Orthostatic hypotension in elderly patients.

Orthostatic hypotension (OH) is defined as a decrease in blood pressure (BP) after changing from supine to standing position and is frequently diagnosed in the elderly population. Information is limited with regard to differences between the various methods to determine OH, and about the consequences when OH is present. It is generally assumed that OH is causally related to falling, cardiovascular complications and mortality, despite the sparse evidence. Antihypertensive treatment is one of the causes of OH. Information regarding the relation between BP and mortality risk is lacking in a nursing home population, a population in which the need for strict antihypertensive treatment is questionable already. Finally, the role of health related quality of life (HRQOL) in this specific population is important and perhaps even more important than clinical parameters. Based on the results of this thesis it can be concluded that the approach to OH in elderly patients needs to be reconsidered. OH measurements according to the current International consensus definition are not related to important clinical endpoints and therefore are not useful in daily practice. Furthermore, the mortality prediction capabilities of BP and HRQOL are very limited in a nursing home population. Since OH measurements in elderly patients do not have additional value in clinical decision-making or predicting outcomes in the majority of elderly patients it can be recommended that OH measurement should not be part of usual care in clinical decision-making. It seems to be more useful to inquire after orthostatic complaints rather than measuring OH

The impact of local hydrodynamics on high-rate activated sludge flocculation in laboratory and full-scale reactors

High rate activated sludge (HRAS) processes have a high potential for carbon and energy recovery from sewage, yet they suffer frequently from poor settleability due to flocculation issues. The process of flocculation is generally optimized using jar tests. However, detailed jar hydrodynamics are often unknown, and average quantities are used, which can significantly differ from the local conditions. The presented work combined experimental and numerical data to investigate the impact of local hydrodynamics on HRAS flocculation for two different jar test configurations (i.e., radial vs. axial impellers at different impeller velocities) and compared the hydrodynamics in these jar tests to those in a representative section of a full scale reactor using computational fluid dynamics (CFD). The analysis showed that the flocculation performance was highly influenced by the impeller type and its speed. The axial impeller appeared to be more appropriate for floc formation over a range of impeller speeds as it produced a more homogeneous distribution of local velocity gradients compared to the radial impeller. In contrast, the radial impeller generated larger volumes (%) of high velocity gradients in which floc breakage may occur. Comparison to local velocity gradients in a full scale system showed that also here, high velocity gradients occurred in the region around the impeller, which might significantly hamper the HRAS flocculation process. As such, this study showed that a model based approach was necessary to translate lab scale results to full scale. These new insights can help improve future experimental setups and reactor design for improved HRAS flocculation

Исторический роман о Максиме Греке и его место в творчестве Мицоса Александропулоса

Целью статьи является анализ творчества Мицоса Александропулоса (Αλεξανδρόπουλος Μήτσος, 1924- 2008) в контексте развития современного греческого исторического романа (на примере романа «Сцены из жизни Максима Грека» («Σκηνές από το βίο του Μάξιμου του Γραικού», 1967-1969))

Особенности трансформации символа креста на территории средневековой Таврики

BACKGROUND: Cow's milk-derived whey hydrolysates are nutritional substitutes for allergic infants. Safety or residual allergenicity assessment of these whey hydrolysates is crucial. Currently, rat basophilic leukemia RBL-2H3 cells expressing the human IgE receptor α-chain (huFcεRIα-RBL-2H3), sensitized with serum IgE from cow's milk allergic children, are being employed to assess in vitro residual allergenicity of these whey hydrolysates. However, limited availability and inter-lot variation of these allergic sera impede standardization of whey hydrolysate safety testing in degranulation assays. OBJECTIVE: An oligoclonal pool of chimeric human (chu)IgE antibodies against bovine β-lactoglobulin (a major allergen in whey) was generated to increase sensitivity, specificity, and reproducibility of existing degranulation assays. METHODS: Mice were immunized with bovine β-lactoglobulin, and subsequently the variable domains of dissimilar anti-β-lactoglobulin mouse IgG antibodies were cloned and sequenced. Six chimeric antibodies were generated comprising mouse variable domains and human constant IgE/κ domains. RESULTS: After sensitization with this pool of anti-β-lactoglobulin chuIgEs, huFcεRIα-expressing RBL-2H3 cells demonstrated degranulation upon cross-linking with whey, native 18 kDa β-lactoglobulin, and 5-10 kDa whey hydrolysates, whereas a 3 kDa whey hydrolysate and cow's milk powder (mainly casein) showed no degranulation. In parallel, allergic serum IgEs were less sensitive. In addition, our pool anti-β-lactoglobulin chuIgEs recognized multiple allergenic immunodominant regions on β-lactoglobulin, which were also recognized by serum IgEs from cow's milk allergic children. CONCLUSION: Usage of our 'unlimited' source and well-defined pool of β-lactoglobulin-specific recombinant chuIgEs to sensitize huFcεRIα on RBL-2H3 cells showed to be a relevant and sensitive alternative for serum IgEs from cow's milk allergic patients to assess safety of whey-based non-allergic hydrolyzed formula

Within-Sulfonylurea-Class Evaluation of Time to Intensification with Insulin (ZODIAC-43)

Previous studies have shown that many within-class differences exist between sulfonylureas (SUs), however, whether differences exist regarding the time it takes between initiating an SU and the need to intensify treatment with insulin is unclear. The aim of this study was investigate the relationships between the three frequently used sulphonylureas, prescribed as dual therapy next to metformin, and the time needed to treatment intensification with either insulin or oral triple therapy in patients with type 2 diabetes mellitus.Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC) is a prospective observational cohort study set in primary care in the Netherlands. Annually collected data on diabetes medication and clinical variables within ZODIAC are used to evaluate the primary outcome, time to insulin and secondary outcome, time to either insulin or triple oral therapy. For statistical analysis a time-dependent cox proportional hazard model was used.3507 patients were included in the analysis, with a mean age of 61 (SD 11.4) and a median HbA1c of 6.8% [IQR 6.4-7.4] (50.8 mmol/mol [IQR 46.4-57.4]).The hazard ratio (HR) for the primary endpoint was 1.10 (95% CI 0.78-1.54) for metformin/glimepiride and 0.93 (95% CI 0.67-1.30) for metformin/tolbutamide with metformin/gliclazide as reference group. The HR for the secondary outcome was 1.04 (95% CI 0.78-1.40) and 0.85 (95% CI 0.64-1.13), respectively.In this large Dutch primary care cohort, new users of neither gliclazide, glimepiride nor tolbutamide as dual therapy with metformin, resulted in differences in the time needed for further treatment intensification

Patient Activation in Type 2 Diabetes:Does It Differ between Men and Women?

Background. Aim was to investigate whether the degree of patient activation of patients with type 2 diabetes (T2D) is different between men and women. Furthermore, we investigated which factors are associated with patient activation in men and women. Methods. This cross-sectional study included 1615 patients with T2D from general practices. Patient activation was measured with the Patient Activation Measure (PAM) questionnaire. Multivariate linear regression analyses were used to investigate the association between gender and patient activation. Stratified analyses according to gender were performed to investigate which factors are associated with patient activation. Results. No association between gender and PAM score was found after adjustment for all selected confounders (p=0.094). In men, lower age (p=0.001), a higher WHO-5 score (p<0.001), and a lower BMI (p=0.013) were associated with a higher PAM score. In women, a higher WHO-5 score (p<0.017) and the absence of macrovascular complications (p<0.031) were associated with a higher PAM score. Conclusion. There is no difference in the degree of patient activation of men and women with T2D. Age, well-being, and BMI were found to be associated with patient activation in men, whereas well-being and macrovascular complications were found to be associated with patient activation in women

SARS-CoV-2-specific immune responses converge in kidney disease patients and controls with hybrid immunity

Healthy individuals with hybrid immunity, due to a SARS-CoV-2 infection prior to first vaccination, have stronger immune responses compared to those who were exclusively vaccinated. However, little is known about the characteristics of antibody, B- and T-cell responses in kidney disease patients with hybrid immunity. Here, we explored differences between kidney disease patients and controls with hybrid immunity after asymptomatic or mild coronavirus disease-2019 (COVID-19). We studied the kinetics, magnitude, breadth and phenotype of SARS-CoV-2-specific immune responses against primary mRNA-1273 vaccination in patients with chronic kidney disease or on dialysis, kidney transplant recipients, and controls with hybrid immunity. Although vaccination alone is less immunogenic in kidney disease patients, mRNA-1273 induced a robust immune response in patients with prior SARS-CoV-2 infection. In contrast, kidney disease patients with hybrid immunity develop SARS-CoV-2 antibody, B- and T-cell responses that are equally strong or stronger than controls. Phenotypic analysis showed that Spike (S)-specific B-cells varied between groups in lymph node-homing and memory phenotypes, yet S-specific T-cell responses were phenotypically consistent across groups. The heterogeneity amongst immune responses in hybrid immune kidney patients warrants further studies in larger cohorts to unravel markers of long-term protection that can be used for the design of targeted vaccine regimens.</p