Long-term controlled antihypertensive therapy in Chernobyl liquidators, its effectiveness and benefits

Aim. To compare effectiveness of controlled antihypertenive therapy (AHT) and standard outpatient care among Chernobyl male liquidators (ML) with mild to moderate arterial hypertension (AH). Material and methods. This 12-month, open, comparative randomized study included 81 ML aged 37-70, with mild to moderate AH. The main group consisted of 42 patients, the control group – of 39; mean age 52.2±1.3 and 51.5±1.1 years, mean AH duration 10±1 and 9.6±1 years, respectively. In main group, patients received an ACE inhibitor spirapril, combined with hypothiazide (12.5-25 mg/d), and atenolol (12.5-100 mg/d), if necessary. In control group, AHT and its correction were performed by outpatient physicians. Medical history collection, physical examination, anthropometry, blood pressure (BP) measurement (three times), and electrocardiograpy were performed. Results. During one-year controlled AHT, comparing to standard outpatient care, more effective decrease in systolic and diastolic BP was achieved. Antihypertensive effect was registered in 78.6% and 38.0% of the main and control group patients, respectively. At the end of the study, most participants from the main group ((78.6%) received combined therapy (2 or more drugs); in control group, this number was only 17.2%. Conclusion. The results of the study demonstrated high effectiveness and benefits of long-term controlled AHT, comparing to standard outpatient care

Allylic Amines as Key Building Blocks in the Synthesis of ( E

Nucleophilic imine additions with vinyl organometallics have developed into efficient, high-yielding, and robust methodologies to generate structurally diverse allylic amines. We have used the hydrozirconation/transmetalation/imine addition protocol in the synthesis of allylic amine intermediates for peptide bond isosteres, phosphatase inhibitors, and mitochondria-targeted peptide mimetics. The gramicidin S-derived XJB-5-131 and JP4-039 and their analogues have been prepared on up to 160-g scale for preclinical studies. These (E)-alkene peptide isosteres adopt type II β-turn secondary structures and display impressive biological properties including selective reactions with reactive oxygen species (ROS) and prevention of apoptosis. © 2012 American Chemical Society

Enhanced infection prophylaxis reduces mortality in severely immunosuppressed HIV-infected adults and older children initiating antiretroviral therapy in Kenya, Malawi, Uganda and Zimbabwe: the REALITY trial

Meeting abstract FRAB0101LB from 21st International AIDS Conference 18–22 July 2016, Durban, South Africa. Introduction: Mortality from infections is high in the first 6 months of antiretroviral therapy (ART) among HIV‐infected adults and children with advanced disease in sub‐Saharan Africa. Whether an enhanced package of infection prophylaxis at ART initiation would reduce mortality is unknown. Methods: The REALITY 2×2×2 factorial open‐label trial (ISRCTN43622374) randomized ART‐naïve HIV‐infected adults and children >5 years with CD4 <100 cells/mm3. This randomization compared initiating ART with enhanced prophylaxis (continuous cotrimoxazole plus 12 weeks isoniazid/pyridoxine (anti‐tuberculosis) and fluconazole (anti‐cryptococcal/candida), 5 days azithromycin (anti‐bacterial/protozoal) and single‐dose albendazole (anti‐helminth)), versus standard‐of‐care cotrimoxazole. Isoniazid/pyridoxine/cotrimoxazole was formulated as a scored fixed‐dose combination. Two other randomizations investigated 12‐week adjunctive raltegravir or supplementary food. The primary endpoint was 24‐week mortality. Results: 1805 eligible adults (n = 1733; 96.0%) and children/adolescents (n = 72; 4.0%) (median 36 years; 53.2% male) were randomized to enhanced (n = 906) or standard prophylaxis (n = 899) and followed for 48 weeks (3.8% loss‐to‐follow‐up). Median baseline CD4 was 36 cells/mm3 (IQR: 16–62) but 47.3% were WHO Stage 1/2. 80 (8.9%) enhanced versus 108(12.2%) standard prophylaxis died before 24 weeks (adjusted hazard ratio (aHR) = 0.73 (95% CI: 0.54–0.97) p = 0.03; Figure 1) and 98(11.0%) versus 127(14.4%) respectively died before 48 weeks (aHR = 0.75 (0.58–0.98) p = 0.04), with no evidence of interaction with the two other randomizations (p > 0.8). Enhanced prophylaxis significantly reduced incidence of tuberculosis (p = 0.02), cryptococcal disease (p = 0.01), oral/oesophageal candidiasis (p = 0.02), deaths of unknown cause (p = 0.02) and (marginally) hospitalisations (p = 0.06) but not presumed severe bacterial infections (p = 0.38). Serious and grade 4 adverse events were marginally less common with enhanced prophylaxis (p = 0.06). CD4 increases and VL suppression were similar between groups (p > 0.2). Conclusions: Enhanced infection prophylaxis at ART initiation reduces early mortality by 25% among HIV‐infected adults and children with advanced disease. The pill burden did not adversely affect VL suppression. Policy makers should consider adopting and implementing this low‐cost broad infection prevention package which could save 3.3 lives for every 100 individuals treated

The stiffness of living tissues and its implications for tissue engineering

The past 20 years have witnessed ever- growing evidence that the mechanical properties of biological tissues, from nanoscale to macroscale dimensions, are fundamental for cellular behaviour and consequent tissue functionality. This knowledge, combined with previously known biochemical cues, has greatly advanced the field of biomaterial development, tissue engineering and regenerative medicine. It is now established that approaches to engineer biological tissues must integrate and approximate the mechanics, both static and dynamic, of native tissues. Nevertheless, the literature on the mechanical properties of biological tissues differs greatly in methodology, and the available data are widely dispersed. This Review gathers together the most important data on the stiffness of living tissues and discusses the intricacies of tissue stiffness from a materials perspective, highlighting the main challenges associated with engineering lifelike tissues and proposing a unified view of this as yet unreported topic. Emerging advances that might pave the way for the next decadeâ s take on bioengineered tissue stiffness are also presented, and differences and similarities between tissues in health and disease are discussed, along with various techniques for characterizing tissue stiffness at various dimensions from individual cells to organs.The authors would like to acknowledge financial support from the European Research Council, grant agreement ERC-2012-ADG 20120216-321266 (project ComplexiTE). C.F.G. acknowledges scholarship grant no. PD/BD/135253/2017 from Fundação para a Ciência e Tecnologia (FCT). The authors also thank the peer-reviewers for the constructive comments and suggestions that helped to shape this manuscript