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Novel Gram-positive, catalase-negative, α-haemolytic cocci were isolated from breast milk samples of healthy mothers living in Hanoi, Vietnam. The 16S rRNA gene sequences of these strains varied by 0-2 nucleotide polymorphisms. The 16S rRNA gene sequence of one strain, designated as BME SL 6.1T, showed the highest similarity to those of Streptococcus salivarius NCTC 8618T (99.4â%), Streptococcus vestibularis ATCC 49124T (99.4â%), and Streptococcus thermophilus ATCC 19258T (99.3â%) in the salivarius group. Whole genome sequencing was performed on three selected strains. Phylogeny based on 631 core genes clustered the three strains into the salivarius group, and the strains were clearly distinct from the other species in this group. The average nucleotide identity (ANI) value of strain BME SL 6.1T exhibited the highest identity with S. salivarius NCTC 8618T (88.4â%), followed by S. vestibularis ATCC 49124T (88.3â%) and S. thermophilus ATCC 19258T (87.4â%). The ANI and digital DNA-DNA hybridization values between strain BME SL 6.1T and other species were below the cut-off value (95 and 70â%, respectively), indicating that it represents a novel species of the genus Streptococcus. The strains were able to produce α-galactosidase and acid from raffinose and melibiose. Therefore, we propose to assign the strains to a new species of the genus Streptococcus as Streptococcus raffinosi sp. nov. The type strain is BME SL 6.1T (=VTCC 12812T=NBRC 116368T).
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Técnicas de Tipagem Bacteriana , DNA Bacteriano , Leite Humano , Hibridização de Ácido Nucleico , Filogenia , RNA Ribossômico 16S , Análise de Sequência de DNA , Streptococcus , RNA Ribossômico 16S/genética , Humanos , Feminino , DNA Bacteriano/genética , Leite Humano/microbiologia , Streptococcus/genética , Streptococcus/isolamento & purificação , Streptococcus/classificação , Vietnã , Sequenciamento Completo do GenomaRESUMO
BACKGROUND: In 2019, the EAT-Lancet Commission proposed a healthy dietary pattern that, along with reductions in food waste and improved agricultural practices, could feed the increasing global population sustainably. We developed a Planetary Health Diet Index (PHDI) to quantify adherence to the EAT-Lancet reference diet. OBJECTIVES: We aimed to assess associations between PHDI and total and cause-specific mortality in 3 prospective cohorts of males and females in the United States. METHODS: We followed 66,692 females from the Nurses' Health Study (1986-2019), 92,438 females from the Nurses' Health Study II (1989-2019), and 47,274 males from the Health Professionals Follow-up Study (1986-2018) who were free of cancer, diabetes, and major cardiovascular diseases at baseline. The PHDI was calculated every 4 y using a semiquantitative food frequency questionnaire. Hazard ratios (HRs) were calculated using multivariable proportional-hazards models. RESULTS: During follow-up, we documented 31,330 deaths among females and 23,206 among males. When comparing the highest with the lowest quintile of PHDI, the pooled multivariable-adjusted HRs were 0.77 [95% confidence interval (CI): 0.75, 0.80] for all-cause mortality (P-trend < 0.0001). The PHDI was associated with lower risk of deaths from cardiovascular diseases (HR: 0.86; 95% CI: 0.81, 0.91), cancer (HR: 0.90; 95% CI: 0.85, 0.95), respiratory diseases (HR: 0.53; 95% CI: 0.48, 0.59), and neurodegenerative diseases (HR: 0.72; 95% CI: 0.67, 0.78). In females, but not males, the PHDI was also significantly associated with a lower risk of deaths from infectious diseases (HR: 0.62; 95% CI: 0.51, 0.76). PHDI scores were also associated inversely with greenhouse gas emissions and other environmental impacts. CONCLUSIONS: In 3 large United States-based prospective cohorts of males and females with up to 34 y of follow-up, a higher PHDI was associated with lower risk of total and cause-specific mortality and environment impacts.
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Dieta Saudável , Humanos , Feminino , Masculino , Estudos Prospectivos , Pessoa de Meia-Idade , Adulto , Estados Unidos/epidemiologia , Fatores de Risco , Estudos de Coortes , Causas de Morte , Idoso , Dieta , MortalidadeRESUMO
An exome sequencing strategy employed to identify pathogenic variants in patients with pediatric-onset systemic lupus or Evans syndrome resulted in the discovery of six novel monoallelic mutations in PTPN2. PTPN2 is a phosphatase that acts as an essential negative regulator of the JAK/STAT pathways. All mutations led to a loss of PTPN2 regulatory function as evidenced by in vitro assays and by hyperproliferation of patients' T cells. Furthermore, patients exhibited high serum levels of inflammatory cytokines, mimicking the profile observed in individuals with gain-of-function mutations in STAT factors. Flow cytometry analysis of patients' blood cells revealed typical alterations associated with autoimmunity and all patients presented with autoantibodies. These findings further supported the notion that a loss of function in negative regulators of cytokine pathways can lead to a broad spectrum of autoimmune manifestations and that PTPN2 along with SOCS1 haploinsufficiency constitute a new group of monogenic autoimmune diseases that can benefit from targeted therapy.
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Anemia Hemolítica Autoimune , Autoimunidade , Haploinsuficiência , Lúpus Eritematoso Sistêmico , Proteína Tirosina Fosfatase não Receptora Tipo 2 , Humanos , Haploinsuficiência/genética , Proteína Tirosina Fosfatase não Receptora Tipo 2/genética , Anemia Hemolítica Autoimune/genética , Anemia Hemolítica Autoimune/imunologia , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/imunologia , Feminino , Masculino , Criança , Autoimunidade/genética , Adolescente , Mutação , Trombocitose/genética , Trombocitose/imunologia , Proteína 1 Supressora da Sinalização de Citocina/genética , Autoanticorpos/imunologia , Citocinas/metabolismo , Pré-Escolar , Linfócitos T/imunologia , TrombocitopeniaRESUMO
PURPOSE: This integrative review was conducted to provide a comprehensive picture of the use of standardized nursing languages (SNLs) in long-term care (LTC) systems. METHODS: A comprehensive search was performed with terminological variants of "standardized terminology" and "long-term care" in eight electronic databases up to December 2021. Eligible studies were further identified by screening the reference lists of publications that met the inclusion criteria. The quality of the included studies was appraised using the Joanna Briggs Institute checklists. The study findings were organized into themes, which represent the focus of the study. FINDINGS: Eighty-one publications that studied 12 SNLs in 17 countries are presented in this review. The Omaha System, NANDA-I, NIC, and NOC were the most common SNLs. Study foci were classified into five themes: evaluating the applicability of 10 SNLs (n = 22), characterizing nursing care using six SNLs (n = 16), developing core sets and tools based on seven SNLs (n = 15), documenting nursing care by using four SNLs (n = 14), and implementing intervention programs based on six SNLs (n = 14). CONCLUSIONS AND IMPLICATIONS FOR NURSING: SNLs can be used for various purposes, and the available evidence supports the expansion of their utilization. Further studies should continue to identify gaps in the existing versions of SNLs to reflect the LTC nursing process in multiple societies. Additionally, the successful use of SNLs requires background knowledge of nursing informatics; therefore, preparation should be started in the nursing curriculum and continued in healthcare facilities, including LTC settings. These research findings will assist healthcare managers, researchers, and policymakers in the LTC field in effectively utilizing SNLs.
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BACKGROUND: Although exercise benefits female cancer survivors, clinical decision-making regarding timing, frequency, duration, and intensity is lacking. Optimizing exercise interventions in this population is necessary. This study aimed to describe existing digital home-based exercises and to assess their effectiveness at improving physical health in female cancer survivors upon completion of therapy. DESIGN: We conducted a systematic review using articles from Web of Science, Embase and Medline (Ovid). We included intervention studies examining the effects of digital home-based exercise programs on post-treatment recovery in female cancer survivors. Rob2 and ROBIN I were used to assess quality of studies. Quality-of-life, fatigue score, and physical performance were assessed using meta-analysis. RESULTS: This study involved 1578 female cancer survivors in 21 interventions. Following guidelines and supervised exercise with coaches led to better outcomes than interventions without guidelines, programs without coaches, or lower intensity exercise. Exercise led to significant improvement in some physical performance outcomes. Significant improvements were seen in physical performance outcomes, including the 6-min walk test, metabolic equivalent task, and number of steps per day. CONCLUSION: Providing cancer survivors with standard guidelines for home-based, coach-supervised, vigorous exercise on digital platforms could improve their physical function, health, and quality-of-life.
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Sobreviventes de Câncer , Terapia por Exercício , Qualidade de Vida , Humanos , Sobreviventes de Câncer/psicologia , Sobreviventes de Câncer/estatística & dados numéricos , Feminino , Terapia por Exercício/métodos , Terapia por Exercício/normas , Qualidade de Vida/psicologia , Exercício Físico/psicologiaRESUMO
BACKGROUND: The burden of chronic liver disease (CLD) deaths attributable to the hepatitis B virus (HBV) and hepatitis C virus (HCV) remains unknown. Further research is required to elucidate the extent of this burden in the eventual elimination of these diseases. METHODS: Data on liver cancer, cirrhosis, and other CLD among 204 countries and territories between 1990 and 2019 was extracted from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) published in 2019. The Bayesian age-period-cohort model was used to analyze the temporal trend and predict the disease burden by 2030. RESULTS: The number of HCV-related CLD deaths surpassed that of CLD deaths caused by HBV in 2019 (536833 deaths versus 523003 deaths) and is expected to be maintained until 2030 (689124 deaths versus 628824 deaths). East Asia had the highest burden of chronic HBV and HCV infections during the study period. In 2019, the largest age-standardized death rates (ASDR) of CLD deaths caused by HBV and HCV were mainly observed in Western Sub-Saharan Africa (18.75%) and Eastern Sub-Saharan Africa (16.42%), respectively. South Asia and East Asia are predicted to have the highest number of CLD deaths related to HCV and HBV by 2030. Eastern Europe and South Asia show the largest expected increase in disease burden caused by HCV or HBV between 2019 and 2030. No GBD region is projected to achieve the WHO target of a 65% reduction in mortality from chronic HBV and HCV infections by 2030. CONCLUSIONS: Although the mortality of CLD caused by HBV and HCV decreased in the last three decades (from 1990 to 2019), the number of deaths will continue to increase until 2030. Therefore, governments and international organizations need to strengthen the effectiveness of vaccines, screening, and treatment, especially in potential emerging hotspot regions.
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Saúde Global , Hepatite B Crônica , Hepatite C Crônica , Humanos , Saúde Global/estatística & dados numéricos , Hepatite C Crônica/mortalidade , Hepatite C Crônica/epidemiologia , Hepatite B Crônica/mortalidade , Hepatite B Crônica/epidemiologia , Hepatite B Crônica/complicações , Masculino , Feminino , Fatores de Risco , Pessoa de Meia-Idade , Adulto , Hepatite B/mortalidade , Hepatite B/epidemiologia , Carga Global da Doença , Hepatopatias/mortalidade , Hepatopatias/epidemiologia , Doença Crônica/epidemiologia , Hepatite C/mortalidade , Hepatite C/epidemiologia , Teorema de Bayes , IdosoRESUMO
PURPOSE: We aimed to assess knowledge, attitudes, and perceived barriers among health care professionals (HCPs), policymakers, and regulators in Vietnam related to opioid therapy for cancer pain. METHODS: We conducted a cross-sectional study in Vietnam from June to August 2022. Participants completed a questionnaire on their demographic characteristics, knowledge and attitudes toward opioid therapy, and barriers to accessing opioids for cancer pain. RESULTS: Two hundred seven HCPs and 15 policymakers/regulators completed the questionnaire. Poor knowledge about opioids in cancer pain was found in 63.3% of HCPs and 80.0% of policymakers/regulators. Poor knowledge was associated with a lack of training in cancer pain management or palliative care (PC; prevalence ratio [PR], 1.14 [95% CI, 1.04 to 1.24]). Negative attitudes toward opioid therapy in cancer pain were held by 64.7% of HCPs and 80.0% of policymakers/regulators. Negative attitudes were associated with the unavailability of oral morphine in the workplace (PR, 1.10 [95% CI, 1.01 to 1.20]). The most common major barriers reported were the absence of national policy on pain management and PC (34.7%), inadequate training in opioid use for cancer pain (33.8%), lockdown of health facilities during the COVID-19 pandemic (32.4%), limited opioid availability in local health facilities (32.4%), and excessively restrictive regulation of opioid dispensing in pharmacies (32.4%). CONCLUSION: This study found a knowledge deficit and negative attitudes toward opioid therapy for cancer pain among HCPs and policymakers/regulators. Improving education and training in opioid therapy is essential. Recognizing major barriers can guide strategies to enhance safe opioid accessibility for cancer pain management in Vietnam.
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Analgésicos Opioides , Dor do Câncer , Conhecimentos, Atitudes e Prática em Saúde , Pessoal de Saúde , Manejo da Dor , Humanos , Vietnã , Estudos Transversais , Analgésicos Opioides/uso terapêutico , Dor do Câncer/tratamento farmacológico , Dor do Câncer/psicologia , Masculino , Feminino , Adulto , Pessoal de Saúde/psicologia , Pessoal de Saúde/educação , Pessoa de Meia-Idade , Manejo da Dor/métodos , Inquéritos e Questionários , Atitude do Pessoal de Saúde , COVID-19/epidemiologia , COVID-19/prevenção & controle , Cuidados Paliativos/métodosRESUMO
BACKGROUND: Data on cardiac positron emission tomography (PET) in liver transplantation (LT) candidates are limited with no prior study accounting for poorly metabolized caffeine reducing stress perfusion. METHOD: Consecutive LT candidates (n = 114) undergoing cardiac rest/stress PET were instructed to abstain from caffeine for 2 days extended to 5 and 7 days. Due to persistently high prevalence of measurable blood caffeine after 5-day caffeine abstinence, dipyridamole (n = 41) initially used was changed to dobutamine (n = 73). Associations of absolute flow, coronary flow reserve (CFR), detectable blood caffeine, and Modified End-Stage Liver Disease (MELD) score for liver failure severity were evaluated. Coronary flow data of LT candidates were compared to non-LT control group (n = 102 for dipyridamole, n = 29 for dobutamine). RESULTS: Prevalence of patients with detectable blood caffeine was 63.3%, 36.7% and 33.3% after 2-, 5- and 7-day of caffeine abstinence, respectively. MELD score was associated with detectable caffeine (odd ratio 1.18,P < 0.001). CFR was higher during dipyridamole stress without-caffeine versus with-caffeine (2.22 ± 0.80 vs 1.55 ± 0.37,P = 0.048) but lower than dobutamine stress (2.22 ± 0.80 vs 2.82 ± 1.02,P = 0.026). Mediation analysis suggested that the dominant association between CFR and MELD score in dipyridamole group derived from caffeine-impaired CFR and liver failure/caffeine interaction. CFR in LT candidates was lower than non-LT control population in both dipyridamole and dobutamine group. CONCLUSION: We demonstrate exceptionally high prevalence of detectable blood caffeine in LT candidates undergoing stress PET myocardial perfusion imaging resulting in reduced CFR with dipyridamole compared to dobutamine. The delayed caffeine clearance in LT candidates makes dobutamine a preferred stress agent in this population.
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Tuberculosis (TB)-causing bacterium Mycobacterium tuberculosis (Mtb) utilizes mycolic acids for building the mycobacterial cell wall, which is critical in providing defense against external factors and resisting antibiotic action. MmpL3 is a secondary resistance nodulation division transporter that facilitates the coupled transport of mycolic acid precursor into the periplasm using the proton motive force, thus making it an attractive drug target for TB infection. In 2019, X-ray crystal structures of MmpL3 from M. smegmatis were solved with a promising inhibitor SQ109, which showed promise against drug-resistant TB in Phase II clinical trials. Still, there is a pressing need to discover more effective MmpL3 inhibitors to counteract rising antibiotic resistance. In this study, structure-based high-throughput virtual screening combined with molecular dynamics (MD) simulations identified potential novel MmpL3 inhibitors. Approximately 17 million compounds from the ZINC15 database were screened against the SQ109 binding site on the MmpL3 protein using drug property filters and glide XP docking scores. From this, the top nine compounds and the MmpL3-SQ109 crystal complex structure each underwent 2 × 200 ns MD simulations to probe the inhibitor binding energetics to MmpL3. Four of the nine compounds exhibited stable binding properties and favorable drug properties, suggesting these four compounds could be potential novel inhibitors of MmpL3 for M. tuberculosis.
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BACKGROUND: The rates of suicide and opioid use disorder (OUD) among pregnant and postpartum women continue to increase. This research characterized OUD and suicide attempts among Medicaid-enrolled perinatal women and examined prenatal OUD diagnosis as a marker for postpartum suicide attempts. METHODS: Data from Oregon birth certificates, Medicaid eligibility and claims files, and hospital discharge records were linked and analyzed. The sample included Oregon Medicaid women aged 15-44 who became pregnant and gave live births between January 2008 and January 2016 (N = 61,481). Key measures included indicators of suicide attempts (separately for any means and opioid poisoning) and OUD diagnosis, separately assessed during pregnancy and the one-year postpartum period. Probit regression was used to examine the overall relationship between prenatal OUD diagnosis and postpartum suicide attempts. A simultaneous equations model was employed to explore the link between prenatal OUD diagnosis and postpartum suicide attempts, mediated by postpartum OUD diagnosis. RESULTS: Thirty-three prenatal suicide attempts by any means were identified. Postpartum suicide attempts were more frequent with 58 attempts, corresponding to a rate of 94.3 attempts per 100,000. Of these attempts, 79% (46 attempts) involved opioid poisoning. A total of 1,799 unique women (4.6% of the sample) were diagnosed with OUD either during pregnancy or one-year postpartum with 53% receiving the diagnosis postpartum. Postpartum suicide attempts by opioid poisoning increased from 55.5 per 100,000 in 2009 to 105.1 per 100,000 in 2016. The rate of prenatal OUD also almost doubled over the same period. Prenatal OUD diagnosis was associated with a 0.15%-point increase in the probability of suicide attempts by opioid poisoning within the first year postpartum. This increase reflects a three-fold increase compared to the rate for women without a prenatal OUD diagnosis. A prenatal OUD diagnosis was significantly associated with an elevated risk of postpartum suicide attempts by opioid poisoning via a postpartum OUD diagnosis. CONCLUSIONS: The risk of suicide attempt by opioid poisoning is elevated for Medicaid-enrolled reproductive-age women during pregnancy and postpartum. Women diagnosed with prenatal OUD may face an increased risk of postpartum suicides attempts involving opioid poisoning.
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Analgésicos Opioides , Transtornos Relacionados ao Uso de Opioides , Gravidez , Estados Unidos/epidemiologia , Feminino , Humanos , Analgésicos Opioides/uso terapêutico , Tentativa de Suicídio , Oregon/epidemiologia , Medicaid , Período Pós-Parto , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológicoRESUMO
The phytochemical composition of the Combretum trifoliatum leaves was studied for the first time. Two new triterpenoid saponins, named comtrifoside A (1) and comtrifoside B (2), together with two other saponins (3-4) were purified by variously chromatographic techniques. For the first time, compound 3 was informed from the Combretum genus, as well as all of the isolated compounds (1-4) were reported from C. trifoliatum. The chemical structures of them were clearly characterised using extensive UV-VIS, IR, HRMS-ESI, and NMR experimental data. The in vitro anti-inflammatory activities of 1 & 2 were examined against NO overproduction in LPS activation of RAW264.7.
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This study aimed to develop an online health community platform for facilitating the empowerment of people with chronic diseases dwelling in the community regarding disease prevention and health promotion. The user-centered design approach included four main steps: (1) identifying the health problems and needs of target users, (2) developing the content of the platform, (3) constructing the platform, and (4) pilot testing, refinement, and finalization. An online health community platform available both in a mobile application and a Web-enabled application has been launched to facilitate empowerment and self-management by people with chronic conditions. The main components of the application comprised (1) screening for chronic diseases and health problems, (2) setting personal goals for health promotion and action planning to achieve the goals themselves, (3) offering an online health community with shared group goals that help users engage with their peers to attain their goals, and (4) creating one's own online health community and inviting others to participate. The platform has the potential to encourage people with chronic conditions to proactively engage in their own health promotion. Future studies are needed to determine the impact of the application on self-management and empowerment for its users.
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Empoderamento , Promoção da Saúde , Internet , Humanos , Promoção da Saúde/métodos , Doença Crônica/prevenção & controle , Aplicativos Móveis , Design Centrado no Usuário , Autogestão/métodosRESUMO
Histone deacetylase 6 (HDAC6) contributes to cancer metastasis in several cancers, including triple-negative breast cancer (TNBC)-the most lethal form that lacks effective therapy. Although several efforts have been invested to develop selective HDAC6 inhibitors, none have been approved by the FDA. Toward this goal, existing computational studies used smaller compound libraries and shorter MD simulations. Here, we conducted a structure-based virtual screening of ZINC "Druglike" library containing 17,900,742 compounds using a Glide virtual screening protocol comprising various filters with increasing accuracy. The top 20 hits were subjected to molecular dynamics simulation, MM-GBSA binding energy calculations, and further ADMET prediction. Furthermore, enzyme inhibition assay and cell viability assay were performed on six available compounds from the identified hits. C4 (ZINC000077541942) with a good profile of predicted drug properties was found to inhibit HDAC6 (IC50: 4.7 ± 11.6 µM) with comparative affinity to that of the known HDAC6 selective inhibitor Tubacin (TA) in our experiments. C4 also demonstrated cytotoxic effects against triple-negative breast cancer (TNBC) cell line MDA-MB-231 with EC50 of 40.6 ± 12.7 µM comparable to that of TA (2-20 µM). Therefore, this compound, with pharmacophore features comprising a non-hydroxamic acid zinc-binding group, heteroaromatic linker, and cap group, is proposed as a novel HDAC6 inhibitor.
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Simulação de Dinâmica Molecular , Neoplasias de Mama Triplo Negativas , Humanos , Sobrevivência Celular , Desacetilase 6 de Histona/antagonistas & inibidores , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/química , Simulação de Acoplamento Molecular , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , ZincoRESUMO
Overexpression of the chromosome 21 DYRK1A gene induces morphological defects and cognitive impairments in individuals with Down syndrome (DS) and in DS mice models. Aging neurons of specific brain regions of patients with Alzheimer's disease, DS and Pick's disease have increased DYRK1A immunoreactivity suggesting a possible association of DYRK1A with neurofibrillary tangle pathology. Epigallocatechin-3-gallate (EGCG) displays appreciable inhibition of DYRK1A activity and, contrary to all other published inhibitors, EGCG is a non-competitive inhibitor of DYRK1A. Prenatal exposure to green tea polyphenols containing EGCG protects from brain defects induced by overexpression of DYRK1A. In order to produce more robust and possibly more active analogues of the natural compound EGCG, here we synthetized new EGCG-like molecules with several structural modifications to the EGCG skeleton. We replaced the ester boun of EGCG with a more resistant amide bond. We also replaced the oxygen ring by a methylene group. And finally, we positioned a nitrogen atom within this ring. The selected compound was shown to maintain the non-competitive property of EGCG and to correct biochemical and behavioral defects present in a DS mouse model. In addition it showed high stability and specificity.
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Catequina/análogos & derivados , Síndrome de Down , Humanos , Feminino , Gravidez , Camundongos , Animais , Síndrome de Down/tratamento farmacológico , Proteínas Serina-Treonina Quinases , Proteínas Tirosina Quinases , Camundongos Transgênicos , CogniçãoRESUMO
OBJECTIVES: To identify hospital capabilities associated with behavioral health (BH) processes in emergency departments (EDs). RESEARCH DESIGN: Six hundred two hospital responses to the 2017/2018 National Survey of Healthcare Organizations and Systems were linked to 2017 American Hospital Association Annual Survey data. Separate multivariable regressions estimated how hospital capabilities (the use of quality improvement methods, approaches to disseminate best patient-care practices, barriers to using care delivery innovations, and inpatient beds for psychiatric or substance use) were associated with each of 4 ED-based BH processes: mental health and substance use disorder screening, team-based approaches to BH, telepsychiatry, and direct referrals to community-based BH clinicians. Models controlled for hospital structural characteristics and area-level socioeconomic factors. RESULTS: Most hospitals screened for BH conditions and provided direct referrals to community-based BH clinicians. Approximately half of the hospitals used a team approach to BH. A minority had implemented telepsychiatry. Each additional process used to disseminate best patient-care practices was associated with more screening for BH conditions (an increase of 4.07 points on the screening index, P <0.01) and greater likelihood of using a team approach to BH [4.41 percentage point ( P <0.01) increase]. Hospitals reporting more barriers to the use of care delivery innovations reported less screening and use of a team approach [a decrease of 0.15 points on the screening index ( P <0.01) and 0.28 percentage points reduction in likelihood of team approach use ( P <0.001) for 1-point increase in the barrier index]. CONCLUSIONS: Research and interventions focused on removing innovation barriers or adding processes to disseminate best practices offer a path to accelerate BH integration in hospital EDs.
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Psiquiatria , Transtornos Relacionados ao Uso de Substâncias , Telemedicina , Humanos , Hospitais , Serviço Hospitalar de EmergênciaRESUMO
BACKGROUND AND AIMS: Coronary flow capacity (CFC) is associated with an observed 10-year survival probability for individual patients before and after actual revascularization for comparison to virtual hypothetical ideal complete revascularization. METHODS: Stress myocardial perfusion (mL/min/g) and coronary flow reserve (CFR) per pixel were quantified in 6979 coronary artery disease (CAD) subjects using Rb-82 positron emission tomography (PET) for CFC maps of artery-specific size-severity abnormalities expressed as percent left ventricle with prospective follow-up to define survival probability per-decade as fraction of 1.0. RESULTS: Severely reduced CFC in 6979 subjects predicted low survival probability that improved by 42% after revascularization compared with no revascularization for comparable severity (P = .0015). For 283 pre-and-post-procedure PET pairs, severely reduced regional CFC-associated survival probability improved heterogeneously after revascularization (P < .001), more so after bypass surgery than percutaneous coronary interventions (P < .001) but normalized in only 5.7%; non-severe baseline CFC or survival probability did not improve compared with severe CFC (P = .00001). Observed CFC-associated survival probability after actual revascularization was lower than virtual ideal hypothetical complete post-revascularization survival probability due to residual CAD or failed revascularization (P < .001) unrelated to gender or microvascular dysfunction. Severely reduced CFC in 2552 post-revascularization subjects associated with low survival probability also improved after repeat revascularization compared with no repeat procedures (P = .025). CONCLUSIONS: Severely reduced CFC and associated observed survival probability improved after first and repeat revascularization compared with no revascularization for comparable CFC severity. Non-severe CFC showed no benefit. Discordance between observed actual and virtual hypothetical post-revascularization survival probability revealed residual CAD or failed revascularization.
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Doença da Artéria Coronariana , Humanos , Radioisótopos de Rubídio , Estudos Prospectivos , Tomografia por Emissão de Pósitrons/métodos , Angiografia Coronária/métodosRESUMO
SETD2 (SET-domain containing protein 2) is a histone methyltransferase (HMT) of the SET family responsible for the trimethylation of K36 of histone H3, thus producing the epigenetic mark H3K36me3. Recent studies have shown that certain SET family HMTs, such as SMYD2, SMYD3 or SETDB1 can also methylate protein kinases and therefore be involved in signaling pathways. Here we provide structural and enzymatic evidence showing that SETD2 methylates the protein tyrosine kinase ACK1 in vitro. ACK1 is recognized as a major integrator of signaling from various receptor tyrosine kinases. Using ACK1 peptides and recombinant proteins, we show that SETD2 methylates the K514 residue of ACK1 generating K514 mono, di or tri-methylation. Interestingly, K514 is found in a "H3K36-like" motif of ACK1 which is known to be post-translationally modified and to be involved in protein-protein interaction. The crystal structure of SETD2 catalytic domain in complex with an ACK1 peptide further provides the structural basis for the methylation of ACK1 K514 by SETD2. Our work therefore strongly suggests that ACK1 could be a novel non-histone substrate of SETD2 and further supports that SET HMTs, such as SETD2, could be involved in both epigenetic regulations and cell signaling.
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Histonas , Proteínas Tirosina Quinases , Proteínas Tirosina Quinases/metabolismo , Histonas/metabolismo , Metilação , Histona-Lisina N-Metiltransferase/genética , Processamento de Proteína Pós-TraducionalRESUMO
A new approach that combines analytical two-parameter kinematic theory (2PKT) with machine learning (ML) models for estimating the shear capacity of embedded through-section (ETS)-strengthened reinforced concrete (RC) beams is proposed. The 2PKT was first developed to validate its representativeness and confidence against the available experimental data of ETS-retrofitted RC beams. Given the deficiency of the test data, the developed 2PKT was utilized to generate a large data pool with 2643 samples. The aim was to optimize the ML algorithms, namely, the random forest, extreme gradient boosting (XGBoost), light gradient boosting machine, and artificial neural network (ANN) algorithm. The optimized ANN model exhibited the highest accuracy in predicting the total shear strength of ETS-strengthened beams and ETS shear contribution. In terms of predicting the total shear strength of ETS-strengthened beams, the ANN model achieved R2 values of 0.99, 0.98, and 0.96 for the training, validation, and testing data, respectively. By contrast, the ANN model could predict ETS shear contribution with high accuracy, with R2 values of 0.99, 0.99, and 0.97 for the training, validation, and testing data, respectively. Then, the effects of all design variables on the shear capacity of the ETS-strengthened beams were investigated using the hybrid 2PKT-ML. The obtained trends could well appraise the reasonability of the proposed approach.
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Background: Few standardized and open-source tools exist for calculating dietary pattern indexes from dietary intake data in epidemiological and clinical studies. Miscalculations of dietary indexes, with suspected erroneous findings, are occasionally noted in the literature. Objective: The primary aim is to develop and validate dietaryindex, a user-friendly and versatile R package that standardizes the calculation of dietary indexes. Methods: Dietaryindex utilizes a two-step process: an initial calculation of serving size for each food and nutrient category, followed by the calculation of individual dietary indexes. It includes generic functions that accept any preprocessed serving sizes of food groups and nutrients, with the standard serving sizes defined according to the methodologies used in well-known prospective cohort studies. For ease of use, dietaryindex also offers one-step functions that directly reference common datasets and tools, including the National Health and Nutrition Examination Survey (NHANES) and Block Food Frequency Questionnaire, eliminating the need for data preprocessing. At least two independent researchers validated the serving size definitions and scoring algorithms of dietaryindex. Results: Dietaryindex can calculate multiple dietary indexes of high interest in research, including Healthy Eating Index (HEI) - 2020, Alternative Healthy Eating Index 2010, Dietary Approaches to Stop Hypertension Index, Alternate Mediterranean Diet Score, Dietary Inflammatory Index, American Cancer Society 2020 dietary index, and Planetary Health Diet Index from the EAT-Lancet Commission. In our validation process, dietaryindex demonstrated full accuracy (100%) in all generic functions with two-decimal rounding precision in comparison to hand-calculated results. Similarly, using NHANES 2017-2018 data and ASA24 and DHQ3 example data, the HEI2015 outputs from dietaryindex aligned (99.95%-100%) with results using the SAS codes from the National Cancer Institute. Conclusions: Dietaryindex is a user-friendly, versatile, and validated informatics tool for standardized dietary index calculations. We have open-sourced all the validation files and codes with detailed tutorials on GitHub (https://github.com/jamesjiadazhan/dietaryindex).