Modulation of homologous recombination repair gene polymorphisms on genetic damage in chromate exposed workers

Hexavalent chromium [Cr(VI)] is one of the most common environmental carcinogens, which is associated with DNA damage, genetic instability and increase the risk of cancer development. However, the mechanisms of genetic damage induced by Cr(VI) remains to be thoroughly illustrated. A molecular epidemiological study was conducted on 120 chromate exposed workers and 97 controls. Results indicated that,the rs12432907 of XRCC3 carrying T allele, the rs144848 of BRCA2 with C allele and the rs1805800 of NBS1 with genotype(TT) of individuals were associated with lower genetic damage, while the rs2295152 of XRCC3 carrying T allele, the rs13312986 (CC and CT genotypes) and the rs2697679 of NBS1 with A allele were associated with higher genetic damage in workers exposed to chromate. The interaction of chromate exposure with rs2295152 of XRCC3 had a significant effect on micronuclei frequency (MNF). The gene polymorphisms in homologous recombination repair pathway could modulate chromate-induced genetic damage.     

Evaluation of hepatic perfusion and function with modified hepatobiliary scintigraphy

The quantitative relationship between changes in portal vein pressure and the perfusion index was studied, and hepatocellular function was evaluated. A modified protocol of hepatobiliary dynamic scintigraphy with Tc-99m-labeled ethylene hepatobiliary iminodiacetic acid (EHIDA) was performed in 37 patients with hepatic cirrhosis and 12 healthy controls. In 18 patients, the portal vein pressure (PVP) was measured intra-operatively during the portal vein bypass procedure. The portal vein perfusion index (PVI) was obtained by a two-compartment model of hepatic perfusion. A three-compartment model was applied in the hepatocellular extracted and excreted time-radioactivity curves, and the hepatic functional index was calculated including the hepatic uptake index (UI), the mean residual index (MRI), the uptake speed index (UsI), the descent speed index (DsI), the peak uptake (PU), and the peak time (PT) of hepatic uptake. These function indices in the cirrhotic patients were compared to the indices in the healthy controls with a two-sided t-test; specifically, the PU (18.94 ± 6.80 vs. 29.67 ± 18.98, P < 0.01), UI (0.84 ± 5.99 vs. 18.41 ± 13.87, P < 0.05), and UsI (0.58 ± 0.39 vs. 1.23 ± 0.81, P < 0.01) were slower in patients with hepatic cirrhosis compared with the healthy controls. The PT (16.83 ± 4.89 vs. 10.95 ± 2.79, P < 0.001) and MRI (5.93 ± 2.96 vs. 2.74 ± 0.97, P < 0.001) were more prolonged and the DsI (0.07 ± 0.09 vs. 0.18 ± 0.14, P < 0.01) was less compared to controls. The PVI were significantly higher in cirrhotic patients than in controls (46.17 ± 7.83 vs. 29.07 ± 5.71, P < 0.001), and the PVI correlated to the PVP (r = 0.79, P < 0.01).In conclusion, modified quantitative hepatobiliary dynamic scintigraphy can evaluate the changes of portal vein blood flow and monitor hepatocellular function, in which the portal vein blood flow can estimate portal vein pressure.     

Snakebite Envenomation and Heart: Systematic Review

Snakebite envenomation is a neglected tropical disease which can result in morbidity and mortality. Cardiac implications are poorly understood due to the low frequency of cardiotoxicity combined with a lack of robust information, as snakebites commonly occur in remote and rural areas. This review aims to assess cardiovascular implications of snakebite envenoming and proposes an algorithm for screening of cardiovascular manifestations. A systematic review was performed and 29 articles relating to cardiovascular involvement in snakebite envenomation were selected. Cardiovascular involvement seems to be rare and includes a wide spectrum of outcomes, such as myocardial infarction, ventricular dysfunction, hypotension, cardiac arrest, and myocarditis. In a significant proportion of the cases analyzed (24.39%), the cardiovascular manifestations had major consequences (cardiac arrest, myocardial infarction, malignant ventricular arrhythmias, or death). Clinical monitoring, physical examination, and early electrocardiogram should be considered as key measures to detect cardiovascular involvement in patients with evidence of systemic illness.     

遗传性出血性毛细血管扩张症致严重鼻出血的早期基因诊断

目的:探讨遗传性出血性毛细血管扩张症(HHT)致严重鼻出血的早期基因诊断。方法:对2个HHT家系共23例成员进行详细的临床检查及评估,提取外周静脉血DNA,聚合酶链反应扩增目的基因ENG和ACVRL-1,测序并进行序列分析,判断突变的致病性。结果:NMG-1家系采集到静脉血标本的11例中有6例携带ACVRL-1基因的错义突变c.263A>G。GD-2家系采集到静脉血标本的12例中有5例携带ACVRL-1基因的错义突变c.199C>G。有鼻出血病史者突变基因检出率为100%,无鼻出血者史突变基因检出率为25%。结论:基因诊断极高的灵敏度和特异性在HHT早期诊断中具有重要的应用价值,可成为临床常规检测项目。     

Effects of sequential aeromedical evacuations following traumatic brain injury in swine

IntroductionTraumatic brain injuries (TBI) represent a significant percentage of critical injuries in military conflicts. Following injury, wounded warfighters are often subjected to multiple aeromedical evacuations (AE) and associated hypobaria, yet the impact in TBI patients remains to be characterized. This study evaluated the impact of two consecutive simulated AEs in a fluid-percussion TBI model in swine to characterize these effects.MethodsFollowing instrumentation, anesthetized Yorkshire swine underwent a frontal TBI via fluid-percussion. A hypobaric chamber was then used to simulate AE at simulated cabin pressure equivalent to 8000ft (hypobaria) in a 6 h initial flight on day 3, followed by a 9 h flight on day 6, and were monitored for 14 days. Animals in the normobaria group were subjected to the same steps at sea level while Sham animals in both groups were instrumented but not injured. Parameters measured included physiologic response, intracranial pressure (ICP), hematology, chemistry, and serum cytokines. Histopathology of brain, lung, intestine, and kidney was performed, as well as fluorojade staining to evaluate neurodegeneration. All animals were divided into sub-groups by block randomization utilizing a 2-way ANOVA to analyze independent variables.ResultsSurvival was 100% in all groups. Physiologic parameters were largely similar across groups as well during both 6 and 9 h AE. Animals exposed to hypobaria in both the TBI and Sham groups had elevated heart rate (HR) during the 6 h flight (p<0.05). Three animals in the TBI hypo group demonstrated leukocytosis with histologic evidence of meningeal inflammatory response. Expression of serum cytokines was low across all groups. No significant neuronal degeneration was identified in areas away from the site of injury.ConclusionAeromedical evacuation in swine was not associated with significant differences in physiologic measures, cytokine expression or levels of neuronal degeneration. Histological examination revealed higher risk of meningeal inflammatory response and leucocytosis in swine exposed to hypobaria.