A multi-institutional study on the association between BRCA1/BRCA2 mutational status and triple-negative breast cancer in familial breast cancer patients

Triple-negative breast cancer (TNBC) accounts for 12–24 % of all breast cancers. Here, we studied 221 familial breast and/or ovarian cancer patients from 37 hospitals using a comprehensive approach to identify large genomic rearrangements (LGRs) as well as sequence variants, and investigated the association between BRCA1/2 mutational status and TNBC. We performed direct sequencing or mutation scanning followed by direct sequencing. Then, 143 BRCA1/2 mutation-negative patients were screened for LGRs. In this study, the prevalence of BRCA1/2 mutations was high (36.9 %). The prevalence of BRCA1 mutations was similar to that of BRCA2 mutations: 49.4 versus 50.6 %, respectively. TNBC was diagnosed in 35.2 % of BRCA1/2 mutation carriers and 57.1 % of BRCA1 mutation carriers. Conversely, two-thirds of TNBC patients carried BRCA1/2 mutation(s), and about half were BRCA1 mutation carriers. When stratified by the mutated gene, TNBC prevalence in BRCA1 mutation carriers was significantly lower when there was a family history of ovarian cancer. Our multinomial logistic regression model demonstrated that no single factor was sufficient, and at least two factors, such as a patient with family history of both breast cancer and ovarian cancer or a patient diagnosed at a relatively young age (<40 years) with a TNBC phenotype, are necessary to indicate BRCA1/2 genetic testing in this population. Our results suggest that TNBC is a strong predictor for the presence of a BRCA1 mutation in this population, but additional risk factors should also be evaluated to ascertain a 10 % or higher prior probability of BRCA1/2 mutation testing.     

Inhibitory action of water soluble fraction of Terminalia chebula on systemic and local anaphylaxis

We investigated the effects of the water soluble fraction of Terminalia chebula (Combretaceae) (WFTC) on systemic and local anaphylaxis. WFTC administered 1h before compound 48/80 injection inhibited compound 48/80-induced anaphylactic shock 100% with doses of 0.01-1.0 g/kg. When WFTC was administered 5 or 10 min after compound 48/80 injection, the mortality also decreased in a dose-dependent manner. Passive cutaneous anaphylaxis was inhibited by 63.5+/-7.8% by oral administration of WFTC (1.0 g/kg). When WFTC was pretreated at concentrations ranging from 0.005 to 1.0 g/kg, the serum histamine levels were reduced in a dose-dependent manner. WFTC (0.01-1.0 mg/ml) also significantly inhibited histamine release from rat peritoneal mast cells (RPMC) by compound 48/80. However, WFTC (1.0 mg/ml) had a significant increasing effect on anti-dinitrophenyl IgE-induced tumor necrosis factor-alpha production from RPMC. These results indicate that WFTC may possess a strong antianaphylactic action.     

The association between the serum vitamin D levels and the stroke lesion size,functional ability,and cognition in elderly Korean ischemic stroke patients

The purpose of this study was to confirm the association between the serum vitamin D levels and ischemic stroke lesion size, functional ability, and cognitive function in elderly ischemic stroke patients. This study included Korean ischemic stroke patients aged 65 to 85 years. The size of the lesion was measured in brain images taken within 24 hours of hospitalization. The level of 25-(OH) Vitamin D (ng/mL), a metabolite of vitamin D, in the serum collected within 48 hours of hospitalization, and the modified Barthel index (MBI), gait performance, the muscle power of hip and knee extensors on the hemiplegic side, and mini-mental status examination (MMSE) were recorded within 1 week of the onset of the disease. Each factor was compared through correlation analysis, and the significance was confirmed using the Spearman correlation coefficient method. The association between the serum vitamin D levels and the size of the ischemic stroke lesion, the MBI, gait performance, the muscle power of hip and knee extensors on the hemiplegic side, and the MMSE were analyzed. It was confirmed that there was a significant correlation between all the factors (P < .005). In patients with serum vitamin D levels of ≥ 30 ng/mL, both the functional ability and cognitive functions were better than in patients lower than 30 ng/mL. We confirmed the lower the level of serum vitamin D levels, the larger the size of the ischemic stroke lesion when it occurred in elderly Koreans. And we confirmed that serum vitamin D levels affected the functional ability and cognitive function. And we recommend that elderly Koreans should maintain their blood vitamin D level above 30 ng/mL. We believe that this will help preserve the functional ability and cognitive function when ischemic stroke occurred.     

Serum total cholesterol level as a potential predictive biomarker for neurological outcomes in cardiac arrest survivors who underwent target temperature management

Cholesterol is an essential substance to maintain cell membranes. Low levels of total cholesterol (TC) are associated with poor prognosis in critically ill patients. Cardiac arrest-induced whole-body ischemia and reperfusion injury cause a sepsis-like syndrome. The Cholesterol level in post-cardiac arrest patients may indicate the degree of endotoxemia or inflammation caused by ischemic and reperfusion injury. We aimed to investigate the association of TC levels with neurologic outcome of out-of-hospital cardiac arrest (OHCA) survivors who underwent target temperature management (TTM). This was a retrospective single-center observational study from May 2018 to April 2021 on a cohort of 106 patients. TC levels were determined in samples obtained immediately and at 24, 48, and 72 hours after the return of spontaneous circulation (ROSC). The primary outcome was poor neurologic outcome at 3 months after ROSC. Poor neurologic outcome was defined by cerebral performance categories 3 to 5. Sixty patients had a poor neurologic outcome. TC levels were significantly lower in the poor neurologic outcome group at each time point. The TC levels for predicting poor neurologic outcome had a sensitivity of 80.8%, with 67.6% specificity at 48 hours (TC₄₈) after ROSC. The areas under the curve value of TC₄₈ was 0.771 (0.670–0.853), with a cutoff value of 114 mg/dL. TC level at 48 hours after ROSC was a helpful marker for the 3-month poor neurologic outcome. This might be an easily accessible predictive marker of neurologic outcome in OHCA survivors treated with TTM.     

Development and Validation of a Bioinformatic Workflow for the Rapid Detection of Viruses in Biosecurity

The field of biosecurity has greatly benefited from the widespread adoption of high-throughput sequencing technologies, for its ability to deeply query plant and animal samples for pathogens for which no tests exist. However, the bioinformatics analysis tools designed for rapid analysis of these sequencing datasets are not developed with this application in mind, limiting the ability of diagnosticians to standardise their workflows using published tool kits. We sought to assess previously published bioinformatic tools for their ability to identify plant- and animal-infecting viruses while distinguishing from the host genetic material. We discovered that many of the current generation of virus-detection pipelines are not adequate for this task, being outperformed by more generic classification tools. We created synthetic MinION and HiSeq libraries simulating plant and animal infections of economically important viruses and assessed a series of tools for their suitability for rapid and accurate detection of infection, and further tested the top performing tools against the VIROMOCK Challenge dataset to ensure that our findings were reproducible when compared with international standards. Our work demonstrated that several methods provide sensitive and specific detection of agriculturally important viruses in a timely manner and provides a key piece of ground truthing for method development in this space.     

Impact of Hepatitis B Virus Infection,Non-alcoholic Fatty Liver Disease,and Hepatitis C Virus Co-infection on Liver-Related Death among People Tested for Hepatitis B Virus in British Columbia: Results from a Large Longitudinal Population-Based Cohort Study

Data on the contribution of hepatitis B virus (HBV) infection and related comorbidities to liver-related mortality in Canada are limited. We assessed the concurrent impact of HBV infection, non-alcoholic fatty liver disease (NAFLD), and hepatitis C virus (HCV) coinfection on liver-related deaths in British Columbia (BC), Canada. We used data from the BC Hepatitis Testers Cohort (BC-HTC). We used Fine–Gray multivariable sub-distributional hazards models to assess the effect of HBV, NAFLD, and HCV coinfection on liver-related mortality, while adjusting for confounders and competing mortality risks. The liver-related mortality rate was higher among people with HBV infection than those without (2.57 per 1000 PYs (95%CI: 2.46, 2.69) vs. 0.62 per 1000 PYs (95%CI: 0.61, 0.64), respectively). Compared with the HBV negative groups, HBV infection was associated with increased liver-related mortality risk in almost all of the subgroups: HBV mono-infection (adjusted subdistribution hazards ratio (asHR) of 3.35, 95% CI 3.16, 3.55), NAFLD with HBV infection, (asHR 12.5, 95% CI 7.08, 22.07), and HBV/HCV coinfection (asHR 8.4, 95% CI 7.62, 9.26). HBV infection is associated with a higher risk of liver-related mortality, and has a greater relative impact on people with NAFLD and those with HCV coinfection. The diagnosis and treatment of viral and fatty liver disease are required to mitigate liver-related morbidity and mortality.