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1.
Conserv Biol ; : e14273, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38775248

RESUMO

The use of celebrity endorsement in environmental conservation interventions aiming to influence human behavior has increased in recent decades. Although good practice in designing, implementing, and evaluating behavioral interventions is outlined in recent publications, guidance on developing conservation interventions with celebrity endorsement remains limited. To fill this gap, we devised a guide for decision-making relating to celebrity-endorsed behavioral interventions based on the behavioral, project design, and celebrity endorsement literatures. The guide advises conducting research to understand the behavior system in question; defining endorser selection models and celebrities based on the research; developing an endorsement strategy with the appropriate communication channels; testing the celebrity, channels, and strategy with the target audience and making adjustments as needed; and, finally, evaluating the intervention after implementation. We applied this strategy to a case study, the aim of which was to design a celebrity-endorsed intervention to reduce consumption of wild meat in Ho Chi Minh City, Vietnam. Following our guide, we found that employing evidence-based decision-making substantially enhanced our ability to understand the complexity and potential cost associated with using celebrity endorsements in behavioral interventions.


Diseño de intervenciones conductuales para la conservación apoyadas por celebridades Resumen En las últimas décadas se ha incrementado el uso del apoyo de celebridades en las intervenciones de conservación ambiental que buscan influir sobre la conducta humana. Aunque las publicaciones recientes describen las buenas prácticas en el diseño, implementación y evaluación de las intervenciones conductuales, todavía son limitadas las directrices sobre el desarrollo de intervenciones de conservación apoyadas por celebridades. Para llenar este vacío, diseñamos una guía para decidir en relación con las intervenciones conductuales apoyadas por celebridades con base en la literatura sobre las conductas, diseño de proyectos y apoyo de celebridades. La guía recomienda investigar para entender el sistema conductual en cuestión; definir los modelos de selección de patrocinadores y celebridades con base en esta investigación; desarrollar una estrategia de apoyo con los canales adecuados de comunicación; probar los canales, estrategia y celebridades con el público objetivo y realizar los ajustes necesarios; y, por último, la evaluación de la intervención posterior a la implementación. Aplicamos esta estrategia a un estudio de caso, cuyo objetivo era diseñar una intervención con apoyo de celebridades para reducir el consumo de fauna en Ciudad Ho Chi Minh, Vietnam. Con nuestra guía encontramos que el uso de decisiones basadas en evidencias mejoró sustancialmente nuestra capacidad para entender la complejidad y el costo potencial asociado con el uso de apoyo de celebridades en las intervenciones conductuales.

2.
J Evol Biol ; 37(1): 1-13, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38285665

RESUMO

Climate change is associated with the increase in both the mean and variability of thermal conditions. Therefore, the use of more realistic fluctuating thermal regimes is the most appropriate laboratory method for predicting population responses to thermal heterogeneity. However, the long- and short-term implications of evolving under such conditions are not well understood. Here, we examined differences in key life-history traits among populations of seed beetles (Callosobruchus maculatus) that evolved under either constant control conditions or in an environment with fluctuating daily temperatures. Specifically, individuals from two distinct genetic backgrounds were kept for 19 generations at one of two temperatures, a constant temperature (T = 29 °C) or a fluctuating daily cycle (Tmean = 33 °C, Tmax = 40 °C, and Tmin = 26 °C), and were assayed either in their evolved environment or in the other environment. We found that beetles that evolved in fluctuating environments but were then switched to constant 29 °C conditions had far greater lifetime reproductive success compared with beetles that were kept in their evolved environments. This increase in reproductive success suggests that beetles raised in fluctuating environments may have evolved greater thermal breadth than control condition beetles. In addition, the degree of sexual dimorphism in body size and development varied as a function of genetic background, evolved thermal environment, and current temperature conditions. These results not only highlight the value of incorporating diel fluctuations into climate research but also suggest that populations that experience variability in temperature may be better able to respond to both short- and long-term changes in environmental conditions.


Assuntos
Besouros , Características de História de Vida , Animais , Besouros/genética , Aclimatação , Temperatura , Sementes
3.
J Transl Med ; 22(1): 40, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38195568

RESUMO

BACKGROUND: Dietary sulfur amino acid restriction (SAAR) improves metabolic health in animals. In this study, we investigated the effect of dietary SAAR on body weight, body composition, resting metabolic rate, gene expression profiles in white adipose tissue (WAT), and an extensive blood biomarker profile in humans with overweight or obesity. METHODS: N = 59 participants with overweight or obesity (73% women) were randomized stratified by sex to an 8-week plant-based dietary intervention low (~ 2 g/day, SAAR) or high (~ 5.6 g/day, control group) in sulfur amino acids. The diets were provided in full to the participants, and both investigators and participants were blinded to the intervention. Outcome analyses were performed using linear mixed model regression adjusted for baseline values of the outcome and sex. RESULTS: SAAR led to a ~ 20% greater weight loss compared to controls (ß 95% CI - 1.14 (- 2.04, - 0.25) kg, p = 0.013). Despite greater weight loss, resting metabolic rate remained similar between groups. Furthermore, SAAR decreased serum leptin, and increased ketone bodies compared to controls. In WAT, 20 genes were upregulated whereas 24 genes were downregulated (FDR < 5%) in the SAAR group compared to controls. Generally applicable gene set enrichment analyses revealed that processes associated with ribosomes were upregulated, whereas processes related to structural components were downregulated. CONCLUSION: Our study shows that SAAR leads to greater weight loss, decreased leptin and increased ketone bodies compared to controls. Further research on SAAR is needed to investigate the therapeutic potential for metabolic conditions in humans. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04701346, registered Jan 8th 2021, https://www. CLINICALTRIALS: gov/study/NCT04701346.


Assuntos
Aminoácidos Sulfúricos , Sobrepeso , Feminino , Humanos , Masculino , Corpos Cetônicos , Leptina , Obesidade , Redução de Peso
4.
J Psychopathol Clin Sci ; 133(1): 90-102, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38059934

RESUMO

Predicting mood disorders in adolescence is a challenge that motivates research to identify neurocognitive predictors of symptom expression and clinical profiles. This study used machine learning to test whether neurocognitive variables predicted future manic or anhedonic symptoms in two adolescent samples risk-enriched for lifetime mood disorders (Sample 1, n = 73, ages = 13-25, M [SD] = 19.22 [2.49] years, 68% lifetime mood disorder) or familial mood disorders (Sample 2, n = 154, ages = 13-21, M [SD] = 16.46 [1.95] years, 62% first-degree family history of mood disorder). Participants completed cognitive testing and functional magnetic resonance imaging at baseline, for behavioral and neural measures of reward processing and executive functioning. Next, participants completed a daily diary procedure for 8-16 weeks. Penalized mixed-effects models identified neurocognitive predictors of future mood symptoms and stress-reactive changes in mood symptoms. Results included the following. In both samples, adolescents showing ventral corticostriatal reward hyposensitivity and lower reward performance reported more severe stress-reactive anhedonia. Poorer executive functioning behavior was associated with heightened anhedonia overall in Sample 1, but lower stress-reactive anhedonia in both samples. In Sample 1, adolescents showing ventral corticostriatal reward hypersensitivity and poorer executive functioning reported more severe stress-reactive manic symptoms. Clustering analyses identified, and replicated, five neurocognitive subgroups. Adolescents characterized by neural or behavioral reward hyposensitivities together with average-to-poor executive functioning reported unipolar symptom profiles. Adolescents showing neural reward hypersensitivity together with poor behavioral executive functioning reported a bipolar symptom profile (Sample 1 only). Together, neurocognitive phenotypes may hold value for predicting symptom expression and profiles of mood pathology. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Assuntos
Anedonia , Transtornos do Humor , Adolescente , Humanos , Transtornos do Humor/diagnóstico , Transtornos do Humor/psicologia , Afeto , Testes Neuropsicológicos , Função Executiva , Mania
5.
Mol Cancer Ther ; 23(1): 3-13, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-37748190

RESUMO

The Hippo pathway and its downstream effectors, the YAP and TAZ transcriptional coactivators, are deregulated in multiple different types of human cancer and are required for cancer cell phenotypes in vitro and in vivo, while largely dispensable for tissue homeostasis in adult mice. YAP/TAZ and their main partner transcription factors, the TEAD1-4 factors, are therefore promising anticancer targets. Because of frequent YAP/TAZ hyperactivation caused by mutations in the Hippo pathway components NF2 and LATS2, mesothelioma is one of the prime cancer types predicted to be responsive to YAP/TAZ-TEAD inhibitor treatment. Mesothelioma is a devastating disease for which currently no effective treatment options exist. Here, we describe a novel covalent YAP/TAZ-TEAD inhibitor, SWTX-143, that binds to the palmitoylation pocket of all four TEAD isoforms. SWTX-143 caused irreversible and specific inhibition of the transcriptional activity of YAP/TAZ-TEAD in Hippo-mutant tumor cell lines. More importantly, YAP/TAZ-TEAD inhibitor treatment caused strong mesothelioma regression in subcutaneous xenograft models with human cells and in an orthotopic mesothelioma mouse model. Finally, SWTX-143 also selectively impaired the growth of NF2-mutant kidney cancer cell lines, suggesting that the sensitivity of mesothelioma models to these YAP/TAZ-TEAD inhibitors can be extended to other tumor types with aberrations in Hippo signaling. In brief, we describe a novel and specific YAP/TAZ-TEAD inhibitor that has potential to treat multiple Hippo-mutant solid tumor types.


Assuntos
Mesotelioma Maligno , Mesotelioma , Adulto , Humanos , Animais , Camundongos , Via de Sinalização Hippo , Proteínas de Sinalização YAP , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Mesotelioma/tratamento farmacológico , Mesotelioma/genética , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Supressoras de Tumor/metabolismo
6.
Dev Psychol ; 60(2): 211-227, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37843515

RESUMO

Culture is a key determinant of children's development both in its own right and as a measure of generalizability of developmental phenomena. Studying the role of culture in development requires information about participants' demographic backgrounds. However, both reporting and treatment of demographic data are limited and inconsistent in child development research. A barrier to reporting demographic data in a consistent fashion is that no standardized tool currently exists to collect these data. Variation in cultural expectations, family structures, and life circumstances across communities make the creation of a unifying instrument challenging. Here, we present a framework to standardize demographic reporting for early child development (birth to 3 years of age), focusing on six core sociodemographic construct categories: biological information, gestational status, health status, community of descent, caregiving environment, and socioeconomic status. For each category, we discuss potential constructs and measurement items and provide guidance for their use and adaptation to diverse contexts. These items are stored in an open repository of context-adapted questionnaires that provide a consistent approach to obtaining and reporting demographic information so that these data can be archived and shared in a more standardized format. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Assuntos
Desenvolvimento Infantil , Classe Social , Criança , Humanos , Pré-Escolar , Inquéritos e Questionários , Nível de Saúde
7.
Adv Sci (Weinh) ; 11(11): e2307103, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38158637

RESUMO

Understanding the mechanisms of antibiotic resistance is critical for the development of new therapeutics. Traditional methods for testing bacteria are often limited in their efficiency and reusability. Single bacterial cells can be studied at high throughput using double emulsions, although the lack of control over the oil shell permeability and limited access to the droplet interior present serious drawbacks. Here, a straightforward strategy for studying bacteria-encapsulating double emulsion-templated giant unilamellar vesicles (GUVs) is introduced. This microfluidic approach serves to simultaneously load bacteria inside synthetic GUVs and to permeabilize their membrane with the pore-forming peptide melittin. This enables antibiotic delivery or the influx of fresh medium into the GUV lumen for highly parallel cultivation and antimicrobial efficacy testing. Polymer-based GUVs proved to be efficient culture and analysis microvessels, as microfluidics allow easy selection and encapsulation of bacteria and rapid modification of culture conditions for antibiotic development. Further, a method for in situ profiling of biofilms within GUVs for high-throughput screening is demonstrated. Conceivably, synthetic GUVs equipped with biopores can serve as a foundation for the high-throughput screening of bacterial colony interactions during biofilm formation and for investigating the effect of antibiotics on biofilms.


Assuntos
Ensaios de Triagem em Larga Escala , Microfluídica , Permeabilidade , Antibacterianos/farmacologia , Lipossomas Unilamelares
8.
Front Psychol ; 14: 1239001, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37901078

RESUMO

Studying at university involves demanding academic and clinical training requirements for students from Psychology and other health-allied fields, potentially having severe physical and mental health implications. Existing training programs for addressing burnout have focused thus far on specific areas (e.g., stress management, physical exercise, mindfulness meditation, etc.) with promising outcomes. However, no comprehensive programs have been developed to train students and staff in the early identification of burnout signs and characteristics as well as in self-assessing personal needs and habits (i.e., primary prevention), or in identifying community resources and evidence-based strategies to overcome burnout (i.e., secondary prevention). This paper describes the content development, refinement, and piloting process of the BENDiT-EU program as part of a European collaborative to address academic burnout for health-allied students. Piloting results showed that participants viewed the program positively and provided helpful suggestions for content improvement and training delivery. Future research directions should target experimental investigations of the program's effectiveness and the longitudinal interaction of burnout with other variables (e.g., resilience).

9.
Arch Pathol Lab Med ; 2023 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-37776247

RESUMO

CONTEXT.­: In 2018 the College of American Pathologists Diagnostic Immunology and Flow Cytometry Committee designed and implemented a new plasma cell neoplasia flow cytometry proficiency testing program-PCNEO-to allow clinical flow cytometry laboratories to monitor and assess their performance compared with a peer group. OBJECTIVE.­: To report the results from the first 4 years of the PCNEO program. DESIGN.­: Program participants were sent 2 sets of challenges per year, each including 1 wet challenge and 2 dry challenges, with associated clinical and laboratory findings. The wet challenges were composed of myeloma cell line specimens (with or without dilution in preserved whole blood) for flow cytometric analysis. The dry (paper) challenges were composed of clinical case summaries and images of flow cytometric test results from various flow cytometry laboratories of committee members. RESULTS.­: A total of 116 to 145 laboratories from 17 countries enrolled in the proficiency testing program. For the wet challenges, almost all participants (97%-100%; cumulative, 98.2%) correctly identified the presence of neoplastic plasma cell populations based on flow cytometric analysis of undiluted myeloma cell lines. Slightly fewer participants (89.0%-97.4%; cumulative, 95.2%) correctly identified the presence of neoplastic plasma cell populations based on flow cytometric analysis of diluted myeloma cell lines (10% or 50% dilutions into peripheral blood) intended to better represent a typical clinical sample. There was generally agreement among 80% or more of participants for positive or negative staining for CD38, CD138, CD19, CD20, and surface and cytoplasmic κ and λ light chains. Similarly, 84% to 100% of participants were able to correctly identify the presence of neoplastic plasma cell populations in paper challenges, including the presence of small, neoplastic plasma cell populations (0.01%-5.0% clonal plasma cells), or the presence of nonneoplastic plasma cell populations (correctly identified by 91%-96% of participants). CONCLUSIONS.­: Participant performance in the new proficiency testing program was excellent overall, with the vast majority of participants able to perform flow cytometric analysis and identify neoplastic plasma cell populations, and to identify small plasma cell clones or expanded populations of reactive plasma cells in dry challenge flow cytometry results. This program will allow laboratories to verify the accuracy of their testing program and test interpretations for the assessment of patients suspected of having a plasma cell neoplasm.

11.
Curr Dev Nutr ; 7(8): 101971, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37560461

RESUMO

Background: There remains a need to identify low-cost interventions to improve coronavirus disease 2019 (COVID-19) outcomes. Vitamin D and zinc play a role in respiratory infections and could hold value as part of therapeutic regimens. Objectives: To determine the effect of vitamin D or zinc supplementation on recovery from COVID-19. Methods: We conducted a double-blind, randomly assigned 2 x 2 factorial placebo-controlled trial with 1:1:1:1 allocation ratio, enrolling nonpregnant adults with COVID-19 from hospitals in Mumbai and Pune, India (NCT04641195). Participants (N = 181) were randomly assigned to vitamin D3 (180,000 IU bolus, then 2000 IU daily), zinc (40 mg daily), vitamin D3 and zinc, or placebo, for 8 wk. Participants were followed until 8 wk. The primary outcome was time to resolution of fever, cough, and shortness of breath. Secondary outcomes were duration of individual symptoms; need for assisted ventilation; duration of hospital stay; all-cause mortality; and blood biomarkers, including nutritional, inflammatory, and immunological markers. Results: We observed no effect of vitamin D or zinc supplementation on time to resolution of all 3 symptoms [vitamin D hazard ratio (HR): 0.92; 95% confidence interval (95% CI): 0.66, 1.30; P = 0.650; zinc HR: 0.94; 95% CI: 0.67, 1.33; P = 0.745)]. Neither vitamin D nor zinc supplementation was associated with secondary outcomes, except for increased endline serum vitamin D with vitamin D supplementation [median (interquartile range) difference between endline and baseline for vitamin D: 5.3 ng/mL (-2.3 to 13.7); for no vitamin D: -1.4 ng/mL (-5.6 to 3.9); P = 0.003]. We observed nonsignificant increases in serum zinc at endline following zinc supplementation. There was no evidence of interaction between vitamin D and zinc supplementation, no effect of either on hypercalcemia, and no adverse events. Conclusions: Results suggest that neither vitamin D nor zinc supplementation improves COVID-19 treatment outcomes in this population. However, much larger-scale evidence, particularly from populations with vitamin D or zinc deficiency and severe infection, is required to corroborate our findings. This trial was registered at ClinicalTrials.gov and the Clinical Trials Registry of India as NCT04641195 and CTRI/2021/04/032593 respectively.

12.
Healthcare (Basel) ; 11(16)2023 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-37628436

RESUMO

(1) Background: There is a fundamental shift in healthcare toward shared decision making (SDM). This study explores SDM from the perspective of individuals affected by mental illness and their family members and investigates factors which promote and hinder the process. (2) Methods: We conducted N = 15 telephone interviews (n = 4 adults affected by mental illness, n = 5 family members, n = 6 both applicable, the majority reporting experiences with affective and anxiety disorders). Data were recorded, transcribed, and analyzed according to procedures established by Mayring. (3) Results: Individuals affected by mental illness and their family members have a strong desire to be involved in treatment decisions and to participate in finding a diagnosis. Often these stakeholders are denied the opportunity to participate; sometimes enabling behaviors impede participation. The stigmatization of mental illnesses is a major barrier. There are also structural barriers to SDM within the healthcare system. Peer support, self-help associations, and psychosocial counseling services are important to empowering individuals and promoting SDM. (4) Conclusions: SDM has the potential to improve the quality of mental healthcare. Barriers can be mitigated and new approaches for interventions in the psychiatric sector have been identified. This study has also shown the importance of understanding SDM as a process that should begin at the diagnostic phase.

13.
Circulation ; 148(14): 1099-1112, 2023 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-37602409

RESUMO

BACKGROUND: Cardiac reprogramming is a technique to directly convert nonmyocytes into myocardial cells using genes or small molecules. This intervention provides functional benefit to the rodent heart when delivered at the time of myocardial infarction or activated transgenically up to 4 weeks after myocardial infarction. Yet, several hurdles have prevented the advancement of cardiac reprogramming for clinical use. METHODS: Through a combination of screening and rational design, we identified a cardiac reprogramming cocktail that can be encoded in a single adeno-associated virus. We also created a novel adeno-associated virus capsid that can transduce cardiac fibroblasts more efficiently than available parental serotypes by mutating posttranslationally modified capsid residues. Because a constitutive promoter was needed to drive high expression of these cell fate-altering reprogramming factors, we included binding sites to a cardiomyocyte-restricted microRNA within the 3' untranslated region of the expression cassette that limits expression to nonmyocytes. After optimizing this expression cassette to reprogram human cardiac fibroblasts into induced cardiomyocyte-like cells in vitro, we also tested the ability of this capsid/cassette combination to confer functional benefit in acute mouse myocardial infarction and chronic rat myocardial infarction models. RESULTS: We demonstrated sustained, dose-dependent improvement in cardiac function when treating a rat model 2 weeks after myocardial infarction, showing that cardiac reprogramming, when delivered in a single, clinically relevant adeno-associated virus vector, can support functional improvement in the postremodeled heart. This benefit was not observed with GFP (green fluorescent protein) or a hepatocyte reprogramming cocktail and was achieved even in the presence of immunosuppression, supporting myocyte formation as the underlying mechanism. CONCLUSIONS: Collectively, these results advance the application of cardiac reprogramming gene therapy as a viable therapeutic approach to treat chronic heart failure resulting from ischemic injury.


Assuntos
MicroRNAs , Infarto do Miocárdio , Ratos , Camundongos , Humanos , Animais , Dependovirus/genética , Miócitos Cardíacos/metabolismo , Infarto do Miocárdio/terapia , Infarto do Miocárdio/tratamento farmacológico , MicroRNAs/genética , MicroRNAs/metabolismo , Terapia Genética/métodos , Proteínas de Fluorescência Verde/genética , Reprogramação Celular , Fibroblastos/metabolismo
14.
J Wildl Dis ; 59(4): 815-817, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37578742

RESUMO

A free-living Bald Eagle (Haliaeetus leucocephalus) displayed acute onset neurologic signs. Postmortem analysis of adipose tissue identified desmethylbromethalin, the active metabolite of bromethalin. Antemortem signs, detection of desmethylbromethalin, and results of other diagnostics support the possibility of secondary bromethalin toxicosis. Investigation of bromethalin's potential risk to wildlife is critically needed.


Assuntos
Águias , Animais , Animais Selvagens , Compostos de Anilina/análise , Tecido Adiposo/química
15.
PLOS Glob Public Health ; 3(7): e0000713, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37450441

RESUMO

There is very limited data on the extent and determinants of COVID-19 vaccine hesitancy among adults living in sub-Saharan Africa since the global roll-out of vaccines began in 2021. This multi-country survey sought to investigate COVID-19 vaccine hesitancy and other predictors of readiness to get vaccinated. We conducted surveys among adults residing in nine urban and rural areas in Burkina Faso, Ethiopia, Ghana, Nigeria, and Tanzania in late 2021. Log binomial regression models were used to identify prevalence and factors associated with vaccine hesitancy and beliefs around COVID-19 misinformation. We completed a total of 2,833 interviews. Among all respondents, 9% had never heard of a COVID-19 vaccine, 12% had been vaccinated, and 20% knew someone else who had been vaccinated. The prevalence of vaccine hesitancy varied by country (Ethiopia 29%, Burkina Faso 33%, Nigeria 34%, Ghana 42%, Tanzania 65%), but not by rural or urban context. People who did not think the vaccine was safe or effective, or who were unsure about it, were more likely to be vaccine hesitant. Those who reported they did not have a trusted source of information about the vaccine (aPR: 1.25, 95% CI: 1.18,1.31) and those who thought the vaccine would not be made available to them within the year were more likely to be vaccine hesitant. Women were more likely to be vaccine hesitant (aPR: 1.31, 95% CI: 1.19,1.43) and believe COVID-19 falsehoods (aPR: 1.05, 95% CI: 1.02,1.08). The most commonly believed falsehoods were that the vaccine was developed too fast and that there was not enough information about whether the vaccine was effective or not. Educational campaigns targeted at misinformation and tailored to suit each country are recommended to build trust in COVID-19 vaccines and reduce hesitancy.

16.
J Immunother Cancer ; 11(6)2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37270183

RESUMO

Immune checkpoint inhibitors (ICI) target the PD-1/PD-L1 and CTLA-4 pathways and allows the immune system to deliver antitumor effects. However, it is also associated with well-documented immune-related cutaneous adverse events (ircAEs), affecting up to 70-90% of patients on ICI. In this study, we describe the characteristics of and patient outcomes with ICI-associated steroid-refractory or steroid-dependent ircAEs treated with dupilumab. Patients with ircAEs treated with dupilumab between March 28, 2017, and October 1, 2021, at Memorial Sloan Kettering Cancer Center were included in this retrospective study, which assessed the rate of clinical response of the ircAE to dupilumab and any associated adverse events (AEs). Laboratory values were compared before and after dupilumab. All available biopsies of the ircAEs were reviewed by a dermatopathologist. Thirty-four of 39 patients (87%, 95% CI: 73% to 96%) responded to dupilumab. Among these 34 responders, 15 (44.1%) were complete responders with total ircAE resolution and 19 (55.9%) were partial responders with significant clinical improvement or reduction in severity. Only 1 patient (2.6%) discontinued therapy due to AEs, specifically, injection site reaction. Average eosinophil counts decreased by 0.2 K/mcL (p=0.0086). Relative eosinophils decreased by a mean of 2.6% (p=0.0152). Total serum immunoglobulin E levels decreased by an average of 372.1 kU/L (p=0.0728). The most common primary inflammatory patterns identified on histopathological examination were spongiotic dermatitis (n=13, 33.3%) and interface dermatitis (n=5, 12.8%). Dupilumab is a promising option for steroid-refractory or steroid-dependent immune-related cutaneous adverse events, particularly those that are eczematous, maculopapular, or pruritic. Among this cohort, dupilumab was well-tolerated with a high overall response rate. Nonetheless, prospective, randomized, controlled trials are warranted to confirm these observations and confirm its long-term safety.


Assuntos
Anticorpos Monoclonais , Dermatite , Humanos , Anticorpos Monoclonais/uso terapêutico , Estudos Retrospectivos , Estudos Prospectivos , Dermatite/tratamento farmacológico
17.
Clin Psychol Sci ; 11(2): 308-325, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37309523

RESUMO

Adolescence is critical period of neurocognitive development as well as increased prevalence of mood pathology. This cross-sectional study replicated developmental patterns of neurocognition and tested whether mood symptoms moderated developmental effects. Participants were 419 adolescents (n=246 with current mood disorders) who completed reward learning and executive functioning tasks, and reported on age, puberty, and mood symptoms. Structural equation modeling revealed a quadratic relationship between puberty and reward learning performance that was moderated by symptom severity: in early puberty, adolescents reporting higher manic symptoms exhibited heightened reward learning performance (better maximizing of rewards on learning tasks), whereas adolescents reporting elevated anhedonia showed blunted reward learning performance. Models also showed a linear relationship between age and executive functioning that was moderated by manic symptoms: adolescents reporting higher mania showed poorer executive functioning at older ages. Findings suggest neurocognitive development is altered in adolescents with mood pathology and suggest directions for longitudinal studies.

18.
Environ Pollut ; 333: 122076, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37336352

RESUMO

Little is known about the ecologic fate of the neurotoxic rodenticide bromethalin, which is currently registered for use in the United States, Canada, and other countries including Australia. There is minimal research on bromethalin's potential to cause secondary toxicosis in nontarget wildlife. The aim of this study was to evaluate adipose tissue in four species of birds of prey presented to a wildlife clinic in Massachusetts, USA, for desmethylbromethalin (DMB), the active metabolite of bromethalin. Birds were also screened for anticoagulant rodenticides (ARs) in liver tissue to present a more complete picture of rodenticide exposures in this geographic area and to evaluate the impact of current mitigation measures in place during the time of sampling, 2021-2022. A total of 44 hawks and owls were included; DMB was found in 29.5% of birds and ARs were present in 95.5%. All birds with DMB detections also had residues of ARs. Among birds positive for ARs, 81% had two or more compounds. To the authors' knowledge the data presented here represent the first published monitoring study to document bromethalin/DMB bioaccumulation in obligate carnivores. As DMB is a more potent neurotoxicant than its parent compound, these results are cause for concern and an indication that further monitoring and study of the potential risk of bromethalin to wildlife species is needed. These findings have global implications as increasing concern regarding exposure to and toxicosis from ARs in nontarget wildlife worldwide leads to a search for alternatives and effective mitigation approaches.


Assuntos
Aves Predatórias , Rodenticidas , Animais , Estados Unidos , Rodenticidas/toxicidade , Rodenticidas/metabolismo , Anticoagulantes/toxicidade , Aves/metabolismo , New England , Animais Selvagens/metabolismo , Aves Predatórias/metabolismo
19.
J Nutr ; 153(7): 2027-2040, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37164267

RESUMO

BACKGROUND: Plasma sulfur amino acids (SAAs), i.e., methionine, total cysteine (tCys), total homocysteine (tHcy), cystathionine, total glutathione (tGSH), and taurine, are potential risk factors for obesity and cardiometabolic disorders. However, except for plasma tHcy, little is known about how dietary intake modifies plasma SAA concentrations. OBJECTIVE: To investigate whether the intake of SAAs and proteins or diet quality is associated with plasma SAAs. METHODS: Data from a cross-sectional subset of The Maastricht Study (n = 1145, 50.5% men, 61 interquartile range: [55, 66] y, 22.5% with prediabetes and 34.3% with type 2 diabetes) were investigated. Dietary intake was assessed using a validated food frequency questionnaire. The intake of SAAs (total, methionine, and cysteine) and proteins (total, animal, and plant) was estimated from the Dutch and Danish food composition tables. Diet quality was assessed using the Dutch Healthy Diet Index, the Mediterranean Diet Score, and the Dietary Approaches to Stop Hypertension score. Fasting plasma SAAs were measured by liquid chromatography (LC) tandem mass spectrometry (MS) (LC/MS-MS). Associations were investigated with multiple linear regressions with tertiles of dietary intake measures (main exposures) and z-standardized plasma SAAs (outcomes). RESULTS: Intake of total SAAs and total proteins was positively associated with plasma tCys and cystathionine. Associations were stronger in women and in those with normal body weight. Higher intake of cysteine and plant proteins was associated with lower plasma tHcy and higher cystathionine. Higher methionine intake was associated with lower plasma tGSH, whereas cysteine intake was positively associated with tGSH. Higher intake of methionine and animal proteins was associated with higher plasma taurine. Better diet quality was consistently related to lower plasma tHcy concentrations, but it was not associated with the other SAAs. CONCLUSION: Targeted dietary modifications might be effective in modifying plasma concentrations of tCys, tHcy, and cystathionine, which have been associated with obesity and cardiometabolic disorders.


Assuntos
Aminoácidos Sulfúricos , Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Feminino , Humanos , Cisteína , Cistationina , Estudos Transversais , Dieta , Metionina , Obesidade , Taurina , Homocisteína
20.
Cognit Ther Res ; 47(3): 350-366, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37168696

RESUMO

Background: Maladaptive and adaptive emotion regulation are putative risk and protective factors for depression and anxiety, but most prior research does not differentiate within-person effects from between-person individual differences. The current study does so during the early part of the Covid-19 pandemic when internalizing symptoms were high. Methods: A sample of emerging adult undergraduate students (N = 154) completed online questionnaires bi-weekly on depression, anxiety, and emotion regulation across eight weeks during the early days of the Covid-19 pandemic (April 2nd to June 27th, 2020). Results: Depression demonstrated significantly positive between-person correlations with overall maladaptive emotion regulation, catastrophizing, and self-blame, and negative correlations with overall adaptive emotion regulation and reappraisal. Anxiety demonstrated significantly positive between-person correlations with overall maladaptive emotion regulation, rumination, and catastrophizing, and a negative correlation with reappraisal. After controlling for these between-person associations, however, there were generally no within-person associations between emotion regulation and internalizing symptoms. Conclusions: Emotion regulation and internalizing symptoms might be temporally stable individual differences that cooccur with one another as opposed to having a more dynamic relation. Alternatively, these dynamic mechanisms might operate over much shorter or longer periods compared to the two-week time lag in the current study. Supplementary Information: The online version contains supplementary material available at 10.1007/s10608-023-10366-9.

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