The developmental basis of adult arrhythmia: atrial fibrillation as a paradigm

Normal cardiac rhythm is one of the most fundamental physiologic phenomena, emerging early in the establishment of the vertebrate body plan. The developmental pathways underlying the patterning and maintenance of stable cardiac electrophysiology must be extremely robust, but are only now beginning to be unraveled. The step-wise emergence of automaticity, AV delay and sequential conduction are each tightly regulated and perturbations of these patterning events is now known to play an integral role in pediatric and adult cardiac arrhythmias. Electrophysiologic patterning within individual cardiac chambers is subject to exquisite control and is influenced by early physiology superimposed on the underlying gene networks that regulate cardiogenesis. As additional cell populations migrate to the developing heart these too bring further complexity to the organ, as it adapts to the dynamic requirements of a growing organism. A comprehensive understanding of the developmental basis of normal rhythm will inform not only the mechanisms of inherited arrhythmias, but also the differential regional propensities of the adult heart to acquired arrhythmias. In this review we use atrial fibrillation as a generalizable example where the various factors are perhaps best understood

Clinical profile of patients with pancytopenia in a tertiary care centre

Background: Pancytopenia is a condition in which all three cell lines i.e. erythroid, myeloid and megakaryocytic are affected resulting in anaemia, leukopenia and thrombocytopenia. It can be a manifestation of a wide variety of disorders which primarily or secondarily affect the bone marrow. Early diagnosis of these conditions will help in implementing the appropriate treatment. The objective of the study was to know the clinical presentation and etiology of patients presenting with pancytopenia.Methods: A one year study from April 2016 to March 2017 was conducted in the department of medicine at a tertiary care centre. Total 32 patients with pancytopenia were studied to determine their clinical features and etiology through relevant investigations.Results: Our study revealed megaloblastic anaemia (46.87%) as the most common cause of pancytopenia, followed by malaria (12.5%). Other causes included hypothyroidism (6.2%), hypersplenism (6.2%), drugs (12.5%) and miscellaneous (9.43%).Conclusions: Megaloblastic anaemia was found to be the major cause of pancytopenia in patients. Other causes of pancytopenia were malaria, drugs, hypersplenism and hypothyroidism. These should be kept in mind while evaluating patients with pancytopenia

First fossil marsupials from India: early Eocene Indodelphis n. gen. and Jaegeria n. gen. from the Vastan Lignite mine, District Surat, Gujarat

We report the discovery of fossil marsupials (Didelphidae: Mammalia) from India, based on well-preserved lower molars of two taxa (Indodelphis Inoi n. gen. and n. sp. and Jaegeria cambayensis n. gen. and n. sp.) from the early Eocene (middle Ypresian, approximately 52 Ma) deposits of Vastan Lignite Mine, District Surat, Gujarat, western India. These species probably represent the oldest known record of Cenozoic marsupials from Asia, and they occur in association with a diverse land mammal fauna comprising perissodactyls, artiodactyls, insectivores, proteutherians, apatotherians, bats, rodents, and several other taxa currently under study

Early eocene primates from Vastan lignite mine, Gujarat, western India

A new primate fauna of early Eocene (Ypresian, approximately 52 Ma) age is reported from the Vastan Lignite Mine, District Surat, Gujarat, western India. From the Indian subcontinent, this is the oldest known Cenozoic rocord as well as the largest single sample of Eocene primates, consisting of 3 fragmentary jaws and 4 isolated upper cheek teeth. The assemblage comprises at least three, but possibly 4 taxa, of which only two are being named here, an adapiform Marcgodinotius indicus n. gen. & n. sp., and an omomyid Vastanomys gracilis n. gen. & n. sp., distinguished mainly on the basis of their lower dental formula and lower molar characteristics. The fauna indicates considerable diversity of Eocene primates in Indo-Pakistan and is important in understanding early primate evolution in Asia and the mammalian dispersal into, or out of, from India in response to changing paleogeographic settings associated with the initiation of India-Asia collision

"The fruits of independence": Satyajit Ray, Indian nationhood and the spectre of empire

Challenging the longstanding consensus that Satyajit Ray's work is largely free of ideological concerns and notable only for its humanistic richness, this article shows with reference to representations of British colonialism and Indian nationhood that Ray's films and stories are marked deeply and consistently by a distinctively Bengali variety of liberalism. Drawn from an ongoing biographical project, it commences with an overview of the nationalist milieu in which Ray grew up and emphasizes the preoccupation with colonialism and nationalism that marked his earliest unfilmed scripts. It then shows with case studies of Kanchanjangha (1962), Charulata (1964), First Class Kamra (First-Class Compartment, 1981), Pratidwandi (The Adversary, 1970), Shatranj ke Khilari (The Chess Players, 1977), Agantuk (The Stranger, 1991) and Robertsoner Ruby (Robertson's Ruby, 1992) how Ray's mature work continued to combine a strongly anti-colonial viewpoint with a shifting perspective on Indian nationhood and an unequivocal commitment to cultural cosmopolitanism. Analysing how Ray articulated his ideological positions through the quintessentially liberal device of complexly staged debates that were apparently free, but in fact closed by the scenarist/director on ideologically specific notes, this article concludes that Ray's reputation as an all-forgiving, ‘everybody-has-his-reasons’ humanist is based on simplistic or even tendentious readings of his work

Biochemical Properties of a Novel Cysteine Protease of Plasmodium vivax, Vivapain-4

Plasmodium vivax affects hundreds of millions each year and results in severe morbidity and mortality. Plasmodial cysteine proteases (CPs) play crucial roles during the progression of malaria since inhibition of these molecules impairs parasite growth. These CPs might be targeted for new antimalarial drugs. We characterized a novel P. vivax CP, vivapain-4 (VX-4), which appeared to evolve differentially among primate Plasmodium species. VX-4 showed highly unique substrate preference depending on surrounding micro-environmental pH. It effectively hydrolyzed benzyloxycarbonyl-Leu-Arg-4-methyl-coumaryl-7-amide (Z-Leu-Arg-MCA) and Z-Phe-Arg-MCA at acidic pH and Z-Arg-Arg-MCA at neutral pH. Three amino acids (Ala90, Gly157 and Glu180) that delineate the S2 pocket were found to be substituted in VX-4. Alteration of Glu180 abolished hydrolytic activity against Z-Arg-Arg-MCA at neutral pH, indicating Glu180 is intimately involved in the pH-dependent substrate preference. VX-4 hydrolyzed actin at neutral pH and hemoglobin at acidic pH, and participated in plasmepsin 4 activation at neutral/acidic pH. VX-4 was localized in the food vacuoles and cytoplasm of the erythrocytic stage of P. vivax. The differential substrate preferences depending on pH suggested a highly efficient mechanism to enlarge biological implications of VX-4, including hemoglobin degradation, maturation of plasmepsin, and remodeling of the parasite architecture during growth and development of P. vivax

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries