Automated office blood pressure measurements in primary care are misleading in more than one third of treated hypertensives: The VALENTINE-Greece Home Blood Pressure Monitoring study

Abstract Background This study assessed the diagnostic reliability of automated office blood pressure (OBP) measurements in treated hypertensive patients in primary care by evaluating the prevalence of white coat hypertension (WCH) and masked uncontrolled hypertension (MUCH) phenomena. Methods Primary care physicians, nationwide in Greece, assessed consecutive hypertensive patients on stable treatment using OBP (1 visit, triplicate measurements) and home blood pressure (HBP) measurements (7 days, duplicate morning and evening measurements). All measurements were performed using validated automated devices with bluetooth capacity (Omron M7 Intelli-IT). Uncontrolled OBP was defined as ≥140/90 mmHg, and uncontrolled HBP was defined as ≥135/85 mmHg. Results A total of 790 patients recruited by 135 doctors were analyzed (age: 64.5 ± 14.4 years, diabetics: 21.4%, smokers: 20.6%, and average number of antihypertensive drugs: 1.6 ± 0.8). OBP (137.5 ± 9.4/84.3 ± 7.7 mmHg, systolic/diastolic) was higher than HBP (130.6 ± 11.2/79.9 ± 8 mmHg; difference 6.9 ± 11.6/4.4 ± 7.6 mmHg, p Conclusions In primary care, automated OBP measurements are misleading in approximately 40% of treated hypertensive patients. HBP monitoring is mandatory to avoid overtreatment of subjects with WCH phenomenon and prevent undertreatment and subsequent excess cardiovascular disease in MUCH

Modeling the oral glucose tolerance test in normal and impaired glucose tolerant states: a population approach

<p><b>Objective:</b> The conventional approach to analyzing data from oral glucose tolerance testing (OGTT) requires model identification in each individual separately (standard two stage, STS), ignoring knowledge about the population as a whole. In practice, however, the OGTT is sparsely sampled and individual estimates are often not resolvable from available data. This weakness is often encountered in large scale trials or epidemiological studies, leading to either multiple imputations or simply much less data available for analysis.</p> <p><b>Methods:</b> We have applied a population approach, nonlinear mixed effects modeling, to plasma glucose, insulin and C-peptide data obtained from a 120 minute OGTT undertaken by 106 subjects with varying glucose tolerance. This method provides estimates of population means, variances and covariances of model parameters and empirical Bayes estimates of individual parameter values, as well as measures of intra-individual (within-subject) and inter-individual (between-subject) variability. The recently developed oral glucose minimal model was used to evaluate insulin sensitivity, and a combined model approach was used to assess β-cell secretion.</p> <p><b>Results:</b> Applying these models allowed for the reconstruction of insulin secretion and glucose absorption profiles and gave population indexes of insulin sensitivity (<i>S_I</i> = 6.51 ± 1.20 × 10⁻⁴ min⁻¹·μU⁻¹·ml), fractional hepatic extraction of insulin (<i>F</i> = 0.522 ± 0.291) and fractional insulin clearance (<i>k_I</i> = 0.258 ± 0.151 min⁻¹). Whereas the traditional approach to parameter estimation failed to recover estimates in more than one third of the population, the population approach provided individual estimates in all subjects. Examination of the empirical Bayes estimates showed that individual parameter estimates were able to differentiate well between individuals at glucose tolerant states ranging from euglycemia to overt type 2 diabetes.</p> <p><b>Conclusions:</b> Our findings suggest that population analysis is a powerful tool for obtaining accurate assessments of indexes of insulin sensitivity and β-cell function from the OGTT, especially in epidemiological studies with large numbers of sparsely sampled subjects.</p

ProMyelocytic Leukemia protein (PML) controls breast cancer cell proliferation by modulating Forkhead transcription factors

he multitasking Promyelocytic leukemia (PML) protein was originally recognized as a tumor suppressive factor, but more recent evidence has implicated PML in tumor cell pro‐survival actions and poor patient prognosis in specific cancer settings. Here, we report that inducible PMLIV expression inhibits cell proliferation as well as self‐renewal, and impairs cell cycle progression of breast cancer cell lines in a reversible manner. Transcriptomic profiling identified a large number of PML‐deregulated genes associated with various cell processes. Among them, cell cycle and division related genes and their cognitive regulators are highly ranked. In this study, we focused on previously unknown PML targets, namely the Forkhead transcription factors. PML suppresses the Forkhead box subclass M1 (FOXM1) transcription factor at both the RNA and protein level, along with many of its gene targets. We show that FOXM1 interacts with PMLIV primarily via its DNA binding domain and dynamically co‐localizes in PML nuclear bodies. In parallel, PML modulates the activity of FOXO3, a factor opposing certain FOXM1 activities, to promote cell survival and stress resistance. Thus, PMLIV affects the balance of FOXO3 and FOXM1 transcriptional programs by acting on discrete gene subsets to favour both growth inhibition and survival. Interestingly, PMLIV‐specific knockdown mimicked ectopic expression vis‐à‐vis loss of proliferative ability and self‐renewal, but also led to loss of survival ability as shown by increased apoptosis. We propose that divergent or similar effects on cell physiology may be elicited by high or low PMLIV levels dictated by other concurrent genetic or epigenetic cancer cell states that may additionally account for its disparate effects in various cancer types

Priorities for Inclusive Growth: Increasing Employment, Decreasing Inequality and Fighting Corruption

This chapter looks in detail at citizens\u2019 views on the extent to which their governments are meeting their demands for inclusive economic development, decent employment and fighting corruptions. It concludes that they are generally dissatisfied with the way governments are managing the economy and providing basic services, although there are some differences between countries. In particular, they are concerned about a lack of employment opportunities and they do not think that their governments are fighting corruption. Migration is mainly motivated by economic factors, with those considering migration being educated young to middle-aged men

Mediterranean diet and cognitive health: Initial results from the Hellenic Longitudinal Investigation of Ageing and Diet

Background: The Mediterranean dietary pattern has been associated with a decreased risk of many degenerative diseases and cognitive function in particular; however, relevant information from Mediterranean regions, where the prototype Mediterranean diet is typically adhered to, have been very limited. Additionally, predefined Mediterranean diet (MeDi) scores with use of a priori cut-offs have been used very rarely, limiting comparisons between different populations and thus external validity of the associations. Finally, associations between individual components of MeDi (i.e., food groups, macronutrients) and particular aspects of cognitive performance have rarely been explored. We evaluated the association of adherence to an a priori defined Mediterranean dietary pattern and its components with dementia and specific aspects of cognitive function in a representative population cohort in Greece. Methods: Participants from the Hellenic Longitudinal Investigation of Ageing and Diet (HELIAD), an on-going population-based study, exploring potential associations between diet and cognitive performance in a representative sample from Greek regions, were included in this analysis. Diagnosis of dementia was made by a full clinical and neuropsychological evaluation, while cognitive performance was assessed according to five cognitive domains (memory, language, attention-speed, executive functioning, visuospatial perception) and a composite cognitive score. Adherence to MeDi was evaluated by an a priori score (range 0–55), derived from a detailed food frequency questionnaire. Results: Among 1,865 individuals (mean age 73±6 years, 41% male), 90 were diagnosed with dementia and 223 with mild cognitive impairment. Each unit increase in the Mediterranean dietary score (MedDietScore) was associated with a 10% decrease in the odds for dementia. Adherence to the MeDi was also associated with better performance in memory, language, visuospatial perception and the composite cognitive score; the associations were strongest for memory. Fish consumption was negatively associated with dementia and cognitive performance positively associated with non-refined cereal consumption. Conclusions: Our results suggest that adherence to the MeDi is associated with better cognitive performance and lower dementia rates in Greek elders. Thus, the MeDi in its a priori constructed prototype form may have cognitive benefits in traditional Mediterranean populations. © 2017 Anastasiou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited