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1.
Med Law Rev ; 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39135367

RESUMO

As the use of Artificial Intelligence (AI) technologies in healthcare is expanding, patients in the European Union (EU) are increasingly subjected to automated medical decision-making. This development poses challenges to the protection of patients' rights. A specific patients' right not to be subject to automated medical decision-making is not considered part of the traditional portfolio of patients' rights. The EU AI Act also does not contain such a right. The General Data Protection Regulation (GDPR) does, however, provide for the right 'not to be subject to a decision based solely on automated processing' in Article 22. At the same time, this provision has been severely critiqued in legal scholarship because of its lack of practical effectiveness. However, in December 2023, the Court of Justice of the EU first provided an interpretation of this right in C-634/21 (SCHUFA)-although in the context of credit scoring. Against this background, this article provides a critical analysis of the application of Article 22 GDPR to the medical context. The objective is to evaluate whether Article 22 GDPR may provide patients with the right to refuse automated medical decision-making. It proposes a health-conformant reading to strengthen patients' rights in the EU.

2.
Anxiety Stress Coping ; : 1-22, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38988052

RESUMO

BACKGROUND: Adopting a person-centered approach to coping potentially allows researchers to explore the multifaceted nature of the construct. However, this increasingly adopted approach also has limitations. Namely, employing cluster or latent profile analysis to investigate coping through a person-centered lens often brings a lack of generalizability and subjectivity in interpreting the generated profiles. As such, this study aimed to explore the impact of varied methodology in person-centered investigations of coping profiles. METHODS: 682 university students' (M = 21.3 years old, SD = 3.5) responses to the COPE Inventory were analyzed across item, subscale, and higher-order category levels using cluster and latent profile analysis to produce 6 finalized models for cross-method comparison. RESULTS: Throughout 19 analyses, approach coping, avoidance coping, low coping, and help-seeking profiles were consistently identified, alluding to the potential of universal coping trends. However, membership overlap across COPE structures and methodology was largely inconsistent, with individual participants classified into theoretically distinct profiles based on the methodology employed. CONCLUSION: While evidence suggests latent profile analysis provides a more rigorous approach, the significant impact of minor methodological variations urges a reevaluation of person-centered approaches and incorporation of multi-construct data to enhance the understanding of coping profiles.

3.
J Subst Use Addict Treat ; 165: 209459, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39067768

RESUMO

BACKGROUND: Recovery community centers (RCCs) are a relatively new resource in the recovery support landscape aimed at building their members' recovery capital. In recent years, interest in the value of RCCs has grown, however, no studies have used within-person methods to consider how RCCs may impact the day-to-day lives of their attendees. Using within-person data drawn from members of RCCs, this study examined how visiting RCCs was associated with several same-day indicators of recovery wellbeing and risk: daily sense of meaningfulness, recovery identity, negative affect, and positive affect. METHODS: Participants were 94 visitors of six RCCs in western Pennsylvania. Daily diary methods collected 10 nightly reports of daily RCC attendance and end-of-day meaningfulness, recovery identity, negative affect, and positive affect. Multilevel modeling accounted for nesting in the intensive longitudinal data. In independent models, the study regressed meaningfulness, recovery identity, negative affect, and positive affect onto day- and person-level RCC attendance. RESULTS: Within-person associations between RCC attendance and meaningfulness (b = 6.96, SE = 1.66, p < .001), recovery identity (b = 4.75, SE = 1.08, p < .001), and PA (b = 3.82, SE = 1.45, p < .01) were significant, although NA was not (b = -2.41, SE = 1.34, n.s.). All day- by person-level RCC attendance interactions (in preliminary models) and between-person associations were non-significant across recovery outcomes. CONCLUSIONS: The results indicated that on days participants visited RCCs, they reported significantly higher levels of meaningfulness, recovery identity, and positive affect, although negative affect levels did not significantly differ. Also, those who attended RCCs more frequently did not generally report different levels of recovery wellbeing and risk. Taken together, results suggest visiting RCCs works on a daily basis to support interpersonal processes related to positive recovery outcomes. That RCC visits do not appear to reduce negative affect suggests that additional programs may be needed to address negative affect. The within-person design provided insight into the dynamic processes that contribute to the intrapersonal states that support recovery and a practical approach to examining whether and how RCCs might support recovery. By using individuals as their own controls, the study design provided strong counterfactual inference.

4.
Psychotherapy (Chic) ; 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39023965

RESUMO

There is a rich history of psychological movements that call upon the field to collaborate with clients to both acknowledge and resist oppression, as well as an increasing emphasis in professional guidelines on conceptualizing clients with attention to the role of the social and physical environment, to contemporary experience with power, privilege, and oppression, and to institutional barriers and related disparities. These calls indicate the need for psychological case conceptualization to move beyond preconceived assessments of which aspects of clients' identities are salient to them, to engage with clients' sociocultural identities as situated within systems of power and oppression, and to engage in advocacy to improve clients' socioenvironmental contexts and to challenge structural oppression. In this article, we attend to the foundational contributions of Black psychology, intersectionality, liberation psychology, Indigenous healing, and radical healing for using case conceptualization to guide structurally responsive and impactful treatment and advocacy. We then present a case example drawn from a composite of clinical encounters that captures client distress interwoven with structural forces such as addiction stigma, intersecting classism and sexism, White privilege, and caregiver leave policies. To demonstrate how to integrate structural forces with theory, we present how this case would be conceptualized utilizing psychodynamic frameworks infused with attention to the ways in which structural forces shape and perpetuate the client's distress. To move from naming to integrating structural competency in case conceptualization, psychotherapy training must address how structural forces shape how client distress develops and is maintained and necessitates advocacy outside of the session. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

5.
Artigo em Inglês | MEDLINE | ID: mdl-39051138

RESUMO

Sleep is associated with many costs, but is also important to survival, with a lack of sleep impairing cognitive function and increasing mortality. Sleeping in groups could alleviate sleep-associated costs, or could introduce new costs if social sleeping disrupts sleep. Working with the Jamaican fruit bat (Artibeus jamaicensis), we aimed to: (1) describe sleep architecture, (2) assess how sleeping in groups affects sleep, and (3) quantify total sleep time and identify rapid eye movement (REM) sleep using behavioral indicators that complement physiological evidence of sleep. Twenty-five adult bats were captured in Panama and recorded sleeping in an artificial roost enclosure. Three bats were fitted with an electromyograph and accelerometer and video recorded sleeping alone in controlled laboratory settings. The remaining 22 bats were assigned to differing social configurations (alone, dyad, triad, and tetrad) and video recorded sleeping in an outdoor flight cage. We found that sleep was highly variable among individuals (ranging from 2 h 53 min to 9 h 39 min over a 12-h period). Although we did not detect statistically significant effects and our sample size was limited, preliminary trends suggest that male bats may sleep longer than females, and individuals sleeping in groups may sleep longer than individuals sleeping alone. We also found a high correspondence between total sleep time quantified visually and quantified using actigraphy (with a 2-min immobility threshold) and identified physiological correlates of behaviorally-defined REM. These results serve as a starting point for future work on the ecology and evolution of sleep in bats and other wild mammals.


Dormir está asociado con muchos costos, pero también es importante para la supervivencia, ya que la falta de sueño perjudica la función cognitiva y aumenta la mortalidad. Dormir en grupos podría disminuir los costos asociados con el sueño o podría introducir nuevos costos si este descanso grupal interrumpe el sueño. Trabajando con el murciélago frugívoro jamaicano (A. jamaicensis), nos propusimos: (1) describir la arquitectura del sueño, (2) evaluar cómo dormir en grupos afecta el sueño y (3) cuantificar el tiempo total de sueño e identificar el sueño REM empleando indicadores de comportamiento que complementen la evidencia fisiológica del sueño. Se capturaron 25 murciélagos adultos en Panamá y se les grabó durmiendo en un recinto artificial de descanso. A tres murciélagos se les equipó con un electromiógrafo y un acelerómetro y se les grabó en video durmiendo solos en entornos de laboratorio controlados. Los 22 murciélagos restantes fueron asignados a diferentes configuraciones sociales (solo, díada, tríada, tétrada) y se grabaron en video durmiendo en una jaula de vuelo al aire libre. El sueño fue muy variable entre individuos (desde 2 h 53 min hasta 9 h 39 min durante un período de 12 h). Aunque no detectamos efectos estadísticamente significativos, y nuestro tamaño muestral fue limitado, las tendencias preliminares sugieren que los murciélagos macho pueden dormir más que las hembras, y que los individuos que duermen en grupos pueden dormir más que los individuos que duermen solos. Encontramos una alta correspondencia entre el tiempo total de sueño cuantificado visualmente y cuantificado mediante actigrafía (con un umbral de inmovilidad de 2 minutos) e identificamos correlaciones fisiológicas de lo que definimos como REM en términos de comportamiento. Estos resultados sirven como punto de partida para futuros estudios sobre la ecología y la evolución del sueño en murciélagos y otros mamíferos salvajes.

6.
Cancer Res ; 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38900938

RESUMO

Obesity is associated with increased incidence and metastasis of triple-negative breast cancer (TNBC), an aggressive breast cancer subtype. The extracellular matrix (ECM) is a major component of the tumor microenvironment that drives metastasis. To characterize the temporal effects of age and high-fat diet-driven weight gain on the ECM, we injected allograft tumor cells at 4-week intervals into mammary fat pads of mice fed a control or high-fat diet (HFD), assessing tumor growth and metastasis and evaluating the ECM composition of the mammary fat pads, lungs, and livers. Tumor growth was increased in obese mice after 12 weeks on the HFD. Liver metastasis increased in obese mice only at 4 weeks, and elevated body weight correlated with increased metastasis to the lungs but not the liver. Whole decellularized ECM coupled with proteomics indicated that early stages of obesity were sufficient to induce changes in the ECM composition. Obesity led to increased abundance of the pro-invasive ECM proteins collagen IV and collagen VI in the mammary glands and enhanced the invasive capacity of cancer cells. Cells of stromal vascular fraction and adipose stem and progenitor cells were primarily responsible for secreting collagen IV and VI, not adipocytes. Longer exposure to HFD increased the invasive potential of ECM isolated from lung and liver, with significant changes in ECM composition found in the liver with short-term HFD exposure. Together, this data suggests that changes in the breast, lung, and liver ECM underlie some of the effects of obesity on TNBC incidence and metastasis.

7.
Bioengineering (Basel) ; 11(6)2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38927779

RESUMO

While ovarian tissue cryopreservation (OTC) is an important fertility preservation option, it has its limitations. Improving OTC and ovarian tissue transplantation (OTT) must include extending the function of reimplanted tissue by reducing the extensive activation of primordial follicles (PMFs) and eliminating the risk of reimplanting malignant cells. To develop a more effective OTT, we must understand the effects of the ovarian microenvironment on folliculogenesis. Here, we describe a method for producing decellularized extracellular matrix (dECM) hydrogels that reflect the protein composition of the ovary. These ovarian dECM hydrogels were engineered to assess the effects of ECM on in vitro follicle growth, and we developed a novel method for selectively removing proteins of interest from dECM hydrogels. Finally, we validated the depletion of these proteins and successfully cultured murine follicles encapsulated in the compartment-specific ovarian dECM hydrogels and these same hydrogels depleted of EMILIN1. These are the first, optically clear, tailored tissue-specific hydrogels that support follicle survival and growth comparable to the "gold standard" alginate hydrogels. Furthermore, depleted hydrogels can serve as a novel tool for many tissue types to evaluate the impact of specific ECM proteins on cellular and molecular behavior.

8.
Subst Use ; 18: 29768357241259947, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38881556

RESUMO

This study used the National Survey on Drug Use and Health to assess a nationally representative sample (N = 4596) weighted to represent 35.2 million adults with DSM-5 criteria-determined substance use disorders (SUDs). This study explored substance use treatment utilization in 2020, emphasizing populations with high vulnerability (e.g., criminal justice involvement (CJI) through parole or probation, polysubstance use, severe mental illness, and HIV/STI). Substance use treatment was broadly defined (any inpatient, outpatient/doctor's office, self-help/other for alcohol/drugs). Our results indicated that among adults with SUDs in 2020, 7 million (20%) had multiple SUDs, 1.75 million (5%) had CJI, 5.3 million (15%) had a severe mental illness, and 1.8 million (5%) had a diagnosis of HIV/STI in the last year. Only 7% of individuals with SUD sought any substance use treatment in the past year. CJI (aOR: 13.39, 95% CI: [7.82, 22.94]), serious mental illness (aOR: 3.27, 95% CI: [1.93, 5.55]), and having both 2 (aOR: 2.10, 95% CI: [1.29, 3.42]) or 3 or more SUDs (aOR: 3.46, 95% CI: [1.82, 6.58]) were all associated with a greater likelihood of receiving treatment. Marriage (aOR: 0.43, 95% CI: [0.25, 0.74]) and having an income twice the poverty threshold (aOR: 0.53, 95% CI: [0.29, 0.94]) were associated with reduced odds of receiving any substance use treatment. Compared to those 18 to 25, older individuals had increased odds (2-4 times) of receiving treatment. Interventions are crucially needed to increase access to treatment among those with SUDs.

9.
Biol Psychiatry ; 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38901723

RESUMO

BACKGROUND: Substance use disorder is characterized by long-lasting changes in reward-related brain regions, such as the nucleus accumbens. Previous work has shown that cocaine exposure induces plasticity in broad, genetically defined cell types in the nucleus accumbens; however, in response to a stimulus, only a small percentage of neurons are transcriptionally active-termed an ensemble. Here, we identify an Arc-expressing neuronal ensemble that has a unique trajectory of recruitment and causally controls drug self-administration after repeated, but not acute, cocaine exposure. METHODS: Using Arc-CreERT2 transgenic mice, we expressed transgenes in Arc+ ensembles activated by cocaine exposure (either acute [1 × 10 mg/kg intraperitoneally] or repeated [10 × 10 mg/kg intraperitoneally]). Using genetic, optical, and physiological recording and manipulation strategies, we assessed the contribution of these ensembles to behaviors associated with substance use disorder. RESULTS: Repeated cocaine exposure reduced the size of the ensemble while simultaneously increasing its control over behavior. Neurons within the repeated cocaine ensemble were hyperexcitable, and their optogenetic excitation was sufficient for reinforcement. Finally, lesioning the repeated cocaine, but not the acute cocaine, ensemble blunted cocaine self-administration. Thus, repeated cocaine exposure reduced the size of the ensemble while simultaneously increasing its contributions to drug reinforcement. CONCLUSIONS: We showed that repeated, but not acute, cocaine exposure induced a physiologically distinct ensemble characterized by the expression of the immediate early gene Arc, which was uniquely capable of modulating reinforcement behavior.

10.
Reproduction ; 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38888996

RESUMO

This work describes a valuable and reproducible method for generating optically clear bovine ovary-derived hydrogels that support in vitro murine follicle growth. These techniques are the foundation in which follicle growth dynamics and matrisome protein composition may be correlated to reveal the role of these proteins in folliculogenesis.

11.
PLoS One ; 19(6): e0301157, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38917104

RESUMO

Participants between the ages of 10-86 years old were vaccinated with split-inactivated influenza vaccine (Fluzone®) in six consecutive influenza seasons from 2016-2017 to 2021-2022. Vaccine effectiveness varies from season to season as a result of both host immune responses as well as evolutionary changes in the influenza virus surface glycoproteins that provide challenges to vaccine manufacturers to produce more effective annual vaccines. Next generation influenza vaccines are in development and may provide protective immune responses against a broader number of influenza viruses and reduce the need for annual vaccination. An improved understanding how current influenza vaccines are influenced by human host immune responses in people of different ages and co-morbidities is necessary for designing the next-generation of 'universal' or broadly-protective influenza vaccines. Overall, pre-existing immune responses to previous influenza virus exposures, either by past infections or vaccinations, is a critical factor influencing host responses to seasonal influenza vaccination. Participants vaccinated in consecutive seasons had reduced serum hemagglutination-inhibition (HAI) activity against strains included in the vaccine compared to participants that had not been vaccinated in the preceding 1-2 years prior to entering this study. The magnitude and breadth of these antibody responses were also modulated by the age of the participant. Elderly participants over 65 years of age, in general, had lower pre-existing HAI titers each season prior to vaccination with lower post-vaccination titers compared to children or young adults under the age of 35. The administration of higher doses (HD) of the split-inactivated vaccine enhanced the antibody titers in the elderly. This report showcases 6 consecutive years of antibody HAI activity in human subjects receiving seasonal split-inactivated influenza vaccine.


Assuntos
Anticorpos Antivirais , Vacinas contra Influenza , Influenza Humana , Estações do Ano , Vacinas de Produtos Inativados , Humanos , Vacinas contra Influenza/imunologia , Vacinas contra Influenza/administração & dosagem , Adulto , Idoso , Pessoa de Meia-Idade , Adolescente , Criança , Idoso de 80 Anos ou mais , Masculino , Influenza Humana/prevenção & controle , Influenza Humana/imunologia , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , Feminino , Adulto Jovem , Vacinas de Produtos Inativados/imunologia , Vacinação , Testes de Inibição da Hemaglutinação , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Estudos Longitudinais
12.
Environ Microbiol Rep ; 16(3): e13251, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38778789

RESUMO

We conducted a research campaign in a neotropical rainforest in Costa Rica throughout the drought phase of an El-Nino Southern Oscillation event to determine microbial community dynamics and soil C fluxes. Our study included nests of the leafcutter ant Atta cephalotes, as soil disturbances made by these ecosystem engineers may influence microbial drought response. Drought decreased the diversity of microbes and the abundance of core microbiome taxa, including Verrucomicrobial bacteria and Sordariomycete fungi. Despite initial responses of decreasing diversity and altered composition, 6 months post-drought the microbiomes were similar to pre-drought conditions, demonstrating the resilience of soil microbial communities to drought events. A. cephalotes nests altered fungal composition in the surrounding soil, and reduced both fungal mortality and growth of Acidobacteria post-drought. Drought increased CH4 consumption in soils due to lower soil moisture, and A. cephalotes nests decrease the variability of CH4 emissions in some soil types. CH4 emissions were tracked by the abundance of methanotrophic bacteria and fungal composition. These results characterize the microbiome of tropical soils across both time and space during drought and provide evidence for the importance of leafcutter ant nests in shaping soil microbiomes and enhancing microbial resilience during climatic perturbations.


Assuntos
Formigas , Bactérias , Secas , Fungos , Microbiota , Floresta Úmida , Microbiologia do Solo , Clima Tropical , Formigas/microbiologia , Formigas/fisiologia , Animais , Fungos/classificação , Fungos/fisiologia , Fungos/isolamento & purificação , Costa Rica , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Solo/química , Florestas
13.
Inorg Chem ; 63(20): 9237-9244, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38722713

RESUMO

Mixed-donor ligands, such as those containing a combination of O/N or O/S, have been studied extensively for the selective extraction of trivalent actinides, especially Am3+ and Cm3+, from lanthanides during the recycling of used nuclear fuel. Oxygen/sulfur donor ligand combinations also result from the hydrolytic and/or radiolytic degradation of dithiophosphates, such as the Cyanex class of extractants, which are initially converted to monothiophosphates. To understand potential differences between the binding of such degraded ligands to Nd3+ and Am3+, the monothiophosphate complexes [M(OPS(OEt)2)5(H2O)2]2- (M3+ = Nd3+, Am3+) were prepared and characterized by single-crystal X-ray diffraction and optical spectroscopy and studied as a function of pressure up to ca. 14 GPa using diamond-anvil techniques. Although Nd3+ and Am3+ have nearly identical eight-coordinated ionic radii, these structures reveal that while the M-O bond distances in these complexes are almost equal, the M-S distances are statistically different. Moreover, for [Nd(OPS(OEt)2)5(H2O)2]2-, the hypersensitive 4I9/2 → 4G5/2 transition shifts as a function of pressure by -11 cm-1/GPa. Whereas for [Am(OPS(OEt)2)5(H2O)2]2-, the 7F0 → 7F6 transition shows a slightly stronger pressure dependence with a shift of -13 cm-1/GPa and also exhibits broadening of the 5f → 5f transitions at high pressures. These data likely indicate an increased involvement of the 5f orbitals in bonding with Am3+ relative to that of Nd3+ in these complexes.

14.
PLoS One ; 19(5): e0300373, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38696403

RESUMO

Captive and domestic animals are often required to engage in physical activity initiated or organised by humans, which may impact their body temperature, with consequences for their health and welfare. This is a particular concern for animals such as elephants that face thermoregulatory challenges because of their body size and physiology. Using infrared thermography, we measured changes in skin temperature associated with two types of physical activity in ten female Asian elephants (Elephas maximus) at an eco-tourism lodge in Nepal. Six elephants took part in an activity relatively unfamiliar to the elephants-a polo tournament-and four participated in more familiar ecotourism activities. We recorded skin temperatures for four body regions affected by the activities, as well as an average skin temperature. Temperature change was used as the response variable in the analysis and calculated as the difference in elephant temperature before and after activity. We found no significant differences in temperature change between the elephants in the polo-playing group and those from the non-polo playing group. However, for both groups, when comparing the average skin body temperature and several different body regions, we found significant differences in skin temperature change before and after activity. The ear pinna was the most impacted region and was significantly different to all other body regions. This result highlights the importance of this region in thermoregulation for elephants during physical activity. However, as we found no differences between the average body temperatures of the polo and non-polo playing groups, we suggest that thermoregulatory mechanisms can counteract the effects of both physical activities the elephants engaged in.


Assuntos
Elefantes , Temperatura Cutânea , Animais , Elefantes/fisiologia , Feminino , Temperatura Cutânea/fisiologia , Condicionamento Físico Animal/fisiologia , Temperatura Corporal/fisiologia , Regulação da Temperatura Corporal/fisiologia , Termografia/métodos
15.
J Endocr Soc ; 8(6): bvae073, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38698870

RESUMO

The last 20 years have seen substantial improvements in fertility and hormone preservation and restoration technologies for a growing number of cancer survivors. However, further advancements are required to fill the gaps for those who cannot use current technologies or to improve the efficacy and longevity of current fertility and hormone restoration technologies. Ovarian tissue cryopreservation (OTC) followed by ovarian tissue transplantation (OTT) offers those unable to undergo ovarian stimulation for egg retrieval and cryopreservation an option that restores both fertility and hormone function. However, those with metastatic disease in their ovaries are unable to transplant this tissue. Therefore, new technologies to produce good-quality eggs and restore long-term cyclic ovarian function are being investigated and developed to expand options for a variety of patients. This mini-review describes current and near future technologies including in vitro maturation, in vitro follicle growth and maturation, bioprosthetic ovaries, and stem cell applications in fertility restoration research by their proximity to clinical application.

16.
Biochem Soc Trans ; 52(3): 1085-1098, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38716888

RESUMO

In vivo, muscle and neuronal cells are post-mitotic, and their function is predominantly regulated by proteostasis, a multilayer molecular process that maintains a delicate balance of protein homeostasis. The ubiquitin-proteasome system (UPS) is a key regulator of proteostasis. A dysfunctional UPS is a hallmark of muscle ageing and is often impacted in neuromuscular disorders (NMDs). Malfunction of the UPS often results in aberrant protein accumulation which can lead to protein aggregation and/or mis-localization affecting its function. Deubiquitinating enzymes (DUBs) are key players in the UPS, controlling protein turnover and maintaining the free ubiquitin pool. Several mutations in DUB encoding genes are linked to human NMDs, such as ATXN3, OTUD7A, UCHL1 and USP14, whilst other NMDs are associated with dysregulation of DUB expression. USP5, USP9X and USP14 are implicated in synaptic transmission and remodeling at the neuromuscular junction. Mice lacking USP19 show increased maintenance of lean muscle mass. In this review, we highlight the involvement of DUBs in muscle physiology and NMDs, particularly in processes affecting muscle regeneration, degeneration and inflammation following muscle injury. DUBs have recently garnered much respect as promising drug targets, and their roles in muscle maturation, regeneration and degeneration may provide the framework for novel therapeutics to treat muscular disorders including NMDs, sarcopenia and cachexia.


Assuntos
Enzimas Desubiquitinantes , Humanos , Animais , Enzimas Desubiquitinantes/metabolismo , Músculo Esquelético/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Ubiquitina/metabolismo , Doenças Neuromusculares/metabolismo , Doenças Neuromusculares/genética , Doenças Neuromusculares/fisiopatologia , Doenças Neuromusculares/enzimologia , Doenças Musculares/metabolismo , Doenças Musculares/genética , Camundongos , Proteostase
17.
Proc Natl Acad Sci U S A ; 121(22): e2215051121, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38768346

RESUMO

A representative democracy requires citizens to be politically engaged; however, a substantial portion of eligible United States voters do not vote. While structural (e.g., ease or difficulty of voting) and individual (e.g., political efficacy, civic knowledge) factors contribute to (a lack of) turnout, the present work adopts a sociocultural perspective to investigate an additional contributor: how people construe-or make sense of-the duty to vote. We examine whether, and for whom, construing voting as interdependent (i.e., voting as a duty to others), compared to independent (i.e., voting as a duty to self), is associated with increased perceived duty and political engagement. Archival analysis (n[Formula: see text] 10,185) documents how perceived duty to vote relates to voter turnout in a nationally representative sample of Americans (Study 1). Two preregistered studies (total n[Formula: see text] 1,256) provide evidence that naturalistically construing one's duty to vote as interdependent (Study 2) and experimentally reflecting on interdependence (Study 3) both predict increases in perceived voting duty. Perceived duty to vote, in turn, is associated with heightened political engagement intentions. Taken together, the present work suggests that how voting is construed-as an independent duty to the self or an interdependent duty to others-may meaningfully influence political engagement, with implications for voter turnout interventions.


Assuntos
Política , Humanos , Estados Unidos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Votação
18.
Pharmacopsychiatry ; 57(4): 191-203, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38698605

RESUMO

BACKGROUND: Approximately 15-25% of depressed patients suffer from difficult-to-treat depression (DTD). Patients with DTD require a thorough examination to avoid the oversight of treatable (psychiatric/somatic) comorbidities or (pseudo-)resistance to antidepressant drugs (ADs). Polymorphisms of the cytochrome P450 (CYP) enzymes 2D6 and 2C19, which play a major role in the metabolism of ADs, may contribute to resistance to ADs. Patients with DTD might benefit from electroconvulsive therapy (ECT). METHODS: We enrolled 109 patients with DTD and 29 untreated depressed controls (UDC). We assessed risk phenotypes, comorbidities, and treatment, including ECT. We also performed pharmacokinetic analyses of CYP2D6 and CYP2C19. RESULTS: DTD patients significantly more often suffered from comorbid psychiatric diseases, especially ICD-10: F40-F48 (DTD:40.4%, UDC:17.2%, OR 11.87, p=0.011) than UDC patients. DTD patients receiving ECT were more likely to achieve remission (37.7% vs. 11.8%, OR=3.96, p=0.023). Treatment with ADs did not differ between remitters and non-remitters. No significant differences were observed in the distribution of CYP2D6 and CYP2C19 variants between both groups. CONCLUSION: Patients with DTD appear to experience comorbid neurotic stress and somatoform disorders (ICD-10: F40 - F48) more frequently. Therefore, a comprehensive differential diagnosis is crucial when patients do not respond sufficiently to antidepressant medication. Genotyping CYP2D6 and CYP2C19 should be considered.


Assuntos
Antidepressivos , Comorbidade , Citocromo P-450 CYP2C19 , Citocromo P-450 CYP2D6 , Eletroconvulsoterapia , Fenótipo , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Antidepressivos/uso terapêutico , Citocromo P-450 CYP2D6/genética , Citocromo P-450 CYP2C19/genética , Idoso , Adulto , Transtorno Depressivo Resistente a Tratamento/terapia , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Transtorno Depressivo Resistente a Tratamento/genética , Estudos de Coortes , Resultado do Tratamento
19.
J Patient Exp ; 11: 23743735241240881, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38699654

RESUMO

Understanding differences in how demographic groups experience telehealth may be relevant in addressing potential disparities in telehealth usage. We seek to identify and examine themes most pertinent to patients' negative telehealth experiences by age and race in order to inform interventions to improve patients' future telehealth experiences. We performed a content analysis of Press Ganey patient experience surveys from adult patients at 17 primary care sites of a large, public healthcare system with visits from April 30, 2020 to August 27, 2021. We used sentiment analysis to identify negative comments. We coded for content themes and analyzed their frequency, stratifying by age and race. We analyzed 745 negative comments. Most frequent themes differed by demographic categories, but overall, the most commonly applied codes were "Contacting the Clinic" (n = 97), "Connectivity" (n = 84), and "Webside Manner" (n = 79). The top three codes accounted for >40% of the negative codes in each race category and >35% of the negative codes in each age category. While there were common negative experiences among groups, patients of different demographics highlighted different aspects of their telehealth experiences for potential improvement.

20.
BMC Gastroenterol ; 24(1): 181, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38783208

RESUMO

BACKGROUND: To assess the outcome of previously untreated patients with perihilar cholangiocarcinoma who present to a cancer referral center with or without pre-existing trans-papillary biliary drainage. METHODS: Consecutive patients with a diagnosis of perihilar cholangiocarcinoma presenting between January 1, 2013, and December 31, 2017, were identified from a prospective surgical database and by a query of the institutional database. Of 237 patients identified, 106 met inclusion criteria and were reviewed. Clinical information was obtained from the Electronic Medical Record and imaging studies were reviewed in the Picture Archiving and Communication System. RESULTS: 73 of 106 patients (69%) presenting with a new diagnosis of perihilar cholangiocarcinoma underwent trans-papillary biliary drainage (65 endoscopic and 8 percutaneous) prior to presentation at our institution. 8 of the 73 patients with trans-papillary biliary drainage (11%) presented with and 5 developed cholangitis; all 13 (18%) required subsequent intervention; none of the patients without trans-papillary biliary drainage presented with or required drainage for cholangitis (p = 0.008). Requiring drainage for cholangitis was more likely to delay treatment (p = 0.012) and portended a poorer median overall survival (13.6 months, 95%CI [4.08, not reached)] vs. 20.6 months, 95%CI [18.34, 37.51] p = 0.043). CONCLUSION: Trans-papillary biliary drainage for perihilar cholangiocarcinoma carries a risk of cholangitis and should be avoided when possible. Clinical and imaging findings of perihilar cholangiocarcinoma should prompt evaluation at a cancer referral center before any intervention. This would mitigate development of cholangitis necessitating additional drainage procedures, delaying treatment and potentially compromising survival.


Assuntos
Neoplasias dos Ductos Biliares , Drenagem , Tumor de Klatskin , Humanos , Masculino , Tumor de Klatskin/cirurgia , Tumor de Klatskin/mortalidade , Feminino , Neoplasias dos Ductos Biliares/cirurgia , Idoso , Pessoa de Meia-Idade , Colangite , Idoso de 80 Anos ou mais , Resultado do Tratamento , Adulto , Estudos Retrospectivos
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