Metformin modifies disparity in hepatocellular carcinoma incidence in men with type 2 diabetes but without chronic liver diseases.

Background: We assessed racial/ethnic disparity in hepatocellular carcinoma (HCC) incidence among men with type 2 diabetes (T2D) but without chronic liver diseases (CLD), and whether metformin use modified the disparity.

Methods: Study cohort: the nationwide Veterans Administration Health Care System electronic medical records among 40-89 years old men with T2D; without CLD, cancer, cardiovascular or renal diseases previously; insulin and thiazolidinedione naive. Logistic regression analyses compared HCC incidence between race/ethnicity groups under no metformin use adjusted for covariates and inverse propensity score weights (IPSW) for race/ethnicity.

Group 3 ITI Consensus Report: Patient-reported outcome measures associated with implant dentistry.

Objectives: The aim of Working Group 3 was to focus on three topics that were assessed using patient-reported outcome measures (PROMs). These topics included the following: (a) the aesthetics of tooth and implant-supported fixed dental prostheses focusing on partially edentulous patients, (b) a comparison of fixed and removable implant-retained prostheses for edentulous populations, and (c) immediate versus early/conventional loading of immediately placed implants in partially edentate patients. PROMs include ratings of satisfaction and oral health-related quality of life (QHRQoL), as well as other indicators, that is, pain, general health-related quality of life (e.

Brachial Plexus Chemical Neurolysis with Ethanol for Cancer Pain.

Chemical neurolytic nerve blocks have been successfully used to treat a variety of cancer-related pain. However, the literature has been sparse regarding neurolysis of the brachial plexus for cancer pain. We present a unique case report of a successful chemical neurolysis of the brachial plexus with dehydrated ethanol for a patient suffering from metastatic mammary carcinoma with tumor invasion of the right brachial plexus.

Hypoxia-activated evofosfamide for treatment of recurrent bevacizumab-refractory glioblastoma: a phase I surgical study.

Background: Anti-angiogenic therapy is known to induce a greater degree of hypoxia, including in glioblastoma (GBM). Evofosfamide (Evo) is a hypoxia-activated prodrug which is reduced, leading to the release of the alkylating agent bromo-isophosphoramide mustard. We assessed the safety, tolerability, preliminary efficacy, and biomarkers of Evo plus bevacizumab (Bev) in Bev-refractory GBM.

New HIF2α inhibitors: potential implications as therapeutics for advanced pheochromocytomas and paragangliomas.

Two recent independent studies published in show robust responses of clear cell renal cell carcinoma (ccRCC) cell lines, preclinical ccRCC xenograft models and, remarkably, a patient with progressive ccRCC despite receiving multiple lines of treatment, to the long-awaited, recently developed inhibitors of hypoxia-inducible factor 2-alpha (HIF2α). This commentary published in is based on the recognition of similar molecular drivers in ccRCC and the endocrine neoplasias pheochromocytomas and paragangliomas (PPGLs), ultimately leading to stabilization of HIFs. HIF-stabilizing mutations have been detected in the von Hippel-Lindau (VHL) gene, as well as in other genes, such as succinate dehydrogenase (SDHx), fumarate hydratase (FH) and transcription elongation factor B subunit 1 (TCEB1), as well as the gene that encodes HIF2α itself: EPAS1 Importantly, the recent discovery of mutations in PPGLs and the results of comprehensive and studies revealing their oncogenic roles characterized a hitherto unknown direct mechanism of HIF2α activation in human cancer.

Genetics of Pheochromocytomas and Paragangliomas: An Overview on the Recently Implicated Genes MERTK, MET, Fibroblast Growth Factor Receptor 1, and H3F3A.

Genomic studies conducted by different centers have uncovered various new genes mutated in pheochromocytomas and paragangliomas (PPGLs) at germline, mosaic, and/or somatic levels, greatly expanding our knowledge of the genetic events occurring in these tumors. The current review focuses on very new findings and discusses the previously not recognized role of MERTK, MET, fibroblast growth factor receptor 1, and H3F3A genes in syndromic and nonsyndromic PPGLs. These 4 new genes were selected because although their association with PPGLs is very recent, mounting evidence was generated that rapidly consolidated the prominence of these genes in the molecular pathogenesis of PPGLs.

Melatonin Reduces Angiogenesis in Serous Papillary Ovarian Carcinoma of Ethanol-Preferring Rats.

Angiogenesis is a hallmark of ovarian cancer (OC); the ingrowth of blood vessels promotes rapid cell growth and the associated metastasis. Melatonin is a well-characterized indoleamine that possesses important anti-angiogenic properties in a set of aggressive solid tumors. Herein, we evaluated the role of melatonin therapy on the angiogenic signaling pathway in OC of an ethanol-preferring rat model that mimics the same pathophysiological conditions occurring in women.

Fungal Keratitis Secondary to Trametes betulina: A Case Report and Review of Literature.

Purpose: We report the first case of human infection and keratitis secondary to Trametes betulina, a rare filamentous fungus.

Methods: Clinical examination including external and slit-lamp examination and corneal scrapings with microbiologic evaluation were performed on a patient with chronic allergic conjunctivitis, entropion and a long-standing corneal ulcer resistant to treatment.

Results: The culture from the corneal scraping revealed a basidiomycetous fungus which was submitted for identification.

"You Are Not Alone" Strategies for Addressing Mental Health and Health Promotion with a Refugee Women's Sewing Group.

Resettlement can be an uncertain time for refugees as they have often suffered life-threatening circumstances prior to flight from their countries, yet few resettlement programs screen for mental health. The purpose of this study was to pilot the Refugee Health Screener-15 (RHS-15) to assess mental health and the Pathways to Wellness intervention to identify internal and structural barriers affecting resettlement with a refugee women's sewing group. Community collaborations that create healthy social and physical environments through access to resources, economic opportunities, and social support promote a holistic approach to health and can improve quality of life for this vulnerable population.

Melatonin and sirtuins: A "not-so unexpected" relationship.

Epigenetic modifications, including methylation or acetylation as well as post-transcriptional modifications, are mechanisms used by eukaryotic cells to increase the genome diversity in terms of differential gene expression and protein diversity. Among these modifying enzymes, sirtuins, a class III histone deacetylase (HDAC) enzymes, are of particular importance. Sirtuins regulate the cell cycle, DNA repair, cell survival, and apoptosis, thus having important roles in normal and cancer cells.

Drug Overdose: Differing Risk Models for Women and Men among Opioid Users with Non-Cancer Pain.

Objective: To examine risk factors for drug overdose by sex reflecting differing patterns of opioid and other drug use.

Design: National privately insured cohort.

Subjects: 206,869 subjects filling ≥2 opioid prescriptions from January 2009 through July 2012.

Consensus Statement on next-generation-sequencing-based diagnostic testing of hereditary phaeochromocytomas and paragangliomas.

Phaeochromocytomas and paragangliomas (PPGLs) are neural-crest-derived tumours of the sympathetic or parasympathetic nervous system that are often inherited and are genetically heterogeneous. Genetic testing is recommended for patients with these tumours and for family members of patients with hereditary forms of PPGLs. Due to the large number of susceptibility genes implicated in the diagnosis of inherited PPGLs, next-generation sequencing (NGS) technology is ideally suited for carrying out genetic screening of these individuals.

Comparing two sampling methods to engage hard-to-reach communities in research priority setting.

Background: Effective community-partnered and patient-centered outcomes research needs to address community priorities. However, optimal sampling methods to engage stakeholders from hard-to-reach, vulnerable communities to generate research priorities have not been identified.

Methods: In two similar rural, largely Hispanic communities, a community advisory board guided recruitment of stakeholders affected by chronic pain using a different method in each community: 1) snowball sampling, a chain- referral method or 2) purposive sampling to recruit diverse stakeholders.

Vive La France: Three Delusional Disorders Originally Reported in the French Medical Literature.

Delusions as a feature of psychosis have long captured the fascination of both psychiatry and the public at large. The French first described three famous delusions: the Cotard delusion, folie à deux, and Capgras delusion. In this article, we examine a case illustrating each delusion and the hallmark features of each as well as a brief discussion about the current understanding of these disorders.

Context Matters: Distinct Disease Outcomes as a Result of Crebbp Hemizygosity in Different Mouse Bone Marrow Compartments.

Perturbations in CREB binding protein (CREBBP) are associated with hematopoietic malignancies, including myelodysplastic syndrome (MDS). Mice hemizygous for Crebbp develop myelodysplasia with proliferative features, reminiscent of human MDS/myeloproliferative neoplasm-unclassifiable (MDS/MPN-U), and a proportion goes on to develop acute myeloid leukemia (AML). We have also shown that the Crebbp+/- non-hematopoietic bone marrow microenvironment induces excessive myeloproliferation of wild-type cells.

Co-targeting ALK and EGFR parallel signaling in oral squamous cell carcinoma.

Squamous cell carcinoma (SCC) comprises 90% of all head and neck cancers and has a poor survival rate due to late-stage disease that is refractive to traditional therapies. Epidermal growth factor receptor (EGFR) is over-expressed in greater than 80% of head and neck SCC (HNSCC). However, EGFR targeted therapies yielded little to no efficacy in clinical trials.

Mechanisms regulating proteostasis are involved in sympatric speciation of the blind mole rat, Spalax galili.

Genome-wide analysis demonstrates extensive genomic adaptive complexes involved in sympatric speciation between blind mole rats (Spalax galili) in abutting populations living in basalt and chalk soils. Among the gene ontology (GO) enrichment, musculature and metabolism stood out in basalt dwellers while nutrition and neurogenetics were highlighted in chalk residents. Measurements of mechanisms regulating protein homeostasis inspired by these GO terms suggest that at the proteomic level there is also a habitat/soil-type driven divergence with the basalt residents exhibiting higher proteasome activity whereas elevated levels of markers of autophagy are evident in the chalk inhabitants.

Determinants of rodent longevity in the chaperone-protein degradation network.

Proteostasis is an integral component of healthy aging, ensuring maintenance of protein structural and functional integrity with concomitant impact upon health span and longevity. In most metazoans, increasing age is accompanied by a decline in protein quality control resulting in the accrual of damaged, self-aggregating cytotoxic proteins. A notable exception to this trend is observed in the longest-lived rodent, the naked mole-rat (NMR, Heterocephalus glaber) which maintains proteostasis and proteasome-mediated degradation and autophagy during aging.

Graded Proteasome Dysfunction in Caenorhabditis elegans Activates an Adaptive Response Involving the Conserved SKN-1 and ELT-2 Transcription Factors and the Autophagy-Lysosome Pathway.

The maintenance of cellular proteins in a biologically active and structurally stable state is a vital endeavor involving multiple cellular pathways. One such pathway is the ubiquitin-proteasome system that represents a major route for protein degradation, and reductions in this pathway usually have adverse effects on the health of cells and tissues. Here, we demonstrate that loss-of-function mutants of the Caenorhabditis elegans proteasome subunit, RPN-10, exhibit moderate proteasome dysfunction and unexpectedly develop both increased longevity and enhanced resistance to multiple threats to the proteome, including heat, oxidative stress, and the presence of aggregation prone proteins.

Linking Endotoxins, African Dust PM10 and Asthma in an Urban and Rural Environment of Puerto Rico.

African Dust Events (ADE) are a seasonal phenomenon that has been suggested to exacerbate respiratory and proinflammatory diseases in Puerto Rico (PR). Increases in PM10 concentration and the effects of biological endotoxins (ENX) are critical factors to consider during these storms. ENX promote proinflammatory responses in lungs of susceptible individuals through activation of the Toll-like receptors (TLR2/4) signaling pathways.

Novel Measure of Opioid Dose and Costs of Care for Diabetes Mellitus: Opioid Dose and Health Care Costs.

Unlabelled: Diabetes mellitus (DM) has well known costly complications but we hypothesized that costs of care for chronic pain treated with opioid analgesic (OA) medications would also be substantial. In a statewide, privately insured cohort of 29,033 adults aged 18 to 64 years with DM and noncancer pain who filled OA prescription(s) from 2008 to 2012, our outcomes were costs for specific health care services and total costs per 6-month intervals after the first filled OA prescription. Average daily OA dose (4 categories) and total dose (quartiles) in morphine-equivalent milligrams were calculated per 6-month interval after the first OA prescription and combined into a novel OA dose measure.

Feasibility of spirometry testing in preschool children.

Rationale: The primary purpose of this study was to evaluate the feasibility of obtaining acceptable and reproducible spirometry data in preschool aged children (3-5 years) by technicians without prior experience with spirometry.

Methods: Two technicians were trained to perform spirometry testing (ndd Easy on-PC) and to administer standardized questionnaires. Preschool aged children were enrolled from two Head Start centers and a local primary care clinic.

Age-Related Effects of Advanced Glycation End Products (Ages) in Bone Matrix on Osteoclastic Resorption.

Advanced glycation end products (AGEs) accumulate in bone extracellular matrix as people age. Previous studies have shown controversial results regarding the role of in situ AGEs accumulation in osteoclastic resorption. To address this issue, this study cultured human osteoclast cells directly on human cadaveric bone slices from different age groups (young and elderly) to warrant its relevance to in vivo conditions.