Diabetes is a major public health emergency of the 21st century. Results of the Indian Council of Medical Research-INdia DIABetes (ICMR-INDIAB) study have found prevalence of diabetes and prediabetes ...in India to be as high as 7.3% and 10.3%, respectively with nation-wide projection of 77.2 million people with prediabetes and 69.2 million with diabetes. It is well established that insulin resistance (IR) and islet β-cell failure are the two major features of T2D Multiple mechanisms including glucotoxicity, lipotoxicity, oxidative stress, endoplasmic reticulum stress, formation of amyloid deposits in the islets, etc. have been hypothesized to participate in the pathology of the disease. In the concluding decade of the last century, numerous studies - prospective and cross-sectional, have confirmed the role of chronic low-grade inflammation as a pathogenetic factor of T2D. It has been shown that increased levels of various inflammatory markers and mediators including fundamental markers like white blood cell count, C-reactive protein (CRP) to the more specific circulating cytokines like, interleukin-6 (IL-6), IL-1β, plasminogen activator inhibitor-1 (PAI-1), etc. correlate with incident T2D. Based on the robust evidence implying the role of inflammation in T2D pathogenesis, several studies have proven that the proinflammatory cytokines play a central role in the development of microvascular diabetic complications such as nephropathy, retinopathy, and neuropathy. Inflammation in T2D causes accelerated atherosclerosis which predisposes to CVD, the leading cause of mortality in these patients. Recently there is a considerable increase in the interest among the researchers about anti-inflammatory therapies in the setting of chronic disorders such as T2D and CV diseases. In a multi-country study conducted in Asia, approximately 50% of Indian respondents had poor diabetes control. Most patients initially respond to sulfonylurea and/or metformin, and later these agents lose their effectiveness with time. Therapeutic option in patients uncontrolled on two-drug combination therapy is either to add third oral drug or insulin. However, use of insulin is limited due to its high cost and poor compliance. Majority of new treatment options like GLP1 agonists, insulin analogs and SGLT2 inhibitors are costly considering they are still under patent. The thiazolidinedione class of drugs is associated with adverse effects like fluid retention and weight gain that may result in or exacerbate edema and congestive heart failure. Thus there is a need for a safe and inexpensive treatment option for the management of uncontrolled T2D. Considering the role of inflammation in T2D pathogenesis, the drug should not only have antihyperglycemic effects but also reduce inflammatory burden thus reducing the progression and complications of T2D. The current interest is apparently directed towards drugs targeting inflammation acting at different stages of the inflammatory cascade. In the recently published CANTOS study, canakinumab, a selective, high-affinity, fully human monoclonal antibody which inhibits IL-1β, has no consistent long-term benefits on HbA1c. Other selective inhibitors like anakinra (IL-1 receptor antagonist) and etanercept (TNF inhibitor) too have yielded modest effects on glycemic parameters and insulin sensitivity. However, hydroxychloroquine (HCQ), a broad anti-inflammatory agent has been shown to reduce HbA1c by 0.87%. Hydroxychloroquine (HCQ) is considered as one of the safest disease modifying anti-rheumatic drug, used widely for the treatment of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). The effect of HCQ in preventing development of diabetes in patients with chronic inflammatory diseases was highlighted in a prospective observational study of 4905 adults with rheumatoid arthritis and no diabetes with 21.5 years of follow-up. Patients who took HCQ for more than 4 years had a significant 77% lower risk of diabetes compared with non users of HCQ (RR, 0.23; 95% CI, 0.11-0.50). Taking cue from this study highlighting the anti-diabetic effect of HCQ, pioneering research studies evaluating these effects of HCQ were conducted in India. In 2014, hydroxychloroquine 400 mg got DCGI approval as an adjunct to diet and exercise to improve glycemic control of patients on metformin, sulfonylurea combination in Type 2 diabetes.
Carotid stenting is being increasingly used for revascularization of the moderate to severe carotid stenosis and thus its complications are increasingly being recognized. We report a rare ...complication of induced by iodine contrast in a patient undergoing carotid stenting. s. A 51 year old man after the second stenting developed multiple small infarcts in spite of the distal device. He also had painful parotid swelling which improved within a week. One should be aware of iodine parotitis s in the patients undergoing iodinated contrast study.
According to the current understanding of cosmic structure formation, the precursors of the most massive structures in the Universe began to form shortly after the Big Bang, in regions corresponding ...to the largest fluctuations in the cosmic density field. Observing these structures during their period of active growth and assembly-the first few hundred million years of the Universe-is challenging because it requires surveys that are sensitive enough to detect the distant galaxies that act as signposts for these structures and wide enough to capture the rarest objects. As a result, very few such objects have been detected so far. Here we report observations of a far-infrared-luminous object at redshift 6.900 (less than 800 million years after the Big Bang) that was discovered in a wide-field survey. High-resolution imaging shows it to be a pair of extremely massive star-forming galaxies. The larger is forming stars at a rate of 2,900 solar masses per year, contains 270 billion solar masses of gas and 2.5 billion solar masses of dust, and is more massive than any other known object at a redshift of more than 6. Its rapid star formation is probably triggered by its companion galaxy at a projected separation of 8 kiloparsecs. This merging companion hosts 35 billion solar masses of stars and has a star-formation rate of 540 solar masses per year, but has an order of magnitude less gas and dust than its neighbour and physical conditions akin to those observed in lower-metallicity galaxies in the nearby Universe. These objects suggest the presence of a dark-matter halo with a mass of more than 100 billion solar masses, making it among the rarest dark-matter haloes that should exist in the Universe at this epoch.
Data on 1,28,075 artificial inseminations (AI) performed during 6 years (January 2010 to November 2015) on 1,02,386 field animals owned by 55,685 farmers’ from 69 cattle development centres spread ...across four districts of Bihar were collected and analyzed. Whole data set was classified according to districts (Chhapra, Samastipur, Siwan, Vaishali), economic status of farmers (APL, BPL), animal breed (HF cross, Indigenous, Jersey cross, Nondescript), lactation order/parity of animal (heifer, first, second, third, fourth, fifth, sixth and above), animal body condition score (all ribs exposed, no rib exposed, one rib exposed, two ribs exposed, three ribs exposed), heat stage (early, mid, late), season of AI (rainy-June to September, winter-October to January, summer-February to May) and sire used for AI (Gir, HF purebreed, HF crossbreed, Jersey purebred, Jersey crossbreed, Sahiwal). Logistic regression analysis was used to compute the odds ratio and probability of conception rate. The results revealed that overall mean conception rate as 52.16% and it was noticed significantly higher in Chhapra district, BPL group of farmers, Jersey crossbreed animals, animals having third lactation, animals exhibiting three ribs exposed, mid heat and animals inseminated with HF purebred semen compared with respective groups of parameters under study. However, effect of season of AI did not affect conception rate in rural animals under field conditions of Bihar. ACKNOWLEDGEMENT Authors are very much grateful to the President, BAIF for his encouragement. Financial support from Department of Animal Husbandry, Government of Bihar and help rendered by Godhan project team for data compilation is gratefully acknowledged
Massive galaxy clusters have been found that date to times as early as three billion years after the Big Bang, containing stars that formed at even earlier epochs
. The high-redshift progenitors of ...these galaxy clusters-termed 'protoclusters'-can be identified in cosmological simulations that have the highest overdensities (greater-than-average densities) of dark matter
. Protoclusters are expected to contain extremely massive galaxies that can be observed as luminous starbursts
. However, recent detections of possible protoclusters hosting such starbursts
do not support the kind of rapid cluster-core formation expected from simulations
: the structures observed contain only a handful of starbursting galaxies spread throughout a broad region, with poor evidence for eventual collapse into a protocluster. Here we report observations of carbon monoxide and ionized carbon emission from the source SPT2349-56. We find that this source consists of at least 14 gas-rich galaxies, all lying at redshifts of 4.31. We demonstrate that each of these galaxies is forming stars between 50 and 1,000 times more quickly than our own Milky Way, and that all are located within a projected region that is only around 130 kiloparsecs in diameter. This galaxy surface density is more than ten times the average blank-field value (integrated over all redshifts), and more than 1,000 times the average field volume density. The velocity dispersion (approximately 410 kilometres per second) of these galaxies and the enormous gas and star-formation densities suggest that this system represents the core of a cluster of galaxies that was already at an advanced stage of formation when the Universe was only 1.4 billion years old. A comparison with other known protoclusters at high redshifts shows that SPT2349-56 could be building one of the most massive structures in the Universe today.
Summary
Background Hypohidrotic/anhidrotic ectodermal dysplasia (HED) is a rare Mendelian disorder affecting ectodermal tissues. The disease is primarily caused by inactivation of any one of three ...genes, namely ectodysplasin A1 (EDA‐A1), which encodes a ligand belonging to the tumour necrosis factor (TNF) superfamily; ectodysplasin A receptor (EDAR), encoding the EDA‐A1 receptor and ectodysplasin A receptor‐associated death domain (EDARADD), encoding an adaptor protein. X‐linked recessive (EDA‐A1), the predominant form of HED, as well as autosomal recessive and dominant (EDAR and EDARADD) inheritance patterns have been identified in affected families.
Objectives To determine the common genes causing HED in India.
Methods We performed mutation analysis on 26 HED families from India (including 30 patients). In addition, we carried out sequence and structural analysis of missense/nonsense and insertion/deletion mutations.
Results Among the 26 families analysed, disease‐causing EDAR mutations were identified in 12 (46%) while EDA‐A1 mutations were detected in 11 (42%). Four novel mutations in EDAR and five in EDA‐A1 were identified. More importantly, a possible founder EDAR mutation, namely c.1144G>A, was identified in five independent families, thus accounting for about one‐fifth of affected families in whom mutation was detected. A majority of EDA‐A1 mutations localized to the TNF‐like domain while the location of EDAR mutations was more widespread.
Conclusions This is the first report of a founder EDAR mutation and of a significantly high frequency of autosomal recessive HED.
Change history: In this Letter, the Acknowledgements section should have included the following sentence: "The National Radio Astronomy Observatory is a facility of the National Science Foundation ...operated under cooperative agreement by Associated Universities, Inc.". This omission has been corrected online.
The diurnal variations in daytime airglow emission intensity measurements at three wavelengths OI 777.4 nm, OI 630.0 nm, and OI 557.7 nm made from a low-latitude location, Hyderabad (17.5° N, ...78.4° E; 8.9° N MLAT) in India have been investigated. The intensity patterns showed both symmetric and asymmetric behaviour in their respective diurnal emission variability with respect to local noon. The asymmetric diurnal behaviour is not expected considering the photochemical nature of the production mechanisms. The reason for this observed asymmetric diurnal behaviour has been found to be predominantly the temporal variation in the equatorial electrodynamics. The plasma that is transported across latitudes due to the action of varying electric field strengths over the magnetic equator in the daytime contributes to the asymmetric diurnal behaviour in the neutral daytime airglow emissions. Independent magnetic and radio measurements support this finding. It is also noted that this asymmetric diurnal behaviour in the neutral emission intensities has a solar cycle dependence with a greater number of days during high solar activity period showing asymmetric diurnal behaviour compared to those during a low solar activity epoch. These intensity variations over a long timescale demonstrate that the daytime neutral optical emissions are extremely sensitive to the changes in the eastward electric field over low and equatorial latitudes.
UPDATEThis article was updated on September 26, 2014, because of a previous error. The statement in the Abstract that had previously read“Intraobserver agreement was high (intraclass correlation ...coefficient = 0.89)” now reads “Interobserver agreement was high (intraclass correlation coefficient = 0.89)”.An erratum has been publishedJ Bone Joint Surg Am. 2014 Nov 5;96(21)e182.BackgroundWhen a patient is seen with a possible tibial nonunion and equivocal findings on plain radiographs, the surgeon may choose to obtain a computed tomography scan to better delineate the bone anatomy. However, the sensitivity and specificity of computed tomography in this setting is not known. We investigated the accuracy of computed tomography for detecting nonunion in this clinical situation.MethodsThirty-five patients with equivocal findings on plain radiographs underwent computed tomography scanning. The patients were first seen at an average of 9.7 months after the injury and had undergone a mean of 2.6 prior operations. A so-called gold standard of union or nonunion was determined by either surgical findings (for twenty-five patients who were operatively treated) or six months of clinical observation (for ten patients who had nonoperative treatment). Computed tomography scans were assessed by two radiologists and one orthopaedic surgeon who were blinded to the clinical outcome.ResultsComputed tomography scans displayed very good diagnostic accuracy. Interobserver agreement was high (intraclass correlation coefficient = 0.89), the sensitivity for detecting nonunion was 100%, and the overall accuracy was 89.9%. Computed tomography was limited by a low specificity of 62%, as three patients who were diagnosed as having tibial nonunion with computed tomography underwent surgery and were found to have a healed fracture.ConclusionsComputed tomography displays very good accuracy in the evaluation of tibial fracture-healing. However, it is limited by low specificity and may sometimes misrepresent a healed fracture as a nonunion. Surgeons must be aware of this pitfall in order to accurately determine which patients need surgical intervention.Level of EvidenceDiagnostic Level I. See Instructions to Authors for a complete description of levels of evidence.
The spread of nano/microplastics (N/MPs) pollution has gained importance due to the associated health concerns. Marine environment including fishes, mussels, seaweed and crustaceans are largely ...exposed to these potential threats. N/MPs are associated with plastic, additives, contaminants and microbial growth, which are transmitted to higher trophic levels. Foods from aquatic origin are known to promote health and have gained immense importance. Recently, aquatic foods are traced to transmit the nano/microplastic and the persistent organic pollutant poising hazard to humans. However, microplastic ingestion, translocation and bioaccumulation of the contaminant have impacts on animal health. The level of pollution depends upon the pollution in the zone of growth for aquatic organisms. Consumption of contaminated aquatic food affects the health by transferring the microplastic and chemicals. This chapter describes the sources and occurrence of N/MPs in marine environment, detailed classification of N/MPs based on the properties influencing associated hazard. Additionally, occurrence of N/MPs and their impact on quality and safety in aquatic food products are discussed. Lastly, existing regulations and requirements of a robust framework of N/MPs are reviewed.
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