Vitamin D deficiency prevails in epidemic proportions all over the Indian subcontinent, with a prevalence of 70%-100% in the general population. In India, widely consumed food items such as dairy ...products are rarely fortified with vitamin D. Indian socioreligious and cultural practices do not facilitate adequate sun exposure, thereby negating potential benefits of plentiful sunshine. Consequently, subclinical vitamin D deficiency is highly prevalent in both urban and rural settings, and across all socioeconomic and geographic strata. Vitamin D deficiency is likely to play an important role in the very high prevalence of rickets, osteoporosis, cardiovascular diseases, diabetes, cancer and infections such as tuberculosis in India. Fortification of staple foods with vitamin D is the most viable population based strategy to achieve vitamin D sufficiency. Unfortunately, even in advanced countries like USA and Canada, food fortification strategies with vitamin D have been only partially effective and have largely failed to attain vitamin D sufficiency. This article reviews the status of vitamin D nutrition in the Indian subcontinent and also the underlying causes for this epidemic. Implementation of population based educational and interventional strategies to combat this scourge require recognition of vitamin D deficiency as a public health problem by the governing bodies so that healthcare funds can be allocated appropriately.
Two or more antihypertensive agents are increasingly used to control blood pressure (BP) in hypertensive patients. However, it is unclear whether fixed-dose combinations (FDCs) of 2 antihypertensive ...agents in a single tablet provide greater benefits than the corresponding free-drug components given separately. A meta-analysis was performed to assess compliance, persistence, BP control, and safety associated with FDCs in comparison with their free-drug components. Fifteen included studies (n=32331) reported on >or=1 of the evaluated outcomes. In 3 cohort studies and 2 trials reporting on drug compliance (n=17 999), the use of FDCs was associated with significantly better compliance (odds ratio: 1.21 95% CI: 1.03 to 1.43; P=0.02) compared with its corresponding free-drug combinations. In 3 cohort studies (n=12 653), there was a nonsignificant improvement in persistence with therapy (odds ratio: 1.54 95% CI: 0.95 to 2.49; P=0.08), and in 5 trials (n=1775) the odds ratio for adverse effects for FDC use compared with free-drug combination use was 0.80 (95% CI: 0.58 to 1.11; P=0.19). In 9 trials (n=1671) with BP data, use of an FDC was associated with nonsignificant changes in systolic and diastolic BPs of 4.1 mm Hg (95% CI: -9.8 to 1.5; P=0.15) and 3.1 mm Hg (95% CI: -7.1 to 0.9; P=0.13), respectively. In these BP-lowering comparisons, there was heterogeneity associated with differences in study design but no publication bias. In conclusion, compared with free-drug combinations, FDCs of antihypertensive agents are associated with a significant improvement in compliance and with nonsignificant beneficial trends in BP and adverse effects.
Ferric citrate hydrate was recently approved in Japan as an oral phosphate binder to be taken with food for the control of hyperphosphatemia in patients with chronic kidney disease (CKD). The daily ...therapeutic dose is about 3 to 6 g, which comprises about 2 to 4 g of citrate. Oral citrate solubilizes aluminum that is present in food and drinking water, and opens the tight junctions in the intestinal epithelium, thereby increasing aluminum absorption and urinary excretion. In healthy animals drinking tap water, oral citrate administration increased aluminum absorption and, over a 4-week period, increased aluminum deposition in brain and bone by about 2- and 20-fold, respectively. Renal excretion of aluminum is impaired in patients with chronic kidney disease, thereby increasing the risk of toxicity. Based on human and animal studies it can be surmised that patients with CKD who are treated with ferric citrate hydrate to control hyperphosphatemia are likely to experience enhanced absorption of aluminum from food and drinking water, thereby increasing the risk of aluminum overload and toxicity.
Summary Background In blinded randomised controlled trials, statin therapy has been associated with few adverse events (AEs). By contrast, in observational studies, larger increases in many different ...AEs have been reported than in blinded trials. Methods In the Lipid-Lowering Arm of the Anglo-Scandinavian Cardiac Outcomes Trial, patients aged 40–79 years with hypertension, at least three other cardiovascular risk factors, and fasting total cholesterol concentrations of 6·5 mmol/L or lower, and who were not taking a statin or fibrate, had no history of myocardial infarction, and were not being treated for angina were randomly assigned to atorvastatin 10 mg daily or matching placebo in a randomised double-blind placebo-controlled phase. In a subsequent non-randomised non-blind extension phase (initiated because of early termination of the trial because efficacy of atorvastatin was shown), all patients were offered atorvastatin 10 mg daily open label. We classified AEs using the Medical Dictionary for Regulatory Activities. We blindly adjudicated all reports of four prespecified AEs of interest—muscle-related, erectile dysfunction, sleep disturbance, and cognitive impairment—and analysed all remaining AEs grouped by system organ class. Rates of AEs are given as percentages per annum. Results The blinded randomised phase was done between February, 1998, and December, 2002; we included 101 80 patients in this analysis (5101 50% in the atorvastatin group and 5079 50% in the placebo group), with a median follow-up of 3·3 years (IQR 2·7–3·7). The non-blinded non-randomised phase was done between December, 2002, and June, 2005; we included 9899 patients in this analysis (6409 65% atorvastatin users and 3490 35% non-users), with a median follow-up of 2·3 years (2·2–2·4). During the blinded phase, muscle-related AEs (298 2·03% per annum vs 283 2·00% per annum; hazard ratio 1·03 95% CI 0·88–1·21; p=0·72) and erectile dysfunction (272 1·86% per annum vs 302 2·14% per annum; 0·88 0·75–1·04; p=0·13) were reported at a similar rate by participants randomly assigned to atorvastatin or placebo. The rate of reports of sleep disturbance was significantly lower among participants assigned atorvastatin than assigned placebo (149 1·00% per annum vs 210 1·46% per annum; 0·69 0·56–0·85; p=0·0005). Too few cases of cognitive impairment were reported for a statistically reliable analysis (31 0·20% per annum vs 32 0·22% per annum; 0·94 0·57–1·54; p=0·81). We observed no significant differences in the rates of all other reported AEs, with the exception of an excess of renal and urinary AEs among patients assigned atorvastatin (481 1·87% per annum vs 392 1·51% per annum; 1·23 1·08–1·41; p=0·002). By contrast, during the non-blinded non-randomised phase, muscle-related AEs were reported at a significantly higher rate by participants taking statins than by those who were not (161 1·26% per annum vs 124 1·00% per annum; 1·41 1·10–1·79; p=0·006). We noted no significant differences between statin users and non-users in the rates of other AEs, with the exception of musculoskeletal and connective tissue disorders (992 8·69% per annum vs 831 7·45% per annum; 1·17 1·06–1·29; p=0·001) and blood and lymphatic system disorders (114 0·88% per annum vs 80 0·64% per annum; 1·40 1·04–1·88; p=0·03), which were reported more commonly by statin users than by non-users. Interpretation These analyses illustrate the so-called nocebo effect, with an excess rate of muscle-related AE reports only when patients and their doctors were aware that statin therapy was being used and not when its use was blinded. these results will help assure both physicians and patients that most AEs associated with statins are not causally related to use of the drug and should help counter the adverse effect on public health of exaggerated claims about statin-related side-effects. Funding Pfizer, Servier Research Group, and Leo Laboratories.
Summary
CRISPR/Cas9 has been widely used for genome editing in many organisms, including important crops like wheat. Despite the tractability in designing CRISPR/Cas9, efficacy in the application of ...this powerful genome editing tool also depends on DNA delivery methods. In wheat, the biolistics based transformation is the most used method for delivery of the CRISPR/Cas9 complex. Due to the high frequency of gene silencing associated with co‐transferred plasmid backbone and low edit rate in wheat, a large T0 transgenic plant population are required for recovery of desired mutations, which poses a bottleneck for many genome editing projects. Here, we report an Agrobacterium‐delivered CRISPR/Cas9 system in wheat, which includes a wheat codon optimized Cas9 driven by a maize ubiquitin gene promoter and a guide RNA cassette driven by wheat U6 promoters in a single binary vector. Using this CRISPR/Cas9 system, we have developed 68 edit mutants for four grain‐regulatory genes, TaCKX2‐1, TaGLW7, TaGW2, and TaGW8, in T0, T1, and T2 generation plants at an average edit rate of 10% without detecting off‐target mutations in the most Cas9‐active plants. Homozygous mutations can be recovered from a large population in a single generation. Different from most plant species, deletions over 10 bp are the dominant mutation types in wheat. Plants homozygous of 1160‐bp deletion in TaCKX2‐D1 significantly increased grain number per spikelet. In conclusion, our Agrobacterium‐delivered CRISPR/Cas9 system provides an alternative option for wheat genome editing, which requires a small number of transformation events because CRISPR/Cas9 remains active for novel mutations through generations.
•Nature-based Solutions (NbS) in Himalayas has sustainable management and restoration of resources.•Most of the NbS of Himalaya adheres the IUCN standard criteria.•Improved NbS interventions in ...Himalaya requires precise planning and engaging multiple stakeholders.
Himalayan countries face many ecological challenges, including biodiversity loss and the many threats of climate change. In response, these countries are implementing Nature-based Solution to minimize these challenges and promote sustainable development. In this article we analyze the NbS programs implemented across the Himalayan region and assess the limitations of these NbS using the IUCN standard criteria of adherence to NbS for selected articles. We perform a systematic review of articles using the PRISMA methodology, through the Scopus, Google Scholar, and ResearchGate databases and followed by screening through the Rayyan web interface. Articles were screened out based on the location and lack of biodiversity and human well-being outcomes of NbS intervention. Nature-based Solutions in the Himalayas primarily use a sustainable management approach (35.29%), followed by restoration (23.53%), conservation (11.76%), holistic management (11.76%), eco-DRR (11.76%) and green infrastructure (5.88%) to address societal and climatic challenges. Institutional execution of NbS was 29.41% more common compared to the implementation of NbS by community or farmer groups. Pineapple based agroforestry (83.04%), forest restoration (78.57%), spring water storage (83.04%), spring restoration (86.61%), groundwater recharge (82.14%), bio-fertilizer and pesticides (77.68%), watershed restoration (78.57%), community-based watershed management (77.68%), community-based DRR (81.25%), community-based forest management (81.25%), sustainable harvest of medicinal plants (77.68%) and wetland restoration (82.14%), adhere to the IUCN criteria. In addition, some interventions adequately meet IUCN criteria, such as ice stupas (72.32%), forest restoration through plantation (73.21%), eco-safe roads (65.18), blue-green infrastructure (68.75%), and traditional ecological knowledge (72.32%). Our evaluation noted that NbS interventions can be improved by precise planning and design before implementation, engaging multiple stakeholders, comparing alternative solutions, and periodic monitoring of the impacts on the environment and society. This study shows that NbS in the Himalayas are contributing to biodiversity conservation and climate risk management. Tackling the limitation of this present review, mainly the exclusion of research not addressing biodiversity and human well-being, will yield more precise outcomes for climate actions and sustainable development.
Context-aware computing processes the mobile user’s query/transaction submitted from anywhere at any time. Basically, location based services (LBSs) are continuous, local, and spatially confined ...applications of computing in the context-aware mobile environment, where queries/transactions are initiated by the mobile users. The smartphones as a resultant of today’s advanced mobile technologies allow these mobile users to access numerous LBSs and provide information interactively to them depending on their locations. The mobile user’s positions and associated confidential information enable more sensitive information to be created; but, it inevitably leads to a threat that these sensitive information may be used for different purposes by the third parties. Also, there is lack of state of the art location privacy preservation procedures to be able to create a balance between user location/ activity privacy preservation and quality of services in LBSs technologies. Therefore, there is a need to do more research efforts to ensure the privacy of these mobile users by developing the secured location-based technologies. Thus, our this study specifically discusses the aforementioned issues, a literature for the taxonomy of the privacy preservation approaches available to the research community with comparative analysis over the common attributes, highlighting limitations/strength, recent advancement and provides possible research directions for the further investigation of the unanswered questions.
Location based service (LBS) is related basically to a local, continuous, and spatially confined computation in the context-aware mobile environment. Hitherto, serving a query within the specified ...timeline becomes possible with the help of caching the data at the client and/or server sites. It enhances the performance of LBSs by the reduction in the network traffic, access latency, server load etc.; however, at the same time, it faces difficulty in maintaining the database consistency as it works in the environment, where frequent disconnections occur. As a result, many fascinating LBS caching issues created in the mobile environment have forced the mobile database specialists and researchers to do extensive research efforts to improve the response time and efficient storage resources by developing the effective location-based technologies. Thus, this study specifically discusses the aforementioned issues with comparative analysis over the common attributes such as highlighting limitations/strength, recent advancement etc. and also possible research directions for the further investigation of the unanswered questions.
Location-based services are an important category of context-aware computing, which play an important role in providing the continuous, local and spatially confined information systems very ...efficiently and accurately to their clients. The key component in location-based services is the current location of a mobile user. Thus, to protect mobile users’ location and their other information to an untrusted party with consideration of minimal waiting time, Optimal Mobility Aware Cache data Pre-fetching and Replacement policy (OMCPR) is being proposed here. In this continuous location-based services model, the system introduces a mediator namely Anonymizer by employing the prefetching facility for spatial K-anonymity that resides in between the user and Query Analyser to form a cloaking region using mobile user inputs (data freshness, the contribution rate of cell’s cache and location). It provides high-quality lossless location-based services by the utilization of the frequent pattern mining of mobile users’ trajectories to forecast their next position as per mobility and multiple constraints. A client–server based queueing model is used to simulate the proposed OMCPR platform. It provides higher privacy protection than the current state of the art strategies available, also minimizes the overhead of the LBS server and waiting time of mobile users by the addition of the prefetching facilities to Anonymizer.
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