Testing for high‐risk HPV in cervical and tonsillar paraffin‐embedded tissue using a cartridge‐based assay

This study evaluates the suitability of Xpert HPV (Cepheid, Sunnyvale, CA, USA) test for cervical and tonsillar formalin‐fixed paraffin‐embedded (FFPE) tissue samples as compared to the tests currently used in diagnostics. Cervical biopsies and liquid cytology (LC) samples were collected from 48 women attending colposcopy. Biopsies were processed for histology and tested for hrHPV using Xpert HPV. LC samples were tested using Xpert and Hybrid Capture 2 (HC2; Qiagen, Hilden, Germany) tests. Also 29 archived tonsillar carcinoma samples were tested using Xpert, and the results were compared with histology and immunohistochemical p16INK4a (p16) staining. Among valid cervical LC samples 46.8% were hrHPV positive using Xpert test and 55.3% with HC2. The sensitivity of Xpert was 84.6% as compared to HC2, and overall test concordance was 91.5%. Test concordance between valid Xpert results from biopsies and LC samples was 84.6%. Among valid tonsillar samples 70.4% were hrHPV positive, and concordance of 96.3% was found between Xpert and p16 staining. To conclude, Xpert HPV test cartridge provides a convenient platform to test individual samples, including FFPE samples. Further studies are needed to establish whether test sensitivity is sufficient to reliably differentiate between hrHPV positive and hrHPV negative head and neck carcinomas.     

Sex Differences in Ischemic Stroke Readmission Rates and Subsequent Outcomes After Coronary Artery Bypass Graft Surgery

Background and PurposePrior studies examining sex-related risk of readmission for ischemic stroke (IS) after coronary artery bypass grafting (CABG) did not adjust for preoperative comorbidities and used small study samples that were single-center or otherwise poorly generalizable. We assessed risk of readmission for IS after CABG for females compared to males in a nationwide sample.MethodsThe 2013 Nationwide Readmissions Database contains data on 49% of all U.S. hospitalizations. We used population weighting to determine national estimates. Using all follow-up data up to 1 year after discharge from CABG hospitalization, we estimated Kaplan-Meier cumulative risk of IS, stratified by sex, using the log-rank test for significance. We created Cox proportional hazard models to calculate hazard ratios (HR) and 95% confidence intervals (CI) for IS readmission, with sex as the main independent variable. We ran unadjusted models and models adjusted for age, vascular risk factors, estimated severity of illness and risk of mortality, hospital characteristics, and income quartile of patient's zip code.ResultsAn estimated 53,270 females and 147,396 males survived index CABG admission in 2013. There was a consistently elevated cumulative risk of readmission for IS after CABG for females versus males (log-rank p-value = 0.0014). In the unadjusted Cox model, the HR of IS in females vs. males was 1.35 (95% CI 1.12–1.62, p = 0.0015). The elevated risk for females remained after adjusting for severity of illness (1.30 [1.08–1.56], p = 0.0056) and risk of mortality (1.28 [1.07–1.54], p = 0.0086). This elevated risk persisted after adjusting for multiple vascular risk factors, hospital characteristics, and income quartile of patient's zip code (1.23 [1.02–1.48], p = 0.03).ConclusionsWe found a 23% increased risk of readmission for IS up to 1 year after CABG for females compared to males in a fully adjusted model utilizing a large, contemporary, nationwide database. Further research would clarify mechanisms of this increased risk among women.     

In vitro models for assessing the potential cardiovascular disease risk associated with cigarette smoking

Atherosclerotic cardiovascular disease is a prevalent human disorder and a significant cause of human morbidity and mortality. A number of risk factors may predispose an individual to developing atherosclerosis, and of these factors, cigarette smoking is strongly associated with the development of cardiovascular disease. Current thinking suggests that exposure to toxicants found in cigarette smoke may be responsible for this elevated disease likelihood, and this gives rise to the idea that reductions in the levels of some smoke toxicants may reduce the harm associated with cigarette smoking. To assess the disease risk of individuals who smoke cigarettes with altered toxicant levels, a weight-of-evidence approach is required examining both exposure and disease-related endpoints. A key element of such an assessment framework are data derived from the use of in vitro models of cardiovascular disease, which when considered alongside other forms of data (e.g. from clinical studies) may support evidence of potential reduced risk. Importantly, such models may also be used to provide mechanistic insight into the effects of smoking and of smoke toxicant exposure in cardiovascular disease development. In this review the use of in vitro models of cardiovascular disease and one of the contributory factors, oxidative stress, is discussed in the context of assessing the risk potential of both conventional and modified cigarettes. Practical issues concerning the use of these models for cardiovascular disease understanding and risk assessment are highlighted and areas of development necessary to enhance the power and predictive capacity of in vitro disease models in risk assessment are discussed.     

Pseudomembranous collagenous colitis with superimposed drug damage

Pseudomembranous collagenous colitis is a rare pathological condition, not related to infectious agents, and characterized by thickening of the subepithelial collagen and formation of pseudomembranes. We report one such case, which responded to budesonide treatment after failures of previous approaches given, being unaware of the correct diagnosis.     

RNAi function, diversity, and loss in the fungal kingdom

RNAi is conserved and has been studied in a broad cross-section of the fungal kingdom, including Neurospora crassa, Schizosaccharomyces pombe, Cryptococcus neoformans, and Mucor circinelloides. And yet well known species, including the model yeast Saccharomyces cerevisiae and the plant pathogen Ustilago maydis, have lost RNAi, providing insights and opportunities to illuminate benefits conferred both by the presence of RNAi and its loss. Some of the earliest studies of RNAi were conducted in Neurospora, contemporaneously with the elucidation of RNAi in Caenorhabditis elegans. RNAi is a key epigenetic mechanism for maintaining genomic stability and integrity, as well as to defend against viruses, and given its ubiquity was likely present in the last eukaryotic common ancestor. In this review, we describe the diversity of RNAi mechanisms found in the fungi, highlighting recent work in Neurospora, S. pombe, and Cryptococcus. Finally, we consider frequent, independent losses of RNAi in diverse fungal lineages and both review and speculate on evolutionary forces that may drive the losses or result therefrom.     

The role of CE-MRA of the supraortic vessels in the detection of associated intracranial pathology

Neurological Sciences - Contrast-enhanced magnetic resonance angiography (CE-MRA) has become a very popular imaging technique in the evaluation of the extracranial vessels pathology, while it is...