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Ecological niche differences are necessary for stable species coexistence but are often difficult to discern. Models of dietary niche differentiation in large mammalian herbivores invoke the quality, quantity, and spatiotemporal distribution of plant tissues and growth forms but are agnostic toward food plant species identity. Empirical support for these models is variable, suggesting that additional mechanisms of resource partitioning may be important in sustaining large-herbivore diversity in African savannas. We used DNA metabarcoding to conduct a taxonomically explicit analysis of large-herbivore diets across southeastern Africa, analyzing â¼4,000 fecal samples of 30 species from 10 sites in seven countries over 6 y. We detected 893 food plant taxa from 124 families, but just two families-grasses and legumes-accounted for the majority of herbivore diets. Nonetheless, herbivore species almost invariably partitioned food plant taxa; diet composition differed significantly in 97% of pairwise comparisons between sympatric species, and dissimilarity was pronounced even between the strictest grazers (grass eaters), strictest browsers (nongrass eaters), and closest relatives at each site. Niche differentiation was weakest in an ecosystem recovering from catastrophic defaunation, indicating that food plant partitioning is driven by species interactions, and was stronger at low rainfall, as expected if interspecific competition is a predominant driver. Diets differed more between browsers than grazers, which predictably shaped community organization: Grazer-dominated trophic networks had higher nestedness and lower modularity. That dietary differentiation is structured along taxonomic lines complements prior work on how herbivores partition plant parts and patches and suggests that common mechanisms govern herbivore coexistence and community assembly in savannas.
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Dieta , Pradaria , Herbivoria , Mamíferos , Plantas , África , Animais , Comportamento Competitivo , Código de Barras de DNA Taxonômico , Dieta/estatística & dados numéricos , Dieta/veterinária , Fabaceae/classificação , Fabaceae/genética , Fezes , Mamíferos/classificação , Mamíferos/fisiologia , Plantas/classificação , Plantas/genética , Poaceae/classificação , Poaceae/genética , ChuvaRESUMO
BACKGROUND: Behaviour support plan (BSP) quality auditing tools like the Behaviour Intervention Plan Quality Evaluation, Version 2 (BIPQEII), assess the quality of a BSP from the perspective of technical compliance with behavioural principles. However, these principles may be inaccessible to interested stakeholders with limited experience and knowledge of positive behaviour support (PBS). The aim of this study was to test if a simplified version of the BIPQEII [the Behaviour Support Plan Audit Tool (BSPA-tool)] offers a reliable and valid assessment of a BSP's technical compliance with behavioural principles when used by professional stakeholders with varying levels of PBS experience and knowledge. METHODS: Four scorers rated 50 de-identified BSPs using the BSPA-tool, with one scorer also rating the BSPs using the BIPQEII. Four weeks later, each scorer rated 25 of the 50 BSPs again using the BSPA-tool. Prior to BSP scoring, a group of PBS practitioners provided feedback on the BSPA-tool's content validity. RESULTS: The BSPA-tool was found to have acceptable content and parallel-form validity; however, acceptable internal consistency and inter-rater and intra-rater reliability were dependent on PBS experience/knowledge, that is, scorers with more experience/knowledge achieved more acceptable levels of reliability. CONCLUSIONS: This study confirms that even with simplification, BSP quality auditing tools based on technical compliance with behavioural principles are still only accessible to stakeholders with extensive experience/knowledge of PBS. To engage less-experienced stakeholders in BSP quality auditing processes, new audit tools need to be developed that focus on other aspects of BSP quality (e.g. readability and consultation).
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Encaminhamento e Consulta , Humanos , Reprodutibilidade dos TestesRESUMO
Objectives: The objectives of this scoping review are to discuss, firstly, the positive aspects of wearing face masks during training (such as a barrier to COVID-19 transmission, air pollutant exposure, and adding load on respiratory resistance flow); secondly, the negative aspects (adverse effects on body temperature and hypoxia risks); and thirdly, the training responses of wearing face masks on aerobic and anaerobic performance. News: Besides social distancing and hand hygiene, wearing a face mask is proposed to be the prime advocacy for virus containment. During the period of high risk of contamination, the return to sport guidelines proposed by international and national sport federations included wearing face masks during training sessions. However, it is necessary to discuss the pros and cons of wearing face masks during exercise. Prospects: Although it was essential to wear a face mask during exercise or sport-specific training, there is conflicting evidence on the implications of the use of face masks on physical, physiological as well as psychological well-being or performance. Based on the conflicting empirical findings and anecdotal evidence, certain recommendations have been made for adequate use of face masks during exercise; both to break the chain of transmission and prevent the physiological compromise expected from wearing face masks during exercise. The present review can help stakeholders balance sport guidelines in the event of a respiratory virus pandemic with athlete safety. Conclusion: Conflicting evidence of mechanistic links between the dose of exercise and the possible adverse effects associated with exercising with face masks is available. Adequately powered studies with strong methodological quality on appropriate selection of masks and usage based on the intensity, duration, and type of sport, age, and gender is needed now for the stakeholders to make informed decisions with respect to exercising with face masks.
Objectifs: Les objectifs de cette revue des connaissances sont de discuter, premièrement, les aspects positifs du port de masques pendant l'entraînement (comme une barrière à la transmission du COVID-19, l'exposition aux polluants atmosphériques et l'ajout de charge sur le flux de résistance respiratoire) ; deuxièmement, les aspects négatifs (effets indésirables sur la température corporelle et risques d'hypoxie) ; et troisièmement, les conséquences du port de masques faciaux à l'entraînement sur les performances aérobie et anaérobie. Nouvelles connaissances: Outre la distanciation physique et l'hygiène des mains, le port d'un masque facial est proposé comme le principal plaidoyer pour la maîtrise des contaminations par le nouveau coronavirus. Pendant la période à haut risque de contamination, les directives de retour au sport proposées par les fédérations sportives internationales et nationales incluaient le port de masques lors des séances d'entraînement. Cependant, il est nécessaire de discuter les avantages et les inconvénients du port de masques faciaux pendant l'exercice. Perspectives: Bien qu'il fut essentiel de porter un masque facial pendant l'exercice ou l'entraînement spécifique au sport, il existe des preuves contradictoires sur les implications des masques faciaux sur les performances physiques, physiologiques, et le bien-être psychologique. Sur la base des résultats contradictoires et de données empiriques, certaines recommandations ont été faites pour une utilisation optimale de masques faciaux pendant l'exercice, à la fois pour briser la chaîne de transmission du virus et éviter le compromis physiologique attendu du port des masques faciaux pendant l'exercice. La présente revue peut aider les parties prenantes à trouver un équilibre entre les directives sportives en cas de pandémie par un virus respiratoire et la sécurité des athlètes. Conclusion: Il existe des données contradictoires sur les liens mécanistiques entre la dose d'exercice et les effets indésirables possibles associés à l'exercice avec des masques faciaux. Des études de qualité au plan méthodologique, sur la sélection des masques, leur utilisation en fonction de l'intensité, de la durée et du type de sport, de l'âge et du sexe des sportifs sont nécessaires pour que les parties prenantes puissent prendre des décisions éclairées en ce qui concerne l'exercice avec des masques faciaux.
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There is growing interest in communicating clinically relevant DNA sequence findings to research participants who join projects with a primary research goal other than the clinical return of such results. Since Geisinger's MyCode Community Health Initiative (MyCode) was launched in 2007, more than 200,000 participants have been broadly consented for discovery research. In 2013 the MyCode consent was amended to include a secondary analysis of research genomic sequences that allows for delivery of clinical results. Since May 2015, pathogenic and likely pathogenic variants from a set list of genes associated with monogenic conditions have prompted "genome-first" clinical encounters. The encounters are described as genome-first because they are identified independent of any clinical parameters. This article (1) details our process for generating clinical results from research data, delivering results to participants and providers, facilitating condition-specific clinical evaluations, and promoting cascade testing of relatives, and (2) summarizes early results and participant uptake. We report on 542 participants who had results uploaded to the electronic health record as of February 1, 2018 and 291 unique clinical providers notified with one or more participant results. Of these 542 participants, 515 (95.0%) were reached to disclose their results and 27 (5.0%) were lost to follow-up. We describe an exportable model for delivery of clinical care through secondary use of research data. In addition, subject and provider participation data from the initial phase of these efforts can inform other institutions planning similar programs.
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Genoma Humano/genética , Estudos de Coortes , Registros Eletrônicos de Saúde , Genômica/métodos , Pessoal de Saúde , Humanos , Análise de Sequência de DNA/métodosRESUMO
Introduction: Patients with acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) have historically poor outcomes with conventional chemotherapy regimens. Current treatment strategies focus on intensive induction therapy followed by allogeneic stem cell transplant or a less intensive approach with hypomethylating agents with or without venetoclax. CPX-351 is a liposomal formulation of cytarabine and daunorubicin that has been shown to significantly improve response rates and survival compared with 7 + 3 (continuous infusion cytarabine plus anthracyclines). Despite the approval of CPX-351 for AML-MRC, overall prognosis remains poor with an unmet need to develop novel therapeutic strategies for this patient population.Areas covered: This article reviews the data for existing therapeutic options for patients with AML-MRC and the emerging therapies undergoing clinical trial development for this patient population.Expert opinion: The development of CPX-351 as a more effective induction therapeutic backbone for patients with AML-MRC presents an opportunity to investigate novel combination regimens in order to further improve outcomes. Promising emerging therapeutic modalities include immunotherapeutic strategies, small-molecule inhibitors and targeted agents. Unfortunately, there have been few clinical trials focusing on patients with AML-MRC with reliance instead on subgroup analyses. Clinical trials focused specifically on this patient population are urgently needed.
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Antineoplásicos , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Síndromes Mielodisplásicas/tratamento farmacológico , PrognósticoRESUMO
BACKGROUND: This study assesses whether increased coverage of the measles, mumps and rubella (MMR) vaccination differs between areas where school nurses deliver catch-up MMR doses to adolescents in school settings, compared to signposting to general practice. METHODS: A retrospective cohort study was conducted using Child Health Information Services records within the NHS England South (South Central) commissioning boundary. The sample population included children born 1 September 2000-31 August 2001, in school year 9 during the 2014-15 academic year. RESULTS: The primary outcome findings show an increase in coverage of at least one dose of MMR by 1.6% (n = 334) in the cohort receiving catch-up MMR, compared to 0.2% (n = 12) in the cohort signposted to general practice. Over time, the difference in increase between the two cohorts was 1.4%, analysed using the chi-squared comparison of proportions test, providing strong evidence (P < 0.0001) that school nurse delivery of catch-up MMR is effective at increasing coverage. The findings also suggest that school nurse delivery of catch-up MMR may benefit Black, Asian and minority ethnic children and those from more deprived backgrounds. CONCLUSIONS: It is recommended that commissioners of school-aged immunization services incorporate the delivery of catch-up MMR doses in their contracts with school nurses.
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Medicina Geral , Sarampo , Enfermeiras e Enfermeiros , Adolescente , Criança , Inglaterra , Humanos , Vacina contra Sarampo-Caxumba-Rubéola , Estudos Retrospectivos , Instituições AcadêmicasRESUMO
BACKGROUND: Exome and genome sequencing are routinely used in clinical care and research. These technologies allow for the detection of pathogenic/likely pathogenic variants in clinically actionable genes. However, fueled in part by a lack of empirical evidence, controversy surrounds the provision of genetic results for adult-onset conditions to minors and their parents. We have designed a mixed-methods, longitudinal cohort study to collect empirical evidence to advance this debate. METHODS: Pediatric participants in the Geisinger MyCode® Community Health Initiative with available exome sequence data will have their variant files assessed for pathogenic/likely pathogenic variants in 60 genes designated as actionable by MyCode. Eight of these genes are associated with adult-onset conditions (Hereditary Breast and Ovarian Cancer Syndrome (HBOC), Lynch syndrome, MUTYH-associated polyposis, HFE-Associated Hereditary Hemochromatosis), while the remaining genes have pediatric onset. Prior to clinical confirmation of results, pediatric MyCode participants and their parents/legal guardians will be categorized into three study groups: 1) those with an apparent pathogenic/likely pathogenic variant in a gene associated with adult-onset disease, 2) those with an apparent pathogenic/likely pathogenic variant in a gene associated with pediatric-onset disease or with risk reduction interventions that begin in childhood, and 3) those with no apparent genomic result who are sex- and age-matched to Groups 1 and 2. Validated and published quantitative measures, semi-structured interviews, and a review of electronic health record data conducted over a 12-month period following disclosure of results will allow for comparison of psychosocial and behavioral outcomes among parents of minors (ages 0-17) and adolescents (ages 11-17) in each group. DISCUSSION: These data will provide guidance about the risks and benefits of informing minors and their family members about clinically actionable, adult-onset genetic conditions and, in turn, help to ensure these patients receive care that promotes physical and psychosocial health. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03832985. Registered 6 February 2019.
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Revelação , Menores de Idade , Adolescente , Adulto , Pré-Escolar , Estudos de Coortes , Feminino , Genômica , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Estudos Observacionais como Assunto , Pais , Literatura de Revisão como AssuntoRESUMO
The COVID-19 pandemic has raised a host of ethical challenges, but key among these has been the possibility that health care systems might need to ration scarce critical care resources. Rationing policies for pandemics differ by institution, health system, and applicable law. Most seem to agree that a patient's ability to benefit from treatment and to survive are first-order considerations. However, there is debate about what clinical measures should be used to make that determination and about other factors that might be ethically appropriate to consider. In this paper, we discuss resource allocation and several related ethical challenges to the healthcare system and society, including how to define benefit, how to handle informed consent, the special needs of pediatric patients, how to engage communities in these difficult decisions, and how to mitigate concerns of discrimination and the effects of structural inequities.
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Comitês Consultivos , Betacoronavirus , Infecções por Coronavirus/epidemiologia , Alocação de Recursos para a Atenção à Saúde/ética , Pneumonia Viral/epidemiologia , Bioética , COVID-19 , Infecções por Coronavirus/prevenção & controle , Humanos , Pandemias/ética , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , SARS-CoV-2 , Estados Unidos/epidemiologiaRESUMO
Acute psychological stress consistently impairs episodic memory, which consists of memory for events that are associated with a specific context. However, researchers have not yet established how stress influences semantic memory, which consists of general knowledge that is devoid of context. In the present study, participants either underwent stress induction or a control task prior to taking a trivia test that was designed to measure semantic memory. In contrast to the wealth of prior research on episodic memory, we found that stress enhanced semantic-memory retrieval. Supporting this finding, higher cortisol reactivity to stress was associated with better performance on the trivia test. Together with the results from previous studies of episodic memory, our findings suggest that stress differentially influences memory retrieval, depending on the degree to which the retrieval of a given memory relies on medial-temporal, neocortical, and striatal brain regions.
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Conhecimento , Memória/fisiologia , Semântica , Estresse Psicológico/psicologia , Doença Aguda , Adolescente , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Mapeamento Encefálico/métodos , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Rememoração Mental/fisiologia , Testes Neuropsicológicos , Estresse Psicológico/diagnóstico , Estresse Psicológico/fisiopatologia , Adulto JovemRESUMO
Smith, Floerke, and Thomas (2016) demonstrated that learning by repeated testing, or retrieval practice, reduced stress-related memory impairment when compared to learning by repeatedly studying material. In the present experiment, we tested whether, relative to study practice, retrieval practice would improve post-stress memory by increasing access to both item and source information. Participants learned two wordlists, which were temporally segregated to facilitate distinction between the two lists. Participants returned one week later for stress induction and two memory tests. Each test featured a recognition test that was given to assess item memory accessibility, and a list-discrimination task that was given to assess source memory. Relative to study practice, successful retrieval practice during learning reduced false alarms but did not improve source memory on the post-stress test. Results are discussed as they relate to current theories surrounding stress effects and retrieval practice effects.
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Rememoração Mental/fisiologia , Prática Psicológica , Reconhecimento Psicológico/fisiologia , Estresse Psicológico/psicologia , Adolescente , Feminino , Humanos , Hidrocortisona/análise , Masculino , Testes Neuropsicológicos , Saliva/química , Adulto JovemRESUMO
PurposeThe clinical utility of screening unselected individuals for pathogenic BRCA1/2 variants has not been established. Data on cancer risk management behaviors and diagnoses of BRCA1/2-associated cancers can help inform assessments of clinical utility.MethodsWhole-exome sequences of participants in the MyCode Community Health Initiative were reviewed for pathogenic/likely pathogenic BRCA1/2 variants. Clinically confirmed variants were disclosed to patient-participants and their clinicians. We queried patient-participants' electronic health records for BRCA1/2-associated cancer diagnoses and risk management that occurred within 12 months after results disclosure, and calculated the percentage of patient-participants of eligible age who had begun risk management.ResultsThirty-seven MyCode patient-participants were unaware of their pathogenic/likely pathogenic BRCA1/2 variant, had not had a BRCA1/2-associated cancer, and had 12 months of follow-up. Of the 33 who were of an age to begin BRCA1/2-associated risk management, 26 (79%) had performed at least one such procedure. Three were diagnosed with an early-stage, BRCA1/2-associated cancer-including a stage 1C fallopian tube cancer-via these procedures.ConclusionScreening for pathogenic BRCA1/2 variants among unselected individuals can lead to occult cancer detection shortly after disclosure. Comprehensive outcomes data generated within our learning healthcare system will aid in determining whether population-wide BRCA1/2 genomic screening programs offer clinical utility.
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Bancos de Espécimes Biológicos , Detecção Precoce de Câncer/métodos , Genes BRCA1 , Genes BRCA2 , Mutação , Neoplasias/diagnóstico , Neoplasias/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Associação Genética , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Síndrome Hereditária de Câncer de Mama e Ovário/diagnóstico , Síndrome Hereditária de Câncer de Mama e Ovário/genética , Humanos , Pessoa de Meia-Idade , Linhagem , Sequenciamento Completo do GenomaRESUMO
BACKGROUND: Little is known about the socio-demographic, clinical and legal determinants of mental health court decisions of unsoundness of mind and unfitness to stand trial for people with cognitive disability. We aimed to estimate the association between severity of cognitive disability and mental health court determinations of unsoundness or unfitness and describe the socio-demographic, clinical and legal factors that predict these determinations. METHODS: Case file data were extracted on 92 individuals who had a criminal case referred to the Queensland Mental Health Court between 1 January 2013 and 31 December 2014 due to cognitive disability. We fit a modified multivariable Poisson regression model to estimate the association between severity of cognitive impairment and mental health court determination, controlling for socio-demographic, clinical and legal factors. RESULTS: Adjusting for covariate effects, severity of cognitive impairment was positively associated with being found unfit to stand trial (adjusted prevalence risk ratio = 1.57; 95% confidence interval: 1.07, 2.33; P = 0.023), and comorbid psychotic disorder predicted an increased risk of being found unsound of mind at the time of offence (adjusted prevalence risk ratio = 3.63; 95% confidence interval: 1.38, 9.54; P = 0.009) by the Queensland Mental Health Court. CONCLUSIONS: Severity of cognitive disability is associated with determinations of unfitness but does not predict determinations of unsoundness in the Queensland Mental Health Court. Psychiatric assessments of cognitive impairment play a pivotal role in mental health court determinations for people with cognitive disability.
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Disfunção Cognitiva , Direito Penal/legislação & jurisprudência , Psiquiatria Legal/legislação & jurisprudência , Deficiência Intelectual , Competência Mental/legislação & jurisprudência , Pessoas Mentalmente Doentes/legislação & jurisprudência , Pessoas com Deficiência Mental/legislação & jurisprudência , Transtornos Psicóticos , Adolescente , Adulto , Disfunção Cognitiva/epidemiologia , Comorbidade , Feminino , Humanos , Deficiência Intelectual/epidemiologia , Masculino , Pessoa de Meia-Idade , Transtornos Psicóticos/epidemiologia , Queensland , Índice de Gravidade de Doença , Adulto JovemRESUMO
BACKGROUND: "Conditional survival probability" is defined as the probability that a patient will survive an additional time, given that the patient has already survived a defined period of time after diagnosis. Such estimates might be more relevant for clinicians and patients during post-diagnosis care, because survival probability projections are based on the patient's survival to date. Here, we provides the first population-based estimates of conditional survival probabilities by histology for brain cancer in Canada. METHODS: Canadian Cancer Registry data were accessed for patients diagnosed with primary brain cancers during 2000-2008. Kaplan-Meier survival probabilities were estimated by histology. Conditional survival probabilities at 6 months (short-term, denoted scs) and 2 years (long-term, denoted lcs) were derived from the Kaplan-Meier survival estimates for a range of time periods. RESULTS: Among the 20,875 patients who met the study criteria, scs increased by a margin of 16-18 percentage points from 6-month survivors to 2-year survivors for the three most aggressive brain cancers. The lcs for 2-year survivors was 66% or greater for all tumour groups except glioblastoma. The lcs for 4-year survivors was 62% or greater for all histologies. For glioblastoma and diffuse astrocytoma, the lcs increased each year after diagnosis. For all other histologies, the lcs first increased and then plateaued from 2 years after diagnosis. The lcs and scs both worsened with increasing older age at diagnosis. SUMMARY: We report histologically specific conditional survival probabilities that can have value for clinicians practicing in Canada as they plan the course of follow-up for individual patients with brain cancer.
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PURPOSE: Geisinger Health System (GHS) provides an ideal platform for Precision Medicine. Key elements are the integrated health system, stable patient population, and electronic health record (EHR) infrastructure. In 2007, Geisinger launched MyCode, a system-wide biobanking program to link samples and EHR data for broad research use. METHODS: Patient-centered input into MyCode was obtained using participant focus groups. Participation in MyCode is based on opt-in informed consent and allows recontact, which facilitates collection of data not in the EHR and, since 2013, the return of clinically actionable results to participants. MyCode leverages Geisinger's technology and clinical infrastructure for participant tracking and sample collection. RESULTS: MyCode has a consent rate of >85%, with more than 90,000 participants currently and with ongoing enrollment of ~4,000 per month. MyCode samples have been used to generate molecular data, including high-density genotype and exome sequence data. Genotype and EHR-derived phenotype data replicate previously reported genetic associations. CONCLUSION: The MyCode project has created resources that enable a new model for translational research that is faster, more flexible, and more cost-effective than traditional clinical research approaches. The new model is scalable and will increase in value as these resources grow and are adopted across multiple research platforms.Genet Med 18 9, 906-913.
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Bancos de Espécimes Biológicos , Pesquisa Biomédica , Registros Eletrônicos de Saúde , Medicina de Precisão , Genótipo , Humanos , Fenótipo , Saúde PúblicaRESUMO
Zika virus is an emerging mosquito-borne flavivirus currently causing large epidemics in the Pacific Ocean region and Brazil. Clinically, Zika fever resembles dengue fever, but is less severe. Whereas the clinical syndrome and laboratory diagnostic procedures have been described, little attention was paid to the immunology of the disease and its possible use for clinical follow-up of patients. Here, we investigate the role of cytokines in the pathogenesis of Zika fever in travelers returning from Asia, the Pacific, and Brazil. Polyfunctional T cell activation (Th1, Th2, Th9, and Th17 response) was seen during the acute phase characterized by respective cytokine level increases, followed by a decrease in the reconvalescent phase.
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Citocinas/sangue , Infecção por Zika virus/imunologia , Infecção por Zika virus/patologia , Adulto , Ásia , Brasil , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ilhas do Pacífico , Linfócitos T Auxiliares-Indutores/imunologia , Fatores de Tempo , ViagemRESUMO
Nearly 100 years ago, Ivan Pavlov demonstrated that dogs could learn to use a neutral cue to predict a biologically relevant event: after repeated predictive pairings, Pavlov's dogs were conditioned to anticipate food at the sound of a bell, which caused them to salivate. Like sustenance, danger is biologically relevant, and neutral cues can take on great salience when they predict a threat to survival. In anxiety disorders such as posttraumatic stress disorder (PTSD), this type of conditioned fear fails to extinguish, and reminders of traumatic events can cause pathological conditioned fear responses for decades after danger has passed. In this review, we use fear conditioning and extinction studies to draw a direct line from Pavlov to PTSD and other anxiety disorders. We explain how rodent studies have informed neuroimaging studies of healthy humans and humans with PTSD. We describe several genes that have been linked to both PTSD and fear conditioning and extinction and explain how abnormalities in fear conditioning or extinction may reflect a general biomarker of anxiety disorders. Finally, we explore drug and neuromodulation treatments that may enhance therapeutic extinction in anxiety disorders.
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Transtornos de Ansiedade , Condicionamento Clássico/fisiologia , Extinção Psicológica/fisiologia , Medo/fisiologia , Transtornos de Estresse Pós-Traumáticos , Animais , Transtornos de Ansiedade/genética , Transtornos de Ansiedade/fisiopatologia , Transtornos de Ansiedade/terapia , Humanos , Transtornos de Estresse Pós-Traumáticos/genética , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Transtornos de Estresse Pós-Traumáticos/terapiaRESUMO
Impulsivity is a complex trait associated with a range of maladaptive behaviors, including many forms of psychopathology. Previous research has implicated multiple neural circuits and neurotransmitter systems in impulsive behavior, but the relationship between impulsivity and organization of whole-brain networks has not yet been explored. Using graph theory analyses, we characterized the relationship between impulsivity and the functional segregation ("modularity") of the whole-brain network architecture derived from resting-state functional magnetic resonance imaging (fMRI) data. These analyses revealed remarkable differences in network organization across the impulsivity spectrum. Specifically, in highly impulsive individuals, regulatory structures including medial and lateral regions of the prefrontal cortex were isolated from subcortical structures associated with appetitive drive, whereas these brain areas clustered together within the same module in less impulsive individuals. Further exploration of the modular organization of whole-brain networks revealed novel shifts in the functional connectivity between visual, sensorimotor, cortical, and subcortical structures across the impulsivity spectrum. The current findings highlight the utility of graph theory analyses of resting-state fMRI data in furthering our understanding of the neurobiological architecture of complex behaviors.
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Mapeamento Encefálico , Comportamento Impulsivo/patologia , Vias Neurais/patologia , Descanso/fisiologia , Adolescente , Feminino , Movimentos da Cabeça , Humanos , Processamento de Imagem Assistida por Computador , Comportamento Impulsivo/classificação , Imageamento por Ressonância Magnética , Masculino , Modelos Neurológicos , Vias Neurais/irrigação sanguínea , Oxigênio , Autorrelato , Adulto JovemRESUMO
OBJECTIVE: Moral distress is a complex phenomenon experienced by healthcare professionals. This study examined the relationships between key dimensions of Organizational Culture in Healthcare (OCHC)-perceived psychological safety, ethical climate, patient safety-and healthcare professionals' perception of moral distress. DESIGN: Cross-sectional survey. SETTING: Pediatric and adult critical care medicine, and adult hospital medicine healthcare professionals in the United States. PARTICIPANTS: Physicians (n = 260), nurses (n = 256), and advanced practice providers (n = 110) participated in the study. MAIN OUTCOME MEASURES: Three dimensions of OCHC were measured using validated questionnaires: Olson's Hospital Ethical Climate Survey, Agency for Healthcare Research and Quality's Patient Safety Culture Survey, and Edmondson's Team Psychological Safety Survey. The perception of moral distress was measured using the Moral Distress Amidst a Pandemic Survey. The hypothesized relationships between various dimensions were tested with structural equation modeling (SEM). RESULTS: Adequate model fit was achieved in the SEM: a root-mean-square error of approximation =0.072 (90% CI 0.069 to 0.075), standardized root mean square residual = 0.056, and comparative fit index =0.926. Perceived psychological safety (ß= -0.357, p <.001) and patient safety culture (ß = -0.428, p<.001) were negatively related to moral distress experience. There was no significant association between ethical climate and moral distress (ß = 0.106, p = 0.319). Ethical Climate, however, was highly correlated with Patient Safety Culture (factor correlation= 0.82). CONCLUSIONS: We used structural equation model to test a theoretical model of multi-dimensional organizational culture and healthcare climate (OCHC) and moral distress.Significant associations were found, supporting mitigating strategies to optimize psychological safety and patient safety culture to address moral distress among healthcare professionals. Future initiatives and studies should account for key dimensions of OCHC with multi-pronged targets to preserve the moral well-being of individuals, teams, and organizations.