Association of the Colorectal CpG Island Methylator Phenotype with Molecular Features, Risk Factors, and Family History

The CpG Island Methylator Phenotype (CIMP) represents a subset of colorectal cancers (CRCs) characterized by widespread aberrant DNA hypermethylation at select CpG islands. The risk factors and environmental exposures contributing to etiologic heterogeneity between CIMP and non-CIMP tumors are not known

Functional Amyloids Composed of Phenol Soluble Modulins Stabilize Staphylococcus aureus Biofilms

Staphylococcus aureus is an opportunistic pathogen that colonizes the skin and mucosal surfaces of mammals. Persistent staphylococcal infections often involve surface-associated communities called biofilms. Here we report the discovery of a novel extracellular fibril structure that promotes S. aureus biofilm integrity. Biochemical and genetic analysis has revealed that these fibers have amyloid-like properties and consist of small peptides called phenol soluble modulins (PSMs). Mutants unable to produce PSMs were susceptible to biofilm disassembly by matrix degrading enzymes and mechanical stress. Previous work has associated PSMs with biofilm disassembly, and we present data showing that soluble PSM peptides disperse biofilms while polymerized peptides do not. This work suggests the PSMs' aggregation into amyloid fibers modulates their biological activity and role in biofilms

Association of the Colorectal CpG Island Methylator Phenotype with Molecular Features, Risk Factors, and Family History

BACKGROUND: The CpG Island Methylator Phenotype (CIMP) represents a subset of colorectal cancers (CRCs) characterized by widespread aberrant DNA hypermethylation at select CpG islands. The risk factors and environmental exposures contributing to etiologic heterogeneity between CIMP and non-CIMP tumors are not known. METHODS: We measured the CIMP status of 3,119 primary population-based CRC tumors from the multinational Colon Cancer Family Registry. Etiologic heterogeneity was assessed by a case-case study comparing risk factor frequency of CRC cases with CIMP and non-CIMP tumors using logistic regression to estimate the case-case odds ratio (ccOR). RESULTS: We found associations between tumor CIMP status and MSI-H (ccOR=7.6), BRAF V600E mutation (ccOR=59.8), proximal tumor site (ccOR=9) (all p<0.0001), female sex (ccOR=1.8; 95% CI=1.5-2.1), older age (ccOR=4.0 comparing over 70 years vs under 50; 95% CI=3.0-5.5) and family history of CRC (ccOR=0.6, 95% CI=0.5-0.7). While use of NSAIDs varied by tumor CIMP status for both males and females (p=0.0001 and p=0.02, respectively), use of multi-vitamin or calcium supplements did not. Only for female CRCs was CIMP status associated with increased pack-years of smoking (trend p < 0.001) and body mass index (BMI) (trend p = 0.03). CONCLUSIONS: The frequency of several CRC risk factors varied by CIMP status, and the associations of smoking and obesity with tumor subtype were evident only for females. IMPACT: Differences in the associations of a unique DNA methylation-based subgroup of CRC with important lifestyle and environmental exposures increase understanding of the molecular pathologic epidemiology of this heavily methylated subset of CRCs

Delayed intracranial hemorrhage in elderly anticoagulated patients sustaining a minor fall.

BACKGROUND: Falls are a common cause of hospitalization, morbidity, and mortality among the elderly in the United States. Evidence-based imaging recommendations for evaluation of delayed intracranial hemorrhage (DICH) are not generally agreed upon. The purpose of this project was to evaluate the incidence of DICH detected by head computer tomography (CT) among an elderly population on pre-injury anticoagulant or antiplatelet (ACAP) therapy. METHODS: Data from a Level 1 Trauma Center trauma registry was used to assess the incidence of DICH in an elderly population of patients (≥65 years) who sustained a minor fall while on pre-injury ACAP medications. Counts and percentages are reported. RESULTS: Data on 1076 elderly trauma patients were downloaded, of which 838 sustained a minor fall and 513 were found to be using a pre-injury ACAP medication. One patient (0.46%) with a DICH was identified out of 218 patients who received a routine repeat head CT. Aspirin and warfarin were the most common pre-injury ACAP medications and 19.27% (42/218) of patients were found to be using multiple ACAP medications. CONCLUSIONS: Universal screening protocols promote immediate-term patient safety, but do so at a great expense with respect to health expenditures and increased radiation exposure. This analysis highlights the need for an effective risk assessment tool for DICH that would reduce the burden of unnecessary screenings while still identifying life-threatening intracranial hemorrhages in affected patients