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Sexting is associated with a range of negative outcomes among youth. While parents and caregivers can play a critical role in the prevention of youth risk behaviors, nationally representative research has yet to examine U.S. caregivers' perceptions of youth's sexting motivations to help inform sexting risk prevention efforts. Using 2018 and 2019 Fall ConsumerStyles online panel survey data (N = 1,034), this study estimated and examined U.S. caregivers' perceptions of youth's sexting motivations and the associations of such perceptions with concerns about their children (ages 10-17) getting and sharing sexts (sexual messages, photos, videos). Weighted percentages were calculated to describe caregivers' perceptions of youth's sexting motivations. Logistic regression analyses were performed to examine associations between caregivers' perceptions and concerns about youth's sexting. Results suggest that many caregivers perceive youth sext because they think it is harmless (72.79%), they want to be popular or boast (70.51%), they have low self-esteem (52.00%), and/or it is part of their sexual exploration process (49.05%). Fewer caregivers perceived that youth sext because they want revenge (21.80%) or to harm others (16.06%). Caregivers' concerns about their children getting and sharing sexts were related to perceiving that youth sext because of low self-esteem, sexual exploration processes, or to harm others. The perception that youth sext because they want to be popular or boast was related to concern about youth getting but not sharing sexts. Odds of concern were significantly higher among caregivers from some racial/ethnic subgroups. Findings can inform sexting prevention efforts that include caregivers.
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This research examines barriers to reporting academic dishonesty in early adulthood (Study 1; N = 92) and adolescence (Study 2; N = 137). Participants were asked to describe a recent time they observed a peer cheating and to reflect on their decision about whether to report the cheating. They also responded to hypothetical scenarios about observing typical cheating actions, and the presence of social motives (e.g., whether people who report tend to gain reputations for being snitches) was manipulated in each scenario. Even though participants judged reporting to be the morally right thing to do, doing so was rare and approval for it was low, especially in adolescence. Participants also tended to say they would rather be friends with people who do not report cheaters than with those who do. Participants reasoned about a variety of social concerns to support their judgments about reporting (e.g., concern about their relationship with the cheater, concerns for others' welfare), and the manipulated social motives in the hypothetical scenarios significantly influenced judgments about reporting. These findings inform our understanding of the social dynamics that contribute to decisions about policing academic honesty.
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Enganação , Tabu , Adolescente , Humanos , Animais , Ratos , Adulto , Estudantes , Julgamento , MotivaçãoRESUMO
Most small molecules are unable to rapidly traverse the outer membrane of Gram-negative bacteria and accumulate inside these cells, making the discovery of much-needed drugs against these pathogens challenging. Current understanding of the physicochemical properties that dictate small-molecule accumulation in Gram-negative bacteria is largely based on retrospective analyses of antibacterial agents, which suggest that polarity and molecular weight are key factors. Here we assess the ability of over 180 diverse compounds to accumulate in Escherichia coli. Computational analysis of the results reveals major differences from the retrospective studies, namely that the small molecules that are most likely to accumulate contain an amine, are amphiphilic and rigid, and have low globularity. These guidelines were then applied to convert deoxynybomycin, a natural product that is active only against Gram-positive organisms, into an antibiotic with activity against a diverse panel of multi-drug-resistant Gram-negative pathogens. We anticipate that these findings will aid in the discovery and development of antibiotics against Gram-negative bacteria.
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Antibacterianos/metabolismo , Antibacterianos/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/metabolismo , Aminas/metabolismo , Aminas/farmacologia , Antibacterianos/química , Produtos Biológicos/metabolismo , Produtos Biológicos/farmacologia , Desenho de Fármacos , Escherichia coli/citologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/metabolismo , Bactérias Gram-Negativas/citologia , Bactérias Gram-Positivas/efeitos dos fármacos , Viabilidade Microbiana/efeitos dos fármacos , Quinolonas/metabolismo , Quinolonas/farmacologiaRESUMO
Self-perception in early childhood and self-esteem in adulthood are related to a variety of aspects of psychological wellbeing. The goal of the present study was to examine genetic and familial influences on self-perception and self-esteem in separate samples of children (153 twin pairs of 5-year-olds) and adults (753 twin pairs between the ages of 25-75 years). Genetic common factor modeling showed that three facets of self-perception (physical competence, peer acceptance, and maternal acceptance) loaded onto a single heritable factor in children. Multilevel modeling showed no effects of self or co-twin sex on self-perception, but authoritative parenting style was negatively related to self-perception in boys. Similarly, in Study 2, with the adult sample, five self-esteem items loaded on a single heritable factor with no effects of co-twin sex on adult self-esteem. Remembered maternal affection, paternal affection, and maternal discipline were positively related to self-esteem in adults; maternal affection was especially significant for women. The reversal in direction of parenting effects between early childhood and adulthood suggests that parents may play different roles in shaping how children and adults think of themselves. These results suggest that self-perception in childhood and self-esteem in adulthood are both influenced by genetic and environmental factors and that parenting is an important environmental factor for both children and adults.
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Dietary fiber has numerous health benefits, such as increasing satiety, and is regularly included in healthy dietary recommendations. However, different types and sources of fiber vary in their chemical properties and biological effects. This double-blind, randomized, placebo-controlled, crossover study investigated the effects of resistant starch type 2 (RS2) from wheat on self-reported perceptions of satiety and associated gut hormones in 30 healthy adults ages 40-65 years of age. Participants consumed rolls made using either RS2-enriched wheat flour or a wild-type flour for one week before a test day during which they ate a mixed meal containing the same roll type. Both self-reported perceptions of satiety and plasma concentrations of gut hormones were measured following the meal to assess whether the RS2-enriched wheat enhanced satiety and suppressed hunger for a longer period than the control wheat. Exploratory analysis indicated that fasting and peak concentration of peptide YY3-36 (PYY3-36; qfast = 0.02, qpeak = 0.02) increased, while peak concentration and iAUC of glucose-dependent insulinotropic peptide (GIP; qpeak < 0.001, qiAUC < 0.001) decreased after ingesting RS2-enriched wheat. However, self-reported perceptions of hunger or fullness using visual analog scales (VAS) did not differ following the test meal.
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Amido Resistente , Triticum , Adulto , Idoso , Glicemia , Estudos Cross-Over , Farinha , Humanos , Pessoa de Meia-Idade , Peptídeo YY , Período Pós-Prandial , AutorrelatoRESUMO
STUDY DESIGN: Retrospective observational cohort study. OBJECTIVES: To describe the trend in length of stay (LOS) and its association with the rate of individuals needing total assistance with bowel management upon discharge from inpatient spinal cord injury (SCI) rehabilitation facilities. SETTING: Participants enrolled in the National Spinal Cord Injury Model Systems (NSCIMS) database. METHODS: The NSCIMS database was used to obtain bowel management characteristics from individuals (n = 15,975) aged 15 years or older discharged from inpatient rehabilitation facilities between 1988 and 2016 with known demographic factors and LOS. Levels of bowel management were defined from the functional independence measure (FIM) based on the level of assistance required to complete a bowel program. To control for changes in participant population and injury characteristics over the study period, the inverse probability of treatment weight (IPTW) technique was used. Linear and logistic regressions and the Spearman correlation coefficient were used for statistical analyses. RESULTS: The LOS significantly decreased more than ¾ of a day on average each year from 1988 (LOS: 83.16 days) to 2016 (LOS: 50.53 days). Concurrently, the odds of needing total assistance in bowel management at discharge increased 4.1% each year. The correlation between these trends was moderate (-0.63). Association analyses yielded that a 1-day decrease in average LOS was associated with a 0.53% increase in those needing total assistance for bowel management at discharge. CONCLUSION: Over the years, as inpatient rehabilitation LOS decreased, rates of those needing total assistance for bowel management at discharge increased.
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Alta do Paciente , Traumatismos da Medula Espinal , Humanos , Pacientes Internados , Tempo de Internação , Recuperação de Função Fisiológica , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: The Diamond Princess cruise ship was the site of a large outbreak of coronavirus disease 2019 (COVID-19). Of 437 Americans and their travel companions on the ship, 114 (26%) tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We interviewed 229 American passengers and crew after disembarkation following a ship-based quarantine to identify risk factors for infection and characterize transmission onboard the ship. RESULTS: The attack rate for passengers in single-person cabins or without infected cabinmates was 18% (58/329), compared with 63% (27/43) for those sharing a cabin with an asymptomatic infected cabinmate, and 81% (25/31) for those with a symptomatic infected cabinmate. Whole genome sequences from specimens from passengers who shared cabins clustered together. Of 66 SARS-CoV-2-positive American travelers with complete symptom information, 14 (21%) were asymptomatic while on the ship. Among SARS-CoV-2-positive Americans, 10 (9%) required intensive care, of whom 7 were ≥70 years. CONCLUSIONS: Our findings highlight the high risk of SARS-CoV-2 transmission on cruise ships. High rates of SARS-CoV-2 positivity in cabinmates of individuals with asymptomatic infections suggest that triage by symptom status in shared quarters is insufficient to halt transmission. A high rate of intensive care unit admission among older individuals complicates the prospect of future cruise travel during the pandemic, given typical cruise passenger demographics. The magnitude and severe outcomes of this outbreak were major factors contributing to the Centers for Disease Control and Prevention's decision to halt cruise ship travel in US waters in March 2020.
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COVID-19 , Navios , Diamante , Surtos de Doenças , Humanos , Quarentena , SARS-CoV-2 , Viagem , Estados Unidos/epidemiologiaRESUMO
Protein intake above the recommended dietary allowance (RDA) and resistance training are known anabolic stimuli to support healthy aging. Specifically, protein supplementation after resistance exercise and nightly are strategies to maximize utilization of protein intake above the RDA in healthy adults. As such, the primary objective was to examine the efficacy of protein supplementation and nutritional counseling resulting in either moderate (MOD: â¼1.0 g·kg-1·day-1) or higher (HIGH: â¼1.6 g·kg-1·day-1) protein intake during resistance training on strength (one-repetition maximum, 1-RM; isokinetic and isometric peak torque) in healthy middle-aged adults. Exploratory analyses include diet-exercise effects on lean body mass (LBM), clinical biomarkers, gut microbiota, and diet composition. In all, 50 middle-aged adults (age: 50 ± 8 yr, BMI: 27.2 ± 4.1 kg/m2) were randomized to either MOD or HIGH protein intake during a 10-wk resistance training program (3 × wk). Participants received dietary counseling and consumed either 15 g (MOD) or 30 g (HIGH) of protein from lean beef in the immediate postexercise period and each evening. Maximal strength (1-RM) for all upper and lower body exercises significantly increased with no effect of protein intake (P < 0.050). There was a main effect of time for LBM (P < 0.005). Cardiovascular, renal, or glycemic biomarkers were not affected by the intervention. Gut microbiota were associated with several health outcomes (P < 0.050). In conclusion, higher protein intake above moderate amounts does not potentiate resistance training adaptations in previously untrained middle-aged adults. This trial was registered at clinicaltrials.gov as NCT03029975.NEW & NOTEWORTHY Our research evaluates the efficacy of higher in comparison with moderate animal-based protein intake on resistance exercise training-induced muscle strength, clinical biomarkers, and gut microbiota in middle-aged adults through a dietary counseling-controlled intervention. Higher protein intake did not potentiate training adaptations, nor did the intervention effect disease biomarkers. Both diet and exercise modified gut microbiota composition. Collectively, moderate amounts of high-quality, animal-based protein is sufficient to promote resistance exercise adaptations at the onset of aging.
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Proteínas Alimentares/administração & dosagem , Microbioma Gastrointestinal/efeitos dos fármacos , Força Muscular/efeitos dos fármacos , Treinamento Resistido , Adulto , Fatores Etários , Dieta , Proteínas Alimentares/farmacologia , Suplementos Nutricionais , Comportamento Alimentar/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Treinamento Resistido/métodos , Fatores de TempoRESUMO
Self-esteem is an attitude about the self that predicts psychopathology and general well-being. Parenting practices have been shown to be related to self-esteem, but these estimates are confounded because parents and children share genes. The aim of the present study was to use the monozygotic (MZ) twin difference design to isolate the non-shared environmental impact of remembered parenting on self-esteem. In a sample of 1328 adults (345 MZ twin pairs, 319 DZ twin pairs), retrospective reports of maternal and paternal affection were related to self-esteem, all of which were significantly heritable. Using MZ difference scores, paternal affection differences, but not maternal affection differences, were significantly related to self-esteem differences. These results suggest that parenting provided by the father directly impacts self-esteem through non-shared environmental mechanisms. Maternal affection, on the other hand, impacts self-esteem through shared genes (not shared environment, as shared environment was not a significant aspect of self-esteem). This has implications for parenting intervention programs.
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Poder Familiar/psicologia , Comportamento Paterno/psicologia , Autoimagem , Adulto , Atitude , Bases de Dados Factuais , Meio Ambiente , Feminino , Humanos , Masculino , Comportamento Materno/psicologia , Relações Pais-Filho , Pais/psicologia , Estudos Retrospectivos , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética , Gêmeos Monozigóticos/psicologia , Estados UnidosRESUMO
We examined interactions among genetic, biological, and ecological variables predicting externalizing behaviors in preschool and middle childhood. Specifically, we examined prediction of externalizing behaviors from birth complications and negative emotionality, each moderated by genetic risk for aggression and ecological risk factors of insensitive parenting and low family income. At ages 4 and 5 years, 170 twin pairs and 5 triplet sets (N = 355 children) were tested; 166 of those children were tested again at middle childhood (M = 7.9 years). Multilevel linear modeling results showed generally that children at high genetic risk for aggression or from low-income families were likely to have high scores on externalizing, but for children not at high risk, those with increased birth complications or more negative emotionality had high scores on externalizing. This study underscores the importance of considering biological variables as moderated by both genetic and ecological variables as they predict externalizing behaviors across early childhood.
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Poder Familiar , Gêmeos , Agressão , Criança , Comportamento Infantil , Pré-Escolar , Humanos , Fatores de RiscoRESUMO
The present article examines how job demands and resources are related to indices of strain among healthcare professionals during virus pandemics. The article also presents the results of a study examining the relationships between COVID-19 demands (e.g., lack of personal protective equipment, concerns about infecting family members), resources (meaningful work, social support), and mental health strain within a sample of emergency medicine personnel over six consecutive weeks. COVID-19-related demands and hours worked were hypothesized to be positively related to mental health strain, whereas meaningful work and social support were hypothesized to be negatively related to mental health strain. Hours worked the prior week were hypothesized to exacerbate the positive relationships between COVID-19 demands and mental health strain, whereas the resources of meaningful work and social support were expected to buffer the relationships. Multilevel models controlling for mental health strain the prior week revealed that COVID-19 demands, along with hours worked, were each related to higher mental health strain during the week. Hours worked magnified the within-person relationship between personal COVID-19 demands and mental health strain. In contrast to the hypotheses, social support and meaningful work were not related to mental health strain. Discussion focuses on the implications of the findings for healthcare professionals.
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OBJECTIVE: To describe differences in outcomes between pregnant women with and without coronavirus dsease 2019 (COVID-19). DESIGN: Prospective cohort study of pregnant women consecutively admitted for delivery, and universally tested via nasopharyngeal (NP) swab for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using reverse transcription-polymerase chain reaction. All infants of mothers with COVID-19 underwent SARS-CoV-2 testing. SETTING: Three New York City hospitals. POPULATION: Pregnant women >20 weeks of gestation admitted for delivery. METHODS: Data were stratified by SARS-CoV-2 result and symptomatic status, and were summarised using parametric and nonparametric tests. MAIN OUTCOME MEASURES: Prevalence and outcomes of maternal COVID-19, obstetric outcomes, neonatal SARS-CoV-2, placental pathology. RESULTS: Of 675 women admitted for delivery, 10.4% were positive for SARS-CoV-2, of whom 78.6% were asymptomatic. We observed differences in sociodemographics and comorbidities among women with symptomatic COVID-10 versus asymptomatic COVID-19 versus no COVID-19. Caesarean delivery rates were 46.7% in symptomatic COVID-19, 45.5% in asymptomatic COVID-19 and 30.9% in women without COVID-19 (P = 0.044). Postpartum complications (fever, hypoxia, readmission) occurred in 12.9% of women with COVID-19 versus 4.5% of women without COVID-19 (P < 0.001). No woman required mechanical ventilation, and no maternal deaths occurred. Among 71 infants tested, none were positive for SARS-CoV-2. Placental pathology demonstrated increased frequency of fetal vascular malperfusion, indicative of thrombi in fetal vessels, in women with COVID-19 versus women without COVID-19 (48.3% versus 11.3%, P < 0.001). CONCLUSION: Among pregnant women with COVID-19 at delivery, we observed increased caesarean delivery rates and increased frequency of maternal complications in the postpartum period. Additionally, intraplacental thrombi may have maternal and fetal implications for COVID-19 remote from delivery. TWEETABLE ABSTRACT: COVID-19 at delivery: more caesarean deliveries, postpartum complications and intraplacental thrombi.
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Betacoronavirus , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/epidemiologia , Adulto , COVID-19 , Teste para COVID-19 , Estudos de Casos e Controles , Cesárea , Estudos de Coortes , Infecções por Coronavirus/complicações , Feminino , Hospitalização , Humanos , Recém-Nascido , Masculino , Cidade de Nova Iorque , Pandemias , Pneumonia Viral/complicações , Gravidez , SARS-CoV-2RESUMO
Diazomethane is one of the most versatile reagents in organic synthesis, but its utility is limited by its hazardous nature. Although alternative methods exist to perform the unique chemistry of diazomethane, these suffer from diminished reactivity and/or correspondingly harsher conditions. Herein, we describe the repurposing of imidazotetrazines (such as temozolomide, TMZ, the standard of care for glioblastoma) for use as synthetic precursors of alkyl diazonium reagents. TMZ was employed to conduct esterifications and metal-catalyzed cyclopropanations, and results show that methyl ester formation from a wide variety of substrates is especially efficient and operationally simple. TMZ is a commercially available solid that is non-explosive and non-toxic, and should find broad utility as a replacement for diazomethane.
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Ciclopropanos/química , Diazometano/química , Compostos de Mostarda Nitrogenada/uso terapêutico , Antineoplásicos/farmacologia , Esterificação , Humanos , Modelos Moleculares , Compostos de Mostarda Nitrogenada/farmacologiaRESUMO
Enantioselective total syntheses of the anticancer isocarbostyril alkaloids (+)-7-deoxypancratistatin, (+)-pancratistatin, (+)-lycoricidine, and (+)-narciclasine are described. Our strategy for accessing this unique class of natural products is based on the development of a Ni-catalyzed dearomative trans-1,2-carboamination of benzene. The effectiveness of this dearomatization approach is notable, as only two additional olefin functionalizations are needed to construct the fully decorated aminocyclitol cores of these alkaloids. Installation of the lactam ring has been achieved through several pathways and a direct interconversion between natural products was established via a late-stage C-7 cupration. Using this synthetic blueprint, we were able to produce natural products on a gram scale and provide tailored analogs with improved activity, solubility, and metabolic stability.
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Alcaloides/química , Alcaloides/síntese química , Benzeno/química , Alcaloides/metabolismo , Catálise , Linhagem Celular Tumoral , Técnicas de Química Sintética , Estabilidade de Medicamentos , Humanos , Modelos Moleculares , Conformação Molecular , Solubilidade , EstereoisomerismoRESUMO
INTRODUCTION: HDL is associated with increased longevity and protection from multiple chronic diseases. The major HDL protein ApoA-I has a half-life of about 4 days, however, the effects of diet on the composition of HDL particles at this time scale have not been studied. OBJECTIVES: The objective of this study is to investigate the short term dietary effect on HDL lipidomic composition. METHODS: In this randomized order cross-over study, ten healthy subjects consumed a Mediterranean (Med) and a fast food (FF) diet for 4 days, with a 4-day wash-out between treatments. Lipidomic composition was analyzed in isolated HDL fractions by an untargeted LC-MS method with 15 internal standards. RESULTS: HDL phosphatidylethanolamine (PE) content was increased by FF diet, and 41 out of 170 lipid species were differentially affected by diet. Saturated fatty acids (FAs) and odd chain FA were enriched after FF diet, while very-long chain FA and unsaturated FA were enriched after Med diet. The composition of phosphatidylcholine (PC), triacylglycerol (TG) and cholesteryl ester (CE) were significantly altered to reflect the FA composition of the diet whereas the composition of sphingomyelin (SM) and ceramides were generally unaffected. CONCLUSION: Results from this study indicate that the HDL lipidome is widely remodeled within 4 days of diet change and that certain lipid classes are more sensitive markers of diet whereas other lipid classes are better indicators of non-dietary factors.
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Dieta Mediterrânea , Fast Foods , Lipidômica , Lipoproteínas HDL/metabolismo , Adolescente , Adulto , Estudos Cross-Over , Feminino , Voluntários Saudáveis , Humanos , Lipoproteínas HDL/análise , Masculino , Projetos Piloto , Adulto JovemRESUMO
OBJECTIVES: Rheumatic heart disease (RHD) is a preventable disease frequently recognized in urban slums. Disease rates in Brazilian slums are incommensurate with the country's economic status and the existence of its universal healthcare system. Our study aimed to investigate what system issues may allow for disease persistence, focusing on issues surrounding access and utilization of primary and specialized healthcare services. STUDY DESIGN: This was a two-part (formative phase followed by implementation phase) qualitative study based on interviews and focus groups and analyzed via content analysis. METHODS: One focus group and 17 in-depth interviews with community health workers, primary care providers, and cardiologists who serve slum residents in Brazil and six interviews with key informants (community health researchers and cardiologists) were performed. Interviews with community health workers and primary care providers were from a single heath post in the neighborhood of Liberdade, a populous and previously unstudied slum in Salvador. Cardiologists were recruited from tertiary care referral hospitals in Salvador. RESULTS: Our findings revealed six major chronological categories/themes of issues and twenty subthemes that patients must overcome to avoid developing RHD or to have it successfully medically managed. Major themes include the effects of living in a slum (1), barriers to access and utilization of primary healthcare services (2), treatment in primary healthcare services (3), access/utilization of specialized healthcare services (4), treatment in specialized healthcare services (5), and certain systemic issues (6). CONCLUSION: Slums make residents sick in a manner of ways, and various bottlenecks impeding medical access to both primary care and specialty care exist, requiring multifaceted interventions. We detail major themes and finally suggest interventions that can allow for the health system to successfully eliminate RHD as a public health concern for slum residents.
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Pessoal de Saúde/psicologia , Acessibilidade aos Serviços de Saúde , Áreas de Pobreza , Cardiopatia Reumática/prevenção & controle , Cobertura Universal do Seguro de Saúde , Brasil/epidemiologia , Cardiologistas/psicologia , Agentes Comunitários de Saúde/psicologia , Grupos Focais , Humanos , Médicos de Atenção Primária/psicologia , Pesquisa Qualitativa , Cardiopatia Reumática/epidemiologia , Determinantes Sociais da SaúdeRESUMO
NDUFB11, a component of mitochondrial complex I, is a relatively small integral membrane protein, belonging to the "supernumerary" group of subunits, but proved to be absolutely essential for the assembly of an active complex I. Mutations in the X-linked nuclear-encoded NDUFB11 gene have recently been discovered in association with two distinct phenotypes, i.e. microphthalmia with linear skin defects and histiocytoid cardiomyopathy. We report on a male with complex I deficiency, caused by a de novo mutation in NDUFB11 and displaying early-onset sideroblastic anemia as the unique feature. This is the third report that describes a mutation in NDUFB11, but all are associated with a different phenotype. Our results further expand the molecular spectrum and associated clinical phenotype of NDUFB11 defects.
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Acidose Láctica/genética , Anemia Sideroblástica/genética , Complexo I de Transporte de Elétrons/genética , Microftalmia/genética , Acidose Láctica/complicações , Acidose Láctica/fisiopatologia , Anemia Sideroblástica/complicações , Anemia Sideroblástica/fisiopatologia , Criança , DNA Mitocondrial/genética , Complexo I de Transporte de Elétrons/deficiência , Predisposição Genética para Doença , Humanos , Masculino , Microftalmia/fisiopatologia , Mutação , Linhagem , Fenótipo , Tirosina-tRNA LigaseRESUMO
Clinical finding of cutis laxa, characterized by wrinkled, redundant, sagging, nonelastic skin, is of growing significance due to its occurrence in several different inborn errors of metabolism (IEM). Metabolic cutis laxa results from Menkes syndrome, caused by a defect in the ATPase copper transporting alpha (ATP7A) gene; congenital disorders of glycosylation due to mutations in subunit 7 of the component of oligomeric Golgi (COG7)-congenital disorders of glycosylation (CDG) complex; combined disorder of N- and O-linked glycosylation, due to mutations in ATPase H+ transporting V0 subunit a2 (ATP6VOA2) gene; pyrroline-5-carboxylate reductase 1 deficiency; pyrroline-5-carboxylate synthase deficiency; macrocephaly, alopecia, cutis laxa, and scoliosis (MACS) syndrome, due to Ras and Rab interactor 2 (RIN2) mutations; transaldolase deficiency caused by mutations in the transaldolase 1 (TALDO1) gene; Gerodermia osteodysplastica due to mutations in the golgin, RAB6-interacting (GORAB or SCYL1BP1) gene; and mitogen-activated pathway (MAP) kinase defects, caused by mutations in several genes [protein tyrosine phosphatase, non-receptor-type 11 (PTPN11), RAF, NF, HRas proto-oncogene, GTPase (HRAS), B-Raf proto-oncogene, serine/threonine kinase (BRAF), MEK1/2, KRAS proto-oncogene, GTPase (KRAS), SOS Ras/Rho guanine nucleotide exchange factor 2 (SOS2), leucine rich repeat scaffold protein (SHOC2), NRAS proto-oncogene, GTPase (NRAS), and Raf-1 proto-oncogene, serine/threonine kinase (RAF1)], which regulate the Ras-MAPK cascade. Here, we further expand the list of inborn errors of metabolism associated with cutis laxa by describing the clinical presentation of a 17-month-old girl with Leigh-like syndrome due to enoyl coenzyme A hydratase, short chain, 1, mitochondria (ECHS1) deficiency, a mitochondrial matrix enzyme that catalyzes the second step of the beta-oxidation spiral of fatty acids and plays an important role in amino acid catabolism, particularly valine.
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Cútis Laxa/genética , Enoil-CoA Hidratase/deficiência , Doença de Leigh/genética , Feminino , Humanos , Lactente , Proto-Oncogene MasRESUMO
BACKGROUND: Delirium is common after surgery, although the aetiology is poorly defined. Brain-derived neurotrophic factor (BDNF) is a neurotrophin important in neurotransmission and neuroplasticity. Decreased levels of BDNF have been associated with poor cognitive outcomes, but few studies have characterized the role of BDNF perioperatively. We hypothesized that intraoperative decreases in BDNF levels are associated with postoperative delirium. METHODS: Patients undergoing spine surgery were enrolled in a prospective cohort study. Plasma BDNF was collected at baseline and at least hourly intraoperatively. Delirium was assessed using rigorous methods, including the Confusion Assessment Method (CAM) and CAM for the intensive care unit. Associations of changes in BDNF and delirium were examined using regression models. RESULTS: Postoperative delirium developed in 32 of 77 (42%) patients. The median baseline BDNF level was 7.6 ng ml -1 [interquartile range (IQR) 3.0-11.2] and generally declined intraoperatively [median decline 61% (IQR 31-80)]. There was no difference in baseline BDNF levels by delirium status. However, the percent decline in BDNF was greater in patients who developed delirium [median 74% (IQR 51-82)] vs in those who did not develop delirium [median 50% (IQR 14-79); P =0.03]. Each 1% decline in BDNF was associated with increased odds of delirium in unadjusted {odds ratio [OR] 1.02 [95% confidence interval (CI) 1.00-1.04]; P =0.01}, multivariable-adjusted [OR 1.02 (95% CI 1.00-1.03); P =0.03], and propensity score-adjusted models [OR 1.02 (95% CI 1.00-1.04); P =0.03]. CONCLUSIONS: We observed an association between intraoperative decline in plasma BDNF and delirium. These preliminary results need to be confirmed but suggest that plasma BDNF levels may be a biomarker for postoperative delirium.