Recent Vitamin K Antagonist Use and Intracranial Hemorrhage After Endovascular Thrombectomy for Acute Ischemic Stroke.

Importance: Use of oral vitamin K antagonists (VKAs) may place patients undergoing endovascular thrombectomy (EVT) for acute ischemic stroke caused by large vessel occlusion at increased risk of complications. Objective: To determine the association between recent use of a VKA and outcomes among patients selected to undergo EVT in clinical practice. Design, Setting, and Participants: Retrospective, observational cohort study based on the American Heart Association's Get With the Guidelines-Stroke Program between October 2015 and March 2020. From 594 participating hospitals in the US, 32 715 patients with acute ischemic stroke selected to undergo EVT within 6 hours of time last known to be well were included. Exposure: VKA use within the 7 days prior to hospital arrival. Main Outcome and Measures: The primary end point was symptomatic intracranial hemorrhage (sICH). Secondary end points included life-threatening systemic hemorrhage, another serious complication, any complications of reperfusion therapy, in-hospital mortality, and in-hospital mortality or discharge to hospice. Results: Of 32 715 patients (median age, 72 years; 50.7% female), 3087 (9.4%) had used a VKA (median international normalized ratio [INR], 1.5 [IQR, 1.2-1.9]) and 29 628 had not used a VKA prior to hospital presentation. Overall, prior VKA use was not significantly associated with an increased risk of sICH (211/3087 patients [6.8%] taking a VKA compared with 1904/29 628 patients [6.4%] not taking a VKA; adjusted odds ratio [OR], 1.12 [95% CI, 0.94-1.35]; adjusted risk difference, 0.69% [95% CI, -0.39% to 1.77%]). Among 830 patients taking a VKA with an INR greater than 1.7, sICH risk was significantly higher than in those not taking a VKA (8.3% vs 6.4%; adjusted OR, 1.88 [95% CI, 1.33-2.65]; adjusted risk difference, 4.03% [95% CI, 1.53%-6.53%]), while those with an INR of 1.7 or lower (n = 1585) had no significant difference in the risk of sICH (6.7% vs 6.4%; adjusted OR, 1.24 [95% CI, 0.87-1.76]; adjusted risk difference, 1.13% [95% CI, -0.79% to 3.04%]). Of 5 prespecified secondary end points, none showed a significant difference across VKA-exposed vs VKA-unexposed groups. Conclusions and Relevance: Among patients with acute ischemic stroke selected to receive EVT, VKA use within the preceding 7 days was not associated with a significantly increased risk of sICH overall. However, recent VKA use with a presenting INR greater than 1.7 was associated with a significantly increased risk of sICH compared with no use of anticoagulants.

Multi-criteria decision making and Dempster-Shafer model-based delineation of groundwater prospect zones from a semi-arid environment.

The present study illustrates the delineation of the groundwater potential zones in one of the most critical and drought-affected areas under Bundelkhand region of Uttar Pradesh (India). Hydrological evaluations were carried out using GIS tools and remote sensing data which ultimately yielded several thematic maps, such as lineament density, land use/land cover, drainage density, lithology, slope, geomorphology, topographic wetness index (TWI), DEM, and soil. Thematic layers were assigned relative weightages as per their groundwater potential prospects under multi-criteria decision making (MCDM) method through analytical hierarchy process (AHP). To recognize the groundwater potential zone, weighted overlay analysis was also performed. Additionally, for testing of the Dempster-Shafer model, 16 wells in the study area have been selected. Based on the probability of the groundwater occurrence, the belief factor was equated to delineate groundwater potential zones which illustrate five different potential zones. According to the AHP model, the northwest side of the study area is characterized with very high potential zones whereas the northeast and southeast regions constitute medium and low groundwater potential zones respectively. According to the DS model, very high groundwater potential zones constitute 17% and the remaining area falls under low potential. Overall accuracy of the DS model is higher than AHP model.

Mosaicism for trisomy 21 and ring (21) in a male born to normal parents: a case report.

We present a case of a ring (21) in a mentally challenged patient with mosaicism for trisomy 21 showing karyotype 47, XY,+21/47,XY,+21(r)/46,XY, born to normal parents. The parents and female sibling were phenotypically normal. This is a unique case report from Central India, on occurrence of trisomy 21 and r (21) in the same individual born to normal parents. Also being documented for the first time is the immuno-FISH analysis revealing differential expression of hTERT and a linked over expression of TRF2 in proband, probably corresponding to a high percentage of acrocentric associations.

Evaluation of antioxidant activity of two important memory enhancing medicinal plants Baccopa monnieri and Centella asiatica.

BACKGROUND: Free radicals or highly reactive oxygen species are capable of inducing oxidative damage to human body. Antioxidants are the compounds which terminate the attack of reactive species and reduce the risk of diseases. Both Baccopa monnieri and Centella asiatica are used in treatment of brain disorders in humans and have almost similar effects. OBJECTIVE: The study was conducted to determine the antioxidant properties of two well-known memory enhancer medicinal plants Baccopa monnieri and Centella asiatica. RESULTS: The antioxidant activity of these two medicinal plants was evaluated by measuring reducing ability, free radical scavenging activity by DPPH and hydrogen peroxide methods. The antioxidants compounds like ascorbic acid, total phenols and tannins were also evaluated in these plants. Baccopa monnieri and Centella asiatica exhibited significant differences (P<0.05) in their antioxidant values. The methanolic extract of whole leaf powder of Baccopa monnieri exhibited significantly higher antioxidant activity than the Centella asiatica. The antioxidant components viz. ascorbic acid, total phenols and tannins were also found in a higher concentration in Baccopa monnieri as compared to Centella asiatica. CONCLUSION: It can be concluded from the study that regular use of Baccopa monnieri as a supplement could be more helpful compared to Centella asiatica in treatment of neurological disorders caused by free radical damage.

Molecular mechanisms of isocyanate induced oncogenic transformation in ovarian epithelial cells.

Ovarian surface epithelium is under constant physiological pressure to maintain its integrity. Environmental toxic exposure can contribute to degenerative pathologies including ovarian cancer. Based on our current understanding, we aimed at listing mechanistic insights that contribute to ovarian carcinogenesis after exposure to methyl isocyanate, an ubiquitous environmental pollutant. Ovarian epithelial cells manifested a persistent DNA damage response along with increased accumulation of GADD45, p21, p16(INK4A) and pRb proteins upon treatment. Increase in cell size and ß-gal positive staining showing inception of premature senescence with morphological transformation and structural and numerical chromosomal abnormalities were also observed. Immuno-FISH analysis illustrated early loss of TRF2 protein suggestive of telomeric dysfunction due to premature senescence and plausible association with chromosomal and microsatellite instability. Soft-agar assay displayed neoplasticity in treated cells demonstrating onset of malignant transformation. These results indicate that isocyanate exposure alters ovarian epithelial cell proliferation and might lead to ovarian dysfunction and carcinogenesis.

Molecular characterization of isocyanate-induced male germ-line genomic instability.

Male reproductive health is exquisitely sensitive to environmental insults as evidenced by the rising incidence of testicular cancers and low and probably declining semen quality. Isocyanates, such as methyl isocyanate (MIC), with their wide industrial applications, are known to exert severe ill health effects. The present study was performed to find out the pathophysiological implications of isocyanate exposure on the male germ line. The investigations were performed in the cultured mouse spermatogonial GC-1 spg cell line using N-succinimidyl N-methylcarbamate, a surrogate chemical to MIC. DNA damage, oxidative stress and apoptosis response parameters increased with time of exposure and dose after treatment. Treated cells also displayed elevated levels of inflammatory cytokines as well as morphological transformation and stress-responsive senescence. Chromosomal aberrations, telomere anomaly, aneuploidy and variable amplification of microsatellite repeats additionally indicated induced genomic instability. This was accompanied by evidence of a deregulation of cell cycle progression, such as substantial fold-changes in the expression of proliferating cell nuclear antigen, Cyclin D1, Bcl-2 and Bax genes; and aberrant expression of p53, cyclin A, cyclin E, CDK-2 and aurora kinase-B proteins. Our results demonstrate that MIC in the form of N-succinimidyl N-methylcarbamate promotes germ-line genomic instability in vitro. We envisage that understanding the interplay between environmental toxin-induced signaling and predisposition to testicular cancers would spur identification of meaningful targets for useful therapeutic translational modalities.

Mitochondrial oxidative stress elicits chromosomal instability after exposure to isocyanates in human kidney epithelial cells.

The role of oxidative stress is often attributed in environmental renal diseases. Isocyanates, a ubiquitous chemical group with diverse industrial applications, are known to undergo bio-transformation reactions upon accidental and occupational exposure. This study delineates the role of isocyanate-mediated mitochondrial oxidative stress in eliciting chromosomal instability in cultured human kidney epithelial cells. Cells treated with 0.005 microM concentration of methyl isocyanate displayed morphological transformation and stress-induced senescence. Along the time course, an increase in DCF fluorescence indicative of oxidative stress, depletion of superoxide dismutase (SOD) and glutathione reductase (GR) and consistent accumulation of 8-oxo-dG were noticed. Thus, endogenous oxidative stress resulted in aberrant expression of p53, p21, cyclin E and CDK2 proteins, suggestive of deregulated cell cycle, chromosomal aberrations, centromeric amplification, aneuploidy and genomic instability.

Critical illness myopathy associated with hyperthyroidism.

A 51-year-old woman was admitted to the intensive care unit for exacerbation of chronic obstructive pulmonary disease. She received antibiotics, neuromuscular blocking agents, and steroids. After 8 days in the intensive care unit, she was noted to be severely weak, her serum creatine kinase had risen to 1,692 U/L (normal, 20-220 U/L), and a muscle biopsy was consistent with critical illness myopathy. As a result of evaluating for resting tachycardia, the patient was found to be hyperthyroid. Her weakness rapidly improved within 1 month after treatment of her hyperthyroidism with iodine-131 and methimazole. The metabolic alterations associated with hyperthyroidism may enhance the risk of developing critical illness myopathy after the administration of antibiotics, neuromuscular blocking agents, and steroids in the intensive care unit.

Channelopathies in pediatric neurology.

Although the genetic neurologic channelopathies are uncommon, they serve as models that further understanding of disease mechanisms in paroxysmal disorders. Many other neurologic channelopathies likely will be identified in the future.