Influence of tissue factor polymorphisms (603A>G and 5466A>G) on plasma tissue factor levels and their impact on deep vein thrombosis risk in young Indian population

Deep vein thrombosis (DVT) is multifactorial disorder and well known to cause substantial morbidity and mortality. There is sparse data in the Asian population, particularly India regarding association of tissue factor (TF) gene single nucleotide polymorphisms (SNPs) with plasma TF levels in DVT. So, we analyzed the distribution of SNPs (603A>G and 5466A>G) in India, to evaluate their effect on TF levels in DVT patients. Plasma level and SNPs (603A>G and 5466A>G) of TF gene were screened in subjects (100 DVT patients and 100 controls). Patients had significantly higher TF levels than controls (patients: 84.95?±?17.16 pg/ml, controls: 70.55?±?15.87 pg/ml, p?G polymorphism was significantly higher in patients than controls (patients: 40.5% controls: 27.5%, p?=?0.004). Subjects with AG and GG genotype had significantly higher TF levels than AA genotype (p?=?0.001). After multiple logistic regression analysis, risk of DVT was increased 1.398 fold (95% CI 0.738–2.651) and 4.41 fold (95% CI 1.404–13.884) with AG and GG genotype respectively. Allelic and genotypic frequencies of 5466A>G polymorphism was neither associated with TF levels nor with DVT. We found high TF level in patients with TF 603A>G polymorphism, which is an important predisposing factor in increasing risk of DVT in young Indians. Furthermore, GG genotype of 603A>G polymorphism augments the risk of thrombosis by 4.4 fold, thus highlighting the significance of this polymorphism in the development of DVT. So, we suggest that inclusion of 603A>G polymorphism in prothrombotic work-up may be helpful in making the treatment strategy in DVT patients.     

Mirror Illusion for Sensori-Motor Training in Stroke: A Randomized Controlled Trial

Background

Poststroke, sensory deficits are not uncommon. In spite of the close association between the sensory and motor recovery, the deficits are usually underemphasized. Mirror therapy (MT), a neural-based approach for the motor deficit has not been explored for the sensory impairment. The objective of the present study was to develop and determine the effect of a MT program for sensori-motor impairment among poststroke subjects.

Intravenous Cocaine Results in an Acute Decrease in Levels of Biomarkers of Vascular Inflammation in Humans

Cocaine use causes significant cardiovascular morbidity from its hemodynamic effects. It is less clear whether cocaine promotes atherosclerosis. Vascular inflammation is one of the earliest steps in the pathophysiology of atherosclerosis. We hypothesized that cocaine results in an increase in inflammatory markers. Study objective was to measure the acute effects of intravenous cocaine on biomarkers of vascular inflammation. Eleven chronic cocaine users were enrolled. After a drug-free period, they received intravenous cocaine at 0.36 mg/kg dose in an in-hospital controlled environment. Serum levels of soluble CD40 ligand, monocyte chemoattractant protein-1, interleukin 6, and soluble intercellular adhesion molecule-1 were measured at baseline, 6 h, 24 h, and 6 days after cocaine challenge and at baseline for controls. After cocaine challenge, sCD40 ligand levels decreased in subjects and were significantly lower at 24 h. MCP-1 levels decreased and were significantly lower at the 6-day time point. No significant changes in IL-6 or sICAM-1 level were found. In conclusion, intravenous cocaine did not result in an increase in levels of inflammatory markers. Levels of MCP-1 and sCD40L decreased significantly. This unexpected finding suggests that chronic effects of cocaine on inflammation may be different from acute effects or that higher dosing may have differential effects as compared to lower dose used here.     

Associations of Peritoneal Glucose Load With Male Sexual Dysfunction and Depression in Peritoneal Dialysis Patients

This cross‐sectional study examined possible associations of peritoneal glucose load with male sexual dysfunction and depression in peritoneal dialysis patients. Compared to patients with peritoneal glucose load ≤3 g/kg per day, those with load >3 g/kg per day had higher Beck Depression Inventory scores, (18.9 ± 5.4 vs. 11.4 ± 5.8, P = 0.002) and lower International Index of Erectile Function scores, serum total testosterone and DHEA [(15.4 ± 6.4 vs. 45.1 ± 20.7, P < 0.001), (8.5 ± 3.0 vs. 13.9 ± 3.2, P < 0.001), (113.9 ± 58.8 vs. 280.2 ± 128.3, P < 0.001); respectively)]. Of participants with peritoneal glucose load >3 g/kg per day, 84.6% had mild to moderate erectile dysfunction and 92.3% had abnormal Beck Depression Inventory scores. Peritoneal glucose load inversely correlated with International Index of Erectile Function scores (P < 0.001), total serum testosterone (P = 0.002) and serum DHEA (P = 0.001); and directly with Beck Depression Inventory scores (P < 0.001) and serum estradiol (P < 0.001). This study demonstrated higher prevalence of sexual dysfunction, depression and sex hormone disturbances in male peritoneal dialysis patients receiving higher peritoneal glucose load.     

Itch in dermatomyositis: the role of increased skin interleukin‐31

Patients with dermatomyositis often suffer from itching, but the mechanism is unknown. The authors of this study, based in USA, Korea and Italy, aimed to find out how common itch is in patients with dermatomyositis, and whether a cytokine called IL‐31 is increased in affected skin. Cytokines are proteins produced by cells in the immune system and a delicate balance of cytokines is needed to maintain health. In some skin disorders, such as atopic eczema, this balance is disrupted, and too many pro‐inflammatory cytokines (meaning ones which cause inflammation) are produced. 191 patients with the condition were surveyed, and the authors took biopsy samples from skin lesions, compared with four healthy controls (people without dermatomyositis). They found that half of the patients had moderate to severe itch, and itch was linked to the severity of the disease. In skin lesions from patients with itchy dermatomyositis, there was increased gene expression of IL‐31and its receptor (meaning more IL‐31 and the receptor that helps it work were released), and this expression was stronger in patients with more severe itch. A new drug under investigation for dermatomyositis, lenabasum, reduces or ‘downregulates’ the expression of IL‐31, and the authors conclude that it may prove to be of value in the treatment of itch in this condition.     

Inclusion of hemimegalencephaly into the phenotypic spectrum of NPRL3 pathogenic variants in familial focal epilepsy with variable foci

Despite tremendous progress through next generation sequencing technologies, familial focal epilepsies are insufficiently understood. We sought to identify the genetic basis in multiplex Palestinian families with familial focal epilepsy with variable foci (FFEVF). Family I with 10 affected individuals and Family II with five affected individuals underwent detailed phenotyping over three generations. The phenotypic spectrum of the two families varied from nonlesional focal epilepsy including nocturnal frontal lobe epilepsy to severe structural epilepsy due to hemimegalencephaly. Whole‐exome sequencing and single nucleotide polymorphism array analysis revealed pathogenic variants in NPRL3 in each family, a partial ~38‐kb deletion encompassing eight exons (exons 8‐15) and the 3′‐untranslated region of the NPRL3 gene in Family I, and a de novo nonsense variant c.1063C>T, p.Gln355* in Family II. Furthermore, we identified a truncating variant in the PDCD10 gene in addition to the NPRL3 variant in a patient with focal epilepsy from Family I. The individual also had developmental delay and multiple cerebral cavernomas, possibly demonstrating a digenic contribution to the individual's phenotype. Our results implicate the association of NPRL3 with hemimegalencephaly, expanding the phenotypic spectrum of NPRL3 in FFEVF and underlining that partial deletions are part of the genotypic spectrum of NPRL3 variants.