Protection from ultraviolet damage and photocarcinogenesis by vitamin d compounds

© Springer Nature Switzerland AG 2020. Exposure of skin cells to UV radiation results in DNA damage, which if inadequately repaired, may cause mutations. UV-induced DNA damage and reactive oxygen and nitrogen species also cause local and systemic suppression of the adaptive immune system. Together, these changes underpin the development of skin tumours. The hormone derived from vitamin D, calcitriol (1,25-dihydroxyvitamin D3) and other related compounds, working via the vitamin D receptor and at least in part through endoplasmic reticulum protein 57 (ERp57), reduce cyclobutane pyrimidine dimers and oxidative DNA damage in keratinocytes and other skin cell types after UV. Calcitriol and related compounds enhance DNA repair in keratinocytes, in part through decreased reactive oxygen species, increased p53 expression and/or activation, increased repair proteins and increased energy availability in the cell when calcitriol is present after UV exposure. There is mitochondrial damage in keratinocytes after UV. In the presence of calcitriol, but not vehicle, glycolysis is increased after UV, along with increased energy-conserving autophagy and changes consistent with enhanced mitophagy. Reduced DNA damage and reduced ROS/RNS should help reduce UV-induced immune suppression. Reduced UV immune suppression is observed after topical treatment with calcitriol and related compounds in hairless mice. These protective effects of calcitriol and related compounds presumably contribute to the observed reduction in skin tumour formation in mice after chronic exposure to UV followed by topical post-irradiation treatment with calcitriol and some, though not all, related compounds

An estimate of the prevalence of hypertension in Nigeria: a systematic review and meta-analysis

Background: Hypertension is a leading cause of morbidity and mortality in Africa, and Nigeria, the most populous country in the continent, hugely contributes to this burden.Objective: To provide an improved estimate of the prevalence and number of cases of hypertension in Nigeria based on the cut-off ‘at least 140/90 mmHg’, towards ensuring better awareness, control and policy response in the country.Methods: We conducted a systematic search of Medline, EMBASE and Global Health from January 1980 to December 2013 for population-based studies providing estimates on the prevalence of hypertension in Nigeria. From the extracted crude prevalence rates, we conducted a random-effects meta-analysis, and further estimated the overall awareness rate of hypertension in Nigeria, expressed as percentage of all hypertension cases. We applied a meta-regression epidemiological modelling, using United Nations population demographics for the years 2010 and 2030, to determine the prevalence and number of cases of hypertension in Nigeria for the 2 years.Results: Our search returned 2260 publications, 27 of which met our selection criteria. From the random-effects meta-analysis, we estimated an overall hypertension prevalence of 28.9% (25.1, 32.8), with a prevalence of 29.5% (24.8, 34.3) among men and 25.0% (20.2, 29.7) among women. We estimated a prevalence of 30.6% (24.5, 36.6) and 26.4% (19.4, 33.4) among urban and rural dwellers, respectively. The pooled awareness rate of hypertension was 17.4% (11.4, 23.3). The overall mean SBP was 128.6 (125.5, 130.8) mmHg, and the DBP was 80.6 (78.5, 82.7) mmHg. From our modelling, we estimated about 20.8 million cases of hypertension in Nigeria among people aged at least 20 years in 2010, with a prevalence of 28.0% (24.6, 31.9) in both sexes – 30.7% (24.9, 33.7) among men and 25.2% (22.7, 31.9) among women. By 2030, we projected an increase to 39.1 million cases of hypertension among people aged at least 20 years with a prevalence of 30.8% (24.5, 33.7) in both sexes – 32.6% (27.3, 38.2) among men and 29.0% (21.9–32.2) among women.Conclusions: Our findings suggest the prevalence of hypertension is high in Nigeria, and the overall awareness of raised blood pressure among hypertension cases is low in the country. We hope this study will inform appropriate public health response towards reducing this burden.</br

Is incremental hemodialysis ready to return on the scene? From empiricism to kinetic modelling

Most people who make the transition to maintenance dialysis therapy are treated with a fixed dose thrice-weekly hemodialysis regimen without considering their residual kidney function (RKF). The RKF provides effective and naturally continuous clearance of both small and middle molecules, plays a major role in metabolic homeostasis, nutritional status, and cardiovascular health, and aids in fluid management. The RKF is associated with better patient survival and greater health-related quality of life, although these effects may be confounded by patient comorbidities. Preservation of the RKF requires a careful approach, including regular monitoring, avoidance of nephrotoxins, gentle control of blood pressure to avoid intradialytic hypotension, and an individualized dialysis prescription including the consideration of incremental hemodialysis. There is currently no standardized method for applying incremental hemodialysis in practice. Infrequent (once- to twice-weekly) hemodialysis regimens are often used arbitrarily, without knowing which patients would benefit the most from them or how to escalate the dialysis dose as RKF declines over time. The recently heightened interest in incremental hemodialysis has been hindered by the current limitations of the urea kinetic models (UKM) which tend to overestimate the dialysis dose required in the presence of substantial RKF. This is due to an erroneous extrapolation of the equivalence between renal urea clearance (Kru) and dialyser urea clearance (Kd), correctly assumed by the UKM, to the clinical domain. In this context, each ml/min of Kd clears the urea from the blood just as 1&nbsp;ml/min of Kru does. By no means should such kinetic equivalence imply that 1&nbsp;ml/min of Kd is clinically equivalent to 1&nbsp;ml/min of urea clearance provided by the native kidneys. A recent paper by Casino and Basile suggested a variable target model (VTM) as opposed to the fixed model, because the VTM gives more clinical weight to the RKF and allows less frequent hemodialysis treatments at lower RKF. The potentially important clinical and financial implications of incremental hemodialysis render it highly promising and warrant randomized controlled trials