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Phosphodiesterase 8 (PDE8), as a member of PDE superfamily, specifically promotes the hydrolysis and degradation of intracellular cyclic adenosine monophosphate (cAMP), which may be associated with pathogenesis of Alzheimer's disease (AD). However, little is currently known about potential role in the central nervous system (CNS). Here we investigated the distribution and expression of PDE8 in brain of mouse, which we believe can provide evidence for studying the role of PDE8 in CNS and the relationship between PDE8 and AD. Here, C57BL/6J mice were used to observe the distribution patterns of two subtypes of PDE8, PDE8A and PDE8B, in different sexes in vivo by western blot (WB). Meanwhile, C57BL/6J mice were also used to demonstrate the distribution pattern of PDE8 in selected brain regions and localization in neural cells by WB and multiplex immunofluorescence staining. Furthermore, the triple transgenic (3×Tg-AD) mice and wild type (WT) mice of different ages were used to investigate the changes of PDE8 expression in the hippocampus and cerebral cortex during the progression of AD. PDE8 was found to be widely expressed in multiple tissues and organs including heart, kidney, stomach, brain, and liver, spleen, intestines, and uterus, with differences in expression levels between the two subtypes of PDE8A and PDE8B, as well as two sexes. Meanwhile, PDE8 was widely distributed in the brain, especially in areas closely related to cognitive function such as cerebellum, striatum, amygdala, cerebral cortex, and hippocampus, without differences between sexes. Furthermore, PDE8A was found to be expressed in neuronal cells, microglia and astrocytes, while PDE8B is only expressed in neuronal cells and microglia. PDE8A expression in the hippocampus of both female and male 3×Tg-AD mice was gradually increased with ages and PDE8B expression was upregulated only in cerebral cortex of female 3×Tg-AD mice with ages. However, the expression of PDE8A and PDE8B was apparently increased in both cerebral cortex and hippocampus in both female and male 10-month-old 3×Tg-AD mice compared WT mice. These results suggest that PDE8 may be associated with the progression of AD and is a potential target for its prevention and treatment in the future.
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3',5'-AMP Cíclico Fosfodiesterases , Doença de Alzheimer , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Animais , Feminino , Masculino , Camundongos , 3',5'-AMP Cíclico Fosfodiesterases/metabolismo , 3',5'-AMP Cíclico Fosfodiesterases/genética , Doença de Alzheimer/metabolismo , Encéfalo/metabolismo , Hipocampo/metabolismoRESUMO
BACKGROUND: Population aging has increased the prevalence of multimorbidity, jeopardizing the sustainability and efficiency of healthcare systems. This study aimed to evaluate the effects of an integrated ambulatory care program (IACP) on healthcare utilization and costs among older patients with multimorbidity while accounting for the confounding effects of frailty. METHODS: A retrospective cohort study using propensity matching including patients aged 65 or older with two or more chronic conditions attending the outpatient clinic at our hospital between June 1 and December 31, 2019, was conducted. Exposure was defined as receipt of IACP care. Patients not undergoing the IACP comprised the unexposed group and were matched at a ratio of 1:4 to patients undergoing the IACP group according to sex, age, Charlson Comorbidity Index score, multimorbidity frailty index score, and number of outpatient visits within 6 months before the index date. Outcomes were changes in healthcare utilization and related costs between 6 months before and after receiving IACP care. Multivariate regression analyses were used for data analysis and the Generalized Estimation Equation method was used to fit the regression models. RESULTS: A total of 166 (IACP) and 664 (non-exposed) patients were analyzed. The mean participant baseline ages were 77.15 ± 7.77 (IACP) and 77.28 ± 7.90 years (unexposed). In univariate analyses, the IACP group demonstrated greater reductions than the unexposed group in the frequency of outpatient visits (-3.16 vs. -1.36, p < 0.001), number of physicians visited (-0.99 vs. -0.17, p < 0.001), diagnostic fees (-1300 New Taiwan Dollar [NTD] vs. -520 NTD, p < 0.001), drug prescription fees (-250 NTD vs. -70 NTD, p < 0.001), and examination fees (-1620 NTD vs. -700 NTD, p = 0.014). Multivariate analyses demonstrated that patients in the IACP group experienced significant reduction in the frequency of outpatient visits (95% CI: -0.357 to -0.181, p < 0.001), number of physicians visited (95% CI: -0.334 to -0.199, p < 0.001), and overall outpatient costs (95% CI: -0.082 to -0.011, p = 0.01). However, emergency department utilization, hospitalization, and costs did not differ significantly. CONCLUSIONS: Expanding IACPs may help patients with multimorbidity reduce their use of outpatient clinics at the 6-month follow-up, reduce care fragmentation, and promote sustainability of the healthcare system.
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Fragilidade , Custos de Cuidados de Saúde , Humanos , Idoso , Estudos de Coortes , Estudos Retrospectivos , Multimorbidade , Pontuação de Propensão , Atenção à Saúde , Assistência Ambulatorial , Aceitação pelo Paciente de Cuidados de SaúdeRESUMO
AIMS: Excess dietary sodium intake and retention lead to hypertension. Impaired dermal lymphangiogenesis and lymphatic dysfunction-mediated sodium and fluid imbalance are pathological mechanisms. The adenosine A2A receptor (A2AR) is expressed in lymphatic endothelial cells (LECs), while the roles and mechanisms of LEC-A2AR in skin lymphangiogenesis during salt-induced hypertension are not clear. METHODS AND RESULTS: The expression of LEC-A2AR correlated with lymphatic vessel density in both high-salt diet (HSD)-induced hypertensive mice and hypertensive patients. Lymphatic endothelial cell-specific A2AR knockout mice fed HSD exhibited 17 ± 2% increase in blood pressure and 17 ± 3% increase in Na+ content associated with decreased lymphatic density (-19 ± 2%) compared with HSD-WT mice. A2AR activation by agonist CGS21680 increased lymphatic capillary density and decreased blood pressure in HSD-WT mice. Furthermore, this A2AR agonist activated MSK1 directly to promote VEGFR2 activation and endocytosis independently of VEGF as assessed by phosphoprotein profiling and immunoprecipitation assays in LECs. VEGFR2 kinase activity inhibitor fruquintinib or VEGFR2 knockout in LECs but not VEGF-neutralizing antibody bevacizumab suppressed A2AR activation-mediated decrease in blood pressure. Immunostaining revealed phosphorylated VEGFR2 and MSK1 expression in the LECs were positively correlated with skin lymphatic vessel density and A2AR level in hypertensive patients. CONCLUSION: The study highlights a novel A2AR-mediated VEGF-independent activation of VEGFR2 signaling in dermal lymphangiogenesis and sodium balance, which might be a potential therapeutic target in salt-sensitive hypertension.
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Hipertensão , Linfangiogênese , Camundongos , Animais , Receptor A2A de Adenosina/metabolismo , Células Endoteliais/metabolismo , Inibidores de Proteínas Quinases , Sódio/metabolismoRESUMO
Objective To explore the influence of extracellular matrix protein ABI-interactor 3-binding protein (ABI3BP) on vesicular stomatitis virus (VSV) genome replication and innate immune signaling pathway.Methods The small interfering RNA (siRNA) was transfected to knock down ABI3BP gene in human skin fibroblast BJ-5ta cells. VSV-green fluorescent protein (VSV-GFP)-infected cell model was established. The morphological changes and F-actin stress fiber formation were detected on ABI3BP knockdown cells by phalloidin immunofluorescence staining. The mRNA level of virus replication was detected by RT-qPCR in BJ-5ta cells after VSV-GFP infection; western blotting was performed to detect the changes in interferon regulatory factor 3 (IRF3) and TANK-binding kinase 1 (TBK1) phosphorylation levels.Results The VSV-GFP-infected BJ-5ta cell model was successfully established. Efficient knockdown of ABI3BP in BJ-5ta cells was achieved. Phalloidin immunofluorescence staining revealed structural rearrangement of intracellular F-actin after ABI3BP gene knockdown. Compared with the control group, the gene copy number of VSV-GFP in ABI3BP knockdown cells increased by 2.2 - 3.5 times (P<0.01) and 2.2 - 4.0 times (P<0.01) respectively when infected with VSV of multiplicity of infection 0.1 and 1. The expression of viral protein significantly increased in ABI3BP knockdown cells after virus infection. The activation of type-I interferon pathway, as determined by phosphorylated IRF3 and phosphorylated TBK1, was significantly decreased in ABI3BP knockdown cells after VSV-GFP infection.Conclusions Extracellular matrix protein ABI3BP plays an important role in maintaining the formation and rearrangement of actin structure. ABI3BP gene deletion promotes RNA virus replication, and ABI3BP is an important molecule that maintains the integrity of type I interferon pathway.
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Estomatite Vesicular , Animais , Humanos , Estomatite Vesicular/metabolismo , Actinas/genética , Actinas/metabolismo , Faloidina/metabolismo , Vírus da Estomatite Vesicular Indiana/genética , Antivirais , Proteínas da Matriz Extracelular/metabolismo , Proteínas de TransporteRESUMO
OBJECTIVE: Obesity can affect periodontal tissues and exacerbate periodontitis. Pyroptosis, a newly identified type of inflammatory cell death, is involved in the development of periodontal inflammation. The saturated fatty acid palmitic acid (PA) is elevated in obese patients. The effect of PA on pyroptosis in periodontal ligament cells (PDLCs) and its underlying mechanisms remain unknown. MATERIALS AND METHODS: Human PDLCs were isolated from healthy individuals and cultured for experiments. The effects of PA on PDLC pyroptosis and the underlying mechanisms were examined by transmission electron microscopy, quantitative real-time PCR and western blotting. RESULTS: The morphology of PDLCs in the PA group indicated pyroptotic characteristics, including swollen cells, plasma membrane rupture and changes in subcellular organelles. PA induced inflammatory responses in PDLCs, as indicated by an increase in IL-1ß in the cell culture supernatant. Furthermore, we found that the pyroptosis-related proteins caspase-1, caspase-4 and GSDMD were involved in PA-induced cell death. GSDMD and caspase-4 inhibitors alleviated pyroptotic death of PDLCs. Moreover, PA promoted NF-κB P65 phosphorylation. A NF-κB inhibitor decreased IL-1ß expression and partly rescued cell death induced by PA. CONCLUSION: PA activated the NF-κB pathway and induced the inflammatory response in PDLCs. Caspase-4/GSDMD mediated PDLC pyroptosis induced by PA.
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Depression is among the most frequent psychiatric comorbid conditions in Alzheimer disease (AD). However, pharmacotherapy for depressive disorders in AD is still a big challenge, and the data on the efffcacy of current antidepressants used clinically for depressive symptoms in patients with AD remain inconclusive. Here we investigated the mechanism of the interactions between depression and AD, which we believe would aid in the development of pharmacological therapeutics for the comorbidity of depression and AD. Female APP/PS1/Tau triple transgenic (3×Tg-AD) mice at 24 months of age and age- and sex-matched wild-type (WT) mice were used. The shuttle-box passive avoidance test (PAT) were implemented to assess the abilities of learning and memory, and the open field test (OFT) and the tail suspension test (TST) were used to assess depression-like behavior. High-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) was used to detect the level of neurotransmitters related to depression in the hippocampus of mice. The data was identified by orthogonal projections to latent structures discriminant analysis (OPLS-DA). Most neurotransmitters exert their effects by binding to the corresponding receptor, so the expression of relative receptors in the hippocampus of mice was detected using Western blot. Compared to WT mice, 3×Tg-AD mice displayed significant cognitive impairment in the PAT and depression-like behavior in the OFT and TST. They also showed significant decreases in the levels of L-tyrosine, norepinephrine, vanillylmandelic acid, 5-hydroxytryptamine, and acetylcholine, in contrast to significant increases in 5-hydroxyindoleacetic acid, L-histidine, L-glutamine, and L-arginine in the hippocampus. Moreover, the expression of the alpha 1a adrenergic receptor (ADRA1A), serotonin 1 A receptor (5HT1A), and γ-aminobutyric acid A receptor subunit alpha-2 (GABRA2) was significantly downregulated in the hippocampus of 3×Tg-AD mice, while histamine H3 receptor (H3R) expression was significantly upregulated. In addition, the ratio of phosphorylated cAMP-response element-binding protein (pCREB) and CREB was significantly decreased in the hippocampus of 3×Tg-AD mice than WT mice. We demonstrated in the present study that aged female 3×Tg-AD mice showed depression-like behavior accompanied with cognitive dysfunction. The complex and diverse mechanism appears not only relevant to the imbalance of multiple neurotransmitter pathways, including the transmitters and receptors of the monoaminergic, GABAergic, histaminergic, and cholinergic systems, but also related to the changes in L-arginine and CREB signaling molecules.
Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Camundongos , Feminino , Animais , Doença de Alzheimer/complicações , Doença de Alzheimer/genética , Doença de Alzheimer/tratamento farmacológico , Camundongos Transgênicos , Espectrometria de Massas em Tandem , Depressão/tratamento farmacológico , Disfunção Cognitiva/metabolismo , Hipocampo/metabolismo , Neurotransmissores/metabolismo , Modelos Animais de Doenças , Peptídeos beta-Amiloides/farmacologia , Proteínas tau/metabolismoRESUMO
Atherosclerosis in the carotid artery is a major cause of ischemic stroke and has a strong genetic component. The aim of this study was to identify genetic factors contributing to carotid atherosclerosis. One hundred fifty-four female F2 mice were generated from an intercross between LP/J and BALB/cJ Apoe-null (Apoe-/-) mice and fed 12 wk of Western diet. Atherosclerotic lesions, body weight, and coat color were measured and genotyping was performed using miniMUGA genotyping arrays. A significant quantitative trait locus (QTL) on chromosome (Chr) 7, named Cath20, and five suggestive QTL on Chr 6, 12, 13, 15, and X were identified for carotid lesions. Three significant QTL, Bwfq2, Bw1n, Bwtq6, on Chr 2, 7, and 15 were identified for body weight. Two significant QTL, Chop2 and Albc2, on Chr 4 and 7 were identified for coat color, with Tyr, encoding tyrosinase, being the causal gene of Albc2. Cath20 overlapped with or was close to QTL Bw1n and Albc2 on Chr7. Carotid lesion sizes were significantly correlated with body weight and graded coat color in F2 mice. Cath20 on Chr7 disappeared after adjustment for coat color but remained after adjustment for body weight. Tyr was abundantly expressed in atherosclerotic lesions. These results demonstrate genetic connections of carotid atherosclerosis with body weight and coat color in hyperlipidemic mice and suggest a potential role for Tyr in carotid atherosclerosis.
Assuntos
Aterosclerose , Doenças das Artérias Carótidas , Animais , Apolipoproteínas E/genética , Aterosclerose/genética , Peso Corporal/genética , Doenças das Artérias Carótidas/genética , Doenças das Artérias Carótidas/patologia , Cruzamentos Genéticos , Feminino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
BACKGROUND/PURPOSE: Early unplanned hospital readmissions are burdensome health care events and indicate low care quality. Identifying at-risk patients enables timely intervention. This study identified predictors for 14-day unplanned readmission. METHODS: We conducted a retrospective, matched, case-control study between September 1, 2018, and August 31, 2019, in an 1193-bed university hospital. Adult patients aged ≥ 20 years and readmitted for the same or related diagnosis within 14 days of discharge after initial admission (index admission) were included as cases. Cases were 1:1 matched for the disease-related group at index admission, age, and discharge date to controls. Variables were extracted from the hospital's electronic health records. RESULTS: In total, 300 cases and 300 controls were analyzed. Six factors were independently associated with unplanned readmission within 14 days: previous admissions within 6 months (OR = 3.09; 95 % CI = 1.79-5.34, p < 0.001), number of diagnoses in the past year (OR = 1.07; 95 % CI = 1.01-1.13, p = 0.019), Malnutrition Universal Screening Tool score (OR = 1.46; 95 % CI = 1.04-2.05, p = 0.03), systolic blood pressure (OR = 0.98; 95 % CI = 0.97-0.99, p = 0.01) and ear temperature within 24 h before discharge (OR = 2.49; 95 % CI = 1.34-4.64, p = 0.004), and discharge with a nasogastric tube (OR = 0.13; 95 % CI = 0.03-0.60, p = 0.009). CONCLUSIONS: Factors presented at admission (frequent prior hospitalizations, multimorbidity, and malnutrition) along with factors presented at discharge (clinical instability and the absence of a nasogastric tube) were associated with increased risk of early 14-day unplanned readmission.
Assuntos
Alta do Paciente , Readmissão do Paciente , Adulto , Estudos de Casos e Controles , Humanos , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: Early unplanned hospital readmissions are associated with increased harm to patients, increased medical costs, and negative hospital reputation. With the identification of at-risk patients, a crucial step toward improving care, appropriate interventions can be adopted to prevent readmission. This study aimed to build machine learning models to predict 14-day unplanned readmissions. METHODS: We conducted a retrospective cohort study on 37,091 consecutive hospitalized adult patients with 55,933 discharges between September 1, 2018, and August 31, 2019, in an 1193-bed university hospital. Patients who were aged < 20 years, were admitted for cancer-related treatment, participated in clinical trial, were discharged against medical advice, died during admission, or lived abroad were excluded. Predictors for analysis included 7 categories of variables extracted from hospital's medical record dataset. In total, four machine learning algorithms, namely logistic regression, random forest, extreme gradient boosting, and categorical boosting, were used to build classifiers for prediction. The performance of prediction models for 14-day unplanned readmission risk was evaluated using precision, recall, F1-score, area under the receiver operating characteristic curve (AUROC), and area under the precision-recall curve (AUPRC). RESULTS: In total, 24,722 patients were included for the analysis. The mean age of the cohort was 57.34 ± 18.13 years. The 14-day unplanned readmission rate was 1.22%. Among the 4 machine learning algorithms selected, Catboost had the best average performance in fivefold cross-validation (precision: 0.9377, recall: 0.5333, F1-score: 0.6780, AUROC: 0.9903, and AUPRC: 0.7515). After incorporating 21 most influential features in the Catboost model, its performance improved (precision: 0.9470, recall: 0.5600, F1-score: 0.7010, AUROC: 0.9909, and AUPRC: 0.7711). CONCLUSIONS: Our models reliably predicted 14-day unplanned readmissions and were explainable. They can be used to identify patients with a high risk of unplanned readmission based on influential features, particularly features related to diagnoses. The operation of the models with physiological indicators also corresponded to clinical experience and literature. Identifying patients at high risk with these models can enable early discharge planning and transitional care to prevent readmissions. Further studies should include additional features that may enable further sensitivity in identifying patients at a risk of early unplanned readmissions.
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Aprendizado de Máquina , Readmissão do Paciente , Adulto , Idoso , Algoritmos , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de RiscoRESUMO
INTRODUCTION: Medical schools employ various tools to select suitable medical students (MS). This study investigated whether MS who were admitted through multiple mini-interviews (MMI) and MS who were admitted through Taiwan's Joint College Entrance Written Test (JCEWT) differed in their characteristics. METHODS AND SUBJECTS: First-year MS from seven medical schools completed a semi-structured questionnaire that inquired into their channel of admission (MMI or JCEWT), gender, location (metropolitan or rural), high school type (public or private), parents' socioeconomic status (SES), and motivations to study medicine. RESULTS: In total, 513 MS participated, 493 (96%) returned valid questionnaires, and 397 were enrolled in the study, (MMI group: 205 MS; JCEWT group: 192 MS). Irrespective of channel of admission, most MS came from metropolitan areas (80%-86%), belonged to high-SES families (73%-76%), and had mixed motivations (51%-96%). Female applicants, private school leavers, and those who were less motivated by the physician's SES were more likely to be selected through the MMI channel than the JCEWT channel. CONCLUSION: Irrespective of the channels of entry, MS had similar demographics and motivations for studying medicine. MS selected through MMI had different characteristics than those selected through a JCEWT.
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Estudantes de Medicina , Teste de Admissão Acadêmica , Demografia , Feminino , Humanos , Motivação , Critérios de Admissão Escolar , Faculdades de MedicinaRESUMO
Phospholipid transfer protein (PLTP) is a complex glycosylated protein that mediates the transfer of phospholipids, unesterified cholesterol, diacylglycerides, specific apolipoproteins, and tocopherols between different classes of lipoproteins as well as between lipoproteins and cells. Many studies have associated PLTP with a variety of lipid metabolic diseases. However, recent studies have indicated that PLTP is highly expressed in the brain of vertebrate and may be related to many central nervous system diseases, such as Alzheimer's disease. Here, we review the data and report the role and mechanisms PLTP in Alzheimer's disease.
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Doença de Alzheimer , Proteínas de Transferência de Fosfolipídeos , Encéfalo/metabolismo , Colesterol , Humanos , Lipoproteínas , Proteínas de Transferência de Fosfolipídeos/metabolismoRESUMO
OBJECTIVES: The host immune response could be an imperative factor in the pathogenesis of neurosyphilis, but the role of T lymphocyte subsets remains unclear. In the present study, we assessed the CD4+ T and CD8+ T cell subsets in the peripheral blood of patients with HIV-negative symptomatic neurosyphilis and then explored the clinical application value of neurosyphilis. METHODS: In total, 24 patients with HIV-negative symptomatic neurosyphilis and 22 patients with syphilis/non-neurosyphilis were included in this study and cerebrospinal fluid (CSF) and blood samples were obtained. Th1, Th2, Th17, Th9, CD8+IFN-γ+, CD8+IL-4+, CD8+IL-9+, and CD8+IL-17 + cells were identified by flow cytometry. RESULTS: The levels of CD8+IFN-γ+ were significantly increased in the peripheral blood of neurosyphilis patients compared to that in syphilis/non-neurosyphilis patients, but it was opposite to Th2, Th9, CD8+IL-4+, CD8+IL-9+, and CD8+IL-17 + cells. Dendritic cells (DCs) of neurosyphilis matured by T. pallidum induced the development of a combination of IFN-γ-producing Th1 cells. The number of CD8+IL-17 + cells was significantly correlated with the CSF RPR and CSF TPPA levels. ROC curve analysis revealed that the number of CD8+IFN-γ+ cells could be a potential biomarker for neurosyphilis from non-neurosyphilis/syphilis. CONCLUSIONS: High expression of CD8+IFN-γ+ cells and low expression of CD8+IL-17 + cells in patients with symptomatic neurosyphilis, which explains the pathogenesis of symptomatic neurosyphilis, meanwhile CD8+IFN-γ+ cells may be a better indicator in classifying symptomatic neurosyphilis from non-neurosyphilis/syphilis among patients without HIV infection.
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Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Neurossífilis/patologia , Subpopulações de Linfócitos T/imunologia , Adulto , Idoso , Células Sanguíneas , Líquido Cefalorraquidiano/citologia , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
PURPOSE: To systematically appraise the clinical and radiological outcomes after osteotome sinus floor elevation (OSFE) with or without grafting in the published dental literature. METHODS: An electronic search was conducted using PubMed, Web of Science, and the Cochrane Central Register of Controlled Trial to identify studies after OSFE from January 1, 1994 to August 30, 2015. The primary outcome was the implant survival rates after OSFE with and without grafting materials. RESULTS: After search and evaluation of the literature according to the inclusion criteria, 7 studies were included in the review. The random-effect model meta-analysis based on 463 implants in patients without grafting and 415 implants in patients with grafting showed that the risk ratio difference of survival rates was 1.010 (95%CI 0.910, 1.120), which did not reach statistical significance (p = 0.99). The membrane perforation rates ranged from 0% to 10.80%. No significant difference of crestal bone loss was reported between graft and nongraft groups. CONCLUSIONS: Based on currently available evidence, OSFE techniques with and without grafting were both predictable in the short term. In addition, survival rates of dental implants in OSFE with or without grafting did not show any significant difference in the short term.
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Transplante Ósseo/métodos , Implantação Dentária Endóssea/métodos , Implantes Dentários , Levantamento do Assoalho do Seio Maxilar , Perda do Osso Alveolar/diagnóstico por imagem , Falha de Restauração Dentária , Humanos , OsteotomiaRESUMO
Nearly all genetic crosses generated from Apoe-/- or Lldlr-/- mice for genetic analysis of atherosclerosis have used C57BL/6 J (B6) mice as one parental strain, thus limiting their mapping power and coverage of allelic diversity. SM/J-Apoe -/- and BALB/cJ-Apoe -/- mice differ significantly in atherosclerosis susceptibility. 224 male F2 mice were generated from the two Apoe -/- strains to perform quantitative trait locus (QTL) analysis of atherosclerosis. F2 mice were fed 5 weeks of Western diet and analyzed for atherosclerotic lesions in the aortic root. Genome-wide scans with 144 informative SNP markers identified a significant locus near 20.2 Mb on chromosome 10 (LOD score: 6.03), named Ath48, and a suggestive locus near 49.5 Mb on chromosome 9 (LOD: 2.29; Ath29) affecting atherosclerotic lesion sizes. Using bioinformatics tools, we prioritized 12 candidate genes for Ath48. Of them, Tnfaip3, an anti-inflammatory gene, is located precisely underneath the linkage peak and contains two non-synonymous SNPs leading to conservative amino acid substitutions. Thus, this study demonstrates the power of forward genetics involving the use of a different susceptible strain and bioinformatics tools in finding atherosclerosis susceptibility genes.
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Apolipoproteínas E/genética , Aterosclerose/genética , Inflamação/genética , Locos de Características Quantitativas/genética , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/genética , Alelos , Animais , Aorta/patologia , Aterosclerose/patologia , Mapeamento Cromossômico , Cruzamentos Genéticos , Dieta Ocidental/efeitos adversos , Ligação Genética , Predisposição Genética para Doença , Genoma , Humanos , Inflamação/patologia , Camundongos , Fenótipo , Polimorfismo de Nucleotídeo Único , Receptores de LDL/genéticaRESUMO
Aim To establish the effectiveness of a restorative home support service on institutional-free survival in frail older people referred for needs assessment. Method A randomised controlled trial of Community Flexible Integrated Responsive Support Team versus usual care in 113 older people at risk of institutionalisation in New Zealand. Primary outcome was death or permanent institutional care evaluated in a Cox proportional hazards model adjusted for baseline prognostic variables. A variety of secondary outcomes including the health of informal caregivers were also evaluated. Results The primary outcome was lower, but not statistically significant, in the intervention group (adjusted hazard ratio 0.69, 95% confidence interval 0.4 to 1.16). Informal caregivers of interventional participants had significantly better physical and mental component scores on the 36-item Short-Form questionnaire. Conclusion Restorative home support may reduce the risk of death and institutionalisation in frail older people without affecting the health of informal caregivers.
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Idoso Fragilizado/estatística & dados numéricos , Serviços de Assistência Domiciliar , Institucionalização/estatística & dados numéricos , Análise de Sobrevida , Idoso , Cuidadores/psicologia , Cuidadores/estatística & dados numéricos , Pesquisa sobre Serviços de Saúde , Humanos , Avaliação das Necessidades , Nova Zelândia , Encaminhamento e Consulta , Inquéritos e QuestionáriosRESUMO
A ruthenium-based biomimetic hydrogen cluster, [Ru2 (CO)6 (µ-SCH2 CH2 CH2 S)] (1), has been synthesized and, in the presence of the P ligand tri(o-tolyl)phosphine, demonstrated efficient photocatalytic hydrogen generation from formic acid decomposition. Turnover frequencies (TOFs) of 5500 h(-1) and turnover numbers (TONs) over 24 700 were obtained with less than 50 ppm of the catalyst, thus representing the highest TOFs for ruthenium complexes as well as the best efficiency for photocatalytic hydrogen production from formic acid. Moreover, 1 showed high stability with no significant degradation of the photocatalyst observed after prolonged photoirradiation at 90 °C.
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Biomimética , Formiatos/química , Hidrogênio/química , Catálise , Ligantes , Fosfinas/química , Processos Fotoquímicos , Rutênio/química , TemperaturaRESUMO
BACKGROUND: Phthalates are widely used as plasticizer and are considered as a typical endocrine-disrupting chemical. Epidemiological studies have associated serum or urinary phthalate metabolites with the prevalence of type 2 diabetes or related phenotypes. However, direct evidence supporting a causal role for exposure to phthalates in type 2 diabetes is lacking. METHODS: To determine the potential influence of phthalates on glucose homeostasis and atherosclerosis, female apolipoprotein E-deficient (Apoe(-/-)) mice were started at 6 weeks of age on a Western diet together with or without Bis-(2-ethylhexyl) phthalate. Phthalate was administered in drinking water at a daily dosage of 100 mg/kg. We examined glucose and insulin tolerance, plasma glucose and triglyceride levels, body weight, and atherosclerotic lesions in the aortic root. RESULTS: Two weeks after treatment, phthalate-exposed mice had significantly higher fasting blood glucose level (97.9 ± 2.1 vs. 84.3 ± 5.3 mg/dl, P = 0.034) and exhibited a trend of increased glucose intolerance compared to control mice. Insulin tolerance test on non-fasted mice 3 weeks after treatment revealed that phthalate had little influence on insulin sensitivity though phthalate-treated mice had a higher glucose concentration (159.2 ± 6.0 vs. 145.2 ± 3.6 mg/dl; P = 0.086). On the Western diet, Apoe(-/-) mice showed a time-dependent rise in fasting plasma glucose and triglyceride levels. However, no significant differences were observed between phthalate-treated and control mice in either phenotype after 4, 8, and 12 weeks of phthalate exposure. Neither body weight nor atherosclerotic lesions of Apoe(-/-) mice was affected. CONCLUSION: This study indicates that exposure to phthalates gives rise to a brief interference of glucose homeostasis but has little impact on the development of type 2 diabetes and atherosclerosis in Apoe(-/-) mice.
Assuntos
Aterosclerose/etiologia , Glicemia/efeitos dos fármacos , Poluentes Ambientais/farmacologia , Homeostase/efeitos dos fármacos , Hiperlipidemias/complicações , Hiperlipidemias/metabolismo , Ácidos Ftálicos/farmacologia , Animais , Apolipoproteínas E/genética , Aterosclerose/metabolismo , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/metabolismo , Disruptores Endócrinos/farmacologia , Feminino , Hiperlipidemias/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fatores de RiscoRESUMO
AIMS AND OBJECTIVES: To compare the influence of a systematic nursing intervention on primary caregivers' knowledge and skills about nasogastric tube feeding and the number of nasogastric tube-related complications with that of routine nursing instructions BACKGROUND: To ensure the quality of care and reduce the incidence of complications, it is crucial that primary caregivers receive comprehensive health education about nasogastric tube feeding before hospital discharge. DESIGN: A quasi-experimental research with pretest/post-test evaluations. METHODS: The control group included 127 inpatients whose caregivers received routine education about nasogastric tube feeding, while the experimental group included 106 inpatients whose caregivers received systematic nursing intervention including comprehensive educational pamphlets and video education. The evaluation questionnaire included demographic variables, a nasogastric tube care knowledge scale, and a nasogastric tube skills assessment scale. The post-test was administered after the caregiver performed nasogastric tube feeding for the first time, and complications were noted at follow-up within three months of discharge. RESULTS: In terms of post-test knowledge and skills, the experimental group scored significantly higher than the control group, despite no difference in the pretests. In addition, the incidence rates for constipation, diarrhoea and abdominal distention were lower in the experimental group. CONCLUSIONS: Systematic nursing intervention, including comprehensive educational pamphlets and video education, significantly improved the knowledge and skills of primary caregivers for nasogastric tube feeding. The increased ability of caregivers may have contributed to less incidence of complication. RELEVANCE TO CLINICAL PRACTICE: The results of this study underlined the importance of developing nasogastric tube-related nursing interventions and educational strategies for clinical nurses, home care nurses and caregivers. The research tool used here may serve as a reference for assessing the technical operations of healthcare professionals and the knowledge and skills of caregivers.
Assuntos
Cuidadores , Nutrição Enteral/enfermagem , Conhecimentos, Atitudes e Prática em Saúde , Intubação Gastrointestinal/enfermagem , Educação de Pacientes como Assunto , Adulto , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Alta do Paciente , Inquéritos e Questionários , TaiwanRESUMO
BACKGROUND: frail older people often require tailored rehabilitation in order to remain at home, especially following a period of hospitalisation. Restorative care services aim to enhance an older person's ability to remain improve physical functioning, either at home or in residential care but evidence of their effectiveness is limited. OBJECTIVE: to evaluate the effectiveness of a restorative care service on institutional-free survival and health outcomes in frail older people referred for needs assessment in New Zealand. METHODS: a randomised controlled trial of restorative care or usual care in 105 older people at risk of permanent residential who were follow-up over 24 months. The restorative care service was delivered in short-stay residential care facilities and at participants' residences with the aim of reducing the requirement for permanent residential care. It included a comprehensive geriatric assessment and care plan developed and delivered, initially by a multi-disciplinary team and subsequently by home care assistants. RESULTS: compared with usual care, there was a non-significant absolute risk reduction of 14.3% for death or permanent residential care (8.8% for residential care and 7.2% for death alone) for the restorative care approach. There was no difference in levels of burden among caregivers. CONCLUSIONS: restorative care models that utilise case management and multi-disciplinary care may positively impact on institutional-free survival for frail older people without adversely impacting on the health of caregivers.