Accelerometer-Derived "Weekend Warrior" Physical Activity and Incident Cardiovascular Disease.
JAMA
Importance:Guidelines recommend 150 minutes or more of moderate to vigorous physical activity (MVPA) per week for overall health benefit, but the relative effects of concentrated vs more evenly distributed activity are unclear. Objective:To examine associations between an accelerometer-derived "weekend warrior" pattern (ie, most MVPA achieved over 1-2 days) vs MVPA spread more evenly with risk of incident cardiovascular events. Design, Setting, and Participants:Retrospective analysis of UK Biobank cohort study participants providing a full week of accelerometer-based physical activity data between June 8, 2013, and December 30, 2015. Exposures:Three MVPA patterns were compared: active weekend warrior (active WW, ≥150 minutes with ≥50% of total MVPA achieved in 1-2 days), active regular (≥150 minutes and not meeting active WW status), and inactive (<150 minutes). The same patterns were assessed using the sample median threshold of 230.4 minutes or more of MVPA per week. Main Outcomes and Measures:Associations between activity pattern and incident atrial fibrillation, myocardial infarction, heart failure, and stroke were assessed using Cox proportional hazards regression, adjusted for age, sex, racial and ethnic background, tobacco use, alcohol intake, Townsend Deprivation Index, employment status, self-reported health, and diet quality. Results:A total of 89 573 individuals (mean [SD] age, 62 [7.8] years; 56% women) who underwent accelerometry were included. When stratified at the threshold of 150 minutes or more of MVPA per week, a total of 37 872 were in the active WW group (42.2%), 21 473 were in the active regular group (24.0%), and 30 228 were in the inactive group (33.7%). In multivariable-adjusted models, both activity patterns were associated with similarly lower risks of incident atrial fibrillation (active WW: hazard ratio [HR], 0.78 [95% CI, 0.74-0.83]; active regular: 0.81 [95% CI, 0.74-0.88; inactive: HR, 1.00 [95% CI, 0.94-1.07]), myocardial infarction (active WW: 0.73 [95% CI, 0.67-0.80]; active regular: 0.65 [95% CI, 0.57-0.74]; and inactive: 1.00 [95% CI, 0.91-1.10]), heart failure (active WW: 0.62 [95% CI, 0.56-0.68]; active regular: 0.64 [95% CI, 0.56-0.73]; and inactive: 1.00 [95% CI, 0.92-1.09]), and stroke (active WW: 0.79 [95% CI, 0.71-0.88]; active regular: 0.83 [95% CI, 0.72-0.97]; and inactive: 1.00 [95% CI, 0.90-1.11]). Findings were consistent at the median threshold of 230.4 minutes or more of MVPA per week, although associations with stroke were no longer significant (active WW: 0.89 [95% CI, 0.79-1.02]; active regular: 0.87 [95% CI, 0.74-1.02]; and inactive: 1.00 [95% CI, 0.90-1.11]). Conclusions and Relevance:Physical activity concentrated within 1 to 2 days was associated with similarly lower risk of cardiovascular outcomes to more evenly distributed activity.
10.1001/jama.2023.10875
S100 proteins in atherosclerosis.
Xiao Xuan,Yang Chen,Qu Shun-Lin,Shao Yi-Duo,Zhou Chu-Yi,Chao Ru,Huang Liang,Zhang Chi
Clinica chimica acta; international journal of clinical chemistry
Atherosclerosis is an arterial disease associated with dyslipidemia, abnormal arterial calcification and oxidative stress. It has been shown that a continued chronic inflammatory state of the arterial wall contributes to the development of atherosclerosis. The inflammatory stimulation, recruitment of inflammatory cells and production of pro-inflammatory cytokines enhances vascular inflammation. Some members of the S100 proteins family bind with their receptors, such as advanced glycation end products (RAGE), scavenger receptors (CD36) and toll-like receptor 4 (TLR-4), contributing to the cellular response in atherosclerotic progression. This review summarizes the roles of S100 proteins (S100A8, S100A9 and S100A12) in the vascular inflammation, vascular calcification and vascular oxidative stress. S100 proteins are released from monocytes, smooth muscle cells and endothelial cells in response to cellular stress stimuli, and then the binding of S100 proteins to RAGE activate downstream signaling such as transcription factor kappa B (NF-κB) translocation and reactive oxygen species (ROS) production, which act as a positive feedback loop for inducing pro-inflammatory phenotype in a wide variety of cell types including endothelial cells, vascular smooth muscle cells and leukocytes. Thus, it suggests that the inhibition of S100 proteins-mediated RAGE and TLR4 activation appears to be a promising approach to treat atherosclerosis. In addition, recent study showed that serum S100A12 can predict future cardiovascular events, highlighting that S100A12 is likely to be a potential biomarker of therapeutic efficacy and disease progression in coronary heart disease. Future studies of patients with coronary heart disease may provide more evidences supporting that S100 proteins is promising drug target in the prevention and therapy of atherosclerosis.
10.1016/j.cca.2019.11.019
Pancreatic Cancer: Pathogenesis and Diagnosis.
Goral Vedat
Asian Pacific journal of cancer prevention : APJCP
Pancreatic cancer is a fatal malignancies which is predominantly seen in men and at advanced age (40-85 years) and has an aggressive course. Its frequency is gradually increasing over the past years. It accounts for 2% of all cancers and 5% of cancer-related deaths. Pancreatic cancer takes the first place among asymptomatic cancers. Ninety percent of cases are adenocarcinomas. Ten percent of the patients have a familial disposition. The disease is very difficult to detect as it has no early signs and spreads rapidly to surrounding organs is one of the most deadly types of cancer. Pancreatic cancer may result from hereditary germline or somatic acquired mutations in cancer-related genes and mutations also cause cancer progression and metastasis.
10.7314/apjcp.2015.16.14.5619
Resistant hypertension: patient characteristics, risk factors, co-morbidities and outcomes.
Oliveras A,de la Sierra A
Journal of human hypertension
Among the vast population of hypertensive subjects, between 10 and 15% do not achieve an adequate blood pressure (BP) control despite the use of at least three antihypertensive agents. This group, designated as having resistant hypertension (RH), represents one of the most important clinical challenges in hypertension evaluation and management. Resistant hypertensives are characterized by several clinical particularities, such as a longer history of hypertension, obesity and other accompanying factors, such as diabetes, left ventricular hypertrophy, albuminuria and renal dysfunction. In addition to other diagnostic and therapeutic maneuvers, such as excluding secondary hypertension, ensuring treatment adherence and optimizing therapeutic schemes, ambulatory BP monitoring (ABPM) is crucial in the clinical evaluation of patients with RH. ABPM distinguish between those with out-of-office BP elevation (true resistant hypertensives) and those having white-coat RH (WCRH; normalcy of 24-h BPs), the prevalence of the latter estimated in about one-third of the population with RH. True resistant hypertensives also exhibit more frequently other co-morbidities, more severe target organ damage and a worse cardiovascular prognosis, in comparison to those with WCRH. Some device-based therapies have recently been developed for treatment of RH. This requires a better characterization of a potential candidate population. A better knowledge of the clinical features of resistant hypertensive subjects, the confirmation of elevated BP values out of the doctor's office, and improvements in the search for secondary causes would help to select those candidates for newer therapies, once the pharmacological possibilities have been exhausted.
10.1038/jhh.2013.77
Reliable Model Selection without Reference Values by Utilizing Model Diversity with Prediction Similarity.
Spiers Robert C,Kalivas John H
Journal of chemical information and modeling
Predictive modeling (calibration or training) with various data formats, such as near-infrared (NIR) spectra and quantitative structure-activity relationship (QSAR) data, provides essential information if a proper model is selected. Similarly, with a general model selection approach, spectral model maintenance (updating) from original modeling conditions to new conditions can be performed for dynamic modeling. Fundamental modeling (partial least-squares (PLS) and others) and maintenance processes (domain adaptation or transfer learning and others) require selection of tuning parameter(s) values to isolate models that can accurately predict new samples or molecules, e.g., number of PLS latent variables to predict analyte concentration. Regardless of the modeling task, model selection is complex and without a reliable protocol. Tuning parameter selection typically depends on only one model quality measure assessing model bias using prediction accuracy. Developed in this paper is a generic model selection process using concepts from consensus modeling and QSAR activity landscapes. It is a consensus filtering approach that prioritizes model diversity (MD) while conserving prediction similarity (PS) fused with a common bias-variance trade-off measure. A significant feature of MDPS is that a cross-validation scheme is not needed because models are selected relative to predicting new samples or molecules, i.e., model selection uses unlabeled samples (without reference values) for active predictions. The versatility and reliability of MDPS model selection is shown using four NIR data sets and a QSAR data set. The study also substantiates the Rashomon effect where there is not one best model tuning parameter value that provides accurate predictions.
10.1021/acs.jcim.0c01493
The role of tumor-associated macrophages and soluble mediators in pulmonary metastatic melanoma.
Frontiers in immunology
Skin malignant melanoma is a highly aggressive skin tumor, which is also a major cause of skin cancer-related mortality. It can spread from a relatively small primary tumor and metastasize to multiple locations, including lymph nodes, lungs, liver, bone, and brain. What's more metastatic melanoma is the main cause of its high mortality. Among all organs, the lung is one of the most common distant metastatic sites of melanoma, and the mortality rate of melanoma lung metastasis is also very high. Elucidating the mechanisms involved in the pulmonary metastasis of cutaneous melanoma will not only help to provide possible explanations for its etiology and progression but may also help to provide potential new therapeutic targets for its treatment. Increasing evidence suggests that tumor-associated macrophages (TAMs) play an important regulatory role in the migration and metastasis of various malignant tumors. Tumor-targeted therapy, targeting tumor-associated macrophages is thus attracting attention, particularly for advanced tumors and metastatic tumors. However, the relevant role of tumor-associated macrophages in cutaneous melanoma lung metastasis is still unclear. This review will present an overview of the origin, classification, polarization, recruitment, regulation and targeting treatment of tumor-associated macrophages, as well as the soluble mediators involved in these processes and a summary of their possible role in lung metastasis from cutaneous malignant melanoma. This review particularly aims to provide insight into mechanisms and potential therapeutic targets to readers, interested in pulmonary metastasis melanoma.
10.3389/fimmu.2022.1000927
Prospective Assessment of a Symptomatic Cerebral Vasospasm Predictive Neural Network Model.
Dumont Travis M
World neurosurgery
INTRODUCTION:The author introduced a symptomatic cerebral vasospasm (SCV) prediction model built with freeware based on a 91-patient dataset. In a prospective test group of 22 patients at the same hospital, this model outperformed logistic regression models in vasospasm prediction on the basis of the same datasets. One of the model's limitations was a question of reproducibility in other centers. In this report, the author describes his experience with the prospective use of the model at a different hospital with a different population setting. METHODS:Patient data of 25 consecutive cases of aneurysm rupture were prospectively assessed by the model to predict SCV. The prediction was then compared with actual outcome. For the purpose of this report, SCV is defined as a delayed focal decline in neurological examination correlated with an area of radiographic vasospasm. This serves as the primary end point of the predictive model. Each case prediction is reported, along with strength of prediction, which is built into the model. The model's positive predictive value, negative predictive value, and sensitivity and specificity are reported. RESULTS:Twenty-five patients are included in the analysis. Six patients (24%) were diagnosed with SCV. The model predicted 9 patients would have SCV (positive predictive value 67%). The model predicted 16 patients would not have SCV (negative predictive value 100%). The sensitivity of the model was 100%, and the specificity of the model was 84%. DISCUSSION:The present analysis displays the predictive value of a neural network to model symptomatic cerebral vasospasm.
10.1016/j.wneu.2016.06.110
Outrunning Burnout in a GI Fellowship Program During the COVID-19 Pandemic.
Ong Andrew Ming-Liang
Digestive diseases and sciences
Many GI training programs have needed to adjust to the serious disruption to the training and education of fellows worldwide due to the COVID-19 pandemic. A silent problem that has arisen within programs is the issue of burnout among their trainees. Burnout is common among gastroenterologists, especially in fellows (Keswani et al. in Gastroenterology 147(1):11-14, 2014. https://doi.org/10.1053/j.gastro.2014.05.023 , Am J Gastroenterol 106(10):1734-1740, 2011. https://doi.org/10.1038/ajg.2011.148 ), with negative consequences to patient care and the safety of the trainees if not effectively dealt with. In this article, the author describes several additional factors potentially contributing to the intensifying burnout of the fellows in their home institution during this pandemic. Moreover, he describes specific practical interventions that the hospital and program have taken in order to address these factors.
10.1007/s10620-020-06401-4
Relationship of sleep duration on workdays and non-workdays with blood pressure components in Chinese hypertensive patients.
Hu Lihua,Huang Xiao,You Chunjiao,Bao Huihui,Zhou Wei,Li Juxiang,Li Ping,Wu Yanqing,Wu Qinghua,Wang Zengwu,Gao Runlin,Liang Qian,Cheng Xiaoshu
Clinical and experimental hypertension (New York, N.Y. : 1993)
: This study aimed to assess the relationship of sleep duration on workdays and non-workdays with BP components [systolic BP (SBP), diastolic (DBP), pulse pressure (PP), and mean arterial pressure (MAP)] among Chinese hypertensive adults. : The study included 3,376 hypertensive patients without antihypertensive treatment. Self-reported sleep durations on workdays and non-workdays were measured by the questionnaire. Multiple linear regression analyses were performed to evaluate the association of sleep duration with BP components. : Overall, compared with a sleep duration of 5-9 h, individuals who slept ≥10 h on both workdays and non-workdays were positively correlated with SBP [β (95% CIs) = 3.99 (1.06, 6.93) and 4.33 (1.79, 6.87)] and PP [β (95% CIs) = 3.25 (0.71, 5.79) and 3.05 (0.85, 5.25)], but not with DBP. Moreover, individuals who slept ≥10 h only on non-workdays had higher MAP [β (95% CIs) = 2.30 (0.63, 3.97)]. The stratified analyses showed that subjects with a BMI ≥24 kg/m in the longer sleep duration group (≥10 h) only on workdays compared to the reference group had higher SBP, DBP and MAP (all for interaction <0.05). The effect of longer sleep duration on BP components showed no difference in the following subgroups: sex, age, smoking and drinking (all for interaction >0.05). : Compared with a sleep duration of 5-9 h, longer sleep duration (≥10 h) on workdays and non-workdays was associated with high SBP and PP among Chinese hypertensive adults without antihypertensive treatment.
10.1080/10641963.2018.1529777
Sleep and CKD in Chinese Adults: A Cross-Sectional Study.
Clinical journal of the American Society of Nephrology : CJASN
BACKGROUND AND OBJECTIVES:To assess the association between self-reported sleep duration and quality and odds of having CKD in Chinese adults on the basis of a community study. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:In this cross-sectional study, we included 11,040 Chinese adults who participated in an ongoing prospective study, the Kailuan cohort. Survey questionnaire items addressed insomnia, daytime sleepiness, snoring, and sleep duration during their 2012 interview. Overall sleep quality was evaluated by summarizing these four sleep parameters. Fasting blood samples and single random midstream morning urine samples were collected in 2012 and analyzed for serum creatinine and proteinuria. CKD was defined by eGFR<60 ml/min per 1.73 m or proteinuria >300 mg/dl. We also examined those at high or very high risk of having CKD, on the basis of the Kidney Disease Improving Global Outcomes recommendations. The association between sleep quality and CKD was assessed using logistic regression model. RESULTS:Worse overall sleep quality was associated with higher likelihood of being high or very high risk for CKD (multiadjusted odds ratio, 2.69; 95% confidence interval, 1.30 to 5.59 comparing two extreme categories; trend <0.01), but not overall CKD (multiadjusted odds ratio, 1.58; 95% confidence interval, 0.89 to 2.80 comparing two extreme categories; trend =0.46), after adjusting for potential confounders. Specifically, individuals with worse sleep quality were more likely to have proteinuria (multiadjusted odds ratio, 1.95; 95% confidence interval, 1.03 to 3.67 comparing two extreme categories; trend =0.02), rather than lower eGFR level (multiadjusted mean eGFR levels were 96.4 and 93.6 ml/min per 1.73 m in the two extreme sleep categories, respectively; trend =0.13). However, there was no statistically significant association between individual sleep parameters and CKD status. CONCLUSIONS:Worse overall sleep quality was associated with higher odds of being high or very high risk for CKD and proteinuria in Chinese adults.
10.2215/CJN.09270816
Preliminary study of confocal laser endomicroscopy for in vitro specimens of the endometrium.
BMC cancer
BACKGROUND:This study observed and described the morphological characteristics of the endometrium of the resected uterus using confocal laser endomicroscopy. This included benign endometrium, non-atypical endometrial hyperplasia, atypical endometrial hyperplasia, and endometrial carcinoma, thereby laying a foundation for finding the precise localization and resection of endometrial lesions, given the feasibility of confocal laser endomicroscopy-assisted hysteroscopy. METHODS:This prospective study included 32 patients who underwent hysterectomy. We used confocal laser endomicroscopy to observe the endometrium of resected uteruses and described the characteristics of endometrium in different states by comparing histopathological findings (primary objects). The secondary objects of observation were the myometrium, endocervical canal, and surface of the external os of the cervix. RESULTS:A total of 32 patients who underwent hysterectomy for different diseases were included: 9 with endometrial carcinoma (5 with endometrioid carcinoma, 1 with endometrial serous carcinoma, 2 with clear cell carcinoma, and 1 with carcinosarcoma), 2 with atypical endometrial hyperplasia, 9 with benign diseases, 7 with cervical cancer, and 5 with ovarian cancer and borderline tumor. The dynamic images of the endometrium were observed and recorded using probe-based confocal laser endomicroscopy (pCLE). Considering histopathology as the gold standard, the diagnostic concordance rate of pCLE was 96.9% in patients with endometrial carcinoma and precancerous lesions and 100% in patients with endometrial carcinoma. CONCLUSION:Confocal laser endomicroscopy provides real-time high-resolution images of the benign endometrium and endometrial lesions. Compared with histopathology, confocal laser endomicroscopy has high diagnostic accuracy and may become an auxiliary examination tool for hysteroscopy, as it is useful for early identification of endometrial lesions, real-time diagnosis of tumor, and detection of tumor boundaries for complete tumor resection. These findings can lay a foundation for the feasible use of fertility-sparing local excision of tumor lesions by hysteroscopy.
10.1186/s12885-022-10137-x