RESUMO
BACKGROUND: Myelin oligodendrocyte glycoprotein (MOG) IgG seropositivity is a prerequisite for MOG antibody-associated disease (MOGAD) diagnosis. While a significant proportion of patients experience a relapsing disease, there is currently no biomarker predictive of disease course. We aim to determine whether MOG-IgG epitopes can predict a relapsing course in MOGAD patients. METHODS: MOG-IgG-seropositive confirmed adult MOGAD patients were included (n=202). Serum MOG-IgG and epitope binding were determined by validated flow cytometry live cell-based assays. Associations between epitopes, disease course, clinical phenotype, Expanded Disability Status Scale and Visual Functional System Score at onset and last review were evaluated. RESULTS: Of 202 MOGAD patients, 150 (74%) patients had MOG-IgG that recognised the immunodominant proline42 (P42) epitope and 115 (57%) recognised histidine103/serine104 (H103/S104). Fifty-two (26%) patients had non-P42 MOG-IgG and showed an increased risk of a relapsing course (HR 1.7; 95% CI 1.15 to 2.60, p=0.009). Relapse-freedom was shorter in patients with non-P42 MOG-IgG (p=0.0079). Non-P42 MOG-IgG epitope status remained unchanged from onset throughout the disease course and was a strong predictor of a relapsing course in patients with unilateral optic neuritis (HR 2.7, 95% CI 1.06 to 6.98, p=0.038), with high specificity (95%, 95% CI 77% to 100%) and positive predictive value (85%, 95% CI 45% to 98%). CONCLUSIONS: Non-P42 MOG-IgG predicts a relapsing course in a significant subgroup of MOGAD patients. Patients with unilateral optic neuritis, the most frequent MOGAD phenotype, can reliably be tested at onset, regardless of age and sex. Early detection and specialised management in these patients could minimise disability and improve long-term outcomes.
Assuntos
Autoanticorpos , Imunoglobulina G , Glicoproteína Mielina-Oligodendrócito , Recidiva , Humanos , Glicoproteína Mielina-Oligodendrócito/imunologia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Autoanticorpos/sangue , Autoanticorpos/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Epitopos/imunologia , Biomarcadores/sangue , Neurite Óptica/imunologia , Neurite Óptica/sangueRESUMO
Adolescent refugees confront a complex interplay of trauma arising from forced displacement, resettlement, and the challenges of transitioning from childhood to adulthood. Using photovoice methodology, this study engaged 14 Iraqi and Syrian adolescent refugees now residing in the United States with the aim to illuminate their well-being experiences. Our findings show that temporal continuities and discontinuities in adolescent refugees' lives contributed to their sense of well-being by helping satisfy their basic psychological needs for autonomy, competence, relatedness, and safety. Temporal continuities involved drawing upon past resources and formulating future career aspirations based on present experiences. Temporal discontinuities encompassed contrasting past and present and processing adversities endured. This study underscores that, beyond current circumstances, the interpretation of life experiences over extended timeframes influences the well-being of adolescent refugees.
Assuntos
Refugiados , Humanos , Adolescente , Estados Unidos , Criança , Adulto Jovem , Refugiados/psicologiaRESUMO
Children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop less severe coronavirus disease 2019 (COVID-19) than adults. The mechanisms for the age-specific differences and the implications for infection-induced immunity are beginning to be uncovered. We show by longitudinal multimodal analysis that SARS-CoV-2 leaves a small footprint in the circulating T cell compartment in children with mild/asymptomatic COVID-19 compared to adult household contacts with the same disease severity who had more evidence of systemic T cell interferon activation, cytotoxicity and exhaustion. Children harbored diverse polyclonal SARS-CoV-2-specific naïve T cells whereas adults harbored clonally expanded SARS-CoV-2-specific memory T cells. A novel population of naïve interferon-activated T cells is expanded in acute COVID-19 and is recruited into the memory compartment during convalescence in adults but not children. This was associated with the development of robust CD4+ memory T cell responses in adults but not children. These data suggest that rapid clearance of SARS-CoV-2 in children may compromise their cellular immunity and ability to resist reinfection.
Assuntos
COVID-19 , Humanos , Adulto , SARS-CoV-2 , Linfócitos T CD4-Positivos , Imunidade Celular , Ativação Linfocitária , Anticorpos AntiviraisRESUMO
Although a more efficient adaptive humoral immune response has been proposed to underlie the usually favorable outcome of pediatric COVID-19, the breadth of viral and vaccine cross-reactivity toward the ever-mutating Spike protein among variants of concern (VOCs) has not yet been compared between children and adults. We assessed antibodies to conformational Spike in COVID-19-naïve children and adults vaccinated by BNT162b2 and ChAdOx1, and naturally infected with SARS-CoV-2 Early Clade, Delta, and Omicron. Sera were analyzed against Spike including naturally occurring VOCs Alpha, Beta, Gamma, Delta, and Omicron BA.1, BA.2, BA.5, BQ.1.1, BA2.75.2, and XBB.1, and variants of interest Epsilon, Kappa, Eta, D.2, and artificial mutant Spikes. There was no notable difference between breadth and longevity of antibody against VOCs in children and adults. Vaccinated individuals displayed similar immunoreactivity profiles across variants compared with naturally infected individuals. Delta-infected patients had an enhanced cross-reactivity toward Delta and earlier VOCs compared to patients infected by Early Clade SARS-CoV-2. Although Omicron BA.1, BA.2, BA.5, BQ.1.1, BA2.75.2, and XBB.1 antibody titers were generated after Omicron infection, cross-reactive binding against Omicron subvariants was reduced across all infection, immunization, and age groups. Some mutations, such as 498R and 501Y, epistatically combined to enhance cross-reactive binding, but could not fully compensate for antibody-evasive mutations within the Omicron subvariants tested. Our results reveal important molecular features central to the generation of high antibody titers and broad immunoreactivity that should be considered in future vaccine design and global serosurveillance in the context of limited vaccine boosters available to the pediatric population.
Assuntos
COVID-19 , Vacinas , Criança , Humanos , Adulto , SARS-CoV-2 , Formação de Anticorpos , Vacina BNT162 , AnticorposRESUMO
OBJECTIVES: We explore the process of posttraumatic growth for multicultural individuals after experiences of cumulative multicultural identity-relevant adversity. METHOD: We conducted an exploratory sequential mixed methods study with two parts. Study 1 utilized Photovoice methodology and individual interviews (N = 27; 13 women, 14 men) with multicultural individuals living in a Midwestern college town. In Study 2, we tested the relationships between themes revealed by our qualitative analysis in Study 1 in a sample of multicultural individuals living across the U.S. (N = 526; 40.1% men, 59.9% women) using a conditional process analysis. RESULTS: Findings from Study 1 indicate that participants appreciated environments that valued diversity, and this helped participants positively frame their cumulative adversities. Participants also described how the struggle with these adversities fostered psychological wellbeing outcomes of personal growth and positive relations with others. Results from Study 2 indicate that appreciation of diversity mediates and positive framing moderates the relationship between discrimination and personal growth, thus supporting and building on the findings in Study 1. CONCLUSIONS: Together, these studies highlight the significance of including cumulative adversity in the posttraumatic growth process for multicultural individuals, while identifying appreciation of diversity and positive framing as potential postadversarial growth mechanisms. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
Assuntos
Crescimento Psicológico Pós-Traumático , Masculino , Humanos , Feminino , Pesquisa Qualitativa , Diversidade Cultural , Bem-Estar PsicológicoRESUMO
Our research explores the experience of holding a Hybrid Multicultural Identity (a superordinate cultural identity; HMI) and the social contextual experiences hybrid multiculturals describe as influential to the development of an HMI. We conducted a Photovoice study with 10 hybrid multiculturals (age 18-32; 6 women and 4 men) living in a college town in the Midwestern US. The participants valued HMI for the psychological advantages they attributed to this identity. We also found the participants described three broad categories of their social environment that were key to the development of HMI: cultural composition in living environments, perceptions of macro-level marginalization, and culturally related interpersonal experiences. Our research documents (1) the lived experience of being a hybrid multicultural (2) the importance of cultural mixing for HMI development, and (3) how people with HMI describe primarily negative perceptions of the social environment as instrumental to the development of HMI.
Assuntos
Diversidade Cultural , Meio Social , Adolescente , Adulto , Feminino , Humanos , Masculino , Adulto JovemRESUMO
The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) antibody neutralization response and its evasion by emerging viral variants and variant of concern (VOC) are unknown, but critical to understand reinfection risk and breakthrough infection following vaccination. Antibody immunoreactivity against SARS-CoV-2 antigens and Spike variants, inhibition of Spike-driven virus-cell fusion, and infectious SARS-CoV-2 neutralization were characterized in 807 serial samples from 233 reverse transcription polymerase chain reaction (RT-PCR)-confirmed Coronavirus Disease 2019 (COVID-19) individuals with detailed demographics and followed up to 7 months. A broad and sustained polyantigenic immunoreactivity against SARS-CoV-2 Spike, Membrane, and Nucleocapsid proteins, along with high viral neutralization, was associated with COVID-19 severity. A subgroup of "high responders" maintained high neutralizing responses over time, representing ideal convalescent plasma donors. Antibodies generated against SARS-CoV-2 during the first COVID-19 wave had reduced immunoreactivity and neutralization potency to emerging Spike variants and VOC. Accurate monitoring of SARS-CoV-2 antibody responses would be essential for selection of optimal responders and vaccine monitoring and design.
Assuntos
Anticorpos Neutralizantes/imunologia , SARS-CoV-2/patogenicidade , Adulto , Anticorpos Antivirais/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas do Nucleocapsídeo/imunologia , SARS-CoV-2/imunologiaRESUMO
Loss of expression of ACTN3, due to homozygosity of the common null polymorphism (p.Arg577X), is underrepresented in elite sprint/power athletes and has been associated with reduced muscle mass and strength in humans and mice. To investigate ACTN3 gene dosage in performance and whether expression could enhance muscle force, we performed meta-analysis and expression studies. Our general meta-analysis using a Bayesian random effects model in elite sprint/power athlete cohorts demonstrated a consistent homozygous-group effect across studies (per allele OR = 1.4, 95% CI 1.3-1.6) but substantial heterogeneity in heterozygotes. In mouse muscle, rAAV-mediated gene transfer overexpressed and rescued α-actinin-3 expression. Contrary to expectation, in vivo "doping" of ACTN3 at low to moderate doses demonstrated an absence of any change in function. At high doses, ACTN3 is toxic and detrimental to force generation, to demonstrate gene doping with supposedly performance-enhancing isoforms of sarcomeric proteins can be detrimental for muscle function. Restoration of α-actinin-3 did not enhance muscle mass but highlighted the primary role of α-actinin-3 in modulating muscle metabolism with altered fatiguability. This is the first study to express a Z-disk protein in healthy skeletal muscle and measure the in vivo effect. The sensitive balance of the sarcomeric proteins and muscle function has relevant implications in areas of gene doping in performance and therapy for neuromuscular disease.
Assuntos
Actinina/genética , Músculo Esquelético/fisiologia , Anaerobiose , Animais , Animais Recém-Nascidos , Atletas , Calcineurina/metabolismo , Dependovirus/metabolismo , Regulação para Baixo/genética , Estudo de Associação Genômica Ampla , Heterozigoto , Homozigoto , Humanos , Camundongos Endogâmicos C57BL , Fadiga Muscular , Fibras Musculares Esqueléticas/metabolismo , Tamanho do Órgão , OxirreduçãoRESUMO
BACKGROUND: Canine otitis externa (OE) is a common inflammatory disease that is frequently complicated by secondary bacterial and/or yeast infections. The otic microbial population is more complex than appreciated by cytological methods and aerobic culture alone. HYPOTHESIS/OBJECTIVES: Differences in bacterial and fungal populations of the external ear canal will correlate with specific cytological and culture-based definitions of bacterial and Malassezia otitis. ANIMALS: Forty client-owned dogs; 30 with OE and 10 with healthy ears. METHODS AND MATERIALS: Prospective study comparing cytological samples, aerobic bacterial cultures and culture-independent sequencing-based analyses of the external ear canal. Subjects with OE included 10 dogs with only cocci [≥25/high power field (HPF)] on cytological evaluation and culture of Staphylococcus spp.; 10 dogs with rods (≥25/HPF) and exclusive culture of Pseudomonas aeruginosa; 10 dogs with only yeast on cytological results morphologically compatible with Malassezia spp. (≥5/HPF). RESULTS: Staphylococcus was the most abundant taxa across all groups. Ears cytologically positive for cocci had decreased diversity, and all types of OE were associated with decreased fungal diversity compared to controls. CONCLUSIONS AND CLINICAL IMPORTANCE: Cytological and culture-based assessment of the ear canal is not predictive of the diverse microbiota of the ear canal in cases of Pseudomonas or Malassezia otitis. Less abundant bacterial taxa in cases of staphylococcal OE are worth scrutiny for future biological therapy.
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Doenças do Cão/microbiologia , Meato Acústico Externo/microbiologia , Microbiota , Micobioma , Otite Externa/microbiologia , Animais , Bactérias/classificação , Bactérias/isolamento & purificação , Doenças do Cão/epidemiologia , Cães , Meato Acústico Externo/patologia , Feminino , Fungos/classificação , Fungos/isolamento & purificação , Malassezia/patogenicidade , Masculino , Otite Externa/epidemiologia , Estudos Prospectivos , Pseudomonas/patogenicidade , Estados Unidos/epidemiologiaRESUMO
An estimated 1.5 billion people worldwide are deficient in the skeletal muscle protein α-actinin-3 due to homozygosity for the common ACTN3 R577X polymorphism. α-Actinin-3 deficiency influences muscle performance in elite athletes and the general population. The sarcomeric α-actinins were originally characterised as scaffold proteins at the muscle Z-line. Through studying the Actn3 knockout mouse and α-actinin-3 deficient humans, significant progress has been made in understanding how ACTN3 genotype alters muscle function, leading to an appreciation of the diverse roles that α-actinins play in muscle. The α-actinins interact with a number of partner proteins, which broadly fall into three biological pathways-structural, metabolic and signalling. Differences in functioning of these pathways have been identified in α-actinin-3 deficient muscle that together contributes to altered muscle performance in mice and humans. Here we discuss new insights that have been made in understanding the molecular mechanisms that underlie the consequences of α-actinin-3 deficiency.
Assuntos
Actinina/genética , Desempenho Atlético/fisiologia , Músculo Esquelético/fisiologia , Doenças Musculares/genética , Actinina/deficiência , Animais , Humanos , Camundongos , Camundongos Knockout , Doenças Musculares/metabolismo , Doenças Musculares/patologiaRESUMO
Epacadostat (EPA, INCB024360) is a first-in-class, orally active, investigational drug targeting the enzyme indoleamine 2,3-dioxygenase 1 (IDO1). In Phase I studies, EPA has demonstrated promising clinical activity when used in combination with checkpoint modulators. When the metabolism of EPA was investigated in humans, three major, IDO1-inactive, circulating plasma metabolites were detected and characterized: M9, a direct O-glucuronide of EPA; M11, an amidine; and M12, N-dealkylated M11. Glucuronidation of EPA to form M9 is the dominant metabolic pathway, and in vitro, this metabolite is formed by UGT1A9. However, negligible quantities of M11 and M12 were detected when EPA was incubated with a panel of human microsomes from multiple tissues, hepatocytes, recombinant human cytochrome P450s (P450s), and non-P450 enzymatic systems. Given the reductive nature of M11 formation and the inability to define its source, the role of gut microbiota was investigated. Analysis of plasma from mice dosed with EPA following pretreatment with either antibiotic (ciprofloxacin) to inhibit gut bacteria or 1-aminobenzotriazole (ABT) to systemically inhibit P450s demonstrated that gut microbiota is responsible for the formation of M11. Incubations of EPA in human feces confirmed the role of gut bacteria in the formation of M11. Further, incubations of M11 with recombinant P450s showed that M12 is formed via N-dealkylation of M11 by CYP3A4, CYP2C19, and CYP1A2. Thus, in humans three major plasma metabolites of EPA were characterized: two primary metabolites, M9 and M11, formed directly from EPA via UGT1A9 and gut microbiota, respectively, and M12 formed as a secondary metabolite via P450s from M11.
Assuntos
Sistema Enzimático do Citocromo P-450/metabolismo , Glucuronosiltransferase/metabolismo , Intestinos/microbiologia , Microbiota , Oximas/metabolismo , Sulfonamidas/metabolismo , Humanos , Espectroscopia de Prótons por Ressonância Magnética , Espectrometria de Massas por Ionização por Electrospray , UDP-Glucuronosiltransferase 1ARESUMO
BACKGROUND: Although zinc responsive dermatosis is typically a disorder of Arctic breed dogs, this study identifies similar cutaneous lesions on the face and pressure points of Boston terrier dogs. HYPOTHESIS/OBJECTIVES: To document the clinical and histological features of localized parakeratotic hyperkeratosis of Boston terrier dogs, to determine if the lesions respond to zinc supplementation and to determine whether tissue zinc levels were decreased in affected versus unaffected dogs. MATERIAL AND METHODS: Sixteen Boston terrier dogs with similar gross and histological findings were identified retrospectively from two institutions. Follow-up information for nine dogs from one institution was obtained from referring veterinarians using a questionnaire. Tissue zinc levels were measured from formalin-fixed paraffin-embedded skin biopsy samples of affected and unaffected dogs using inductively coupled plasma mass spectrometry. RESULTS: Mild to severe parakeratotic hyperkeratosis with follicular involvement was present in all 16 cases. Of the nine dogs for which follow-up information was available, five dogs received oral zinc supplementation and four dogs had documented clinical improvement or resolution of dermatological lesions. The median skin zinc levels were not significantly different between affected and unaffected dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: To the best of the authors' knowledge this is the first report of localized parakeratotic hyperkeratosis in Boston terrier dogs, some of which improved with oral zinc supplementation. Prospective studies in Boston terrier dogs are warranted to document potential zinc deficiency (serum and/or tissue levels, pre- and post-treatment) and to objectively assess response to zinc supplementation and other therapies.
Assuntos
Doenças do Cão/patologia , Paraceratose/veterinária , Dermatopatias Genéticas/veterinária , Administração Oral , Animais , Doenças do Cão/tratamento farmacológico , Doenças do Cão/genética , Cães , Feminino , Masculino , Paraceratose/genética , Paraceratose/patologia , Estudos Retrospectivos , Dermatopatias/veterinária , Dermatopatias Genéticas/patologia , Zinco/administração & dosagem , Zinco/uso terapêuticoRESUMO
OBJECTIVE: To investigate the safety, tolerability and efficacy of combination phentermine and topiramate therapy for maintenance of weight loss. DESIGN, SETTING AND PATIENTS: Retrospective audit of patients attending the Austin Health Weight Control Clinic who were dispensed phentermine-topiramate between 22 January 2010 and 16 July 2012 and after reaching a target weight by following a very low energy diet (VLED). Data collection continued until July 2013. MAIN OUTCOME MEASURES: Number of patients who ceased pharmacotherapy; duration of use of pharmacotherapy; types and numbers of adverse effects; and mean weight and blood pressure measurements at the initial visit, the end of the VLED and the last observation during pharmacotherapy. RESULTS: Data were available for 103 patients who were dispensed phentermine-topiramate; 61 patients ceased combination pharmacotherapy before the end of the data collection period, 41 due to adverse effects (eg, paraesthesia, cognitive changes, dry mouth and depression). The mean duration of use of pharmacotherapy was 10 months. Mean weight decreased by 10% due to the VLED (from 135.5 kg to 122.5 kg) and this loss was maintained. For 30 patients who continued on phentermine-topiramate, the mean duration of pharmacotherapy was 22 months and the mean weight decreased by 6.7 kg between the end of the VLED and the last observation during pharmacotherapy. CONCLUSION: Phentermine-topiramate therapy was not well tolerated; more than half of the patients in our study stopped taking it because of adverse effects, and more than half of the adverse events reported were ascribed to topiramate. However, in those able to continue with pharmacotherapy, the combination was efficacious for both maintenance of weight loss and ongoing weight loss.
Assuntos
Fármacos Antiobesidade/administração & dosagem , Frutose/análogos & derivados , Obesidade/tratamento farmacológico , Fentermina/administração & dosagem , Redução de Peso , Fármacos Antiobesidade/efeitos adversos , Austrália/epidemiologia , Índice de Massa Corporal , Quimioterapia Combinada , Seguimentos , Frutose/administração & dosagem , Frutose/efeitos adversos , Humanos , Auditoria Médica , Obesidade/epidemiologia , Fentermina/efeitos adversos , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Topiramato , Falha de Tratamento , Resultado do Tratamento , Redução de Peso/efeitos dos fármacosRESUMO
Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is diagnosed by serum MOG-immunoglobulin G (MOG-IgG) in association with typical demyelination. 111/1127 patients with paired CSF/serum samples were seropositive for MOG-IgG. Only 7/1016 (0.7%) seronegative patients had CSF-restricted MOG-IgG. While 3/7 patients had longitudinally extensive transverse myelitis, four had a confirmed alternate diagnosis (three multiple sclerosis, one CNS vasculitis). In a national referral setting, CSF-restricted MOG-IgG had a low sensitivity (2.63%, 95%CI 0.55-7.50%) and low positive predictive value (1.97%, 95%CI 0.45-8.13%). We strongly recommend serum as the preferred diagnostic biospecimen, and urge caution in the interpretation of CSF-restricted MOG-IgG in patients without clinico-radiological features consistent with MOGAD.
RESUMO
Over-consumption of iron-rich red meat and hereditary or genetic iron overload are associated with increased risk of colorectal carcinogenesis, yet the mechanistic basis of how metal-mediated signaling leads to oncogenesis remains enigmatic. Using fresh colorectal cancer (CRC) samples we identify Pirin, an iron sensor, that overcomes a rate-limiting step in oncogenesis, by re-activating the dormant human-reverse-transcriptase (hTERT) subunit of telomerase holoenzyme in an iron-(Fe3+)-dependent-manner and thereby drives CRCs. Chemical genetic screens combined with isothermal-dose response fingerprinting and mass-spectrometry identified a small molecule SP2509, that specifically inhibits Pirin-mediated hTERT reactivation in CRCs by competing with iron-(Fe3+) binding. Our findings, first to document how metal ions reactivate telomerase, provide a molecular mechanism for the well-known association between red meat, and increased incidence of CRCs. Small molecules like SP2509 represent a novel modality to target telomerase that acts as driver of 90% human cancers and is yet to be targeted in clinic.
RESUMO
BACKGROUND: A population pharmacokinetic model for phenytoin in Asian pediatric patients was developed to determine the influence of concurrent medications, patient demographics, and blood biochemistry on the pharmacokinetic profile of phenytoin. METHODS: Retrospective clinical data were obtained from 66 patients (age, 1-16 years) for the determination of pharmacokinetic parameters of phenytoin using WinNonmix. Data from 49 patients (74.2%) were allocated in the "index" group, and the other 17 patients (25.8%) in the "validation" group. Models were compared by final log likelihood, mean error as a measure of bias, and root-mean-squared error as a measure of precision. RESULTS: The Michaelis-Menten constant (km) and volume of distribution (V) were fixed at 9.08 mg/L and 1.23 L/kg, respectively. The saturated elimination rate (V × Vmax) of phenytoin was then found to be 0.525 mg/kg per hour (352.9 4 mg/d for a 28.0 kg individual). Patients' body surface area (in square meter) and catalytic activities of liver enzymes aspartate aminotransferase (U/L) and alkaline phosphatase (U/L) appeared to have significant correlation with Vmax, whereas coadministrating drugs with phenytoin did not yield any significant effect. The final model for the saturated elimination rate was (Equation is included in full-text article.) In validation of the final model, the mean error was found to be -0.805 (95% confidence interval, -3.67 to 2.06), and the root-mean-squared error was 7.92 (95% confidence interval, 3.41-12.43). CONCLUSIONS: The obtained results indicated the need to consider patients' body surface area and the catalytic activities of liver enzymes aspartate aminotransferase and alkaline phosphatase when dosing phenytoin. Based on the population pharmacokinetic parameters, a nomogram was subsequently developed for dose individualization of phenytoin in Asian pediatric patients.
Assuntos
Fenitoína/administração & dosagem , Fenitoína/farmacocinética , Fosfatase Alcalina/metabolismo , Povo Asiático , Aspartato Aminotransferases/metabolismo , Criança , Feminino , Humanos , Masculino , Modelos Biológicos , Nomogramas , Fenitoína/efeitos adversos , Medicina de Precisão/métodos , Estudos Retrospectivos , Convulsões/tratamento farmacológico , Convulsões/metabolismoRESUMO
Despite a growing literature on social support networks in religious settings (i.e., church-based social support), little is known about mosque-based support among Muslims. This study investigates the demographic and religious behavior correlates of mosque-based social support among a multi-racial and ethnic sample of 231 young Muslims from southeast Michigan. Several dimensions of mosque-based support are examined including receiving emotional support, giving emotional support, anticipated emotional support and negative interactions with members of one's mosque. Results indicated that women both received and anticipated receiving greater support than did men. Higher educational attainment was associated with receiving and giving less support compared to those with the lowest level of educational attainment. Moreover, highly educated members reported fewer negative interactions than less educated members. Mosque attendance and level of congregational involvement positively predicted receiving, giving, and anticipated emotional support from congregants, but was unrelated to negative interactions. Overall, the study results converge with previously established correlates of church-based emotional support.
RESUMO
We live in a time of disappearing professions, pandemic-related upheaval, and growing social inequality. While recognizing that good opportunities are unequally distributed in society (an injustice that requires rectification), can beliefs about the nature and workings of opportunities help people see the door to their goals as more open than closed, and can these beliefs influence the likelihood of goal attainment? Seven studies (N = 1,031) examined people's beliefs about whether or not opportunities can be changed (growth vs. fixed theory of opportunity). In Studies 1a-4, participants responded to scenarios about competent people (or themselves) with challenging, long-term aspirations. When opportunities were available, both theories predicted high expectations for success and a preference for active strategies to pursue the goal, like being persistent. By contrast, when opportunities seemed unavailable, a stronger fixed theory predicted lower expectations for success and a preference for passive strategies, like simply waiting. We also established the implicit theories' causal role and demonstrated processes explaining how a growth theory leads to higher anticipated success. The final two studies examined unemployed people. In Study 5, those with a stronger growth theory chose to engage more in a task about cultivating new opportunities for employment. Study 6 showed that those with a stronger growth theory were more likely to report securing employment 5 months later, even when controlling for motivation-relevant variables, education, and socioeconomic status. They also engaged in more active job-search strategies. These studies offer a novel perspective on when, how, and why people initiate and maintain goal pursuit. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
Assuntos
Logro , Motivação , Humanos , Fatores Socioeconômicos , Classe Social , EscolaridadeRESUMO
OBJECTIVE: The aim of the study is to investigate the association between patient self-efficacy, impression of exercise education, and physical activity among stroke survivors. We hypothesized that low self-efficacy and/or poor impressions of exercise education after stroke would be associated with reduced exercise participation. DESIGN: This is a cross-sectional investigation of patients' poststroke with physical activity as the primary outcome variable. Physical activity was measured with the Physical Activity Scale for Individuals with Physical Disabilities. Self-efficacy was measured with the Self-Efficacy for Exercise questionnaire. Impression of exercise education measured by the Exercise Impression Questionnaire. RESULTS: There was a low but significant correlation between Self-Efficacy for Exercise questionnaire and Physical Activity Scale for Individuals with Physical Disabilities ( r (66) = 0.272, P = 0.012). There was an insignificant correlation between Exercise Impression Questionnaire and Physical Activity Scale for Individuals with Physical Disabilities ( r (66) = 0.174, P = 0.078). There was a low but significant correlation between age and Physical Activity Scale for Individuals with Physical Disabilities ( r (66) = -0.269, P = 0.013). There was no correlation between sex and Physical Activity Scale for Individuals with Physical Disabilities ( r (66) = 0.051, P = 0.339). Age, sex, Exercise Impression Questionnaire, and Self-Efficacy for Exercise questionnaire predict 17.1% of Physical Activity Scale for Individuals with Physical Disabilities variance ( R2 = 0.171). CONCLUSION: Self-efficacy was the strongest predictor of physical activity participation. There was a lack of association between the impressions of exercise education and physical activity. Addressing patient confidence to complete exercise has the potential to improve exercise participation in patients after stroke.
Assuntos
Exercício Físico , Acidente Vascular Cerebral , Humanos , Estudos Transversais , Escolaridade , Autoeficácia , Inquéritos e QuestionáriosRESUMO
Biliary atresia is a fibroinflammatory neonatal disease with no effective therapies. A subset of cases (10-20%) is associated with laterality defects - labeled biliary atresia splenic malformation (BASM) syndrome. Recently, whole-exome sequencing of patients with BASM identified deleterious variants in PKD1L1. PKD1L1 is involved in left-right axis determination; however, its role in cholangiocytes is unknown. We generated the pkd1l1hsc117 allele using CRISPR/Cas9 mutagenesis in zebrafish to determine the role of Pkd1l1 in biliary development and function. Wild-type and mutant larvae were assessed for laterality defects, biliary function and biliary tree architecture at 5â days post fertilization. pkd1l1hsc117 mutant larvae exhibited early left-right patterning defects. The gallbladder was positioned on the left in 47% of mutants compared to 4% of wild-type larvae. Accumulation of PED6 in the gallbladder, an indicator of hepatobiliary function, was significantly reduced in pkd1l1hsc117 mutants (46%) compared to wild-type larvae (4%). pkd1l1hsc117 larvae exhibited fewer biliary epithelial cells and reduced density of the intrahepatic biliary network compared to those in wild-type larvae. These data highlight the essential role of pkd1l1 in normal development and function of the zebrafish biliary system, supporting a role for this gene as a cause of BASM.