To date, there is indisputable evidence of significant CTC heterogeneity in carcinomas, in particular breast cancer. The heterogeneity of CTCs is manifested in the key characteristics of tumor cells ...related to metastatic progression - stemness and epithelial-mesenchymal (EMT) plasticity. It is still not clear what markers can characterize the phenomenon of EMT plasticity in the range from epithelial to mesenchymal phenotypes. In this article we examine the manifestations of EMT plasticity in the CTCs in breast cancer. The prospective study included 39 patients with invasive carcinoma of no special type. CTC phenotypes were determined by flow cytometry before any type of treatment. EMT features of CTC were assessed using antibodies against CD45, CD326 (EpCam), CD325 (N-cadherin), CK7, Snail, and Vimentin. Circulating tumor cells in breast cancer are characterized by pronounced heterogeneity of EMT manifestations. The results of the study indicate that the majority of heterogeneous CTC phenotypes (22 out of 24 detectable) exhibit epithelial-mesenchymal plasticity. The variability of EMT manifestations does not prevent intravasation. Co-expression of EpCAM and CK7, regardless of the variant of co-expression of Snail, N-cadherin, and Vimentin, are associated with a low number of CTCs. Intrapersonal heterogeneity is manifested by the detection of several CTC phenotypes in each patient. Interpersonal heterogeneity is manifested by various combinations of CTC phenotypes in patients (from 1 to 17 phenotypes).
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In previous studies, of which several were underpowered, the relation between cardiovascular outcome and blood pressure (BP) variability was inconsistent. We followed health outcomes in 8938 subjects ...(mean age53.0 years; 46.8% women) randomly recruited from 11 populations. At baseline, we assessed BP variability from the SD and average real variability in 24-hour ambulatory BP recordings. We computed standardized hazard ratios (HRs) while stratifying by cohort and adjusting for 24-hour BP and other risk factors. Over 11.3 years (median), 1242 deaths (487 cardiovascular) occurred, and 1049, 577, 421, and 457 participants experienced a fatal or nonfatal cardiovascular, cardiac, or coronary event or a stroke. Higher diastolic average real variability in 24-hour ambulatory BP recordings predicted (P≤0.03) total (HR1.14) and cardiovascular (HR1.21) mortality and all types of fatal combined with nonfatal end points (HR≥1.07) with the exception of cardiac and coronary events (HR≤1.02; P≥0.58). Higher systolic average real variability in 24-hour ambulatory BP recordings predicted (P<0.05) total (HR1.11) and cardiovascular (HR1.16) mortality and all fatal combined with nonfatal end points (HR≥1.07), with the exception of cardiac and coronary events (HR≤1.03; P≥0.54). SD predicted only total and cardiovascular mortality. While accounting for the 24-hour BP level, average real variability in 24-hour ambulatory BP recordings added <1% to the prediction of a cardiovascular event. Sensitivity analyses considering ethnicity, sex, age, previous cardiovascular disease, antihypertensive treatment, number of BP readings per recording, or the night:day BP ratio were confirmatory. In conclusion, in a large population cohort, which provided sufficient statistical power, BP variability assessed from 24-hour ambulatory recordings did not contribute much to risk stratification over and beyond 24-hour BP.
We and other investigators previously reported that isolated nocturnal hypertension on ambulatory measurement (INH) clustered with cardiovascular risk factors and was associated with intermediate ...target organ damage. We investigated whether INH might also predict hard cardiovascular endpoints.
We monitored blood pressure (BP) throughout the day and followed health outcomes in 8711 individuals randomly recruited from 10 populations (mean age 54.8 years, 47.0% women). Of these, 577 untreated individuals had INH (daytime BP <135/85 mmHg and night-time BP ≥120/70 mmHg) and 994 untreated individuals had isolated daytime hypertension on ambulatory measurement (IDH; daytime BP ≥135/85 mmHg and night-time BP <120/70 mmHg). During follow-up (median 10.7 years), 1284 deaths (501 cardiovascular) occurred and 1109 participants experienced a fatal or nonfatal cardiovascular event. In multivariable-adjusted analyses, compared with normotension (n = 3837), INH was associated with a higher risk of total mortality (hazard ratio 1.29, P = 0.045) and all cardiovascular events (hazard ratio 1.38, P = 0.037). IDH was associated with increases in all cardiovascular events (hazard ratio 1.46, P = 0.0019) and cardiac endpoints (hazard ratio 1.53, P = 0.0061). Of 577 patients with INH, 457 were normotensive (<140/90 mmHg) on office BP measurement. Hazard ratios associated with INH with additional adjustment for office BP were 1.31 (P = 0.039) and 1.38 (P = 0.044) for total mortality and all cardiovascular events, respectively. After exclusion of patients with office hypertension, these hazard ratios were 1.17 (P = 0.31) and 1.48 (P = 0.034).
INH predicts cardiovascular outcome in patients who are normotensive on office or on ambulatory daytime BP measurement.
Previous studies on the prognostic significance of the morning blood pressure surge (MS) produced inconsistent results. Using the International Database on Ambulatory Blood Pressure in Relation to ...Cardiovascular Outcome, we analyzed 5645 subjects (mean age53.0 years; 54.0% women) randomly recruited in 8 countries. The sleep-through and the preawakening MS were the differences in the morning blood pressure with the lowest nighttime blood pressure and the preawakening blood pressure, respectively. We computed multivariable-adjusted hazard ratios comparing the risk in ethnic- and sex-specific deciles of the MS relative to the average risk in the whole study population. During follow-up (median11.4 years), 785 deaths and 611 fatal and nonfatal cardiovascular events occurred. While accounting for covariables and the night:day ratio of systolic pressure, the hazard ratio of all-cause mortality was 1.32 (95% CI1.09 to 1.59; P=0.004) in the top decile of the systolic sleep-through MS (≥37.0 mm Hg). For cardiovascular and noncardiovascular death, these hazard ratios were 1.18 (95% CI0.87 to 1.61; P=0.30) and 1.42 (95% CI1.11 to 1.80; P=0.005). For all cardiovascular, cardiac, coronary, and cerebrovascular events, the hazard ratios in the top decile of the systolic sleep-through MS were 1.30 (95% CI1.06 to 1.60; P=0.01), 1.52 (95% CI1.15 to 2.00; P=0.004), 1.45 (95% CI1.04 to 2.03; P=0.03), and 0.95 (95% CI0.68 to 1.32; P=0.74), respectively. Analysis of the preawakening systolic MS and the diastolic MS generated consistent results. In conclusion, a MS above the 90th percentile significantly and independently predicted cardiovascular outcome and might contribute to risk stratification by ambulatory blood pressure monitoring.
Hypertension is a major global health problem, but prevalence rates vary widely among regions. To determine prevalence, treatment, and control rates of hypertension, we measured conventional blood ...pressure (BP) and 24-hour ambulatory BP in 6546 subjects, aged 40 to 79 years, recruited from 10 community-dwelling cohorts on 3 continents. We determined how between-cohort differences in risk factors and socioeconomic factors influence hypertension rates. The overall prevalence was 49.3% (range between cohorts, 40.0%–86.8%) for conventional hypertension (conventional BP ≥140/90 mm Hg) and 48.7% (35.2%–66.5%) for ambulatory hypertension (ambulatory BP ≥130/80 mm Hg). Treatment and control rates for conventional hypertension were 48.0% (33.5%–74.1%) and 38.6% (10.1%–55.3%) respectively. The corresponding rates for ambulatory hypertension were 48.6% (30.5%–71.9%) and 45.6% (18.6%–64.2%). Among 1677 untreated subjects with conventional hypertension, 35.7% had white coat hypertension (23.5%–56.2%). Masked hypertension (conventional BP <140/90 mm Hg and ambulatory BP ≥130/80 mm Hg) occurred in 16.9% (8.8%–30.5%) of 3320 untreated subjects who were normotensive on conventional measurement. Exclusion of participants with diabetes mellitus, obesity, hypercholesterolemia, or history of cardiovascular complications resulted in a <9% reduction in the conventional and 24-hour ambulatory hypertension rates. Higher social and economic development, measured by the Human Development Index, was associated with lower rates of conventional and ambulatory hypertension. In conclusion, high rates of hypertension in all cohorts examined demonstrate the need for improvements in prevention, treatment, and control. Strategies for the management of hypertension should continue to not only focus on preventable and modifiable risk factors but also consider societal issues.
To assess the seasonality of cardiovascular risk factors (CVRF) in a large set of population-based studies.
Cross-sectional data from 24 population-based studies from 15 countries, with a total ...sample size of 237 979 subjects. CVRFs included Body Mass Index (BMI) and waist circumference; systolic (SBP) and diastolic (DBP) blood pressure; total, high (HDL) and low (LDL) density lipoprotein cholesterol; triglycerides and glucose levels. Within each study, all data were adjusted for age, gender and current smoking. For blood pressure, lipids and glucose levels, further adjustments on BMI and drug treatment were performed.
In the Northern and Southern Hemispheres, CVRFs levels tended to be higher in winter and lower in summer months. These patterns were observed for most studies. In the Northern Hemisphere, the estimated seasonal variations were 0.26 kg/m(2) for BMI, 0.6 cm for waist circumference, 2.9 mm Hg for SBP, 1.4 mm Hg for DBP, 0.02 mmol/L for triglycerides, 0.10 mmol/L for total cholesterol, 0.01 mmol/L for HDL cholesterol, 0.11 mmol/L for LDL cholesterol, and 0.07 mmol/L for glycaemia. Similar results were obtained when the analysis was restricted to studies collecting fasting blood samples. Similar seasonal variations were found for most CVRFs in the Southern Hemisphere, with the exception of waist circumference, HDL, and LDL cholesterol.
CVRFs show a seasonal pattern characterised by higher levels in winter, and lower levels in summer. This pattern could contribute to the seasonality of CV mortality.
This study investigated 12-year blood lipid trajectories and whether these trajectories are modified by smoking and lipid lowering treatment in older Russians. To do so, we analysed data on 9,218 ...Russian West-Siberian Caucasians aged 45-69 years at baseline participating in the international HAPIEE cohort study. Mixed-effect multilevel models were used to estimate individual level lipid trajectories across the baseline and two follow-up examinations (16,445 separate measurements over 12 years). In all age groups, we observed a reduction in serum total cholesterol (TC), LDL-C and non-HDL-C over time even after adjusting for sex, statin treatment, hypertension, diabetes, social factors and mortality (P<0.01). In contrast, serum triglyceride (TG) values increased over time in younger age groups, reached a plateau and decreased in older age groups (> 60 years at baseline). In smokers, TC, LDL-C, non-HDL-C and TG decreased less markedly than in non-smokers, while HDL-C decreased more rapidly while the LDL-C/HDL-C ratio increased. In subjects treated with lipid-lowering drugs, TC, LDL-C and non-HDL-C decreased more markedly and HDL-C less markedly than in untreated subjects while TG and LDL-C/HDL-C remained stable or increased in treatment naïve subjects. We conclude, that in this ageing population we observed marked changes in blood lipids over a 12 year follow up, with decreasing trajectories of TC, LDL-C and non-HDL-C and mixed trajectories of TG. The findings suggest that monitoring of age-related trajectories in blood lipids may improve prediction of CVD risk beyond single measurements.
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The article deals with integrating the inertial navigation unit implemented into the system of controlling the robot. It analyses the dynamic properties of the sensors of the inertial unit, for ...example, gyroscopes and accelerometers. The implementation of the original system of controlling the mobile robot on the basis of autonomous navigation systems is a dominant part of the article. The integration of navigational information represents the actual issue of reaching higher accuracy of required navigational parameters using more or less accurate navigation systems. The inertial navigation is the navigation based on uninterrupted evaluation of the position of a navigated object by utilizing the sensors that are sensitive to motion, that is, gyroscopes and accelerometers, which are regarded as primary inertial sensors or other sensors located on the navigated object.
light-to-moderate drinking is apparently associated with a decreased risk of physical limitations in middle-aged and older adults.
to investigate the association between alcohol consumption and ...physical limitations in Eastern European populations.
a cross-sectional survey of 28,783 randomly selected residents (45-69 years) in Novosibirsk (Russia), Krakow (Poland) and seven towns of Czech Republic.
physical limitations were defined as <75% of optimal physical functioning using the Physical Functioning (PF-10) Subscale of the Short-Form-36 questionnaire. Alcohol consumption was assessed by a graduated frequency questionnaire, and problem drinking was defined as ≥2 positive responses on the CAGE questionnaire. In the Russian sample, past drinking was also assessed.
the odds of physical limitations were highest among non-drinkers, decreased with increasing drinking frequency, annual consumption and average drinking quantity and were not associated with problem drinking. The adjusted odds ratio (OR) of physical limitations in non-drinkers versus regular moderate drinkers was 1.61 (95% confidence interval: 1.48-1.75). In the Russian sample with past drinking available, the adjusted OR in those who stopped drinking for health reasons versus continuing drinkers was 3.19 (2.58-3.95); ORs in lifetime abstainers, former drinkers for non-health reasons and reduced drinkers for health reasons were 1.27 (1.02-1.57), 1.48 (1.18-1.85) and 2.40 (2.05-2.81), respectively.
this study found an inverse association between alcohol consumption and physical limitations. The high odds of physical limitations in non-drinkers can be largely explained by poor health of former drinkers. The apparently protective effect of heavier drinking was partly due to less healthy former heavy drinkers who moved to lower drinking categories.
Archaeological investigations of Paleometal Epoch in the Primorye (south of the Far East of Russia) are generating insight for the introduction of metals into the Pacific coastal areas of prehistoric ...Eurasia. The chronological framework covers the turn of the 2nd −1st mil. BC to the beginning of 1st mil. AD. The temporal limits of bronze-bearing and iron-bearing cultural units of Primorye region overlap. The limited degree of local metal production and re-working during the Paleometal epoch still suggests progressive changes in the material culture of prehistoric populations of the southern Russian Far East.
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