Venous thromboembolism (VTE), a multi-factorial disease, is the third most common cardiovascular disease. Established genetic and acquired risk factors are responsible for the onset of VTE. High altitude (HA) also poses as an additional risk factor, predisposing individuals to VTE; however, its molecular mechanism remains elusive. This study aimed to identify genes/pathways associated with the pathophysiology of deep vein thrombosis (DVT) at HA. Gene expression profiling of DVT patients, who developed the disease, either at sea level or at HA-DVT locations, resulted in differential expression of 378 and 875 genes, respectively. Gene expression profiles were subjected to bioinformatic analysis, followed by technical and biological validation of selected genes using quantitative reverse transcription-polymerase chain reaction. Both gene ontology and pathway analysis showed enrichment of genes involved in haemostasis and platelet activation in HA-DVT patients with the most relevant pathway being 'response to hypoxia'. Thus, given the environmental condition the differential expression of hypoxia-responsive genes (angiogenin, ribonuclease, RNase A family, 5; early growth response 1; lamin A; matrix metallopeptidase 14 [membrane-inserted]; neurofibromin 1; PDZ and LIM domain 1; procollagen-lysine 1, 2-oxoglutarate 5-dioxygenase 1; solute carrier family 6 [neurotransmitter transporter, serotonin], member 4; solute carrier family 9 [sodium/hydrogen exchanger], member 1; and TEK tyrosine kinase, endothelial) in HA-DVT could be a determining factor to understand the pathophysiology of DVT at HA.

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Background: The pathophysiology of Deep vein thrombosis (DVT) is considered as multifactorial, where thrombus formation is interplay of genetic and acquired risk factors. A little is known about the expression profile and roles of lncRNAs in human subjects developing DVT at high altitude. Methods: Using RNAseq, we compared peripheral blood mRNA and lncRNA expression profile in human High Altitude deep Vein Thrombosis (HA-DVT) patients with high altitude control subjects. We used DESeq to identify differentially expressed (DE) genes. We annotated the long noncoding RNAs using NONCODE 3.0 database. In silico putative lncRNA-miRNA association study unravels the endogenous miRNA sponge associated with our candidate lncRNAs. These findings were validated by siRNA knockdown assay of the candidate lncRNAs conducted in primary endothelial cells. Results: We identified 1524 DE mRNA and 973 DE lncRNAs. Co-expressed protein-coding genes analysis resulted in a list of 722 coexpressed protein-coding genes with a Pearson correlation coefficients >0.7. The functional annotation of co-expressed genes and putative proteins revealed their involvement in the hypoxia, immune response and coagulation cascade. Through its miRNA response elements (MREs) to compete for miR-143 and miR-15, lncRNA-LINC00659 and UXT-AS1 regulates the expression of prothrombotic genes. Furthermore, in vitro RNA interference (siRNA) simultaneously suppressed lncRNAs and target gene mRNA level. Conclusions: This transcriptome profile describes novel potential mechanisms of interaction between lncRNAs, the coding genes, miRNAs and regulatory transcription factors that define the thrombotic signature and may be used in establishing lncRNAs as biomarker in HA-DVT.

Precocious puberty defined as an onset of puberty below eight years in girls and nine years in boys, has an incidence of approximately 1 / 5,000 – 1 / 10,000 subjects with a female / male ratio of 20: 1. It is etiologically classified broadly as central and peripheral. We present to you a case of isosexual (central), precocious puberty in a 16-month-old girl, who was symptomatic since the age of six months, and was later, diagnosed to have hypothalamic hamartoma. It is one of the earliest case records ever in the medical literature of menarche, at an extremely early age (six-month-old child) secondary to a central cause.

BackgroundRadiation-induced xerostomia is a distressing clinical condition that starts appearing from the initial stages of radiotherapy in head and neck cancer patients. Though submandibular glands contribute to maximum of the “resting salivary” secretions, most of the acute xerostomia experiments so far reported have been on animal parotid glands. Therefore, we assessed and quantified the histologic changes in submandibular glands of Sprague-Dawley (SD) rats using histomorphometry, 24 hours after radiation.MethodsThree SD rats were given single-dose radiation of 15 Gray from a gamma cobalt-60 irradiator. Same number of non-radiated animals was the controls. Animals were sacrificed at 24 hours followed by histopathology and histomorphometry of submandibular glands, where the mean values were analyzed by Student’s t-test.ResultsIrradiated submandibular glands showed highly significant reduction in acinar area (53%: 77.16±5.05% to 36.55±4.90%) and acinar size (87%: 3,447.53 ± 461.03 mm2 to 428.25 ± 75.22 mm2) with concomitant increase in inter-acinar space (3.46 ± 0.67 mm to 10.08 ± 0.60 mm). Acini nuclei displayed anisonucleosis, poikilonucleosis and pyknosis. “Serous acini” had marked morphologic changes, with fluid accumulation between cells, generalized cytoplasmic vacuolation and vascular congestion, while “mucous acini” largely retained cell architecture. Similarly, ductal cells and nuclei also did not show apparent differences. This demonstrated radiosensitivity variations among different submandibular gland cell types.ConclusionEvaluation of acute submandibular acinar cell dysfunctions has helped in quantifying the histologic elements, which mainly contribute to the resting salivary secretions. Findings would aid in future research of radioprotector drugs, salivary glandular regeneration modalities and in devising prudent radiotherapy protocols to address radiation-induced xerostomia.