceftriaxona , Microbioma Gastrointestinal , Ratas Sprague-Dawley , Animales , Femenino , Masculino , Ceftriaxona/farmacología , Microbioma Gastrointestinal/efectos de los fármacos , Ratas , Antibacterianos/farmacología , Etanol/farmacología , Etanol/administración & dosificación , Heces/microbiologíaRESUMEN
As the kynurenine pathway's links to inflammation, the immune system, and neurological disorders became more apparent, it attracted more and more attention. It is the main pathway through which the liver breaks down Tryptophan and the initial step in the creation of nicotinamide adenine dinucleotide (NAD+) in mammals. Immune system activation and the buildup of potentially neurotoxic substances can result from the dysregulation or overactivation of this pathway. Therefore, it is not shocking that kynurenines have been linked to neurological conditions (Depression, Parkinson's, Alzheimer's, Huntington's Disease, Schizophrenia, and cognitive deficits) in relation to inflammation. Nevertheless, preclinical research has demonstrated that kynurenines are essential components of the behavioral analogs of depression and schizophrenia-like cognitive deficits in addition to mediators associated with neurological pathologies due to their neuromodulatory qualities. Neurodegenerative diseases have been extensively associated with neuroactive metabolites of the kynurenine pathway (KP) of tryptophan breakdown. In addition to being a necessary amino acid for protein synthesis, Tryptophan is also transformed into the important neurotransmitters tryptamine and serotonin in higher eukaryotes. In this article, a summary of the KP, its function in neurodegeneration, and the approaches being used currently to target the route therapeutically are discussed.