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BACKGROUND: Emergency psychiatric care, unplanned hospital admissions, and inpatient health care are the costliest forms of mental health care. According to Statistics Canada (2018), almost 18% (5.3 million) of Canadians reported needing mental health support. However, just above half of this figure (56.2%) have reported their needs were fully met. In light of this evidence there is a pressing need to provide accessible mental health services in flexible yet cost-effective ways. To further expand capacity and access to mental health care in the province, Nova Scotia Health has launched a novel mental health initiative for people in need of mental health care without requiring emergency department visits or hospitalization. This new service is referred to as the Rapid Access and Stabilization Program (RASP). This study evaluates the effectiveness and impact of the RASP on high-cost health services utilization (e.g. ED visits, mobile crisis visits, and inpatient treatments) and related costs. It also assesses healthcare partners' (e.g. healthcare providers, policymakers, community leaders) perceptions and patient experiences and satisfaction with the program and identifies sociodemographic characteristics, psychological conditions, recovery, well-being, and risk measures in the assisted population. METHOD: This is a hypothesis-driven program evaluation study that employs a mixed methods approach. A within-subject comparison (pre- and post-evaluation study) will examine health services utilization data from patients attending RASP, one year before and one year after their psychiatry assessment at the program. A controlled between-subject comparison (cohort study) will use historical data from a control population will examine whether possible changes in high-cost health services utilization are associated with the intervention (RASP). The primary analysis involves extracting secondary data from provincial information systems, electronic medical records, and regular self-reported clinical assessments. Additionally, a qualitative sub-study will examine patient experience and satisfaction, and health care partners' impressions. DISCUSSION: We expect that RASP evaluation findings will demonstrate a minimum 10% reduction in high-cost health services utilization and corresponding 10% cost savings, and also a reduction in the wait times for patient consultations with psychiatrists to less than 30 calendar days, in both within-subject and between-subject comparisons. In addition, we anticipate that patients, healthcare providers and healthcare partners would express high levels of satisfaction with the new service. CONCLUSION: This study will demonstrate the results of the Mental Health and Addictions Program (MHAP) efforts to provide stepped-care, particularly community-based support, to individuals with mental illnesses. Results will provide new insights into a novel community-based approach to mental health service delivery and contribute to knowledge on how to implement mental health programs across varying contexts.
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Serviços de Saúde Mental , População Norte-Americana , Listas de Espera , Humanos , Avaliação de Programas e Projetos de Saúde/métodos , Estudos de Coortes , Nova EscóciaRESUMO
BACKGROUND: Disasters are becoming more frequent due to the impact of extreme weather events attributed to climate change, causing loss of lives, property, and psychological trauma. Mental health response to disasters emphasizes prevention and mitigation, and mobile health (mHealth) apps have been used for mental health promotion and treatment. However, little is known about their use in the mental health components of disaster management. OBJECTIVE: This scoping review was conducted to explore the use of mobile phone apps for mental health responses to natural disasters and to identify gaps in the literature. METHODS: We identified relevant keywords and subject headings and conducted comprehensive searches in 6 electronic databases. Studies in which participants were exposed to a man-made disaster were included if the sample also included some participants exposed to a natural hazard. Only full-text studies published in English were included. The initial titles and abstracts of the unique papers were screened by 2 independent review authors. Full texts of the selected papers that met the inclusion criteria were reviewed by the 2 independent reviewers. Data were extracted from each selected full-text paper and synthesized using a narrative approach based on the outcome measures, duration, frequency of use of the mobile phone apps, and the outcomes. This scoping review was reported according to the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews). RESULTS: Of the 1398 papers retrieved, 5 were included in this review. A total of 3 studies were conducted on participants exposed to psychological stress following a disaster while 2 were for disaster relief workers. The mobile phone apps for the interventions included Training for Life Skills, Sonoma Rises, Headspace, Psychological First Aid, and Substance Abuse and Mental Health Services Administration (SAMHSA) Behavioural Health Disaster Response Apps. The different studies assessed the effectiveness or efficacy of the mobile app, feasibility, acceptability, and characteristics of app use or predictors of use. Different measures were used to assess the effectiveness of the apps' use as either the primary or secondary outcome. CONCLUSIONS: A limited number of studies are exploring the use of mobile phone apps for mental health responses to disasters. The 5 studies included in this review showed promising results. Mobile apps have the potential to provide effective mental health support before, during, and after disasters. However, further research is needed to explore the potential of mobile phone apps in mental health responses to all hazards.
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Saúde Mental , Aplicativos Móveis , Desastres Naturais , Humanos , Telemedicina/estatística & dados numéricos , DesastresRESUMO
BACKGROUND: Distributed Medical Education (DME), a decentralized model focused on smaller cities and communities, has been implemented worldwide to bridge the gap in psychiatric education. Faculty engagement in teaching activities such as clinical teaching, supervision, and examinations is a crucial aspect of DME sites. Implementing or expanding DME sites requires careful consideration to identify enablers that contribute to success and barriers that need to be addressed. This study aims to examine enablers, barriers, and factors influencing psychiatrists' willingness to start or continue participating in teaching activities within Dalhousie University's Faculty of Medicine DME sites in two provinces in Atlantic Canada. METHODOLOGY: This cross-sectional study was conducted as part of an environmental scan of Dalhousie Faculty of Medicine's DME programs in Nova Scotia (NS) and New Brunswick (NB), Canada. In February 2023, psychiatrists from seven administrative health zones in these provinces anonymously participated in an online survey. The survey, created with OPINIO, collected data on sociodemographic factors, practice-related characteristics, medical education, and barriers to teaching activities. Five key outcomes were assessed, which included psychiatrists' willingness to engage in (i) clinical training and supervision, (ii) lectures or skills-based teaching, (iii) skills-based examinations, (iv) training and supervision of Canadian-trained psychiatrists, and (v) training and supervision of internationally trained psychiatrists. The study employed various statistical analyses, including descriptive analysis, chi-square tests, and logistic regression, to identify potential predictors associated with each outcome variable. RESULTS: The study involved 60 psychiatrists, primarily male (69%), practicing in NS (53.3%), with international medical education (69%), mainly working in outpatient services (41%). Notably, 60.3% lacked formal medical education training, yet they did not perceive the lack of training as a significant barrier, but lack of protected time as the main one. Despite this, there was a strong willingness to engage in teaching activities, with an average positive response rate of 81.98%. The lack of protected time for teaching/training was a major barrier reported by study participants. Availability to take the Royal College of Physicians and Surgeons of Canada Competency by Design training was the main factor associated with psychiatrists' willingness to participate in the five teaching activities investigated in this study: willingness to participate in clinical training and supervision of psychiatry residents (p = .01); provision of lectures or skills-based teaching for psychiatry residents (p < .01); skills-based examinations of psychiatry residents (p < .001); training/supervision of Canadian-trained psychiatrists (p < .01); and training and supervision of internationally trained psychiatrists (p < .01). CONCLUSION: The study reveals a nuanced picture regarding psychiatrists' engagement in teaching activities at DME sites. Despite a significant association between interest in formal medical education training and willingness to participate in teaching activities, clinicians do not consider the lack of formal training as a barrier. Addressing this complexity requires thoughtful strategies, potentially involving resource allocation, policy modifications, and adjustments to incentive structures by relevant institutions.
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Educação Médica , Psiquiatria , Humanos , Masculino , Psiquiatras , Estudos Transversais , Canadá , Psiquiatria/educação , Inquéritos e Questionários , Docentes de MedicinaRESUMO
OBJECTIVES: About 15% of U.S. adults report speech perception difficulties despite showing normal audiograms. Recent research suggests that genetic factors might influence the phenotypic spectrum of speech perception difficulties. The primary objective of the present study was to describe a conceptual framework of a deep phenotyping method, referred to as AudioChipping, for deconstructing and quantifying complex audiometric phenotypes. DESIGN: In a sample of 70 females 18 to 35 years of age with normal audiograms (from 250 to 8000 Hz), the study measured behavioral hearing thresholds (250 to 16,000 Hz), distortion product otoacoustic emissions (1000 to 16,000 Hz), click-evoked auditory brainstem responses (ABR), complex ABR (cABR), QuickSIN, dichotic digit test score, loudness discomfort level, and noise exposure background. The speech perception difficulties were evaluated using the Speech, Spatial, and Quality of Hearing Scale-12-item version (SSQ). A multiple linear regression model was used to determine the relationship between SSQ scores and audiometric measures. Participants were categorized into three groups (i.e., high, mid, and low) using the SSQ scores before performing the clustering analysis. Audiometric measures were normalized and standardized before performing unsupervised k-means clustering to generate AudioChip. RESULTS: The results showed that SSQ and noise exposure background exhibited a significant negative correlation. ABR wave I amplitude, cABR offset latency, cABR response morphology, and loudness discomfort level were significant predictors for SSQ scores. These predictors explained about 18% of the variance in the SSQ score. The k-means clustering was used to split the participants into three major groups; one of these clusters revealed 53% of participants with low SSQ. CONCLUSIONS: Our study highlighted the relationship between SSQ and auditory coding precision in the auditory brainstem in normal-hearing young females. AudioChip was useful in delineating and quantifying internal homogeneity and heterogeneity in audiometric measures among individuals with a range of SSQ scores. AudioChip could help identify the genotype-phenotype relationship, document longitudinal changes in auditory phenotypes, and pair individuals in case-control groups for the genetic association analysis.
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Percepção da Fala , Limiar Auditivo , Potenciais Evocados Auditivos do Tronco Encefálico , Feminino , Humanos , Masculino , Fenótipo , AutorrelatoRESUMO
To investigate patterns of biotic community composition at different spatial scales and biological contexts, we used environmental DNA metabarcoding to characterize eukaryotic and prokaryotic assemblages present in the phytotelmata of three bromeliad species (Aechmea gamosepala, Vriesea friburgensis, and Vriesea platynema) at a single Atlantic Forest site in southern Brazil. We sampled multiple individuals per species and multiple tanks from each individual, totalizing 30 samples. We observed very high levels of diversity in these communities, and remarkable variation across individuals and even among tanks from the same individual. The alpha diversity was higher for prokaryotes than eukaryotes, especially for A. gamosepala and V. platynema samples. Some biotic components appeared to be species-specific, while most of the biota was shared among species, but varied substantially in frequency among samples. Interestingly, V. friburgensis communities (which were sampled at nearby locations) tended to be more heterogeneous across samples, for both eukaryotes and prokaryotes. The opposite was true for V. platynema, whose samples were more broadly spaced but whose communities were more similar to each other. Our results indicate that additional attention should be devoted to within-individual heterogeneity when assessing bromeliad phytotelmata biodiversity, and highlight the complexity of the biotic assemblages gathered in these unique habitats.
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Bromeliaceae/microbiologia , Bromeliaceae/parasitologia , Bactérias/isolamento & purificação , Brasil , Eucariotos/isolamento & purificação , Especificidade da EspécieRESUMO
BACKGROUND: Obesity prevalence has been rising worldwide and currently is one of the most serious public health problems. Nutrition literacy is important to the development of healthier habits that could help prevent and stem obesity and overweight. The aim of this study was to evaluate the impact of using a multimedia web platform to provide nutrition education to Portuguese adolescents. METHODS: The intervention consisted in a two-week period in which students (n = 1291) had access to an interactive multimedia web platform with nutritional content, and designed for a self-paced learning experience. Students completed a knowledge questionnaire at baseline and immediately after the end of the intervention. RESULTS: The results obtained revealed that 85.8% of the students increased their nutrition knowledge. No gender differences were observed post-intervention. There were significant differences in the knowledge acquisition regarding age (P < 0.001). The baseline knowledge seemed to influence the learning process. CONCLUSIONS: Overall, the intervention had a positive impact. The preliminary results observed will be important for the improvement of the intervention, though they need to be confirmed by further research. Nevertheless, it is safe to say that technology-based assets can be important tools to incorporate and complement health-related interventions in schools.
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Educação em Saúde , Multimídia , Adolescente , Humanos , Projetos Piloto , Portugal , Instituições AcadêmicasRESUMO
The cytokine erythropoietin (EPO) is the master regulator of erythropoiesis. Intriguingly, many studies have shown that the cognitive performance of patients receiving EPO for its hematopoietic effects is enhanced, which prompted the growing interest in the use of EPO-based strategies to treat neuropsychiatric disorders. EPO plays key roles in brain development and maturation, but also modulates synaptic transmission. However, the mechanisms underlying the latter have remained elusive. Here, we show that acute (40-60 min) exposure to EPO presynaptically downregulates spontaneous and afferent-evoked excitatory transmission, without affecting basal firing of action potentials. Conversely, prolonged (3 h) exposure to EPO, if followed by a recovery period (1 h), is able to elicit a homeostatic increase in excitatory spontaneous, but not in evoked, synaptic transmission. These data lend support to the emerging view that segregated pathways underlie spontaneous and evoked neurotransmitter release. Furthermore, we show that prolonged exposure to EPO facilitates a form of hippocampal long-term potentiation that requires noncanonical recruitment of calcium-permeable AMPA receptors for its maintenance. These findings provide important new insight into the mechanisms by which EPO enhances neuronal function, learning, and memory.
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Eritropoetina/farmacologia , Hipocampo/citologia , Hipocampo/fisiologia , Homeostase/efeitos dos fármacos , Plasticidade Neuronal/efeitos dos fármacos , Sinapses/efeitos dos fármacos , Animais , Biofísica , Estimulação Elétrica , Técnicas In Vitro , Potenciação de Longa Duração/efeitos dos fármacos , Potenciais da Membrana/efeitos dos fármacos , Rede Nervosa/efeitos dos fármacos , Rede Nervosa/fisiologia , Neurotransmissores/farmacologia , Técnicas de Cultura de Órgãos , Técnicas de Patch-Clamp , Ratos , Receptores de AMPA/metabolismo , Receptores da Eritropoetina/metabolismo , Bloqueadores dos Canais de Sódio/farmacologia , Sinapses/fisiologia , Tetrodotoxina/farmacologia , Fatores de TempoRESUMO
Essential thrombocytosis (ET) is a chronic myeloproliferative neoplasm characterized by the presence of thrombocytosis and it can be complicated by thrombotic and/or hemorrhagic events. Treatment options include low-dose aspirin and cytoreductive agents such as hydroxyurea. In cases of extreme thrombocytosis, therapeutic thrombocytapheresis can be a useful procedure. We present a case of a 61-year-old-man previously diagnosed with CALR-mutated ET, who develop acute myeloid leukemia. When recovering after induction chemotherapy, he developed an extreme thrombocytosis up to 2337 × 109 /L regardless hydroxyurea was started. Two therapeutic trombocytapheresis were performed and anagrelide was added to cytoreductive regimen. Platelet count stabilized around 570 × 109 /L. Both procedures were performed with the Spectra Optia Apheresis System version 11.3 (Terumo BCT) and we decided to use a higher collection preference and lower collection speed than manufacturer's recommendations. Platelet count decreased from 2380 × 109 /L to 1035 × 109 /L in the first procedure and from 1813 × 109 /L to 768 × 109 in the second procedure. Platelet collection efficiency was calculated to be 110.3% and 86.1% in the first and second thrombocytapheresis, respectively. Therapeutic thrombocytapheresis with Spectra Optia is a safe and efficient therapy to treat patients with primary thrombocytosis while effect of cytoreductive agents is attained. Platelet collection efficiency was calculated to be higher than previously reported. We suggest that changes in technical parameters such as a deeper aspiration point and/or lower collection speed may increase procedure's efficiency.
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Plaquetoferese/métodos , Trombocitose/terapia , Humanos , Quimioterapia de Indução/efeitos adversos , Leucemia Mieloide Aguda/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Trombocitose/induzido quimicamente , Resultado do TratamentoRESUMO
Reconstruction of ancestral protein sequences using phylogenetic methods is a powerful technique for directly examining the evolution of molecular function. Although ancestral sequence reconstruction (ASR) is itself very efficient, downstream functional, and structural studies necessary to characterize when and how changes in molecular function occurred are often costly and time-consuming, currently limiting ASR studies to examining a relatively small number of discrete functional shifts. As a result, we have very little direct information about how molecular function evolves across large protein families. Here we develop an approach combining ASR with structure and function prediction to efficiently examine the evolution of ligand affinity across a large family of double-stranded RNA binding proteins (DRBs) spanning animals and plants. We find that the characteristic domain architecture of DRBs-consisting of 2-3 tandem double-stranded RNA binding motifs (dsrms)-arose independently in early animal and plant lineages. The affinity with which individual dsrms bind double-stranded RNA appears to have increased and decreased often across both animal and plant phylogenies, primarily through convergent structural mechanisms involving RNA-contact residues within the ß1-ß2 loop and a small region of α2. These studies provide some of the first direct information about how protein function evolves across large gene families and suggest that changes in molecular function may occur often and unassociated with major phylogenetic events, such as gene or domain duplications.
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Proteínas de Ligação a RNA/genética , Análise de Sequência de DNA/métodos , Sequência de Aminoácidos/genética , Animais , Evolução Biológica , Bases de Dados de Ácidos Nucleicos , Evolução Molecular , Ligantes , Dados de Sequência Molecular , Família Multigênica , Filogenia , Proteínas de Plantas/genética , Plantas/genética , Ligação Proteica/genética , Domínios Proteicos , Proteínas de Ligação a RNA/metabolismo , Relação Estrutura-AtividadeRESUMO
BACKGROUND: One goal of structural biology is to understand how a protein's 3-dimensional conformation determines its capacity to interact with potential ligands. In the case of small chemical ligands, deconstructing a static protein-ligand complex into its constituent atom-atom interactions is typically sufficient to rapidly predict ligand affinity with high accuracy (>70% correlation between predicted and experimentally-determined affinity), a fact that is exploited to support structure-based drug design. We recently found that protein-DNA/RNA affinity can also be predicted with high accuracy using extensions of existing techniques, but protein-protein affinity could not be predicted with >60% correlation, even when the protein-protein complex was available. METHODS: X-ray and NMR structures of protein-protein complexes, their associated binding affinities and experimental conditions were obtained from different binding affinity and structural databases. Statistical models were implemented using a generalized linear model framework, including the experimental conditions as new model features. We evaluated the potential for new features to improve affinity prediction models by calculating the Pearson correlation between predicted and experimental binding affinities on the training and test data after model fitting and after cross-validation. Differences in accuracy were assessed using two-sample t test and nonparametric Mann-Whitney U test. RESULTS: Here we evaluate a range of potential factors that may interfere with accurate protein-protein affinity prediction. We find that X-ray crystal resolution has the strongest single effect on protein-protein affinity prediction. Limiting our analyses to only high-resolution complexes (≤2.5 Å) increased the correlation between predicted and experimental affinity from 54 to 68% (p = 4.32x10-3). In addition, incorporating information on the experimental conditions under which affinities were measured (pH, temperature and binding assay) had significant effects on prediction accuracy. We also highlight a number of potential errors in large structure-affinity databases, which could affect both model training and accuracy assessment. CONCLUSIONS: The results suggest that the accuracy of statistical models for protein-protein affinity prediction may be limited by the information present in databases used to train new models. Improving our capacity to integrate large-scale structural and functional information may be required to substantively advance our understanding of the general principles by which a protein's structure determines its function.
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Aprendizado de Máquina , Modelos Moleculares , Modelos Estatísticos , Proteínas/metabolismo , Animais , Confiabilidade dos Dados , Humanos , Ligação Proteica , Conformação Proteica , Proteínas/químicaRESUMO
Adenosine is an endogenous neuromodulator that decreases excitability of hippocampal circuits activating membrane-bound metabotropic A1 receptor (A1R). The presynaptic inhibitory action of adenosine A1R in glutamatergic synapses is well documented, but its influence on inhibitory GABAergic transmission is poorly known. We report that GABAA receptor (GABAAR)-mediated tonic, but not phasic, transmission is suppressed by A1R in hippocampal neurons. Adenosine A1R activation strongly inhibits GABAAR agonist (muscimol)-evoked currents in Cornu Ammonis 1 (CA1) pyramidal neurons and in a specific subpopulation of interneurons expressing axonal cannabinoid receptor type 1. In addition, A1R suppresses tonic GABAAR currents measured in the presence of elevated ambient GABA as well as in naïve slices. The inhibition of GABAergic currents involves both protein kinase A (PKA) and protein kinase C (PKC) signaling pathways and decreases GABAAR δ-subunit expression. On the contrary, no A1R-mediated modulation was detected in phasic inhibitory postsynaptic currents evoked either by afferent electrical stimulation or by spontaneous quantal release. The results show that A1R modulates extrasynaptic rather than synaptic GABAAR-mediated signaling, and that this modulation selectively occurs in hippocampal pyramidal neurons and in a specific subpopulation of inhibitory interneurons. We conclude that modulation of tonic GABAAR signaling by adenosine A1R in specific neuron types may regulate neuronal gain and excitability in the hippocampus.
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Região CA1 Hipocampal/fisiologia , Interneurônios/fisiologia , Células Piramidais/fisiologia , Receptor A1 de Adenosina/metabolismo , Receptores de GABA-A/metabolismo , Animais , Região CA1 Hipocampal/citologia , Região CA1 Hipocampal/efeitos dos fármacos , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Immunoblotting , Imuno-Histoquímica , Potenciais Pós-Sinápticos Inibidores/efeitos dos fármacos , Potenciais Pós-Sinápticos Inibidores/fisiologia , Interneurônios/citologia , Interneurônios/efeitos dos fármacos , Masculino , Potenciais Pós-Sinápticos em Miniatura/efeitos dos fármacos , Potenciais Pós-Sinápticos em Miniatura/fisiologia , Inibição Neural/efeitos dos fármacos , Inibição Neural/fisiologia , Técnicas de Patch-Clamp , Proteína Quinase C/metabolismo , Células Piramidais/citologia , Células Piramidais/efeitos dos fármacos , Ratos Wistar , Técnicas de Cultura de TecidosRESUMO
Brain-derived neurotrophic factor (BDNF) and adenosine are widely recognized as neuromodulators of glutamatergic transmission in the adult brain. Most BDNF actions upon excitatory plasticity phenomena are under control of adenosine A2A receptors (A2ARs). Concerning gamma-aminobutyric acid (GABA)-mediated transmission, the available information refers to the control of GABA transporters. We now focused on the influence of BDNF and the interplay with adenosine on phasic GABAergic transmission. To assess this, we evaluated evoked and spontaneous synaptic currents recorded from CA1 pyramidal cells in acute hippocampal slices from adult rat brains (6 to 10 weeks old). BDNF (10-100 ng/mL) increased miniature inhibitory postsynaptic current (mIPSC) frequency, but not amplitude, as well as increased the amplitude of inhibitory postsynaptic currents (IPSCs) evoked by afferent stimulation. The facilitatory action of BDNF upon GABAergic transmission was lost in the presence of a Trk inhibitor (K252a, 200 nM), but not upon p75(NTR) blockade (anti-p75(NTR) IgG, 50 µg/mL). Moreover, the facilitatory action of BDNF onto GABAergic transmission was also prevented upon A2AR antagonism (SCH 58261, 50 nM). We conclude that BDNF facilitates GABAergic signaling at the adult hippocampus via a presynaptic mechanism that depends on TrkB and adenosine A2AR activation.
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Fator Neurotrófico Derivado do Encéfalo/metabolismo , Região CA1 Hipocampal/metabolismo , Receptor A2A de Adenosina/metabolismo , Receptor trkB/metabolismo , Transmissão Sináptica/fisiologia , Ácido gama-Aminobutírico/metabolismo , Animais , Potenciais Pós-Sinápticos Inibidores/fisiologia , Masculino , Técnicas de Cultura de Órgãos , Técnicas de Patch-Clamp , Ratos , Ratos WistarRESUMO
Interactions between proteins and other molecules play essential roles in all biological processes. Although it is widely held that a protein's ligand specificity is determined primarily by its three-dimensional structure, the general principles by which structure determines ligand binding remain poorly understood. Here we use statistical analyses of a large number of protein-ligand complexes with associated binding-affinity measurements to quantitatively characterize how combinations of atomic interactions contribute to ligand affinity. We find that there are significant differences in how atomic interactions determine ligand affinity for proteins that bind small chemical ligands, those that bind DNA/RNA and those that interact with other proteins. Although protein-small molecule and protein-DNA/RNA binding affinities can be accurately predicted from structural data, models predicting one type of interaction perform poorly on the others. Additionally, the particular combinations of atomic interactions required to predict binding affinity differed between small-molecule and DNA/RNA data sets, consistent with the conclusion that the structural bases determining ligand affinity differ among interaction types. In contrast to what we observed for small-molecule and DNA/RNA interactions, no statistical models were capable of predicting protein-protein affinity with >60% correlation. We demonstrate the potential usefulness of protein-DNA/RNA binding prediction as a possible tool for high-throughput virtual screening to guide laboratory investigations, suggesting that quantitative characterization of diverse molecular interactions may have practical applications as well as fundamentally advancing our understanding of how molecular structure translates into function.
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DNA/química , Proteínas/química , RNA/química , DNA/metabolismo , Ligação de Hidrogênio , Simulação de Acoplamento Molecular , Ligação Proteica , Proteínas/metabolismo , RNA/metabolismoRESUMO
The Park Grass experiment (PGE) in the UK has been ongoing since 1856. Its purpose is to study the response of biological communities to the long-term treatments and associated changes in soil parameters, particularly soil pH. In this study, soil samples were collected across pH gradient (pH 3.6-7) and a range of fertilizers (nitrogen as ammonium sulfate, nitrogen as sodium nitrate, phosphorous) to evaluate the effects nutrients have on soil parameters and microbial community structure. Illumina 16S ribosomal RNA (rRNA) amplicon sequencing was used to determine the relative abundances and diversity of bacterial and archaeal taxa. Relationships between treatments, measured soil parameters, and microbial communities were evaluated. Clostridium, Bacteroides, Bradyrhizobium, Mycobacterium, Ruminococcus, Paenibacillus, and Rhodoplanes were the most abundant genera found at the PGE. The main soil parameter that determined microbial composition, diversity, and biomass in the PGE soil was pH. The most probable mechanism of the pH impact on microbial community may include mediation of nutrient availability in the soil. Addition of nitrogen to the PGE plots as ammonium sulfate decreases soil pH through increased nitrification, which causes buildup of soil carbon, and hence increases C/N ratio. Plant species richness and plant productivity did not reveal significant relationships with microbial diversity; however, plant species richness was positively correlated with soil microbial biomass. Plants responded to the nitrogen treatments with an increase in productivity and a decrease in the species richness.
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Archaea/classificação , Bactérias/classificação , Poaceae/microbiologia , Microbiologia do Solo , Solo/química , Sulfato de Amônio/química , Archaea/genética , Archaea/isolamento & purificação , Bactérias/genética , Bactérias/isolamento & purificação , Biodiversidade , Biomassa , Carbono/química , Fertilizantes/análise , Concentração de Íons de Hidrogênio , Nitratos/química , Nitrificação , Nitrogênio/química , Fósforo/química , Poaceae/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNARESUMO
INTRODUCTION: Our department of anesthesiology has been conducting weekly, for several years, a group consultation to educate childbearing people about labor analgesia. The emergence of the COVID-19 pandemic forced an adaptation to a virtual consultation format. Since there are no studies about online group consultation on labor analgesia in order to understand its role, an anonymous questionnaire was created and applied. The objective was to evaluate this new consultation format, namely the ease of access, usefulness of the content provided, and its impact on the satisfaction and experience of childbirth. MATERIALS AND METHODS: An observational prospective study was conducted. A questionnaire was sent by e-mail after childbirth to all childbearing people participating in the online consultation from January 20, 2021, to March 2, 2022. SPSS Statistics version 28.0 (IBM Corp. Released 2021. IBM SPSS Statistics for Windows, Version 28.0. Armonk, NY: IBM Corp) was used for statistical analysis. Internal consistency was analyzed using Cronbach's alpha. RESULTS: A total of 563 participants were eligible, and 404 (71.8%) completed questionnaires were analyzed. A few technical problems were reported. The participants considered their privacy respected, and more than 90% were satisfied with the content of the online consultation, the opportunity to pose questions, and the help managing expectations. Considering face-to-face consultation, 89.6% of patients considered the online format an effective alternative, 63.2% believed it could replace the old model, and 96.3% would recommend it. CONCLUSIONS: Our study demonstrates that online consultation on labor analgesia was a good strategy during the COVID-19 pandemic and has the potential to be used in this format in the future.
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Objective: High stress levels can be problematic for teachers and indirectly affect students. Resilience may be a protective factor for overcoming stress. Knowledge about the prevalence and correlates of high stress and low resilience will provide information about the extent of the problem among teachers in Canada. Methods: This is a cross-sectional study among teachers in Alberta, Nova Scotia, and Newfoundland and Labrador in Canada. Participants self-subscribed to the Wellness4Teachers supportive text messaging program and completed the online survey on enrollment. Baseline data collection occurred from 1 September 2022 to 30 August 2023. Resilience and stress were, respectively, assessed using the Brief Resilience Scale (BRS) and the Perceived Stress Scale (PSS-10). The data were analyzed with SPSS version 28 using chi-squared tests and binary logistic regression analysis. Results: A total of 1912 teachers subscribed to the Wellness4Teachers program, and 810 completed the baseline survey, yielding a response rate of 42.40%. Most of the participants, 87.8%, were female, and 12.2% were aged 18 to 61 and above. The prevalence of low resilience was 40.1%, and high stress had a prevalence of 26.3%. After controlling for all the other variables in the logistic regression model, participants with low resilience were 3.10 times more likely to experience high-stress symptoms than those with normal to high resilience (OR = 3.10; 95% CI: 2.18-4.41). Conversely, participants who reported high stress were 3.13 times more likely to have low resilience than those with low to moderate stress (OR = 3.13; 95% CI: 2.20-4.44). Additionally, junior and senior high school teachers were, respectively, 2.30 times (OR = 2.30; 95% CI: 1.25-4.23) and 2.12 times (OR = 2,12; 95% CI: 1.08-4.18) more likely to have low resilience compared to elementary school teachers. Conclusions: Our study findings suggest a high prevalence of stress and low resilience among teachers in the three Canadian provinces. Administrators, policymakers in the educational field, school boards, and governments should integrate stress management and resilience-building strategies into teachers' training and continuing professional development programs.
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PURPOSE: Tinnitus, the perception of sound without any external sound source, is a prevalent hearing health concern. Mounting evidence suggests that a confluence of genetic, environmental, and lifestyle factors can influence the pathogenesis of tinnitus. We hypothesized that alteration in DNA methylation, an epigenetic modification that occurs at cytosines of cytosine-phosphate-guanine (CpG) dinucleotide sites, where a methyl group from S-adenyl methionine gets transferred to the fifth carbon of the cytosine, could contribute to tinnitus. DNA methylation patterns are tissue-specific, but the tissues involved in tinnitus are not easily accessible in humans. This pilot study used saliva as a surrogate tissue to identify differentially methylated CpG regions (DMRs) associated with tinnitus. The study was conducted on healthy young adults reporting bilateral continuous chronic tinnitus to limit the influence of age-related confounding factors and health-related comorbidities. METHODS: The present study evaluated the genome-wide methylation levels from saliva-derived DNA samples from 24 healthy young adults with bilateral continuous chronic tinnitus (> 1 year) and 24 age, sex, and ethnicity-matched controls with no tinnitus. Genome-wide DNA methylation was evaluated for > 850,000 CpG sites using the Infinium Human Methylation EPIC BeadChip. The association analysis used the Bumphunter algorithm on 23 cases and 20 controls meeting the quality control standards. The methylation level was expressed as the area under the curve of CpG sites within DMRs.The FDR-adjusted p-value threshold of 0.05 was used to identify statistically significant DMRs associated with tinnitus. RESULTS: We obtained 25 differentially methylated regions (DMRs) associated with tinnitus. Genes within or in the proximity of the hypermethylated DMRs related to tinnitus included LCLAT1, RUNX1, RUFY1, NUDT12, TTC23, SLC43A2, C4orf27 (STPG2), and EFCAB4B. Genes within or in the proximity of hypomethylated DMRs associated with tinnitus included HLA-DPB2, PM20D1, TMEM18, SNTG2, MUC4, MIR886, MIR596, TXNRD1, EID3, SDHAP3, HLA-DPB2, LASS3 (CERS3), C10orf11 (LRMDA), HLA-DQB1, NADK, SZRD1, MFAP2, NUP210L, TPM3, INTS9, and SLC2A14. The burden of genetic variation could explain the differences in the methylation levels for DMRs involving HLA-DPB2, HLA-DQB1, and MUC4, indicating the need for replication in large independent cohorts. CONCLUSION: Consistent with the literature on comorbidities associated with tinnitus, we identified genes within or close to DMRs involved in auditory functions, chemical dependency, cardiovascular diseases, psychiatric conditions, immune disorders, and metabolic syndromes. These results indicate that epigenetic mechanisms could influence tinnitus, and saliva can be a good surrogate for identifying the epigenetic underpinnings of tinnitus in humans. Further research with a larger sample size is needed to identify epigenetic biomarkers and investigate their influence on the phenotypic expression of tinnitus.
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Background: Burnout is a longstanding issue among educators and has been associated with psychological and physical health problems such as depression, and insomnia. Objective: To assess the prevalence and predictors of the three dimensions of burnout (emotional exhaustion, depersonalization and lack of professional accomplishment) among elementary and high school teachers. Methods: This is a quantitative cross-sectional study with data collected via an online survey. The Maslach Burnout Inventory-Educator Survey (MBI-ES), the Brief Resilience Scale (BRS) and the Perceived Stress Scale were used, respectively, to assess burnout, resilience and stress among teachers. Data was collected between September 1st, 2022 and August 30th, 2023. SPSS (version 28, IBM Corp) was used for the data analysis. Results: Overall, 1912 educators received a link to the online survey via a text message, and 780 completed the burnout survey questions, resulting in a response rate of 41%. The prevalence of emotional exhaustion, depersonalization, and lack of professional accomplishment were 76.9, 23.2, and 30.8%, respectively. Participants with high-stress symptoms were 6.88 times more likely to experience emotional exhaustion (OR = 6.88; 95% CI: 3.31-14.29), 2.55 times (OR = 2.55; 95% CI: 1.65-3.93) more likely to experience depersonalization and 2.34 times (OR = 2.34; 95% CI: 1.64-3.35) more likely to experience lack of professional fulfilment. Additionally, respondents with low resilience were 3.26 times more likely to experience emotional exhaustion symptoms (OR = 3.26; 95% CI: 2.00-5.31), than those with high resilience. Males were about 2.4 times more likely to present with depersonalization compared to female teachers, whilst those who indicated their marital status as partnered or cohabiting and those who selected "other" were 3.5 and 7.3 times, respectively, more likely to present with depersonalization compared with those who were single. Finally, Physical Education were 3.8 times more likely to present with depersonalization compared with English teachers. Conclusion: The current study highlights the predictive effects of low resilience and high stress on the three dimensions of burnout among teachers in Canada. Interventions aimed at addressing systemic stress and fostering resilience are needed to reduce burnout among teachers.
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Esgotamento Profissional , Professores Escolares , Humanos , Professores Escolares/psicologia , Professores Escolares/estatística & dados numéricos , Esgotamento Profissional/epidemiologia , Esgotamento Profissional/psicologia , Estudos Transversais , Masculino , Feminino , Prevalência , Adulto , Inquéritos e Questionários , Pessoa de Meia-Idade , Canadá/epidemiologia , Resiliência Psicológica , Estresse Psicológico/epidemiologia , Estresse Psicológico/psicologiaRESUMO
Background: Since March 2023, hundreds of fires have burned from coast to coast throughout the country, placing Canada on track to have the worst wildfire season ever recorded. From East to West, provinces such as Quebec, Ontario, Nova Scotia, Alberta, and British Columbia have been particularly affected by large and uncontrollable wildfires. Objectives: The objective of this study was to determine the prevalence of depression symptoms and predictors among residents living in extreme climate conditions during the Canadian wildfires of 2023 in Alberta and Nova Scotia and to update the literature with data related to those wildfires. Methods: A cross-sectional quantitative survey was conducted in this study. REDCap was used to administer an online survey between 14 May and 23 June 2023. Through the Text4Hope program, participants subscribe to receive supportive SMS messages daily. As part of the initial welcome message, participants were invited to complete an online questionnaire, containing demographic information, wildfire-related information, and responses to the Patient Health Questionnaire-9 (PHQ-9) for depression assessment. SPSS version 25 was used to analyze the data. Descriptive, univariate, and multivariate regression analyses were employed. Results: A total of 298 respondents completed the survey out of 1802 who self-subscribed to the Text4Hope program in Alberta and Nova Scotia and received a link to the online survey, producing a response rate of 16.54%. Most of the respondents were females (85.2%, 253), below 40 years of age (28.3%, 84), employed (63.6%, 189), and in a relationship (56.4%, 167). A historical depression diagnosis (OR = 3.15; 95% CI: 1.39-7.14) was a significant predictor of moderate to severe MDD in our study. The unemployed individuals were two times more likely to report moderate to severe symptoms of MDD than employed individuals (OR = 2.46; 95% CI: 1.06-5.67). Among the total sample population, the moderate to severe MDD prevalence was 50.4%, whereas it was 56.1% among those living in areas affected by wildfires. Conclusion: Based on our study findings, unemployment and a history of depression diagnosis were independently significant risk factors associated with the developing moderate to severe MDD symptoms during wildfire disasters. Further research is required to identify robust predictors of mental health disorders in disaster survivors and provide appropriate interventions to the most vulnerable communities and individuals.
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PURPOSE: Age-related hearing loss is the most common form of permanent hearing loss that is associated with various health traits, including Alzheimer's disease, cognitive decline, and depression. The present study aims to identify genetic comorbidities of age-related hearing loss. Past genome-wide association studies identified multiple genomic loci involved in common adult-onset health traits. Polygenic risk scores (PRS) could summarize the polygenic inheritance and quantify the genetic susceptibility of complex traits independent of trait expression. The present study conducted a PRS-based association analysis of age-related hearing difficulty in the UK Biobank sample (N = 425,240), followed by a replication analysis using hearing thresholds (HTs) and distortion-product otoacoustic emissions (DPOAEs) in 242 young adults with self-reported normal hearing. We hypothesized that young adults with genetic comorbidities associated with age-related hearing difficulty would exhibit subclinical decline in HTs and DPOAEs in both ears. METHODS: A total of 111,243 participants reported age-related hearing difficulty in the UK Biobank sample (> 40 years). The PRS models were derived from the polygenic risk score catalog to obtain 2627 PRS predictors across the health spectrum. HTs (0.25-16 kHz) and DPOAEs (1-16 kHz, L1/L2 = 65/55 dB SPL, F2/F1 = 1.22) were measured on 242 young adults. Saliva-derived DNA samples were subjected to low-pass whole genome sequencing, followed by genome-wide imputation and PRS calculation. The logistic regression analyses were performed to identify PRS predictors of age-related hearing difficulty in the UK Biobank cohort. The linear mixed model analyses were performed to identify PRS predictors of HTs and DPOAEs. RESULTS: The PRS-based association analysis identified 977 PRS predictors across the health spectrum associated with age-related hearing difficulty. Hearing difficulty and hearing aid use PRS predictors revealed the strongest association with the age-related hearing difficulty phenotype. Youth with a higher genetic predisposition to hearing difficulty revealed a subclinical elevation in HTs and a decline in DPOAEs in both ears. PRS predictors associated with age-related hearing difficulty were enriched for mental health, lifestyle, metabolic, sleep, reproductive, digestive, respiratory, hematopoietic, and immune traits. Fifty PRS predictors belonging to various trait categories were replicated for HTs and DPOAEs in both ears. CONCLUSION: The study identified genetic comorbidities associated with age-related hearing loss across the health spectrum. Youth with a high genetic predisposition to age-related hearing difficulty and other related complex traits could exhibit sub-clinical decline in HTs and DPOAEs decades before clinically meaningful age-related hearing loss is observed. We posit that effective communication of genetic risk, promoting a healthy lifestyle, and reducing exposure to environmental risk factors at younger ages could help prevent or delay the onset of age-related hearing difficulty at older ages.