DEK :: AFF2 Fusion Sinonasal and Skull Base Nonkeratinizing Squamous Cell Carcinoma : A Clinical Outcome Study Compared With Conventional Sinonasal Squamous Cell Carcinoma.

DEK :: AFF2 fusion nonkeratinizing squamous cell carcinoma (NKSCC) is an emerging entity in the sinonasal tract, temporal bone, and skull base. However, the clinical behavior of these tumors has not been well studied. Here, we report the largest cohort of DEK :: AFF2 carcinomas to determine if morphology, mitotic rate, and/or Ki-67 IHC are associated with patient outcomes, including a comparison with high-risk human papillomavirus (HPV)-associated and independent patients.

Antioxidants green tea extract and nordihydroguaiaretic acid confer species and strain-specific lifespan and health effects in Caenorhabditis nematodes.

The Caenorhabditis Intervention Testing Program (CITP) is an NIH-funded research consortium of investigators who conduct analyses at three independent sites to identify chemical interventions that reproducibly promote health and lifespan in a robust manner. The founding principle of the CITP is that compounds with positive effects across a genetically diverse panel of Caenorhabditis species and strains are likely engaging conserved biochemical pathways to exert their effects. As such, interventions that are broadly efficacious might be considered prominent compounds for translation for pre-clinical research and human clinical applications.

Temporal modelling of the biofilm lifecycle (TMBL) establishes kinetic analysis of plate-based bacterial biofilm dynamics.

Bacterial biofilms are critical to pathogenesis and infection. They are associated with rising rates of antimicrobial resistance. Biofilms are correlated with worse clinical outcomes, making them important to infectious diseases research.

Concurrent Gabapentin and Opioid Use and Risk of Mortality in Medicare Recipients with Non-Cancer Pain.

Gabapentin is prescribed for pain and is perceived as safe generally. However, gabapentin can cause respiratory depression, exacerbated by concomitant central nervous system depressants (e.g.

Duloxetine, Gabapentin, and the Risk for Acute Myocardial Infarction, Stroke, and Out-of-Hospital Death in Medicare Beneficiaries With Non-Cancer Pain.

Objective: Duloxetine is a serotonin-norepinephrine reuptake inhibitor prescribed for musculoskeletal and other forms of chronic pain. Its dual pharmacologic properties have the potential to either raise or lower cardiovascular risk: adrenergic activity may increase the risk for acute myocardial infarction (AMI) and stroke, but antiplatelet activity may decrease risk. Gabapentin is another nonopioid medication used to treat pain, which is not thought to have adrenergic/antiplatelet effects.

Race, Genotype, and Azathioprine Discontinuation : A Cohort Study.

Background: Thiopurines are an important class of immunosuppressants despite their risk for hematopoietic toxicity and narrow therapeutic indices. Benign neutropenia related to an variant (rs2814778-CC) is common among persons of African ancestries.

Objective: To test whether rs2814778-CC was associated with azathioprine discontinuation attributed to hematopoietic toxicity and lower thiopurine dosing.

Predicted expression of genes involved in the thiopurine metabolic pathway and azathioprine discontinuation due to myelotoxicity.

TPMT and NUDT15 variants explain less than 25% of azathioprine-associated myelotoxicity. There are 25 additional genes in the thiopurine pathway that could also contribute to azathioprine myelotoxicity. We hypothesized that among TPMT and NUDT15 normal metabolizers, a score combining the genetically predicted expression of other proteins in the thiopurine pathway would be associated with a higher risk for azathioprine discontinuation due to myelotoxicity.

Extracorporeal photopheresis chargemasters show haphazard billing practices.

Background: United States healthcare spending continues to outpace other developed nations although efforts are being made to increase cost-transparency. Recent legislation requires hospitals to publish a chargemaster, a list of all billable procedure codes together with prices. Chargemaster prices have been shown to be highly variable, if available, and are not typically paid, but contribute to negotiated rates.

Prostate cancer risk variants of the HOXB genetic locus.

The G84E germline mutation of HOXB13 predisposes to prostate cancer and is clinically tested for familial cancer care. We investigated the HOXB locus to define a potentially broader contribution to prostate cancer heritability. We sought HOXB locus germline variants altering prostate cancer risk in three European-ancestry case-control study populations (combined 7812 cases and 5047 controls): the International Consortium for Prostate Cancer Genetics Study; the Nashville Familial Prostate Cancer Study; and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

Oropharyngeal Squamous Cell Carcinoma Morphology and Subtypes by Human Papillomavirus Type and by 16 Lineages and Sublineages.

Oropharyngeal squamous cell carcinoma (SCC) is increasing in incidence and, in Western countries, strongly associated with transcriptionally-active high-risk human papillomavirus (HPV). Within HPV-positive tumors, there is wide morphologic diversity with numerous histologic subtypes of SCC. There are also variable degrees of keratinization, anaplasia, stromal fibrosis, and maturing squamous differentiation.

The morphology of the Late Pleistocene hominin remains from the site of La Cotte de St Brelade, Jersey (Channel Islands).

Thirteen permanent fully erupted teeth were excavated at the Paleolithic site of La Cotte de St Brelade in Jersey in 1910 and 1911. These were all found in the same location, on a ledge behind a hearth in a Mousterian occupation level. They were originally identified as being Neanderthal.

8q24 genetic variation and comprehensive haplotypes altering familial risk of prostate cancer.

The 8q24 genomic locus is tied to the origin of numerous cancers. We investigate its contribution to hereditary prostate cancer (HPC) in independent study populations of the Nashville Familial Prostate Cancer Study and International Consortium for Prostate Cancer Genetics (combined: 2,836 HPC cases, 2,206 controls of European ancestry). Here we report 433 variants concordantly associated with HPC in both study populations, accounting for 9% of heritability and modifying age of diagnosis as well as aggressiveness; 183 reach genome-wide significance.

Automated lifespan determination across Caenorhabditis strains and species reveals assay-specific effects of chemical interventions.

The goal of the Caenorhabditis Intervention Testing Program is to identify robust and reproducible pro-longevity interventions that are efficacious across genetically diverse cohorts in the Caenorhabditis genus. The project design features multiple experimental replicates collected by three different laboratories. Our initial effort employed fully manual survival assays.

Anesthesia and Euthanasia of Brine Shrimp ().

Invertebrates are often overlooked as laboratory animals, yet they are commonly used in toxicology, developmental, cellular and molecular biology, and radiation studies with euthanasia as an endpoint. Little is known regarding appropriate euthanasia methods for invertebrate species, particularly for . Here, we evaluated the AVMA-recommended 2-step method of euthanasia in brine shrimp ().

Correlation of Endoscopic and Histologic Severity Scores in Pediatric Ulcerative Colitis at First Presentation.

Detailed histologic scoring systems have been developed for the assessment of disease activity in ulcerative colitis. Literature from adult patients has shown some correlation between endoscopy and histology, and reproducibility of histologic scoring systems has also been supported. The effectiveness of endoscopic appearance at predicting histologic scores in pediatric patients has not been well studied, and none of the histologic scoring systems used in adults have had interobserver reproducibility assessed in pediatric patients.

Genomic-Epidemiologic Evidence That Estrogens Promote Breast Cancer Development.

Estrogens are a prime risk factor for breast cancer, yet their causal relation to tumor formation remains uncertain. A recent study of 560 breast cancers identified 82 genes with 916 point mutations as drivers in the genesis of this malignancy. Because estrogens play a major role in breast cancer development and are also known to regulate the expression of numerous genes, we hypothesize that the 82 driver genes are likely to be influenced by estrogens, such as 17ß-estradiol (E2), and the estrogen receptor ESR1 (ERα).

Expression and Significance of Cytokeratin 7, a Squamocolumnar Junction Marker, in Head and Neck Squamous Cell Carcinoma.

The favorable features of high-risk human papillomavirus (HPV) in the head and neck are limited to those harboring transcriptionally-active HPV, which occur predominantly in the oropharynx (OP). Factors rendering the OP susceptible to HPV oncogenesis are largely unexplored. The role of cytokeratin 7 (CK7) in predisposition to HPV and cancer in the cervix has been evaluated.

An oral cavity squamous cell carcinoma quantitative histomorphometric-based image classifier of nuclear morphology can risk stratify patients for disease-specific survival.

Oral cavity squamous cell carcinoma is the most common type of head and neck carcinoma. Its incidence is increasing worldwide, and it is associated with major morbidity and mortality. It is often unclear which patients have aggressive, treatment refractory tumors vs those whose tumors will be more responsive to treatment.

Is tumor cellularity in primary invasive breast carcinoma of prognostic significance?

Many methods of analysis to predict survival of invasive mammary carcinoma in the post-neoadjuvant setting utilize tumor cellularity alone or in combination with other tumor features. The goal of this study was to evaluate the prognostic value of tumor cellularity in primary non-treated carcinoma. We used 366 cases of invasive breast carcinoma to determine invasive tumor cellularity (%) by reviewing a representative excisional tumor section and correlated this with breast cancer recurrence (BCR) and overall mortality (OM).

Impact of genetic background and experimental reproducibility on identifying chemical compounds with robust longevity effects.

Limiting the debilitating consequences of ageing is a major medical challenge of our time. Robust pharmacological interventions that promote healthy ageing across diverse genetic backgrounds may engage conserved longevity pathways. Here we report results from the Caenorhabditis Intervention Testing Program in assessing longevity variation across 22 Caenorhabditis strains spanning 3 species, using multiple replicates collected across three independent laboratories.

Optimal diagnostic thresholds for diagnosis of orthostatic hypotension with a 'sit-to-stand test'.

Objective: This study aimed to identify optimal blood pressure cut-offs to diagnose orthostatic hypotension during a sit-to-stand manoeuvre.

Methods: This was a cross-sectional study of patients and healthy controls from the Vanderbilt Autonomic Dysfunction Center. Blood pressure was measured while supine, seated and standing.

The diagnosis of adult-onset haemophagocytic lymphohistiocytosis: lessons learned from a review of 29 cases of bone marrow haemophagocytosis in two large academic institutions.

Aims: Haemophagocytic lymphohistiocytosis (HLH) is divided into paediatric (primary) and adult (secondary) types. While paediatric-HLH has been extensively characterised, similar studies in adults are limited. This study aims to evaluate the significance of the HLH diagnostic criteria as well as other clinical parameters in adults with bone marrow evidence of haemophagocytosis.