Cutting Edge Issues in Autoimmune Gastritis

Autoimmune gastritis is the outcome of a pathological CD4 T cell-mediated autoimmune response directed against the gastric H/K-ATPase. Silent initially, the gastric lesion becomes manifest in humans by the development of megaloblastic pernicious anemia arising from vitamin B12 deficiency. Cutting edge issues in this disease relate to its epidemiology, immunogenetics, a role for Helicobacter pylori as an infective trigger through molecular mimicry, its immunopathogenesis, associated organ-specific autoimmune diseases, laboratory diagnosis, and approaches to curative therapy.     

Changes in Apoptotic Mechanisms Following Penetrating Ballistic-Like Brain Injury

We investigated apoptotic pathways in a model of severe traumatic brain injury, penetrating ballistic-like brain injury (PBBI). TUNEL staining identified increasing apoptosis within 24 h. From targeted arrays, 11 genes were identified for temporal mRNA evaluation. In addition, mRNA levels and enzyme activity for caspases 3, 8, and 9 were examined. In the death receptor-mediated apoptosis pathway, the relative quantities (RQs) of mRNA for tnfr1, fas, and tnf were upregulated while trail mRNA was downregulated. In the anti-apoptotic TNF-R2 pathway, tnfr2 and flip were upregulated while xiap was downregulated. These findings indicate that increases in tnf levels following injury are not only pro-apoptotic but may also signal competing anti-apoptotic mechanisms. For the mitochondria-mediated apoptosis pathway, RQs of anti-apoptotic factors bcl2a1d and birc3 were upregulated while both bcl2 and bax were downregulated. RQs for casp 3 and casp 8 increased while casp9 decreased. Enzymatic activity increased for caspases 3, 8, and 9. While multiple mechanisms promoting and inhibiting apoptosis are at play during the first week after a PBBI, the cumulative result remains increased apoptosis. The ability to understand and dissect these events will assist in the development and evaluation of treatments targeting apoptosis following severe brain injury.     

MAT2A Inhibition Blocks the Growth of MTAP-Deleted Cancer Cells by Reducing PRMT5-Dependent mRNA Splicing and Inducing DNA Damage

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Determination of breast cancer prognosis after neoadjuvant chemotherapy: comparison of Residual Cancer Burden (RCB) and Neo-Bioscore

Background To compare RCB (Residual Cancer Burden) and Neo-Bioscore in terms of prognostic performance and see if adding pathological variables improve these scores.Methods We analysed 750 female patients with invasive breast cancer (BC) treated with neoadjuvant chemotherapy (NAC) at Institut Curie between 2002 and 2012. Scores were compared in global population and by BC subtype using Akaike information criterion (AIC), C-Index (concordance index), calibration curves and after adding lymphovascular invasion (LVI) and pre-/post-NAC TILs levels.Results RCB and Neo-Bioscore were significantly associated to disease-free and overall survival in global population and for triple-negative BC. RCB had the lowest AICs in every BC subtype, corresponding to a better prognostic performance. In global population, C-Index values were poor for RCB (0.66; CI [0.61–0.71]) and fair for Neo-Bioscore (0.70; CI [0.65–0.75]). Scores were well calibrated in global population, but RCB yielded better prognostic performances in each BC subtype. Concordance between the two scores was poor. Adding LVI and TILs improved the performance of both scores.Conclusions Although RCB and Neo-Bioscore had similar prognostic performances, RCB showed better performance in BC subtypes, especially in luminal and TNBC. By generating fewer prognostic categories, RCB enables an easier use in everyday clinical practice.Subject terms: Breast cancer, Breast cancer, Chemotherapy     

RCAM: a proposed model of recovery capital for adolescents

Problematic substance use is a challenge worldwide among adolescents. The recovery process requires holistic support addressing multiple and intersecting substance use risk factors; yet, there remains a lack of evidence on how to best understand and support adolescents in recovery. Recovery capital (RC) is a model that can be used to identify areas of assets that could be enhanced and barriers to address in one’s recovery process; however, this construct was generated through a study of adults who achieved natural recovery and it has since been used to frame adult recovery-related literature across the world. The primary aim of this article is to outline the rationale for and present a Recovery Capital for Adolescents Model (RCAM). The article will discuss the original recovery capital model, describe adolescent development, substance use, and recovery, and detail proposed developmental adaptations. Future qualitative and quantitative research should explore the RCAM to assess whether the proposed dimensions are complete as well as to assess its utility in clinical settings for identifying strengths and barriers for adolescents in or seeking recovery.     

In vivo and in vitro methods for evaluating soil arsenic bioavailability: relevant to human health risk assessment

Arsenic (As) is the most frequently occurring contaminant on the priority list of hazardous substances, which lists substances of greatest public health concern to people living at or near U.S. National Priorities List site. Accurate assessment of human health risks from exposure to As-contaminated soils depends on estimating its bioavailability, defined as the fraction of ingested As absorbed across the gastrointestinal barrier and available for systemic distribution and metabolism. Arsenic bioavailability varies among soils and is influenced by site-specific soil physical and chemical characteristics and internal biological factors. This review describes the state-of-the science that supports our understanding of oral bioavailability of soil As, the methods that are currently being explored for estimating soil As relative bioavailability (RBA), and future research areas that could improve our prediction of the oral RBA of soil As in humans. The following topics are addressed: (1) As soil geochemistry; (2) As toxicology; (3) in vivo models for estimating As RBA; (4) in vitro bioaccessibility methods; and (5) conclusions and research needs.     

Performance of the integrated management of childhood illness algorithm for diagnosis of HIV-1 infection among African infants

OBJECTIVES:: Early infant HIV-1 diagnosis and treatment substantially improve survival. Where virologic HIV-1 testing is unavailable, integrated management of childhood illness (IMCI) clinical algorithms may be used for infant HIV-1 screening. We evaluated the performance of the 2008 WHO IMCI HIV algorithm in a cohort of HIV-exposed Kenyan infants. METHODS:: From 1999 to 2003, 444 infants had monthly clinical assessments and quarterly virologic HIV-1 testing. Using archived clinical data, IMCI sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated using virologic testing as a gold standard. Linear regression and survival analyses were used to determine the effect of age on IMCI performance and timing of diagnosis. RESULTS:: Overall IMCI sensitivity, specificity, PPV, and NPV value were 58, 87, 52, and 90%, respectively. Sensitivity (1.4%) and PPV (14%) were lowest at 1 month of age, when 81% of HIV infections already had occurred. Sensitivity increased with age (P?相似文献