Adult mesenchymal stem cells (MSCs) are a population of multipotent cells found primarily in the bone marrow. They have long been known to be capable of osteogenic, adipogenic and chondrogenic differentiation and are currently the subject of a number of trials to assess their potential use in the clinic. Recently, the plasticity of these cells has come under close scrutiny as it has been suggested that they may have a differentiation potential beyond the mesenchymal lineage. Myogenic and in particular cardiomyogenic potential has been shown in vitro . MSCs have also been shown to have the ability to form neural cells both in vitro and in vivo , although the molecular mechanisms underlying these apparent transdifferentiation events are yet to be elucidated. We describe here the cellular characteristics and differentiation potential of MSCs, which represent a promising stem cell population for future applications in regenerative medicine.

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The Declaration of Helsinki (DoH) was adopted by the World Medical Association (WMA) in 1964, as a statement of ethical principles, to provide guidance to physicians and other participants in medical research involving human subjects. Having undergone several amendments, the most recent version was approved on 18 October 2008, by the WMA General Assembly at Seoul, South Korea, replacing all previous versions. This version highlights issues such as, participant safety, the need to include participants from otherwise underrepresented groups, clinical trial registration, post-study access, usage of data and human tissues, compensating participants with research-related injury, and usage of placebo. In this article, we discuss the major aspects of the 2008 version, including the impact of this version on all stakeholders in research, including, investigators, ethics committee members, sponsors, authors, editors, and reviewers.

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India is a developing country with one of the most diverse populations and diets in the world. Cancer rates in India are lower than those seen in Western countries, but are rising with increasing migration of rural population to the cities, increase in life expectancy and changes in lifestyles. In India, rates for oral and oesophageal cancers are some of the highest in the world. In contrast, the rates for colorectal, prostate, and lung cancers are one of the lowest. Studies of Indian immigrants in Western societies indicate that rates of cancer and other chronic diseases, such as coronary heart disease and diabetes, increase dramatically after a generation in the adopted country. Change of diet is among the factors that may be responsible for the changing disease rates. Diet in India encompasses diversity unknown to most other countries, with many dietary patterns emanating from cultural and religious teachings that have existed for thousands of years. Very little is known, however, about the role of the Indian diet in causation of cancer or its role, if any, in prevention of cancer, although more attention is being focused on certain aspects of the Indian diet, such as vegetarianism, spices, and food additives. Of particular interest for cancer prevention is the role of turmeric (curcumin), an ingredient in common Indian curry spice. Researchers also have investigated cumin, chilies, kalakhar, Amrita Bindu, and various plant seeds for their apparent cancer preventive properties. Few prospective studies, however, have been conducted to investigate the role of Indian diet and its various components in prevention of cancer. From a public health perspective, there is an increasing need to develop cancer prevention programs responsive to the unique diets and cultural practices of the people of India.

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Background: Inconsistent evidence exists regarding the strength, direction, and moderators in the relationship between obesity and psychiatric disorders. Aim: This study aims to summarize the evidence on the association between psychiatric illness and obesity with particular attention to the strength and direction of association and also the possible moderators in each postulated link. Materials and Methods: Systematic electronic searches of MEDLINE through PubMed, ScienceDirect, PsycINFO, and Google Scholar were carried out from inception till October 2016. Generated abstracts were screened for eligibility to be included in the review. Study designs that evaluated the strength of relationship between obesity and psychiatric disorders were included in the study. Quality assessment of included studies was done using the Newcastle–Ottawa checklist tool. Results: From a total of 2424 search results, 21 eligible articles were identified and reviewed. These included studies on obesity and depression (n = 15), obesity and anxiety (four) and one each on obesity and personality disorders, eating disorder (ED), attention deficit hyperactivity disorder, and alcohol use. Maximal evidence existed for the association between depression and obesity with longitudinal studies demonstrating a bidirectional link between the two conditions. The odds ratios (ORs) were similar for developing depression in obesity (OR: 1.21–5.8) and vice versa (OR: 1.18–3.76) with a stronger association observed in women. For anxiety disorders, evidence was mostly cross-sectional, and associations were of modest magnitude (OR: 1.27–1.40). Among other disorders, obesity, and EDs appear to have a close link (OR: 4.5). Alcohol use appears to be a risk factor for obesity and not vice versa but only among women (OR: 3.84). Conclusion: Obesity and depression have a significant and bidirectional association. Evidence is modest for anxiety disorders and inadequate for other psychiatric conditions. Gender appears to be an important mediator in these relationships.

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Leishmaniasis is a parasitic disease caused by a haemoflagellate Leishmania. There are more than 21 species causing human infection. The infection is transmitted to humans through the bites of female sandflies belonging to 30 species. The disease manifests mainly in 3 forms: the visceral, the cutaneous and the mucocutaneous leishmaniasis. The diagnosis of visceral form is conventionally made by the demonstration of amastigotes of the parasite in the aspirated fluid from the bone marrow, the spleen, and rarely from the lymph nodes, or the liver. The parasite demonstration and isolation rates are rather poor from cutaneous and mucocutaneous lesions due to low parasite load and high rate of culture contamination. Recently several recombinant proteins have been developed to accomplish accurate diagnosis. Recombinant kinesin protein of 39 kDa called rK 39 is the most promising of these molecules. The antigen used in various test formats has been proved highly sensitive and specific for visceral leishmaniasis. It is useful in the diagnosis of HIV-Leishmania co-infection and as a prognostic marker. Molecular techniques targeting various genes of the parasite have also been reported, the PCR being the most common molecular technique successfully used for diagnosis and for differentiation of species.

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We conducted a systematic international review of tobacco smoking habits among medical students. Particular attention was paid to countries where smoking rates have been historically well-documented in local journals, but were less often included in larger international review articles. The methodology involved a search of relevant medical subject headings, after which the reference lists of journal papers were also examined to find additional publications. A total of 66 manuscripts met the inclusion criteria. The most common countries previously studied included India, the United States, Australia, Japan, Pakistan, Turkey and the United Kingdom. Overall, our review suggests that the prevalence of smoking among medical students varies widely amongst different countries and also between male and female students within the same areas. Consistently low smoking rates were found in Australia and the United States, while generally high rates were reported in Spain and Turkey. Given their important future role as exemplars, more effective measures to help reduce tobacco smoking among medical students are clearly needed worldwide.

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The intake of 400-600 g/d of fruits and vegetables is associated with reduced incidence of many common forms of cancer, and diets rich in plant foods are also associated with a reduced risk of heart disease and many chronic diseases of ageing. These foods contain phytochemicals that have anti-cancer and anti-inflammatory properties which confer many health benefits. Many phytochemicals are colourful, and recommending a wide array of colourful fruits and vegetables is an easy way to communicate increased diversity of intake to the consumer. For example, red foods contain lycopene, the pigment in tomatoes, which is localized in the prostate gland and may be involved in maintaining prostate health, and which has also been linked with a decreased risk of cardiovascular disease. Green foods, including broccoli, Brussels sprouts and kale, contain glucosinolates which have also been associated with a decreased risk of cancer. Garlic and other white-green foods in the onion family contain allyl sulphides which may inhibit cancer cell growth. Other bioactive substances in green tea and soybeans have health benefits as well. Consumers are advised to ingest one serving of each of the seven colour groups daily, putting this recommendation within the United States National Cancer Institute and American Institute for Cancer Research guidelines of five to nine servings per day. Grouping plant foods by colour provides simplification, but it is also important as a method to help consumers make wise food choices and promote health.

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Leishmaniasis is a major world health problem, which is increasing in incidence. In Northern Europe it is seen in travellers returning from endemic areas. The protozoa is transmitted by sandflies and may produce a variety of clinical syndromes varying from a simple ulcer to fatal systemic disease. This review considers the management of simple cutaneous leishmaniasis. Patients usually have a single ulcer that may heal spontaneously, requiring only topical, or no treatment at all. Lesions caused by Leishmania braziliensis may evolve into the mucocutaneous form, 'espundia', and should be treated with systemic antimony. Sodium stibogluconate 20mg/kg/day i.v. for 20 days is the appropriate first line treatment in these cases. Although it may cause transient bone marrow suppression, liver damage, a chemical pancreatitis, and disturbances in the electrocardiogram, it appears safe. The success of treatment should be assessed 6 weeks after it has been completed and patients should be followed up for 6 months.

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Drug discovery and development is an expensive, time-consuming, and risky enterprise. In order to accelerate the drug development process with reduced risk of failure and relatively lower costs, pharmaceutical companies have adopted drug repositioning as an alternative. This strategy involves exploration of drugs that have already been approved for treatment of other diseases and/or whose targets have already been discovered. Various techniques including data mining, bioinformatics, and usage of novel screening platforms have been used for identification and screening of potential repositioning candidates. However, challenges in clinical trials and intellectual property issues may be encountered during the repositioning process. Nevertheless, such initiatives not only add value to the portfolio of pharmaceutical companies but also provide an opportunity for academia and government laboratories to develop new and innovative uses of existing drugs for infectious and neglected diseases, especially in emerging countries like India.

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Currently, glaucoma is recognised as an optic neuropathy. Selective death of retinal ganglion cells (RGC) is the hallmark of glaucoma, which is also associated with structural changes in the optic nerve head. The process of RGC death is thought to be biphasic: a primary injury responsible for initiation of damage that is followed by a slower secondary degeneration related to noxious environment surrounding the degenerating cells. For example, retinal ishaemia may establish a cascade of changes that ultimately result in cell death: hypoxia leads to excitotoxic levels of glutamate, which cause a rise in intra-cellular calcium, which in turn, leads to neuronal death due to apoptosis or necrosis. Neuroprotection is a process that attempts to preserve the cells that were spared during the initial insult, but are still vulnerable to damage. Although not yet available, a neuroprotective agent would be of great use in arresting the progression of glaucoma. There is evidence that neuroprotection can be achieved both pharmacologically and immunologically. Pharmacological intervention aims at neutralising some of the effects of the nerve-derived toxic factors, thereby increasing the ability of the spared neurons to cope with stressful conditions. On the other hand, immunological interventions boost the body's own repair mechanisms for counteracting the toxic effects of various chemicals generated during the cascade. This review, based on a literature search using MEDLINE, focuses on diverse cellular events associated with glaucomatous neurodegeneration, and discusses some pharmacological agents believed to have a neuroprotective role in glaucoma.

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Background: Reports from India on the prevalence and determinants of female sexual dysfunction (FSD) are scant. Aims: To determine the prevalence and risk factors for FSD. Settings and Design: A cross-sectional survey in a medical outpatient clinic of a tertiary care hospital. Materials and Methods: We administered a Tamil version of the Female Sexual Function Index (FSFI) to 149 married women. We evaluated putative risk factors for FSD. We elicited participant's attributions for their sexual difficulties. Statistical Analysis: We estimated the prevalence of possible FSD and sexual difficulties from published FSFI total and domain cut-off scores. We used logistic regression to identify risk factors for possible FSD. Results: FSFI total scores suggested FSD in two-thirds of the 149 women (73.2%; 95% confidence intervals [CI] 65.5% to 79.6%). FSFI domain scores suggested difficulties with desire in 77.2%; arousal in 91.3%; lubrication in 96.6%; orgasm in 86.6%, satisfaction in 81.2%, and pain in 64.4%. Age above 40 years (odds ratios [OR] 11.7; 95% CI 3.4 to 40.1) and fewer years of education (OR 1.2; 95% CI 1.0 to 1.3) were identified by logistic regression as contributory. Women attributed FSD to physical illness in participant or partner, relationship problems, and cultural taboos but none had sought professional help. Conclusions: Sexual problems suggestive of dysfunction, as suggested by FSFI total and domain scores, are highly prevalent in the clinic setting, particularly among women above 40 and those less educated, but confirmation using locally validated cut-off scores of the FSFI is needed.

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Visceral leishmaniasis (VL) is a severe disease associated with infection of the reticuloendothelial system by Leishmania species. The infection is acquired through sandfly bites. Recent large scale epidemics of VL in east Africa and India and the emergence of a HIV epidemic make VL a priority for the World Health Organization. Pentavalent antimonials have been cornerstone of treatment for the last six decades. The appearance of antimonial-resistance and the development of lipid formulations of amphotericin B have changed the pattern of VL treatment. Within the past five years, miltefosine has been demonstrated as the first effective and safe oral treatment against VL. The price of miltefosine is yet to be determined. However, miltefosine will certainly be cheaper than lipid formulations of amphotericin B, which are beyond the financial capacity of the poor countries. Because it can be administered orally, miltefosine is suited for the treatment of large number of patients who get affected during epidemics, particularly in regions where the parasites are resistant to the currently used agents. Here, we recommend different treatment schedules according to the resistance pattern and the region-specific socio-economical and cultural factors.

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In this article, we test the hypothesis that randomized clinical trials of acupuncture for pain with certain design features (A + B versus B) are likely to generate false positive results. Based on electronic searches in six databases, 13 studies were found that met our inclusion criteria. They all suggested that acupuncture is effected (one only showing a positive trend, all others had significant results). We conclude that the 'A + B versus B' design is prone to false positive results and discuss the design features that might prevent or exacerbate this problem.

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Herein we review the particular aspects of leishmaniasis associated with HIV infection. The data in this review are mainly from papers identified from PubMed searches and from papers in reference lists of reviewed articles and from the authors' personal archives. Epidemiological data of HIV/Leishmania co-infection is discussed, with special focus on the influence of Highly Active Antiretroviral Therapy (HAART) on incidence of leishmaniasis and transmission modalities. Microbiological characteristics, pathogenesis, clinical presentation and specific treatment of the co-infection are also presented.

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Context: Depression is frequently encountered in the primary care setting but is often unrecognized and hence untreated. There is a need for a uniform user-friendly screening instrument for depression for primary healthcare personnel in India. Aims: Translation and validation of the brief patient health questionnaire (BPHQ) as a screening tool for depression in major Indian languages. Materials and Methods: This was a prospective study conducted at 18 sites, in psychiatric and general clinics. The English version of the BPHQ was translated into 11 Indian languages. The translations were reviewed by experts and volunteers and proofread for the final translated BPHQ. The validation exercise included more than 3000 subjects. A psychiatrist and a psychiatry social worker / coordinator conducted the study under the supervision of the principal investigator. For each language, the presence or absence of major depressive disorder (MDD) as diagnosed with the help of a patient-completed BPHQ and the psychiatrist DSM-IV diagnosis was matched. The kappa coefficient was used as a measure of inter-observer agreement between the two diagnostic methods. Results: Seven languages failed the primary validation exercise. These translations were reviewed and the updated versions, after proofreading were re-run for validation. The self-administered BPHQ was successfully translated and validated for diagnosis of MDD against DSM-IV diagnosis made by a psychiatrist, in English, Hindi, Marathi, Oriya, Malayalam, Assamese, Gujarati, Kannada, Telugu, Bengali and Tamil. Conclusions: BPHQ is a simple, quick and reliable instrument, which facilitates rapid and accurate diagnosis of depression in the primary care setting in our country.

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Background: Diabetes mellitus is associated with an increased production of reactive oxygen species (ROS) and a reduction in antioxidant defense. The oxidative stress becomes evident as a result of accumulation of ROS in conditions of inflammation and Type 2 diabetes mellitus (T2DM). The genes involved in redox balance, which determines the susceptibility to T2DM remain unclear. In humans, the glutathione S-transferase (GST) family comprises several classes of GST isozymes, the polymorphic variants of GSTM1, T1 and P1 genes result in decreased or loss of enzyme activity. Aims: The present study evaluated the effect of genetic polymorphisms of the GST gene family on the risk of developing T2DM in the North Indian population. Settings and Design: GSTM1, T1 and P1 polymorphisms were genotyped in 100 T2DM patients and 200 healthy controls from North India to analyze their association with T2DM susceptibility. Materials and Methods: Analysis of GSTM1 and GSTT1 gene polymorphisms was performed by multiplex polymerase chain reaction (PCR) and GSTP1 by PCR-Restriction Fragment Length Polymorphism (RFLP). Statistical Analysis: Fisher's exact test and χ² statistics using SPSS software (Version-15.0). Results: We observed significant association of GSTM1 null (P=0.004, OR= 2.042, 95%CI= 1.254-3.325) and GSTP1 (I/V) (P=0.001, OR= 0.397, 95%CI=0.225-0.701) with T2DM and no significant association with GSTT1 (P=0.493). The combined analysis of the three genotypes GSTM1 null, T1 present and P1 (I/I) demonstrated an increase in T2DM risk (P= 0.005, OR= 2.431 95% CI=1.315-4.496). Conclusions: This is the first study showing the association of a combined effect of GSTM1, T1 and P1 genotypes in a representative cohort of Indian patients with T2DM. Since significant association was seen in GSTM1 null and GSTP1 (I/V) and multiple association in GSTM1 null, T1 present and P1 (I/I), these polymorphisms can be screened in the population to determine the diabetic risk.

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Obesity is a growing health problem in developed nations and in countries that are in the process of westernization like India. Obesity is linked with several health disorders such as hypertension and cardiovascular diseases, Type 2 diabetes, dyslipidemia and certain cancers. Currently, obesity-related malignancies, e.g., cancers of the breast, prostate and colon are the leading cancers in the industrialized societies. An increased amount of fat or adipose tissue in an overweight or obese person probably influences the development of cancer by releasing several hormone-like factors or adipokines. The majority of adipokines are pro-inflammatory, which promote pathological conditions like insulin resistance and cancer. On the other hand, many recent studies have shown that adiponectin, an anti-inflammatory adipokine, has anti-cancer and insulin-sensitizing effects. Adiponectin exerts its physiological functions chiefly by activation of AMP kinase via adiponectin receptors. Interestingly, several fruits and vegetables may contain adiponectin-like molecules or may increase the biosynthesis of adiponectin in our body. Studies on adiponectin analogues or adiponectin receptor agonists are a promising area of cancer chemoprevention research. In general, fruits and vegetables contain various dietary substances such as vitamins, minerals (like calcium and selenium), fiber and phytochemicals or phenolic compounds (like flavonoids and vanilloids), which may act as anti-cancer agents. Similarly, several dietary constituents including phytochemicals may have anti-obesity effects. Consumption of such dietary compounds along with caloric restriction and physical activity may be helpful in preventing obesity-related cancers. For this review article, we searched PubMed primarily to get the relevant literature.

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The oxidative hypothesis of senescence, since its origin in 1956, has garnered significant evidence and growing support among scientists for the notion that free radicals play an important role in ageing, either as "damaging" molecules or as signaling molecules. Age-increasing oxidative injuries induced by free radicals, higher susceptibility to oxidative stress in short-lived organisms, genetic manipulations that alter both oxidative resistance and longevity and the anti-ageing effect of caloric restriction and intermittent fasting are a few examples of accepted scientific facts that support the oxidative theory of senescence. Though not completely understood due to the complex "network" of redox regulatory systems, the implication of oxidative stress in the ageing process is now well documented. Moreover, it is compatible with other current ageing theories (e.g., those implicating the mitochondrial damage/mitochondrial-lysosomal axis, stress-induced premature senescence, biological "garbage" accumulation, etc). This review is intended to summarize and critically discuss the redox mechanisms involved during the ageing process: sources of oxidant agents in ageing (mitochondrial -electron transport chain, nitric oxide synthase reaction- and non-mitochondrial- Fenton reaction, microsomal cytochrome P450 enzymes, peroxisomal β -oxidation and respiratory burst of phagocytic cells), antioxidant changes in ageing (enzymatic- superoxide dismutase, glutathione-reductase, glutathion peroxidase, catalase- and non-enzymatic glutathione, ascorbate, urate, bilirubine, melatonin, tocopherols, carotenoids, ubiquinol), alteration of oxidative damage repairing mechanisms and the role of free radicals as signaling molecules in ageing.

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Each novel vaccine candidate needs to be evaluated for safety, immunogenicity, and protective efficacy in humans before it is licensed for use. After initial safety evaluation in healthy adults, each vaccine candidate follows a unique development path. This article on clinical development gives an overview on the development path based on the expectations of various guidelines issued by the World Health Organization (WHO), the European Medicines Agency (EMA), and the United States Food and Drug Administration (USFDA). The manuscript describes the objectives, study populations, study designs, study site, and outcome(s) of each phase (Phase I-III) of a clinical trial. Examples from the clinical development of a malaria vaccine candidate, a rotavirus vaccine, and two vaccines approved for human papillomavirus (HPV) have also been discussed. The article also tabulates relevant guidelines, which can be referred to while drafting the development path of a novel vaccine candidate.

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The emergence and spread of drug resistant malaria represents a considerable challenge to controlling malaria. To date, malaria control has relied heavily on a comparatively small number of chemically related drugs, belonging to either the quinoline or the antifolate groups. Only recently have the artemisinin derivatives been used but mostly in south east Asia. Experience has shown that resistance eventually curtails the life-span of antimalarial drugs. Controlling resistance is key to ensuring that the investment put into developing new antimalarial drugs is not wasted. Current efforts focus on research into new compounds with novel mechanisms of action, and on measures to prevent or delay resistance when drugs are introduced. Drug discovery and development are long, risky and costly ventures. Antimalarial drug development has traditionally been slow but now various private and public institutions are at work to discover and develop new compounds. Today, the antimalarial development pipeline is looking reasonably healthy. Most development relies on the quinoline, antifolate and artemisinin compounds. There is a pressing need to have effective, easy to use, affordable drugs that will last a long time. Drug combinations that have independent modes of action are seen as a way of enhancing efficacy while ensuring mutual protection against resistance. Most research work has focused on the use of artesunate combined with currently used standard drugs, namely, mefloquine, amodiaquine, sulfadoxine/pyrimethamine, and chloroquine. There is clear evidence that combinations improve efficacy without increasing toxicity. However, the absolute cure rates that are achieved by combinations vary widely and depend on the level of resistance of the standard drug. From these studies, further work is underway to produce fixed dose combinations that will be packaged in blister packs. This review will summarise current antimalarial drug developments and outline recent clinical research that aims to bring artemisinin based combinations to those that need them most.

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To study the effect of hyperbaric oxygen therapy in chronic diabetic foot lesions, a prospective controlled study was undertaken. Thirty diabetics with chronic foot lesions were randomised to study group (conventional management and 4 sessions of hyperbaric oxygen therapy) and control group (conventional management). The patients were assessed for average hospital stay, control of infection and wound healing. The control of infection spread was quicker. Positive cultures decreased from initial 19 to 3 in study group as against from 16 to 12 in the control group. (p < 0.05). This difference was most pronounced for Escherichia coli. Also, the need for major amputation was significantly less in the study group (n = 2) as against the control group (n = 7) (p < 0.05). The average hospital stay was not affected. We conclude that hyperbaric oxygen therapy can be safely used and is beneficial as an adjuvant therapy in chronic diabetic foot lesions.

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Background : Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare immune-mediated severe cutaneous adverse reactions with incidence rate of 0.05 to 2 persons per million populations per year. Drugs are the most commonly implicated in 95% of cases. Aims : To audit the causative drugs, clinical outcome, and cost of management in SJS, TEN, and SJS-TEN overlap. Setting and Design: Tertiary care hospitals-based multicentric retrospective study (case series). Materials and Methods : Indoor case papers of SJS, TEN, and SJS-TEN overlap admitted between January 2006 and December 2009 in four tertiary care hospitals of Gujarat were scrutinized. Data were collected for demographic information, causative drugs, investigations, treatment given, duration of hospital stay, time interval between onset of symptoms and drug intake, clinical outcome, and complications. Data were analyzed to find out proportion of individual drugs responsible, major complications, and clinical outcome in SJS, TEN, and SJS-TEN overlap. Total cost of management was calculated by using cost of drugs, investigations, and consumables used during entire hospital stay. Statistical Analysis : One-way Analysis of Variance followed by Tukey-Kramer multiple comparison test was used for comparison of incubation period, duration of hospital stay, and cost of management. Results : Antimicrobials (50%), nonsteroidal anti-inflammatory drugs (22.41%), and antiseizure drugs (18.96%) were the most commonly associated groups. Nevirapine (28.12%) was the most common drug. Antiseizure drugs were more often associated with serious form of adverse reaction (TEN: 81.8%) than other drugs. Duration of hospital stay (20.6 vs 9.7 days) and cost of management (Rs 7 910/- vs Rs 2 460/-) were significantly higher in TEN than SJS (P=0.020 and P<0.001, respectively). Time duration between drug intake and onset of symptoms (17.7 vs 27.5 days) was nonsignificantly lower in TEN as compared with SJS. Secondary infection (28.12%) was the most common complication noted. Mortality rate was 15.6% among all cases; 9% in SJS and 26.7% in TEN. Conclusion : Antimicrobial drugs are the most commonly implicated drugs and cost of managing these adverse drug reactions is higher than other serious ADRs.

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Bone grafts are necessary to provide support, fill voids, and enhance biologic repair of skeletal defects. They are used by orthopaedic surgeons, neurosurgeons, craniofacial surgeons, and periodontists. Bone harvested from donor sites is the gold standard for this procedure. It is well documented that there are limitations and complications from the use of autograft, including the limited quantity and associated chronic donor site pain. Despite the increase in the number of procedures that require bone grafts, there has not been a single ideal bone graft substitute Scientists, surgeons, and medical companies, thus, have a tremendous responsibility to develop biologic alternatives that will enhance the functional capabilities of the bone graft substitute, and potentially reduce or eliminate the need for autograft. This article is an attempt to review the past and existing bone graft substitutes, and future directions of research. The historical data was extracted after thorough review of the literature. The data for the current concepts and future directions was compiled from the Internet, and from direct correspondence with medical companies. Since many products are undergoing clinical trials, and are yet not commercially available, their data cannot be found in literature. The main purpose of this article is to give the reader an idea about the existing market products and products likely to be available in near future.

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Ketogenic diet (KD) is a high-fat, adequate-protein, and low-carbohydrate diet that leads to nutritional ketosis, long known for antiepileptic effects and has been used therapeutically to treat refractory epilepsy. This review attempts to summarize the evidence and clinical application of KD in diabetes, obesity, and other endocrine disorders. KD is usually animal protein based. An empiric vegetarian Indian variant of KD has been provided keeping in mind the Indian food habits. KD has beneficial effects on cardiac ischemic preconditioning, improves oxygenation in patients with respiratory failure, improves glycemic control in diabetics, is associated with significant weight loss, and has a beneficial impact on polycystic ovarian syndrome. Multivitamin supplementations are recommended with KD. Recently, ketones are being proposed as super-metabolic fuel; and KD is currently regarded as apt dietary therapy for “diabesity.”

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