Is the incidence of invasive vulvar cancer increasing in the United States?

OBJECTIVE: To document incidence rates of vulvar cancer, specifically invasive vulvar cancer, from 1973 to 2004 in the United States. METHODS: Nine US cancer registries from the Surveillance, Epidemiology, and End Results (SEER) databases were used to identify women aged 15-84 years, who were first diagnosed with vulvar cancer during 1973-2004. Age-adjusted incidence rates and annual percentage changes were calculated for different time periods, stage of the disease, age, race, and geographic area. RESULTS: During 1973-2004, the incidence of in situ vulvar tumors increased by an average of 3.5% per year (95% CI: 2.9%, 4.1%), while the incidence of invasive tumors increased 1.0% per year (95% CI: 0.6%, 1.4%). An increasing incidence was observed for localized and regional invasive tumors. To at least some degree, the rise of incidence rates of incidence tumors was evident in every age category, race, and geographic region. CONCLUSIONS: Incidence rates of invasive vulvar cancer have increased in the United States during the last three decades. The reasons for this increase are unknown

Bi-Directional Sexual Dimorphisms of the Song Control Nucleus HVC in a Songbird with Unison Song

Sexually dimorphic anatomy of brain areas is thought to be causally linked to sex differences in behaviour and cognitive functions. The sex with the regional size advantage (male or female) differs between brain areas and species. Among adult songbirds, males have larger brain areas such as the HVC (proper name) and RA (robust nucleus of the arcopallium) that control the production of learned songs. Forest weavers (Ploceus bicolor) mated pairs sing a unison duet in which male and female mates learn to produce identical songs. We show with histological techniques that the volume and neuron numbers of HVC and RA were ≥1.5 times larger in males than in females despite their identical songs. In contrast, using in-situ hybridizations, females have much higher (30–70%) expression levels of mRNA of a number of synapse-related proteins in HVC and/or RA than their male counterparts. Male-typical and female-typical sexual differentiation appears to act on different aspects of the phenotypes within the same brain areas, leading females and males to produce the same behaviour using different cellular mechanisms

Finding needles in haystacks: linking scientific names, reference specimens and molecular data for Fungi

DNA phylogenetic comparisons have shown that morphology-based species recognition often underestimates fungal diversity. Therefore, the need for accurate DNA sequence data, tied to both correct taxonomic names and clearly annotated specimen data, has never been greater. Furthermore, the growing number of molecular ecology and microbiome projects using high-throughput sequencing require fast and effective methods for en masse species assignments. In this article, we focus on selecting and re-annotating a set of marker reference sequences that represent each currently accepted order of Fungi. The particular focus is on sequences from the internal transcribed spacer region in the nuclear ribosomal cistron, derived from type specimens and/or ex-type cultures. Re-annotated and verified sequences were deposited in a curated public database at the National Center for Biotechnology Information (NCBI), namely the RefSeq Targeted Loci (RTL) database, and will be visible during routine sequence similarity searches with NR_prefixed accession numbers. A set of standards and protocols is proposed to improve the data quality of new sequences, and we suggest how type and other reference sequences can be used to improve identification of Fungi

Antimicrobial Peptides and Skin: A Paradigm of Translational Medicine

Antimicrobial peptides (AMPs) are small, cationic, amphiphilic peptides with broad-spectrum microbicidal activity against both bacteria and fungi. In mammals, AMPs form the first line of host defense against infections and generally play an important role as effector agents of the innate immune system. The AMP era was born more than 6 decades ago when the first cationic cyclic peptide antibiotics, namely polymyxins and tyrothricin, found their way into clinical use. Due to the good clinical experience in the treatment of, for example, infections of mucus membranes as well as the subsequent understanding of mode of action, AMPs are now considered for treatment of inflammatory skin diseases and for improving healing of infected wounds. Based on the preclinical findings, including pathobiochemistry and molecular medicine, targeted therapy strategies are developed and first results indicate that AMPs influence processes of diseased skin. Importantly, in contrast to other antibiotics, AMPs do not seem to propagate the development of antibiotic-resistant micro-organisms. Therefore, AMPs should be tested in clinical trials for their efficacy and tolerability in inflammatory skin diseases and chronic wounds. Apart from possible fields of application, these peptides appear suited as an example of the paradigm of translational medicine for skin diseases which is today seen as a `two-way road' - from bench to bedside and backwards from bedside to bench. Copyright (c) 2012 S. Karger AG, Base

A randomized, placebo-controlled, double-blind, prospective trial to evaluate the effect of vildagliptin in new-onset diabetes mellitus after kidney transplantation

<p>Abstract</p> <p>Background</p> <p>New-onset diabetes mellitus after transplantation (NODAT), a frequent and serious complication after transplantation, is associated with decreased graft and patient survival. Currently, it is diagnosed and treated primarily according to existing guidelines for type II diabetes. To date, only a few trials have studied antidiabetic drugs in patients with NODAT. Vildagliptin is a novel dipeptidyl peptidase-4 (DPP-4) inhibitor that improves pancreatic islet function by enhancing both α- and β-cell responsiveness to increased blood glucose. Experimental data show potential protective effects of DPP-4 inhibitors on islet function after exogenous stress stimuli including immunosuppressants. Therefore, the therapy of NODAT with this class of compounds seems attractive. At present, vildagliptin is used to treat type II diabetes as monotherapy or in combination with other antidiabetic drugs, since that it efficiently decreases glycated hemoglobin (HbA1c) values. Additionally, vildagliptin has been shown to be safe in patients with moderately impaired kidney function. This study will evaluate the safety and efficacy of vildagliptin monotherapy in renal transplant recipients with recently diagnosed NODAT.</p> <p>Methods/Design</p> <p>This study is a randomized, placebo-controlled, double-blind, prospective phase II trial. Using the results of routinely performed oral glucose tolerance tests (OGTT) in stable renal transplant patients at our center, we will recruit patients without a history of diabetes and a 2 h glucose value surpassing 200 mg/dl (11.1 mmol/l). They are randomized to receive either 50 mg vildagliptin or placebo once daily. A total of 32 patients with newly diagnosed NODAT will be included. The primary endpoint is the difference in the 2 h glucose value between baseline and the repeated OGTT performed 3 months after treatment start, compared between the vildagliptin- and the placebo-group. Secondary endpoints include changes in HbA1c and fasting plasma glucose (FPG). The safety of vildagliptin in renal transplant patients will be assessed by the number of symptomatic hypoglycemic episodes (glucose <72 mg/dl or 4 mmol/l), the number of adverse events, and possible medication-associated side-effects.</p> <p>Discussion</p> <p>NODAT is a severe complication after kidney transplantation. Few trials have assessed the safety and efficacy of antidiabetic drugs for these patients. The purpose of this study is to assess the safety and efficacy of vildagliptin in renal transplant patients with NODAT.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov NCT00980356</p

Synthetic biology open language visual (SBOL Visual) version 2.3

People who are engineering biological organisms often find it useful to communicate in diagrams, both about the structure of the nucleic acid sequences that they are engineering and about the functional relationships between sequence features and other molecular species. Some typical practices and conventions have begun to emerge for such diagrams. The Synthetic Biology Open Language Visual (SBOL Visual) has been developed as a standard for organizing and systematizing such conventions in order to produce a coherent language for expressing the structure and function of genetic designs. This document details version 2.3 of SBOL Visual, which builds on the prior SBOL Visual 2.2 in several ways. First, the specification now includes higher-level "interactions with interactions," such as an inducer molecule stimulating a repression interaction. Second, binding with a nucleic acid backbone can be shown by overlapping glyphs, as with other molecular complexes. Finally, a new "unspecified interaction" glyph is added for visualizing interactions whose nature is unknown, the "insulator" glyph is deprecated in favor of a new "inert DNA spacer" glyph, and the polypeptide region glyph is recommended for showing 2A sequences

Engineering modular and orthogonal genetic logic gates for robust digital-like synthetic biology

Modular and orthogonal genetic logic gates are essential for building robust biologically based digital devices to customize cell signalling in synthetic biology. Here we constructed an orthogonal AND gate in Escherichia coli using a novel hetero-regulation module from Pseudomonas syringae. The device comprises two co-activating genes hrpR and hrpS controlled by separate promoter inputs, and a σ54-dependent hrpL promoter driving the output. The hrpL promoter is activated only when both genes are expressed, generating digital-like AND integration behaviour. The AND gate is demonstrated to be modular by applying new regulated promoters to the inputs, and connecting the output to a NOT gate module to produce a combinatorial NAND gate. The circuits were assembled using a parts-based engineering approach of quantitative characterization, modelling, followed by construction and testing. The results show that new genetic logic devices can be engineered predictably from novel native orthogonal biological control elements using quantitatively in-context characterized parts