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1.
Cell ; 185(10): 1676-1693.e23, 2022 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-35489334

RESUMO

Epidemiological studies reveal that marijuana increases the risk of cardiovascular disease (CVD); however, little is known about the mechanism. Δ9-tetrahydrocannabinol (Δ9-THC), the psychoactive component of marijuana, binds to cannabinoid receptor 1 (CB1/CNR1) in the vasculature and is implicated in CVD. A UK Biobank analysis found that cannabis was an risk factor for CVD. We found that marijuana smoking activated inflammatory cytokines implicated in CVD. In silico virtual screening identified genistein, a soybean isoflavone, as a putative CB1 antagonist. Human-induced pluripotent stem cell-derived endothelial cells were used to model Δ9-THC-induced inflammation and oxidative stress via NF-κB signaling. Knockdown of the CB1 receptor with siRNA, CRISPR interference, and genistein attenuated the effects of Δ9-THC. In mice, genistein blocked Δ9-THC-induced endothelial dysfunction in wire myograph, reduced atherosclerotic plaque, and had minimal penetration of the central nervous system. Genistein is a CB1 antagonist that attenuates Δ9-THC-induced atherosclerosis.


Assuntos
Cannabis , Doenças Cardiovasculares , Alucinógenos , Analgésicos , Animais , Agonistas de Receptores de Canabinoides/farmacologia , Dronabinol/farmacologia , Células Endoteliais , Genisteína/farmacologia , Genisteína/uso terapêutico , Inflamação/tratamento farmacológico , Camundongos , Receptor CB1 de Canabinoide , Receptores de Canabinoides
3.
Mol Psychiatry ; 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38499656

RESUMO

Autism spectrum disorder (ASD) is a major neurodevelopmental disorder affecting 1 in 36 children in the United States. While neurons have been the focus of understanding ASD, an altered neuro-immune response in the brain may be closely associated with ASD, and a neuro-immune interaction could play a role in the disease progression. As the resident immune cells of the brain, microglia regulate brain development and homeostasis via core functions including phagocytosis of synapses. While ASD has been traditionally considered a polygenic disorder, recent large-scale human genetic studies have identified SCN2A deficiency as a leading monogenic cause of ASD and intellectual disability. We generated a Scn2a-deficient mouse model, which displays major behavioral and neuronal phenotypes. However, the role of microglia in this disease model is unknown. Here, we reported that Scn2a-deficient mice have impaired learning and memory, accompanied by reduced synaptic transmission and lower spine density in neurons of the hippocampus. Microglia in Scn2a-deficient mice are partially activated, exerting excessive phagocytic pruning of post-synapses related to the complement C3 cascades during selective developmental stages. The ablation of microglia using PLX3397 partially restores synaptic transmission and spine density. To extend our findings from rodents to human cells, we established a microglia-incorporated human cerebral organoid model carrying an SCN2A protein-truncating mutation identified in children with ASD. We found that human microglia display increased elimination of post-synapse in cerebral organoids carrying the SCN2A mutation. Our study establishes a key role of microglia in multi-species autism-associated models of SCN2A deficiency from mouse to human cells.

4.
Small ; : e2402525, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38801302

RESUMO

Persistent organic pollutants (POPs), including xenoestrogens and polyfluoroalkyl substances (PFAS), demand urgent global intervention. Fenton oxidation, catalyzed by iron ions, offers a cost-effective means to degrade POPs. However, numerous challenges like acid dependency, catalyst loss, and toxic waste generation hinder practical application. Efforts to create long-lasting heterogeneous Fenton catalysts, capable of simultaneously eliminating acid requirements, sustaining rapid kinetics, and retaining iron efficiently, have been unsuccessful. This study introduces an innovative heterogeneous zwitterionic hydrogel-based Fenton catalyst, surmounting these challenges in a cost-effective and scalable manner. The hydrogel, hosting individually complexed iron ions in a porous scaffold, exhibits substantial effective surface area and kinetics akin to homogeneous Fenton reactions. Complexed ions within the hydrogel can initiate Fenton degradation at neutral pH, eliminating acid additions. Simultaneously, the zwitterionic hydrogel scaffold, chosen for its resistance to Fenton oxidation, forms strong bonds with iron ions, enabling prolonged reuse. Diverging from existing designs, the catalyst proves compatible with UV-Fenton processes and achieves rapid self-regeneration during operation, offering a promising solution for the efficient and scalable degradation of POPs. The study underscores the efficacy of the approach by demonstrating the swift degradation of three significant contaminants-xenoestrogens, pesticides, and PFAS-across multiple cycles at trace concentrations.

5.
Br J Haematol ; 196(1): 193-203, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34786695

RESUMO

Hydroxyurea (hydroxycarbamide) (HU) for sickle cell anaemia (SCA) is underutilised. Case management is an evidence-based health management strategy and in this regard patient navigators (PNs) may provide case management for SCA. We hypothesised that HU-eligible patients exposed to PNs would have improved indicators of starting HU and HU adherence. We randomised 224 HU-eligible SCA adults into the Start Healing in Patients with Hydroxyurea (SHIP-HU) Trial. All patients received care from trained physicians using standardised HU prescribing protocols. Patients in the Experimental arm received case management and education from PNs through multiple contacts. All other patients were regarded as the Control arm and received specialty care alone. Study physicians were blinded to the study arms and did not interact with PNs. At baseline, 6 and 12 months we assessed and compared laboratory parameters and HU adherence indicators. Experimental patients had higher 6-month mean fetal haemoglobin (HbF) levels than controls. But at 12 months, mean HbF was similar, as were white blood cell count, absolute neutrophil count, total haemoglobin, platelet count and mean corpuscular volume. At 12 months there were fewer experimental patients missing HU doses than controls (mean 1·8 vs. 4·5, P = 0·0098), and more recent HU prescriptions filled than for controls (mean 53·8 vs. 92 days, median 27·5 vs. 62 days, P = 0·0082). Mean HU doses were largely similar. We detected behavioural improvements in HU adherence but no haematological improvements by adding PNs to specialty care.


Assuntos
Anemia Falciforme/epidemiologia , Agentes Comunitários de Saúde , Adesão à Medicação , Adulto , Anemia Falciforme/sangue , Anemia Falciforme/diagnóstico , Anemia Falciforme/terapia , Índices de Eritrócitos , Feminino , Humanos , Hidroxiureia/administração & dosagem , Hidroxiureia/efeitos adversos , Hidroxiureia/uso terapêutico , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Assistência ao Paciente , Melhoria de Qualidade , Qualidade de Vida , Resultado do Tratamento , Adulto Jovem
6.
Soft Matter ; 18(24): 4625-4637, 2022 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-35699057

RESUMO

Micelles immobilized in polymer materials are of emerging interest in drug delivery, water treatment and other applications. Immobilization removes the need for membrane-based separation to eliminate micelles from the medium, enabling facile extraction and delivery in diverse industries. This work lays out a coarse-grained molecular dynamics simulations framework for the rapid identification of surfactants for use in immobilized micelle systems. Micelles are immobilized by constraining one end of the constituent surfactants in space, mimicking what would occur in a copolymer system. We demonstrate that constraints affect how the micelles interact with small hydrophobic molecules, making it important to account for their effects in various drug-micelle and pollutant-micelle simulations. Our results show that in several systems there is stronger interaction between hydrophobic small molecules and micelles in immobilized systems compared to unconstrained systems. These strengthened interactions can have important implications for the design of new micelle-based extraction and delivery processes.


Assuntos
Micelas , Simulação de Dinâmica Molecular , Interações Hidrofóbicas e Hidrofílicas , Polímeros , Tensoativos/química
7.
Acta Neurol Taiwan ; 31(4): 179-185, 2022 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-35470412

RESUMO

PURPOSE: Takotsubo syndrome (TTS) is characterized angiographically by transient left ventricular systolic dysfunction sparing the basal segments of the left ventricle and absence of obstructive coronary artery disease. Epileptic seizures as triggering events for TTS are uncommon, having only been described in approximately 100 previous cases Case report: A 64-year-old woman with a history of recent stroke-related seizures was admitted for an acute onset of right hemiparesis with dull response. Neurological examination revealed a forced deviation of the eyeballs to the left side and quadriplegia. No large intracranial artery occlusion was disclosed through computed tomography angiography, but an acute infarction at the right corona radiata was identified through magnetic resonance imaging. Electroencephalography showed frequent spike-and-wave complexes over the right cerebral hemisphere indicating subtle status epilepticus. Her consciousness deteriorated to a stuporous state, and her eyeballs were forced deviated to the right side with persistent twitching of the right limbs 10 hours later. The convulsive status epilepticus (CSE) subsided after intravenous infusion of midazolam. However, atrial flutter with inverted T-wave and elevated high-sensitivity troponin I were observed 12 hours after CSE. Arrhythmia was soon alleviated through appropriate treatment. A further coronary angiography did not show significant coronary artery stenosis but indicated that the midsection and the apex of the left ventricle ballooned out during systole as the base contracted normally, indicating a Takotsubo syndrome. CONCLUSION: Physicians need to monitor unusual arrhythmias, particularly atrial and ventricular arrhythmias, for the possibility of TTS in patients with epileptic seizure.


Assuntos
Estado Epiléptico , Cardiomiopatia de Takotsubo , Eletroencefalografia/efeitos adversos , Feminino , Humanos , Imageamento por Ressonância Magnética/efeitos adversos , Pessoa de Meia-Idade , Convulsões/etiologia , Estado Epiléptico/etiologia , Cardiomiopatia de Takotsubo/complicações , Cardiomiopatia de Takotsubo/diagnóstico por imagem
8.
Stem Cells ; 38(6): 808-814, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32129537

RESUMO

Little is known on the phenotypic characteristics of stem cells (SCs) after they are transplanted to the myocardium, in part due to lack of noninvasive platforms to study SCs directly in the living subject. Reporter gene imaging has played a valuable role in the noninvasive assessment of cell fate in vivo. In this study, we validated a pathway-specific reporter gene that can be used to noninvasively image the phenotype of SCs transplanted to the myocardium. Rat mesenchymal SCs (MSCs) were studied for phenotypic evidence of myogenic characteristics under in vitro conditions. After markers of myogenic characteristics were identified, we constructed a reporter gene sensor, comprising the firefly luciferase (Fluc) reporter gene driven by the troponin T (TnT) promoter (cardio MSCs had threefold expression in polymerase chain reaction compared to control MSCs) using a two-step signal amplification strategy. MSCs transfected with TnT-Fluc were studied and validated under in vitro conditions, showing a strong signal after MSCs acquired myogenic characteristics. Lastly, we observed that cardio MSCs had higher expression of the reporter sensor compared to control cells (0.005 ± 0.0005 vs 0.0025 ± 0.0008 Tnt-Fluc/ubiquitin-Fluc, P < .05), and that this novel sensor can detect the change in the phenotype of MSCs directly in the living subject. Pathway-specific reporter gene imaging allows assessment of changes in the phenotype of MSCs after delivery to the ischemic myocardium, providing important information on the phenotype of these cells. Imaging sensors like the one described here are critical to better understanding of the changes that SCs undergo after transplantation.


Assuntos
Genes Reporter/genética , Células-Tronco Mesenquimais/metabolismo , Diferenciação Celular , Humanos
9.
J Formos Med Assoc ; 120(1 Pt 3): 713-719, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32773262

RESUMO

BACKGROUND: Coronavirus disease-2019 (COVID-19) is a worldwide pandemic. We present the clinical characteristics and outcomes of 28 COVID-19 patients treated in our hospital in Taiwan. METHODS: Patients with COVID-19, confirmed by positive real-time reverse-transcriptase polymerase chain reaction results for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral nucleic acids from oropharyngeal swab specimens between February 4, 2020 and July 6, 2020, were enrolled. Their clinical characteristics and outcomes were reviewed. RESULTS: Seventeen of the 28 patients (60.7%) had pneumonia. The most frequent symptoms were cough (n = 23, 82.1%) and fever (n = 17, 60.7%). The development of pneumonia was associated with age ≥40 years (p < 0.024), body mass index (BMI) ≥25 kg/m2 (p = 0.014), fever (p = 0.007), shortness of breath (p = 0.036), chills ((p = 0.047), and lower platelet counts (<200,000/µL) (p = 0.007). Increased quarantine duration was associated with age ≥40 years (p = 0.026), Charlson index ≥1 (p = 0.037), lower lymphocyte (<1500/uL; p = 0.028) or platelet counts (<200,000/µL) (p = 0.016), lower serum sodium (<140 mEq/L; p = 0.006), and higher C-reactive protein (CRP) level (≥1 mg/dl; p = 0.04). Treatment with hydroxychloroquine or in combination with other medicines did not reduce the quarantine duration. All 28 patients recovered with a median quarantine duration of 27.2 days. CONCLUSION: COVID-19 patients with older age, higher BMI, fever, chills or shortness of breath, lower serum sodium level, lower platelet or lymphocyte count, and higher CRP level may be associated with developing pneumonia or longer quarantine duration.


Assuntos
Teste de Ácido Nucleico para COVID-19/métodos , COVID-19 , Pneumonia Viral , SARS-CoV-2/isolamento & purificação , Adulto , Fatores Etários , Contagem de Células Sanguíneas/métodos , Índice de Massa Corporal , Proteína C-Reativa/análise , COVID-19/sangue , COVID-19/epidemiologia , COVID-19/fisiopatologia , COVID-19/terapia , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/etiologia , Quarentena , Fatores de Risco , Avaliação de Sintomas/métodos , Taiwan/epidemiologia
10.
Bioinformatics ; 35(20): 4200-4202, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-30903160

RESUMO

SUMMARY: The interaction between tumor and immune system plays a crucial role in both cancer development and treatment response. To facilitate comprehensive investigation of tumor-immune interactions, we have designed a user-friendly web portal TISIDB, which integrated multiple types of data resources in oncoimmunology. First, we manually curated 4176 records from 2530 publications, which reported 988 genes related to anti-tumor immunity. Second, genes associated with the resistance or sensitivity of tumor cells to T cell-mediated killing and immunotherapy were identified by analyzing high-throughput screening and genomic profiling data. Third, associations between any gene and immune features, such as lymphocytes, immunomodulators and chemokines, were pre-calculated for 30 TCGA cancer types. In TISIDB, biologists can cross-check a gene of interest about its role in tumor-immune interactions through literature mining and high-throughput data analysis, and generate testable hypotheses and high quality figures for publication. AVAILABILITY AND IMPLEMENTATION: http://cis.hku.hk/TISIDB. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Sistema Imunitário , Neoplasias , Algoritmos , Humanos , Publicações , Software
11.
Circ Res ; 123(4): 443-450, 2018 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-29986945

RESUMO

RATIONALE: Human-induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) have risen as a useful tool in cardiovascular research, offering a wide gamut of translational and clinical applications. However, inefficiency of the currently available iPSC-EC differentiation protocol and underlying heterogeneity of derived iPSC-ECs remain as major limitations of iPSC-EC technology. OBJECTIVE: Here, we performed droplet-based single-cell RNA sequencing (scRNA-seq) of the human iPSCs after iPSC-EC differentiation. Droplet-based scRNA-seq enables analysis of thousands of cells in parallel, allowing comprehensive analysis of transcriptional heterogeneity. METHODS AND RESULTS: Bona fide iPSC-EC cluster was identified by scRNA-seq, which expressed high levels of endothelial-specific genes. iPSC-ECs, sorted by CD144 antibody-conjugated magnetic sorting, exhibited standard endothelial morphology and function including tube formation, response to inflammatory signals, and production of NO. Nonendothelial cell populations resulting from the differentiation protocol were identified, which included immature cardiomyocytes, hepatic-like cells, and vascular smooth muscle cells. Furthermore, scRNA-seq analysis of purified iPSC-ECs revealed transcriptional heterogeneity with 4 major subpopulations, marked by robust enrichment of CLDN5, APLNR, GJA5, and ESM1 genes, respectively. CONCLUSIONS: Massively parallel, droplet-based scRNA-seq allowed meticulous analysis of thousands of human iPSCs subjected to iPSC-EC differentiation. Results showed inefficiency of the differentiation technique, which can be improved with further studies based on identification of molecular signatures that inhibit expansion of nonendothelial cell types. Subtypes of bona fide human iPSC-ECs were also identified, allowing us to sort for iPSC-ECs with specific biological function and identity.


Assuntos
Células Endoteliais/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Transcriptoma , Receptores de Apelina/genética , Receptores de Apelina/metabolismo , Diferenciação Celular , Células Cultivadas , Claudina-5/genética , Claudina-5/metabolismo , Conexinas/genética , Conexinas/metabolismo , Células Endoteliais/citologia , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Proteoglicanas/genética , Proteoglicanas/metabolismo , Análise de Célula Única , Proteína alfa-5 de Junções Comunicantes
12.
BMC Infect Dis ; 20(1): 193, 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32131752

RESUMO

BACKGROUND: Microbial infection is the main cause of increased morbidity and mortality in burn patients, especially infections caused by multiple drug-resistant organisms (MDRO). The purpose of this study was to explore major microbial trends in burn patients. METHODS: This retrospective study was conducted at burn wards and intensive care units, where burn patients were admitted following an event of dust explosion. Data were collected for a number of variables including severity of burns, demographic and clinical characteristics, laboratory data, and therapeutic devices. RESULTS: A total of 1132 specimens were collected from 37 hospitalized burn patients with mean TBSA of 46.1%.The most commonly isolated species were Staphylococcus spp. (22.4%). The highest rate of antibiotic resistance was observed in carbapenem-resistant A. baumannii (14.6%), followed by methicillin-resistant S. aureus (11.3%). For each additional 10% TBSA, the isolation of MDRO increased 2.58-17.57 times (p < 0.05); for each additional 10% of the third-degree burn severity, the risk of MDRO significantly decreased by 47% (95% CI, 0.38-0.73, p < 0.001) by Cox model. CONCLUSIONS: The proportion of overall microbial isolates increased with the increase in TBSA and duration of time after burns. The extent of TBSA was the most important factor affecting MDRO.


Assuntos
Traumatismos por Explosões/microbiologia , Queimaduras por Inalação/microbiologia , Poeira , Explosões , Centros de Atenção Terciária , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/isolamento & purificação , Adolescente , Adulto , Antibacterianos/uso terapêutico , Superfície Corporal , Carbapenêmicos/efeitos adversos , Carbapenêmicos/uso terapêutico , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Feminino , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Estudos Retrospectivos , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Fatores de Tempo , Adulto Jovem
13.
Retina ; 40(12): 2312-2318, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31895093

RESUMO

PURPOSE: Periodontitis is an inflammatory disease that results in loss of connective tissue and bone support. Evidence shows a possible relationship between periodontitis and age-related macular degeneration (AMD). METHODS: This population-based cohort study was conducted using data from the National Health Insurance Research Database in Taiwan, with a 13-year follow-up, to investigate the risk of AMD in patients with periodontitis. The periodontitis cohort included patients with newly diagnosed periodontitis between 2000 and 2012. The nonperiodontitis cohort was frequency-matched with the periodontitis cohort by age and sex, with a sample size of 41,661 in each cohort. RESULTS: Patients with periodontitis had an increased risk of developing AMD compared with individuals without periodontitis (5.95 vs. 3.41 per 1,000 person-years, adjusted hazard ratio = 1.58 [95% confidence interval, 1.46-1.70]). The risk of developing AMD remained significant after stratification by age (adjusted hazard ratio = 1.48 [1.34-1.64] for age <65 years and 1.76 [1.57-1.97] for age ≥65 years), sex (adjusted hazard ratio = 1.40 [1.26-1.55] for women and 1.82 [1.63-2.04] for men), and presence of comorbidity (adjusted hazard ratio = 1.52 [1.40-1.66] for with comorbidity and 1.92 [1.63-2.26] for without comorbidity). In addition, patients with periodontitis showed an increased incidence for both nonexudative type AMD (5.43 vs. 3.13 per 1,000 person-years) and exudative type AMD (0.52 vs. 0.28 per 1,000 person-years). CONCLUSION: People with periodontitis could be at a greater risk of developing AMD than those without periodontitis. However, we need more evidence to support this association.


Assuntos
Degeneração Macular/epidemiologia , Periodontite/complicações , Idoso , Estudos de Coortes , Comorbidade , Bases de Dados Factuais , Feminino , Humanos , Incidência , Degeneração Macular/diagnóstico , Masculino , Pessoa de Meia-Idade , Programas Nacionais de Saúde/estatística & dados numéricos , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologia
14.
J Vasc Res ; 56(1): 11-15, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30763932

RESUMO

Peripartum cardiomyopathy (PPCM) is a rare form of congestive heart failure characterized by left ventricular dysfunction that develops towards the end of pregnancy or during the early postpartum phase. Even though the majority of PPCM patients show partial or complete recovery of their heart functions, the mortality rate of PPCM remains high. Previous research has suggested that vascular dysfunction triggered by late-gestational hormones and potent anti-angiogenic factors play key roles in the pathogenesis of PPCM; however, the exact mechanisms remain elusive due to limited patient tissues for characterization. Here, we report a case of PPCM where the coronary vessels from the patient's explanted heart showed marked vascular dysfunction with impaired nitric oxide response. Importantly, these vessels exhibited deficient adenosine-mediated vasorelaxation when subjected to myograph studies, suggesting impaired Kv7 ion channels. Results from this work may lead to new therapeutic strategies for improving Kv7 function in PPCM patients.


Assuntos
Cardiomiopatias/etiologia , Doença da Artéria Coronariana/etiologia , Vasos Coronários/fisiopatologia , Período Periparto , Vasodilatação , Disfunção Ventricular Esquerda/etiologia , Função Ventricular Esquerda , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/fisiopatologia , Cardiomiopatias/cirurgia , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/fisiopatologia , Doença da Artéria Coronariana/cirurgia , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/metabolismo , Progressão da Doença , Feminino , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/cirurgia , Transplante de Coração , Humanos , Canais de Potássio KCNQ/metabolismo , Pessoa de Meia-Idade , Gravidez , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/fisiopatologia , Disfunção Ventricular Esquerda/cirurgia
15.
J Formos Med Assoc ; 118(6): 1047-1054, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30391109

RESUMO

BACKGROUND/PURPOSE: Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease affecting oral health. Evidence shows possible association between T1DM and periodontal diseases (PDs). We conducted a nationwide population-based study in Taiwan, with a 14-year follow-up to investigate the risk of PDs in T1DM patients. METHODS: We used data from the National Health Insurance Research Database in Taiwan. The T1DM cohort was identified with newly diagnosed T1DM from 1998 to 2011. The non-T1DM cohort was frequency matched with the T1DM cohort. Participants comprised 4248 patients in the T1DM cohort and 16992 persons in the non-T1DM cohort. RESULTS: The T1DM patients showed an increased risk of PDs compared to non-T1DM individuals [adjusted hazard ratio (aHR) = 1.45]. T1DM patients who visited the emergency room more than twice per year had a higher aHR of 13.0 for developing PDs. The aHR for PDs was 13.2 in the T1DM patients who had been hospitalized more than twice per year. CONCLUSION: T1DM patients are at higher risk of developing PDs than non-T1DM individuals. Our results further showed that the number of T1DM interventions; that is, annual emergency visits and hospitalizations were associated with increased the risk of developing PDs.


Assuntos
Diabetes Mellitus Tipo 1/complicações , Doenças Periodontais/epidemiologia , Adolescente , Adulto , Criança , Bases de Dados Factuais , Feminino , Humanos , Incidência , Masculino , Análise Multivariada , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologia , Adulto Jovem
17.
BMC Infect Dis ; 18(1): 4, 2018 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-29291707

RESUMO

BACKGROUND: The operating room (OR) of the hospital is a special unit that requires a relatively clean environment. The microbial concentration of an indoor OR extrinsically influences surgical site infection rates. The aim of this study was to use active sampling methods to assess microbial colony counts in working ORs and to determine the factors affecting air contamination in a tertiary referral medical center. METHODS: This study was conducted in 28 operating rooms located in a 3000-bed medical center in northern Taiwan. The microbiologic air counts were measured using an impactor air sampler from May to August 2015. Information about the procedure-related operative characteristics and surgical environment (environmental- and personnel-related factors) characteristics was collected. RESULTS: A total of 250 air samples were collected during surgical procedures. The overall mean number of bacterial colonies in the ORs was 78 ± 47 cfu/m3. The mean number of colonies was the highest for transplant surgery (123 ± 60 cfu/m3), followed by pediatric surgery (115 ± 30.3 cfu/m3). A total of 25 samples (10%) contained pathogens; Coagulase-negative staphylococcus (n = 12, 4.8%) was the most common pathogen. After controlling for potentially confounding factors by a multiple regression analysis, the surgical stage had the significantly highest correlation with bacterial counts (r = 0.346, p < 0.001). Otherwise, independent factors influencing bacterial counts were the type of surgery (29.85 cfu/m3, 95% CI 1.28-58.42, p = 0.041), site of procedure (20.19 cfu/m3, 95% CI 8.24-32.14, p = 0.001), number of indoor staff (4.93 cfu/m3, 95% CI 1.47-8.38, p = 0.005), surgical staging (36.5 cfu/m3, 95% CI 24.76-48.25, p < 0.001), and indoor air temperature (9.4 cfu/m3, 95% CI 1.61-17.18, p = 0.018). CONCLUSIONS: Under the well-controlled ventilation system, the mean microbial colony counts obtained by active sampling in different working ORs were low. The number of personnel and their activities critically influence the microbe concentration in the air of the OR. We suggest that ORs doing complex surgeries with more surgical personnel present should increase the frequency of air exchanges. A well-controlled ventilation system and infection control procedures related to environmental and surgical procedures are of paramount importance for reducing microbial colonies in the air.


Assuntos
Microbiologia do Ar , Contagem de Colônia Microbiana , Salas Cirúrgicas , Bactérias/isolamento & purificação , Hospitais , Humanos , Controle de Infecções/métodos , Infecção da Ferida Cirúrgica , Taiwan
18.
Am J Physiol Lung Cell Mol Physiol ; 313(2): L252-L266, 2017 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-28473326

RESUMO

Pulmonary arterial hypertension is a complication of methamphetamine use (METH-PAH), but the pathogenic mechanisms are unknown. Given that cytochrome P450 2D6 (CYP2D6) and carboxylesterase 1 (CES1) are involved in metabolism of METH and other amphetamine-like compounds, we postulated that loss of function variants could contribute to METH-PAH. Although no difference in CYP2D6 expression was seen by lung immunofluorescence, CES1 expression was significantly reduced in endothelium of METH-PAH microvessels. Mass spectrometry analysis showed that healthy pulmonary microvascular endothelial cells (PMVECs) have the capacity to both internalize and metabolize METH. Furthermore, whole exome sequencing data from 18 METH-PAH patients revealed that 94.4% of METH-PAH patients were heterozygous carriers of a single nucleotide variant (SNV; rs115629050) predicted to reduce CES1 activity. PMVECs transfected with this CES1 variant demonstrated significantly higher rates of METH-induced apoptosis. METH exposure results in increased formation of reactive oxygen species (ROS) and a compensatory autophagy response. Compared with healthy cells, CES1-deficient PMVECs lack a robust autophagy response despite higher ROS, which correlates with increased apoptosis. We propose that reduced CES1 expression/activity could promote development of METH-PAH by increasing PMVEC apoptosis and small vessel loss.


Assuntos
Hidrolases de Éster Carboxílico/metabolismo , Células Endoteliais/metabolismo , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/metabolismo , Pulmão/metabolismo , Metanfetamina/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Feminino , Humanos , Pulmão/efeitos dos fármacos , Masculino , Microvasos/efeitos dos fármacos , Microvasos/metabolismo , Pessoa de Meia-Idade , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
19.
Pain Med ; 15(9): 1496-507, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25159869

RESUMO

OBJECTIVES: This cross-sectional study examines to whom and how fully sickle cell disease (SCD) patients talk to others about sickle cell pain, how helpful it is to talk with others about these pain episodes, and the association between talking to others about sickle cell pain episodes and patients' psychological adjustment and coping strategies in managing the disease. METHODS: A convenience sample of 73 African American patients with SCD (30 men and 43 women), were recruited from two SCD clinics at the time of routine medical visits. Most participants had been diagnosed with hemoglobin SS, and they reported an average number of 8.61 pain episodes in the previous 12 months. Participants were asked to whom, how fully, and how helpful it was to talk to significant others about SCD pain episodes experienced in the last 12 months. Patients also completed measures of their psychological adjustment as well as how they would manage a future sickle cell pain episode. Self-report ratings were made on Likert-type scales. RESULTS: Based on paired samples t-tests, participants talked significantly more fully about their thoughts and feelings concerning pain episodes to God and to their primary medical providers than to either their parents, siblings, or an intimate partner/close friend. Bivariate correlations indicated that amount and helpfulness of talking about pain episodes to God and to parents were significantly associated with better psychological adjustment on selected measures. Also, bivariate correlations indicated that helpfulness in talking with siblings, intimate partner/close friend, and primary medical providers was positively related with willingness to go to a physician in the event of a future pain episode. CONCLUSIONS: The results document to whom and how helpful it is to talk with others about SCD pain episodes and how SCD disclosure is related to strategies for managing this disease.


Assuntos
Adaptação Psicológica , Anemia Falciforme/psicologia , Negro ou Afro-Americano/psicologia , Relações Interpessoais , Dor/psicologia , Autorrevelação , Apoio Social , Adolescente , Adulto , Idoso , Atitude Frente a Saúde , Comunicação , Estudos Transversais , Feminino , Amigos , Humanos , Masculino , Pessoa de Meia-Idade , Dor/tratamento farmacológico , Pais , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Médicos de Atenção Primária , Religião , Autorrelato , Parceiros Sexuais , Irmãos , Fatores Socioeconômicos , Adulto Jovem
20.
Diagnostics (Basel) ; 14(11)2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38893637

RESUMO

Seizures should be diagnosed and treated to ensure optimal health outcomes in critically ill patients admitted in the medical intensive care unit (MICU). Continuous electroencephalography is still infrequently used in the MICU. We investigated the effectiveness of routine EEG (rEEG) in detecting seizures in the MICU. A total of 560 patients admitted to the MICU between October 2018 and March 2023 and who underwent rEEG were reviewed. Seizure-related rEEG constituted 47% of all rEEG studies. Totally, 39% of the patients experienced clinical seizures during hospitalization; among them, 48% experienced the seizure, and 13% experienced their first seizure after undergoing an rEEG study. Seventy-seven percent of the patients had unfavorable short-term outcomes. Patients with cardiovascular diseases were the most likely to have the suppression/burst suppression (SBS) EEG pattern and the highest mortality rate. The rhythmic and periodic patterns (RPPs) and electrographic seizure (ESz) EEG pattern were associated with seizures within 24 h after rEEG, which was also related to unfavorable outcomes. Significant predictors of death were age > 59 years, the male gender, the presence of cardiovascular disease, a Glasgow Coma Scale score ≤ 5, and the SBS EEG pattern, with a predictive performance of 0.737 for death. rEEG can help identify patients at higher risk of seizures. We recommend repeated rEEG in patients with ESz or RPP EEG patterns to enable a more effective monitoring of seizure activities.

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