A fibromyxoid stromal response is associated with an infiltrative tumor morphology, perineural invasion, and lymph node metastasis in squamous cell carcinoma of the vulva.

Patterns of invasion and stromal response are understudied in vulvar squamous cell carcinoma. The aim of this study was to explore whether histologic features such as an infiltrative pattern of invasion and fibromyxoid stromal response (FMX-SR) are meaningful prognostic factors. We reviewed 143 vulvar squamous cell carcinoma resections and correlated patterns of invasion and stromal response with patient age, ethnicity, depth of invasion, tumor size, perineural invasion (S100/AE1/3 stain), lymph node involvement (LNI), extranodal extension, margin status, pathologic stage, and recurrence.

Contacts Between Alcohols in Water Are Random Rather than Hydrophobic.

Given the importance of water-mediated hydrophobic interactions in a wide range of biological and synthetic self-assembly processes, it is remarkable that both the sign and the magnitude of the hydrophobic interactions between simple amphiphiles, such as alcohols, remain unresolved. To address this question, we have performed Raman hydration-shell vibrational spectroscopy and polarization-resolved femtosecond infrared experiments, as well as random mixing and molecular dynamics simulations. Our results indicate that there are no more hydrophobic contacts in aqueous solutions of alcohols ranging from methanol to tertiary butyl alcohol than in random mixtures of the same concentration.

Clinical relevance of morphologic MRI criteria for the assessment of lymph nodes in patients with rectal cancer.

Aim: The aim of this study is the evaluation of lymph node staging by magnetic resonance imaging (MRI) within clinical routine in patients with rectal cancer.

Method: Routine MRI reports (3 T) of 65 consecutive patients with rectal cancer were retrospectively categorized in lymph node tumor positive or negative (mriN+; mriN0) and compared to the final histopathological results (pN+; pN0). Sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy were calculated.

Drosophila Longevity Assurance Conferred by Reduced Insulin Receptor Substrate Chico Partially Requires d4eBP.

Mutations of the insulin/IGF signaling (IIS) pathway extend Drosophila lifespan. Based on genetic epistasis analyses, this longevity assurance is attributed to downstream effects of the FOXO transcription factor. However, as reported FOXO accounts for only a portion of the observed longevity benefit, suggesting there are additional outputs of IIS to mediate aging.

Inhibition of Cyclooxygenase-2 Prevents Chronic and Recurrent Cystitis.

The spread of multidrug-resistant microorganisms globally has created an urgent need for novel therapeutic strategies to combat urinary tract infections (UTIs). Immunomodulatory therapy may provide benefit, as treatment of mice with dexamethasone during acute UTI improved outcome by reducing the development of chronic cystitis, which predisposes to recurrent infection. Here we discovered soluble biomarkers engaged in myeloid cell development and chemotaxis that were predictive of future UTI recurrence when elevated in the sera of young women with UTI.

Amplicon sequencing of colorectal cancer: variant calling in frozen and formalin-fixed samples.

Next generation sequencing (NGS) is an emerging technology becoming relevant for genotyping of clinical samples. Here, we assessed the stability of amplicon sequencing from formalin-fixed paraffin-embedded (FFPE) and paired frozen samples from colorectal cancer metastases with different analysis pipelines. 212 amplicon regions in 48 cancer related genes were sequenced with Illumina MiSeq using DNA isolated from resection specimens from 17 patients with colorectal cancer liver metastases.

Abdominopelvic actinomycosis in three different locations with invasion of the abdominal wall and ureteric obstruction: An uncommon presentation.

Introduction: Actinomycosis is a rare chronic infectious disease caused by Gram-positive anaerobic bacteria that normally colonize the bronchial system and gastrointestinal tract in humans. The most common diseases associated with actinomycosis are orocervicofacial, thoracic and abdominal infections involving Actinomyces israelii. Due to its rarity, its various clinical presentations and often-infiltrative characteristics in radiological imaging, it can easily be mistaken for other clinical conditions, including malignancy.

Dispositional optimism and terminal decline in global quality of life.

We examined whether dispositional optimism relates to change in global quality of life (QOL) as a function of either chronological age or years to impending death. We used a sample of 2,096 deceased postmenopausal women from the Women's Health Initiative clinical trials who were enrolled in the 2005-2010 Extension Study and for whom at least 1 global QOL and optimism measure were analyzed. Growth curve models were examined.

Rapid on-site evaluation of EBUS-TBNA specimens of lymph nodes: Comparative analysis and recommendations for standardization.

Background: There is no widely accepted rapid on-site evaluation (ROSE) reporting system for endobronchial ultrasound-guided transbronchial needle aspiration. At the University of Arkansas for Medical Sciences, ROSE reporting was unstructured. The goal was to evaluate, compare, and improve upon 2 structured approaches proposed in the literature.

Does the Addition of Cetuximab to Radiochemotherapy Improve Outcome of Patients with Locally Advanced Rectal Cancer? Long-Term Results from Phase II Trials.

Purpose. The addition of cetuximab to radiochemotherapy (RCT) failed to improve complete response rates in locally advanced rectal cancer (LARC). We report the long-term results in patients treated within two sequential clinical trials.

Perineural Invasion Is an Independent Pathologic Indicator of Recurrence in Vulvar Squamous Cell Carcinoma.

Objectives: Vulvar squamous cell carcinoma (vSCC) is a gynecologic malignancy diagnosed in nearly 4500 women in the United States each year. Current criteria for treatment planning provide inadequate assessment of aggressive vSCC cases, resulting in insufficient use of adjuvant treatments and high rates of vSCC recurrence. Perineural invasion (PNI) is a pathologic feature inconsistently included in the assessment of vSCC, because its relevance to clinical outcomes in these women is not well defined.

Systematic review of health branding: growth of a promising practice.

Brands are marketing tools that create mental representations in the minds of consumers about products, services, and organizations. Brands create schema that help consumers decide whether to initiate or continue use of a product or service. Health branding determines behavioral choice by building consumer relationships and identification with health behaviors and their benefits.

Prostaglandins produced during class A scavenger receptor-mediated macrophage adhesion differentially regulate cytokine production.

Inflammation is associated with modification of the extracellular environment, changes in cytokine expression, and the accumulation of immune cells. Such modifications create ligands that support SR-A-mediated macrophage adhesion and retention. This may be particularly important in settings, such as atherosclerosis and diabetes, as modified lipoproteins and gluc-collagen are ligands for SR-A.

Platelets: balancing the septic triad.

In this issue of Blood, de Stoppelaar et al further unravel the relevance of platelets in a mouse model of pneumonia-derived sepsis by illustrating how platelets dynamically modulate infection and the inflammatory response.

Before it is too late: professional responsibilities in late-onset Alzheimer's research and pre-symptomatic prediction.

The development of a wide array of molecular and neuroscientific biomarkers can provide the possibility to visualize the course of Alzheimer's disease (AD) at early stages. Many of these biomarkers are aimed at detecting not only a preclinical, but also a pre-symptomatic state. They are supposed to facilitate clinical trials aiming at treatments that attack the disease at its earliest stage or even prevent it.

Impact of the Mdm2(SNP309-G) allele on a murine model of colorectal cancer.

A single-nucleotide polymorphism (SNP) in the promoter of the Mdm2 gene (Mdm2(SNP309-G)) results in an increased Mdm2 expression, partial attenuation of the p53 pathway and accelerated tumor development. Clinical case-control studies indicate the Mdm2(SNP309-)(G) allele associates with a significant increase in colorectal cancer (CRC) risk that is heightened in women, but the biological significance of this polymorphism has never been directly evaluated. To examine whether the Mdm2(SNP309-)(G) allele contributes to colorectal cancer, we generated cohorts of mice harboring either the G (minor allelic variant) or T (major allelic variant) allele and treated them with azoxymethane (AOM), a carcinogen that induces sporadic colorectal cancer.

Multiple enzyme approach for the characterization of glycan modifications on the C-terminus of the intestinal MUC2mucin.

The polymeric mucin MUC2 constitutes the main structural component of the mucus that covers the colon epithelium. The protein's central mucin domain is highly O-glycosylated and binds water to provide lubrication and prevent dehydration, binds bacteria, and separates the bacteria from the epithelial cells. Glycosylation outside the mucin domain is suggested to be important for proper protein folding and protection against intestinal proteases.

CSN6 drives carcinogenesis by positively regulating Myc stability.

Cullin-RING ubiquitin ligases (CRLs) are critical in ubiquitinating Myc, while COP9 signalosome (CSN) controls neddylation of Cullin in CRL. The mechanistic link between Cullin neddylation and Myc ubiquitination/degradation is unclear. Here we show that Myc is a target of the CSN subunit 6 (CSN6)-Cullin signalling axis and that CSN6 is a positive regulator of Myc.

Global quality of life modifies terminal change in physical functioning among older adult women.

Background: the factors that moderate decline in physical functioning as death approaches are understudied. This study aimed to assess death-related decline in global quality of life (QoL) and physical functioning and to test whether baseline QoL moderates terminal decline in physical functioning.

Methods: four thousand six hundred and fifty-one decedents from the Women's Health Initiative Study (WHI) rated QoL and physical functioning each year throughout 5 years of follow-up.

TRIM24 suppresses development of spontaneous hepatic lipid accumulation and hepatocellular carcinoma in mice.

Background & Aims: Aberrantly high expression of TRIM24 occurs in human cancers, including hepatocellular carcinoma. In contrast, TRIM24 in the mouse is reportedly a liver-specific tumour suppressor. To address this dichotomy and to uncover direct regulatory functions of TRIM24 in vivo, we developed a new mouse model that lacks expression of all Trim24 isoforms, as the previous model expressed normal levels of Trim24 lacking only exon 4.

Routine, empathic and compassionate patient care: definitions, development, obstacles, education and beneficiaries.

Rationale: We believe that this study represents an innovative approach to clarifying the definitions of routine, empathic and compassionate health care, as well as of sympathy. We emphasize the importance of affective empathy and its intensification in the context of patient suffering (compassion), without abandoning the ideal of clinical equanimity.

Methods: We develop a pedagogical model for clinicians and trainees who are weaker in their empathic skills that includes four levels of growth.

Loss of TRIM62 expression is an independent adverse prognostic factor in acute myeloid leukemia.

Background: Tripartite motif (TRIM)-62 is a putative tumor suppressor gene whose role in leukemia is unknown.

Materials And Methods: We evaluated the effect of TRIM62 protein expression in patients with acute myeloid leukemia (AML). We used reverse-phase protein array methodology to determine TRIM62 levels in leukemia-enriched protein samples from 511 patients newly diagnosed with AML.

Free flap reconstruction for head and neck cancer can be safely performed in both young and elderly patients after careful patient selection.

Surgical treatment of head and neck cancer often results in complex defects requiring reconstruction with microvascular free tissue transfer. However, in elderly patients, curative treatment with radical surgery and free flap reconstruction is often withheld. The objective of this study is to assess the outcomes of free flap surgery in elderly patients, using a standard surgical complication classification system.

Relationship-centred care: antidote, guidepost or blind alley? The epistemology of 21st century health care.

Contemporary health care is increasing in complexity and lacks a unifying understanding of epistemology, methodology and goals. Lack of conceptual consistency in concepts such as 'patient-centred care' (PCC) typifies system-wide discordance. We contrast the fragmented descriptions of PCC and related tools to its own origins in the writings of Balint and to a subsequent construct, relationship-centred care (RCC).

Lipid rafts couple class A scavenger receptors to phospholipase A2 activation during macrophage adhesion.

SR-A mediated macrophage adhesion to modified ECM proteins in a process that involves physical attachment of SR-A to modified ECM and activation of Lyn-PI3K and PLA2-12/15-lipoxygenase signaling pathways. Structurally, SR-A-mediated cell adhesion requires a 6-aa membrane-proximal cytoplasmic motif. However, the mechanism that couples SR-A-mediated adhesion to activation of these distinct signaling pathways is not known.