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1.
Pancreas ; 50(4): 556-563, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33939669

RESUMO

OBJECTIVE: The aim of this study was to critically analyze the surgical experience of managing autoimmune pancreatitis (AIP) in an era of modern diagnostics and compare these patients with those who were managed conservatively. METHODS: Two prospectively maintained databases were used to retrospectively identify patients with AIP who were either managed conservatively or underwent pancreatectomy. RESULTS: Eighty-eight patients were included in the study, of which 56 (63.6%) underwent resection and 32 (36.4%) were managed conservatively. Patients who underwent resection were more likely to present with jaundice (64.3% vs 18.1%, P < 0.001) and weight loss (53.6% vs 15.6%, P = 0.005). The cohort who underwent resection had a significantly higher median carbohydrate antigen 19-9 (40.0 vs 18.6 U/mL, P = 0.034) and was less likely to have elevated immunoglobulin G4 (26.1% vs 50.0%, P < 0.001). The most frequent initial diagnosis in the cohort who underwent resection was ductal adenocarcinoma (82.1%). Nine patients (28.1%) in the conservatively managed cohort experienced AIP relapse compared with 6 patients (10.7%) in the cohort who underwent resection. CONCLUSIONS: The most frequent reason for surgical resection of AIP is concern for malignancy. Carbohydrate antigen 19-9 elevations were more common than immunoglobulin G4 in our cohort, suggesting that this laboratory profile is suboptimal for this population.

2.
Acta Paediatr ; 2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-33973271

RESUMO

AIM: Sleep behaviour is correlated and causally related to physical and mental health. Limited longitudinal data exist on the associations of poor sleep behaviour in childhood and adolescence with adult health. Parent-reported sleep behaviours from 1993 participants of the Raine Study (at ages 5, 8, 10, 14, 17) were used to determine sleep trajectories (using latent class growth analysis). METHODS: Measures of physical and mental health were compared between sleep trajectories using generalized linear models (at age 20). RESULTS: Three sleep trajectories were identified; 43% of participants belonged to a trajectory with 'consistently minimal' sleep problems, 49% showed some 'declining' in reporting of sleep problems incidence and 8% had 'persistent' sleep problems. Participants in the 'consistently minimal' trajectory had better physical and mental health outcomes at age 20 compared to those in the 'declining' and 'persistent' trajectories. For example, 'consistently minimal' participants had significantly lower body fat percentage (mean difference: -3.89 % (95 % CI: -7.41 to -0.38)) and a higher (better) SF-12 mental component score (mean difference: 4.78 (95 % CI: 2.35 to 7.21)) compared to participants in the 'persistent' trajectory. CONCLUSION: Poor sleep behaviour across childhood and adolescent years is related to poorer physical and mental health in young adulthood.

4.
Ann Surg ; 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33843794

RESUMO

OBJECTIVE: To develop a predictive model of oncologic outcomes for patients with pancreatic ductal adenocarcinoma (PDAC) undergoing resection after neoadjuvant or induction chemotherapy use. BACKGROUND: Early recurrence following surgical resection for PDAC is common. The use of neoadjuvant chemotherapy prior to resection may increase the likelihood of long-term systemic disease control. Accurately characterizing an individual's likely oncologic outcome in the perioperative setting remains challenging. METHODS: Data from patients with PDAC who received chemotherapy prior to pancreatectomy at a single high-volume institution between 2007-2018 were captured in a prospectively collected database. Core clinicopathologic data were reviewed for accuracy and survival data were abstracted from the electronic medical record and national databases. Cox-proportional regressions were used to model outcomes and develop an interactive prognostic tool for clinical decision-making. RESULTS: A total of 581 patients were included with a median OS and RFS of 29.5 (26.5-32.5) and 16.6 (15.8-17.5) months, respectively. Multivariable analysis demonstrates OS and RFS were associated with type of chemotherapeutic used and the number of chemotherapy cycles received preoperatively. Additional factors contributing to survival models included: tumor grade, histopathologic response to therapy, nodal status, and administration of adjuvant chemotherapy. The models were validated using an iterative bootstrap method and with randomized cohort splitting. The models were well calibrated with concordance indices of 0.68 and 0.65 for the final OS and RFS models, respectively. CONCLUSION: We developed an intuitive and dynamic decision-making tool that can be useful in estimating OS, RFS and location-specific disease recurrence rates. This prognostic tool may add value to patient care in discussing the benefits associated with surgical resection for PDAC.

5.
J Pathol ; 2021 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-33870509

RESUMO

Epigenetic alterations are increasingly recognized as important contributors to the development and progression of pancreatic ductal adenocarcinoma (PDAC). 5-hydroxymethylcytosine (5hmC) is an epigenetic DNA mark generated through the ten-eleven translocation (TET) enzyme-mediated pathway and is closely linked to gene activation. However, the timing of alterations in epigenetic regulation in the progression of pancreatic neoplasia is not well understood. In this study, we hypothesized that aberrant expression of ten-eleven translocation methylcytosine dioxygenase 1 (TET1) and subsequent global 5hmC alteration are linked to early tumorigenesis in the pancreas. Therefore, we evaluated alterations of 5hmC and TET1 levels using immunohistochemistry in pancreatic neoplasms (n = 380) and normal ducts (n = 118). The study cohort included representation of the full spectrum of precancerous lesions from low- and high-grade pancreatic intraepithelial neoplasia (PanINs, n = 95), intraductal papillary mucinous neoplasms (IPMNs, all subtypes, n = 129), intraductal oncocytic papillary neoplasms (IOPNs, n = 12), and mucinous cystic neoplasms (MCNs, n = 144). 5hmC and TET1 were significantly downregulated in all types of precancerous lesions and associated invasive PDACs compared with normal ductal epithelium (all P < 0.001), and expression of 5hmC positively correlated with expression of TET1. Importantly, downregulation of both 5hmC and TET1 was observed in most low-grade precancerous lesions. There were no clear associations between 5hmC levels and clinicopathological factors, thereby suggesting a common epigenetic abnormality across precancerous lesions. We conclude that downregulation of 5hmC and TET1 is an early event in pancreatic tumorigenesis. This article is protected by copyright. All rights reserved.

6.
Stroke Vasc Neurol ; 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33903177

RESUMO

BACKGROUND AND PURPOSE: This study aimed to investigate the association of metabolic syndrome (MetS) with both intracranial atherosclerotic stenosis (ICAS) and imaging markers of cerebral small vessel disease (CSVD) in a community-based sample. METHODS: This study included 943 participants (aged 55.6±9.2 years, 36.1% male) from the community-based Shunyi cohort study. MetS was defined according to the joint interim criteria and quantified by the MetS severity Z-score. ICAS was evaluated by brain magnetic resonance angiography. The MRI markers of CSVD, including white matter hyperintensities (WMHs), lacunes, cerebral microbleeds (CMBs) and enlarged perivascular spaces (EPVS), were assessed. Multiple regression models were used to investigate the association of MetS severity Z-score with ICAS and these CSVD markers. RESULTS: We found that risk of ICAS (OR=1.75, 95% CI 1.39 to 2.21, p<0.001) increased consistently with MetS severity. MetS severity was significantly associated with higher risks of WMH volume (ß=0.11, 95% CI 0.01 to 0.20, p=0.02) and lacunes (OR=1.28, 95% CI 1.03 to 1.59, p=0.03) but not the presence of CMBs (OR=0.93, 95% CI 0.74 to 1.16, p=0.51) and PVS severity (EPVS in basal ganglia: OR=0.96, 95% CI 0.84 to 1.09, p=0.51 and EPVS in white matter: OR=1.09, 95% CI 0.96 to 1.23, p=0.21). CONCLUSIONS: Our findings suggest that WMH and lacunes share risk factors with atherosclerosis of the cerebral artery, whereas the impact of glucose and lipid metabolic disorder to CMB or EPVS might be weak.

7.
Lancet Neurol ; 20(4): 316-326, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33743240

RESUMO

China has approximately 10 million people with epilepsy. There is a vast epilepsy treatment gap in China, mainly driven by deficiencies in health-care delivery and social discrimination resulting from cultural beliefs about epilepsy. WHO's Global Campaign Against Epilepsy project in China showed that it was possible to treat epilepsy in primary care settings, which was a notable milestone. The China Association Against Epilepsy has been a necessary force to stimulate interest in epilepsy care and research by the medical and scientific community. Nearly 20 different anti-seizure medications are now available in China. Non-pharmacological options are also available, but there are still unmet needs for epilepsy management. The Chinese epilepsy research portfolio is varied, but the areas in which there are the most concentrated focus and expertise are epidemiology and clinical research. The challenges for further improvement in delivering care for people with epilepsy in China are primarily related to public health and reducing inequalities within this vast country.


Assuntos
Epilepsia/epidemiologia , China/epidemiologia , Humanos
8.
J Am Heart Assoc ; 10(6): e019605, 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33715383

RESUMO

Background Cardiorespiratory fitness may moderate the association between obesity and all-cause mortality (ie, the "fat-but-fit" hypothesis), but unaddressed sources of bias are a concern. Methods and Results Cardiorespiratory fitness was estimated as watts per kilogram from a submaximal bicycle test in 77 169 men and women from the UK Biobank cohort and combined with World Health Organization standard body mass index categories, yielding 9 unique fitness-fatness combinations. We also formed fitness-fatness combinations based on bioimpedance as a direct measure of body composition. All-cause mortality was ascertained from death registries. Multivariable-adjusted Cox regression models were used to estimate hazard ratios and 95% CIs. We examined the association between fitness-fatness combinations and all-cause mortality in models with progressively more conservative approaches for accounting for reverse causation, misclassification of body composition, and confounding. Over a median follow-up of 7.7 years, 1731 participants died. In our base model, unfit men and women had higher risk of premature mortality irrespective of levels of adiposity, compared with the normal weight-fit reference. This pattern was attenuated but maintained with more conservative approaches in men, but not in women. In analysis stratified by sex and excluding individuals with prevalent major chronic disease and short follow-up and using direct measures of body composition, mortality risk was 1.78 (95% CI, 1.17-2.71) times higher in unfit-obese men but not higher in obese-fit men (0.94 [95% CI, 0.60-1.48]). In contrast, there was no increased risk in obese-unfit women (1.09 [95% CI, 0.44-1.05]) as compared with the reference. Conclusions Cardiorespiratory fitness modified the association between obesity and mortality in men, but this pattern appeared susceptible to biases in women.

9.
J Int Med Res ; 49(3): 300060521997586, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33682491

RESUMO

OBJECTIVE: To explore the correlations of radiomic features of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with microvessel density (MVD) in patients with hepatocellular carcinoma (HCC), based on single-input and dual-input two-compartment extended Tofts (SITET and DITET) models. METHODS: We compared the quantitative parameters of SITET and DITET models for DCE-MRI in 30 patients with HCC using paired sample t-tests. The correlations of SITET and DITET model parameters with CD31-MVD and CD34-MVD were analyzed using Pearson's correlation analysis. A diagnostic model of CD34-MVD was established and the diagnostic abilities of models for MVD were analyzed using receiver operating characteristic curve (ROC) analysis. RESULTS: There were significant differences between the quantitative parameters in the two kinds of models. Compared with SITET, DITET parameters showed better correlations with CD31-MVD and CD34-MVD. The Ktrans and Ve radiomics features of the DITET model showed high efficiency for predicting the level of CD34-MVD according to ROC analysis, with areas under curves of 0.83 and 0.94, respectively. CONCLUSION: Compared with SITET, the DITET model provides a better indication of the microcirculation of HCC and is thus more suitable for examining patients with HCC.

10.
Reprod Biomed Online ; 42(5): 963-972, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33771466

RESUMO

RESEARCH QUESTION: Multiple morphological abnormalities of the flagella (MMAF) is characterized by excessive immotile spermatozoa with severe flagellar abnormalities in the ejaculate. Previous studies have reported a heterogeneous genetic profile associated with MMAF. What other genetic variants might explain the cause of MMAF? DESIGN: Whole-exome sequencing was conducted in a cohort of 90 Chinese patients with MMAF. The pathogenicity of identified mutations was assessed through electron microscopy and immunofluorescent examinations. RESULTS: Three unrelated men with bi-allelic DNAH2 variants were identified. Sanger sequencing verified that the six novel variants originated from every parent. All these variants were located at the conserved domains of DNAH2 and predicted to be deleterious by bioinformatic tools. Haematoxylin and eosin staining and scanning electron microscopy revealed that spermatozoa harbouring DNAH2 variants displayed severely aberrant morphology mainly with absent and short flagella (≥78%). Moreover, transmission electron microscopy revealed the obvious absence of a central pair of microtubules and inner dynein arms in the spermatozoa with mutated DNAH2. Immunofluorescence data further validated these findings, showing reduced DNAH2 protein expression in the spermatozoa with DNAH2 variants, compared with normal spermatozoa. Intracytoplasmic sperm injection using spermatozoa from the three men with mutated DNAH2 resulted in blastocyst formation in all cases. Embryo transfer was carried out in two couples, both resulting in clinical pregnancy. CONCLUSIONS: These experimental and clinical data suggest that bi-allelic DNAH2 variants might induce MMAF-associated asthenoteratozoospermia, which can be overcome through intracytoplasmic sperm injection. These findings contribute to the knowledge of the genetic landscape of asthenoteratozoospermia and clinical counselling of male infertility.

11.
Int J Behav Nutr Phys Act ; 18(1): 40, 2021 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-33731132

RESUMO

BACKGROUND: COVID-19 lockdowns may lead to physical inactivity, a major risk factor for non-communicable diseases. This study aims to determine: 1) the trajectory in daily step counts before, during and after the lockdown in China, and 2) the characteristics associated with the trajectories. METHODS: From December 2019 to July 2020, smartphone-based step counts were continuously collected in 815 Chinese adults residing in Shanghai over 202 days across three phases: before, during, and after the lockdown. Participant characteristics were reported, and height, weight and body composition measured before the lockdown. A 'sharp' regression discontinuity design with cluster robust standard errors was used to test the effect of the lockdown and reopening on daily steps and a linear mixed model was used to examine the characteristics associated with trajectories during the observed period. RESULTS: Based on 164,630 person-days of data, we found a sharp decline in daily step counts upon the lockdown (24/01/2020) by an average of 3796 (SE = 88) steps, followed by a significant trend of increase by 34 steps/day (SE = 2.5; p < .001) until the end of the lockdown (22/03/2020). This increasing trend continued into the reopening phase at a slower rate of 5 steps per day (SE = 2.3; p = 0.029). Those who were older, married, university educated, insufficiently active, had an 'at risk' body composition, and those in the control group, were slower at recovering step counts during the lockdown, and those who were older, married, without university education and with an 'at risk' body composition recovered step counts at a slower pace after the reopening. CONCLUSIONS: Despite later increases in step counts, COVID-19 lockdown led to a sustained period of reduced physical activity, which may have adverse health implications. Governments and health professionals around the world should continue to encourage and facilitate physical activity during the pandemic.


Assuntos
/prevenção & controle , Coleta de Dados/estatística & dados numéricos , Exercício Físico , Monitores de Aptidão Física , Aplicativos Móveis , Comportamento Sedentário , Adulto , China/epidemiologia , Controle de Doenças Transmissíveis/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Smartphone
12.
Zool Res ; 42(2): 170-181, 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33738989

RESUMO

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly worldwide with high rates of transmission and substantial mortality. To date, however, no effective treatments or enough vaccines for COVID-19 are available. The roles of angiotensin converting enzyme 2 (ACE2) and spike protein in the treatment of COVID-19 are major areas of research. In this study, we explored the potential of ACE2 and spike protein as targets for the development of antiviral agents against SARS-CoV-2. We analyzed clinical data, genetic data, and receptor binding capability. Clinical data revealed that COVID-19 patients with comorbidities related to an abnormal renin-angiotensin system exhibited more early symptoms and poorer prognoses. However, the relationship between ACE2 expression and COVID-19 progression is still not clear. Furthermore, if ACE2 is not a good targetable protein, it would not be applicable across a wide range of populations. The spike-S1 receptor-binding domain that interacts with ACE2 showed various amino acid mutations based on sequence analysis. We identified two spike-S1 point mutations (V354F and V470A) by receptor-ligand docking and binding enzyme-linked immunosorbent assays. These variants enhanced the binding of the spike protein to ACE2 receptors and were potentially associated with increased infectivity. Importantly, the number of patients infected with the V354F and V470A mutants has increased with the development of the SARS-CoV-2 pandemic. These results suggest that ACE2 and spike-S1 are likely not ideal targets for the design of peptide drugs to treat COVID-19 in different populations.


Assuntos
/genética , /genética , Glicoproteína da Espícula de Coronavírus/genética , Alelos , /genética , /virologia , Humanos , Mutação Puntual , Ligação Proteica , Glicoproteína da Espícula de Coronavírus/metabolismo
13.
Nanomaterials (Basel) ; 11(2)2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33669399

RESUMO

Driving signal reflection on traveling wave electrodes (TWEs) is a critical issue in Mach-Zehnder modulators. Fabrication variation often causes a random variation in the electrode impedance and the signal reflection, which induces modulation characteristics variation. The variation of reflection could be intertwined with the variation of other electrode characteristics, such as microwave signal attenuation, resulting in complexity. Here, we characterize the (partial) correlation coefficients between the reflection and modulation characteristics at different bit rates. Decreasing correlation at higher bit rates is observed. Device physics analysis shows how the observed variation can be related to nanoscale variation of material properties, particularly in the embedded diode responsible for electro-optic modulation. We develop a detailed theory to analyze two variation modes of the diode (P-i-N diode or overlapping P/N regions), which reveal insight beyond simplistic diode models. Microwave signal attenuation tends to reduce the correlation with on-electrode reflection, particularly at high bit rates. The theory shows the relative importance of conductor-induced attenuation and "dielectric"-induced attenuation, with different dependence on the frequency and fabrication variation. Strategies on how to mitigate the effect of variation for better fabrication tolerance are discussed by considering three key factors: pre-shift in structural design, bias condition, and fabrication control accuracy.

14.
Materials (Basel) ; 14(4)2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33672750

RESUMO

The Curie temperature (Tc) and magnetic entropy change (-ΔSm), and their relationship to the alloy composition of Tb-Co metallic glasses, were studied systematically in this paper. It was found that, in contrast to the situation in amorphous Gd-Co ribbons, the dependence of Tc on Tb content and the maximum -ΔSm vs. Tc -2/3 plots in Tb-Co binary amorphous alloys do not follow a linear relationship, both of which are supposed to be closely related to the non-linear compositional dependence of Tb-Co interaction due to the existence of orbital momentum in Tb.

15.
Hum Exp Toxicol ; : 9603271211002886, 2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33779332

RESUMO

OBJECTIVE: To explore the effects of myocardin-related transcription factor A (MRTF-A) knockout on mice with nonalcoholic steatohepatitis (NASH) induced by high-fat diet (HFD). METHODS: Normal-fat diet (NFD) or HFD was fed to MRTF-A-knockout (MRTF-A-/-) and wild-type (WT) mice for 16 weeks. Liver histopathological status was observed using Hematoxylin and Eosin (HE) staining, Oil Red O staining, Sirius Red staining, and Immunohistochemical staining. The mRNA and protein levels in liver tissues were measured through quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot. RESULTS: Compared with WT + HFD group, mice in MRTF-A-/- + HFD group were decreased in body weight, blood glucose, plasma insulin, liver TG and NAFLD activity score (NAS), with liver function recovery. Besides, compared with HFD-fed WT mice, HFD-fed MRTF-A-/- mice were improved in hepatic fibrosis, accompanied by decreased collagen content (%) and down-regulated expressions of α-SMA, COL1A2, TGFß1, and SMAD3. In mice fed with HFD, the expression of MCP-1, CCR2, F4/80 and CD68 declined in liver tissues of MRTF-A-/- mice as compared with WT mice. Besides, in hepatic macrophages isolated from HFD-fed mice, the observed increased expression of TNF-α, IL-1ß, MCP-1, as well as decreased expression of CCR2. Compared with WT + HFD group, MRTF-A-/- + HFD group mice were decreased regarding NF-κB p65 in liver tissues. CONCLUSION: MRTF-A knockout reduced macrophage infiltration, down-regulated NF-κB p65 expression, and ameliorated inflammation and fibrosis of liver tissues in mice, thereby becoming a potential therapeutic target for NASH treatment.

16.
Cancer Biol Med ; 18(1): 206-214, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33628595

RESUMO

Objective: Pancreatic ductal adenocarcinoma (PDAC) is a deadly malignancy, due in large part to its resistance to conventional therapies, including radiotherapy (RT). Despite RT exerting a modest antitumor response, it has also been shown to promote an immunosuppressive tumor microenvironment. Previous studies demonstrated that focal adhesion kinase inhibitors (FAKi) in clinical development inhibit the infiltration of suppressive myeloid cells and T regulatory (T regs) cells, and subsequently enhance effector T cell infiltration. FAK inhibitors in clinical development have not been investigated in combination with RT in preclinical murine models or clinical studies. Thus, we investigated the impact of FAK inhibition on RT, its potential as an RT sensitizer and immunomodulator in a murine model of PDAC. Methods: We used a syngeneic orthotopic murine model to study the effect of FAKi on hypofractionated RT. Results: In this study we showed that IN10018, a small molecular FAKi, enhanced antitumor response to RT. Antitumor activity of the combination of FAKi and RT is T cell dependent. FAKi in combination with RT enhanced CD8+ T cell infiltration significantly in comparison to the radiation or FAKi treatment alone (P < 0.05). FAKi in combination with radiation inhibited the infiltration of granulocytes but enhanced the infiltration of macrophages and T regs in comparison with the radiation or FAKi treatment alone (P < 0.01). Conclusions: These results support the clinical development of FAKi as a radiosensitizer for PDAC and combining FAKi with RT to prime the tumor microenvironment of PDAC for immunotherapy.

17.
J Cachexia Sarcopenia Muscle ; 12(2): 298-307, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33543604

RESUMO

BACKGROUND: Regular stair climbing has the potential to lower the risk of premature death, but current evidence is scarce. We aimed to examine whether daily stair climbing is associated with lower risk of all-cause, cancer, and cardiovascular disease (CVD) mortality. METHODS: Using the UK Biobank cohort, we extracted information of self-reported daily flights of stairs climbed at home, categorized as none, 1 to 5, 6 to 10, 11 to 15, and ≥16 flights per day. Associations between flights of stair climbed per day and mortality were examined as hazard ratios (HRs) from Cox proportional hazards models adjusted for demographic, clinical, and behavioural covariates including time spent in other physical activities. We calculated the restricted mean survival time as an absolute measure of association. The risk of residual confounding was examined using propensity score matching and by using lung cancer as negative control outcome. Participants were followed from baseline (2006-2010) through 31 March 2020. RESULTS: A total of 280 423 participants (median follow-up 11.1 years, during which 9445 deaths occurred) were included. Compared with not climbing any stairs, climbing more than five flights of stairs at home per day was associated with lower risk of premature mortality. The lowest risk was found for those climbing 6-10 flights per day: 0.91; 95% confidence interval (CI): 0.85, 0.98, translated to approximately 44 to 55 days of additional survival. A similar pattern was found after applying propensity score matching and for cancer mortality (6-10 flights per day HR: 0.88; 95% CI: 0.80, 0.97), but not for CVD mortality (6-10 flights per day HR: 1.08; 95% CI: 0.91, 1.29). The association between stair climbing and lung cancer was similar to that of all-cause mortality. CONCLUSIONS: Climbing more than five flights of stairs at home per day was associated with a lower risk of all-cause and cancer mortality, but not CVD mortality, compared with those who did not take the stairs. The magnitude of the association was small and appeared susceptible to residual confounding. It is unlikely that at-home stair climbing is sufficient physical activity stimuli to lower the risk of premature mortality.

18.
Sci China Life Sci ; 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33439457

RESUMO

We aimed to assess the associations of large artery stenosis (LAS) and cerebral small vessel disease (CSVD) with the risk of ischemic stroke and to investigate their respective and combined contributions. In the prospective population-based Shunyi Study, 1,082 stroke-free participants aged 55.9±9.1 years were included. Participants were followed for incident stroke throughout the study period (2013-2019). Total small vessel disease score was used to measure CSVD burden. Cervico-cerebral large artery stenosis was evaluated via brain magnetic resonance angiography and carotid ultrasound. We estimated the risk of ischemic stroke in relation to LAS and CSVD with Cox regression models. During a mean follow-up of 4.2 years, 34 participants (3.1%) experienced at least one ischemic stroke. Severe LAS (≥50% stenosis versus no stenosis: HR=3.27 (95% CI: 1.31-8.18)) and high CSVD burden (total small vessel disease score 2-4 versus 0 point: HR=12.73 (4.83-33.53)) were associated with increased stroke risk independently. In multivariate models, CSVD burden (7.72%) explained a larger portion of the variation in stroke risk than severity of LAS (3.49%). Our findings identified that both LAS and CSVD were associated with future ischemic stroke in asymptomatic subjects, while those with high CSVD burden deserve more attention in primary prevention of stroke.

19.
J Sport Health Sci ; 2021 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-33434635

RESUMO

BACKGROUND: Emerging epidemiological evidence suggests that compared to engaging in 1 activity mode alone, a combination of moderate-to-vigorous physical activity (MVPA: brisk walking/jogging, cycling) and muscle-strengthening exercise (MSE: push-ups/sit-ups, using weight machines) has more favorable associations with optimal weight status. However, few studies have examined the dose-dependent and joint associations of MVPA and MSE with obesity. METHODS: Based on cross-sectional analyses of the European Health Interview Survey Wave 2 (2013-2014), we examined prevalence ratios (PRs) of joint and stratified associations between MVPA (4 categories: (i) 0 min/week, (ii) 1-149 min/week, (iii) 150-299 min/week, and (iv) ≥300 min/week) and MSE (3 categories: (i) 0 day/week, (ii) 1 day/week, and (iii) ≥2 days/week) with body mass index-defined obesity (body mass index of ≥30.0 kg/m2) using Poisson regression with robust error variance. PRs were examined unadjusted and adjusted for sociodemographic and lifestyle characteristics (e.g., sex, age, education, income, and smoking status). RESULTS: Data were available for 280,456 adults (≥18 years), of which 46,166 (15.5%) were obese. The interaction MVPA × MSE guideline adherence was statistically significant for obesity (p ≤ 0.05). The joint MVPA-MSE analysis showed that compared to the reference group (i.e., no MVPA and no MSE), the PRs followed a dose-dependent pattern, with the lowest observed among those reporting ≥150 MVPA min/week and ≥1 MSE days/week (PR: 0.43; 95% confidence interval: 0.41-0.46). When stratified across each MVPA strata, the PRs were mostly lower among those engaging in MSE 1 day/week, as compared to those doing MSE ≥2 days/week. CONCLUSION: There was evidence for a dose-dependent association between joint MVPA-MSE with a reduced prevalence of obesity. Public health strategies for the prevention and management of obesity should recommend both MVPA and MSE.

20.
Phytochemistry ; 183: 112628, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33412403

RESUMO

Nine undescribed guaiane-type sesquiterpenoids stelleraterpenoids A‒I, along with seven reported congeners, were isolated and identified from the 70% EtOH extract of the roots of Stellera chamaejasme L. Their chemical structures were elucidated on the basis of various spectral data. The relative configurations were determined by their NOESY spectra and comparison between their experimental and calculated NMR data. The absolute configurations were established by the comparison between the experimental and calculated ECD spectra and further by X-ray single-crystal diffraction analysis. The neuroprotective effects of these compounds on the H2O2-induced damage in human neuroblastoma SH-SY5Y cells were evaluated. Stelleraguaianone B exhibited the better activity with 71.62% cell viability compared to the positive control Trolox (65.05%) at 12.5 µM, which might be achieved by inhibiting the apoptosis of SH-SY5Y cells based on an annexin V-FITC/PI staining experiment.


Assuntos
Fármacos Neuroprotetores , Sesquiterpenos , Thymelaeaceae , Peróxido de Hidrogênio , Estrutura Molecular , Fármacos Neuroprotetores/farmacologia , Sesquiterpenos/farmacologia , Sesquiterpenos de Guaiano
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