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

The chemopreventive polyphenol Curcumin prevents hematogenous breast cancer metastases in immunodeficient mice

Dissemination of metastatic cells probably occurs long before diagnosis of the primary tumor. Metastasis during early phases of carcinogenesis in high risk patients is therefore a potential prevention target. The plant polyphenol Curcumin has been proposed for dietary prevention of cancer. We therefore examined its effects on the human breast cancer cell line MDA-MB-231 in vitro and in a mouse metastasis model. Curcumin strongly induces apoptosis in MDA- MB- 231 cells in correlation with reduced activation of the survival pathway NF kappa B, as a consequence of diminished I kappa B and p65 phosphorylation. Curcumin also reduces the expression of major matrix metalloproteinases (MMPs) due to reduced NF kappa B activity and transcriptional downregulation of AP-1. NF kappa B/p65 silencing is sufficient to downregulate c-jun and MMP expression. Reduced NF kappa B/AP-1 activity and MMP expression lead to diminished invasion through a reconstituted basement membrane and to a significantly lower number of lung metastases in immunodeficient mice after intercardiac injection of 231 cells (p=0.0035). 68% of Curcumin treated but only 17% of untreated animals showed no or very few lung metastases, most likely as a consequence of down-regulation of NF kappa B/AP-1 dependent MMP expression and direct apoptotic effects on circulating tumor cells but not on established metastases. Dietary chemoprevention of metastases appears therefore feasible. Copyright (c) 2007 S. Karger AG, Basel

Behaviour change interventions to reduce second-hand smoke (SHS) exposure at home in pregnant women - A systematic review and intervention appraisal

Abstract Background Second-hand smoke (SHS) exposure during pregnancy is associated with poor pregnancy and foetal outcomes. Theory-based behaviour change interventions (BCI) have been used successfully to change smoking related behaviours and offer the potential to reduce exposure of SHS in pregnant women. Systematic reviews conducted so far do not evaluate the generalisability and scalability of interventions. The objectives of this review were to (1) report the BCIs for reduction in home exposure to SHS for pregnant women; and (2) critically appraise intervention-reporting, generalisability, feasibility and scalability of the BCIs employed. Methods Standard methods following PRISMA guidelines were employed. Eight databases were searched from 2000 to 2015 in English. The studies included used BCIs on pregnant women to reduce their home SHS exposure by targeting husbands/partners. The Workgroup for Intervention Development and Evaluation Research (WIDER) guidelines were used to assess intervention reporting. Generalisability, feasibility and scalability were assessed against criteria described by Bonell and Milat. Results Of 3479 papers identified, six studies met the inclusion criteria. These studies found that BCIs led to increased knowledge about SHS harms, reduction or husbands quitting smoking, and increased susceptibility and change in level of actions to reduce SHS at home. Two studies reported objective exposure measures, and one reported objective health outcomes. The studies partially followed WIDER guidelines for reporting, and none met all generalisability, feasibility and scalability criteria. Conclusions There is a dearth of literature in this area and the quality of studies reviewed was moderate to low. The BCIs appear effective in reducing SHS, however, weak study methodology (self-reported exposure, lack of objective outcome assessment, short follow-up, absence of control group) preclude firm conclusion. Some components of the WIDER checklist were followed for BCI reporting, scalability and feasibility of the studies were not described. More rigorous studies using biochemical and clinical measures for exposures and health outcomes in varied study settings are required. Studies should report interventions in detail using WIDER checklist and assess them for generalisability, feasibility and scalability. Trial registration CRD40125026666

Role of potassium and calcium channels in sevoflurane-mediated vasodilation in the foeto-placental circulation

<p>Abstract</p> <p>Background</p> <p>Sevoflurane has been demonstrated to vasodilate the foeto-placental vasculature. We aimed to determine the contribution of modulation of potassium and calcium channel function to the vasodilatory effect of sevoflurane in isolated human chorionic plate arterial rings.</p> <p>Methods</p> <p>Quadruplicate <it>ex vivo </it>human chorionic plate arterial rings were used in all studies. <b><it>Series 1 and 2 </it></b>examined the role of the K⁺channel in sevoflurane-mediated vasodilation. Separate experiments examined whether tetraethylammonium, which blocks large conductance calcium activated K⁺(K_Ca++) channels (<b><it>Series 1A+B</it></b>) or glibenclamide, which blocks the ATP sensitive K⁺(K_ATP) channel (<b><it>Series 2</it></b>), modulated sevoflurane-mediated vasodilation. <b><it>Series 3 – 5 </it></b>examined the role of the Ca⁺⁺channel in sevoflurane induced vasodilation. Separate experiments examined whether verapamil, which blocks the sarcolemmal voltage-operated Ca⁺⁺channel (<b><it>Series 3</it></b>), SK&F 96365 an inhibitor of sarcolemmal voltage-independent Ca⁺⁺channels (<b><it>Series 4A+B</it></b>), or ryanodine an inhibitor of the sarcoplasmic reticulum Ca⁺⁺channel (<b><it>Series 5A+B</it></b>), modulated sevoflurane-mediated vasodilation.</p> <p>Results</p> <p>Sevoflurane produced dose dependent vasodilatation of chorionic plate arterial rings in all studies. Prior blockade of the K_Ca++and K_ATPchannels augmented the vasodilator effects of sevoflurane. Furthermore, exposure of rings to sevoflurane in advance of TEA occluded the effects of TEA. Taken together, these findings suggest that sevoflurane blocks K⁺channels. Blockade of the voltage-operated Ca⁺⁺channels inhibited the vasodilator effects of sevoflurane. In contrast, blockade of the voltage-independent and sarcoplasmic reticulum Ca⁺⁺channels did not alter sevoflurane vasodilation.</p> <p>Conclusion</p> <p>Sevoflurane appears to block chorionic arterial K_Ca++and K_ATPchannels. Sevoflurane also blocks voltage-operated calcium channels, and exerts a net vasodilatory effect in the <it>in vitro </it>foeto-placental circulation.</p

Bacterial endosymbiont Cardinium cSfur genome sequence provides insights for understanding the symbiotic relationship in Sogatella furcifera host

Background: Sogatella furcifera is a migratory pest that damages rice plants and causes severe economic losses. Due to its ability to annually migrate long distances, S.furcifera has emerged as a major pest of rice in several Asian countries. Symbiotic relationships of inherited bacteria with terrestrial arthropods have significant implications. The genus Cardinium is present in many types of arthropods, where it influences some host characteristics. We present a report of a newly # identified strain of the bacterial endosymbiont Cardinium cSfur in S. furcifera. Result: From the whole genome of S. furcifera previously sequenced by our laboratory, we assembled the whole genome sequence of Cardinium cSfur. The sequence comprised 1,103,593 bp with a GC content of 39.2%. The phylogenetic tree of the Bacteroides phylum to which Cardinium cSfur belongs suggests that Cardinium cSfur is closely related to the other strains (Cardinium cBtQ1 and cEper1) that are members of the Amoebophilaceae family. Genome comparison between the host-dependent endosymbiont including Cardinium cSfur and freeliving bacteria revealed that the endosymbiont has a smaller genome size and lower GC content, and has lost some genes related to metabolism because of its special environment, which is similar to the genome pattern observed in other insect symbionts. Cardinium cSfur has limited metabolic capability, which makes it less contributive to metabolic and biosynthetic processes in its host. From our findings, we inferred that, to compensate for its limited metabolic capability, Cardinium cSfur harbors a relatively high proportion of transport proteins, which might act as the hub between it and its host. With its acquisition of the whole operon related to biotin synthesis and glycolysis related genes through HGT event, Cardinium cSfur seems to be undergoing changes while establishing a symbiotic relationship with its host. Conclusion: A novel bacterial endosymbiont strain (Cardinium cSfur) has been discovered. A genomic analysis of the endosymbiont in S. furcifera suggests that its genome has undergone certain changes to facilitate its settlement in the host. The envisaged potential reproduction manipulative ability of the new endosymbiont strain in its S. furcifera host has vital implications in designing eco-friendly approaches to combat the insect pest

The crystal structure of the Sgt1-Skp1 complex: the link between Hsp90 and both SCF E3 ubiquitin ligases and kinetochores

The essential cochaperone Sgt1 recruits Hsp90 chaperone activity to a range of cellular factors including SCF E3 ubiquitin ligases and the kinetochore in eukaryotes. In these pathways Sgt1 interacts with Skp1, a small protein that heterodimerizes with proteins containing the F-box motif. We have determined the crystal structure of the interacting domains of Saccharomyces cerevisiae Sgt1 and Skp1 at 2.8 Å resolution and validated the interface in the context of the full-length proteins in solution. The BTB/POZ domain of Skp1 associates with Sgt1 via the concave surface of its TPR domain using residues that are conserved in humans. Dimerization of yeast Sgt1 occurs via an insertion that is absent from monomeric human Sgt1. We identify point mutations that disrupt dimerization and Skp1 binding in vitro and find that the interaction with Skp1 is an essential function of Sgt1 in yeast. Our data provide a structural rationale for understanding the phenotypes of temperature-sensitive Sgt1 mutants and for linking Skp1-associated proteins to Hsp90-dependent pathways

Comparative study of enteric viruses, coliphages and indicator bacteria for evaluating water quality in a tropical high-altitude system

<p>Abstract</p> <p>Background</p> <p>Bacteria used as indicators for pathogenic microorganisms in water are not considered adequate as enteric virus indicators. Surface water from a tropical high-altitude system located in Mexico City that receives rainwater, treated and non-treated wastewater used for irrigation, and groundwater used for drinking, was studied.</p> <p>Methods</p> <p>The presence of enterovirus, rotavirus, astrovirus, coliphage, coliform bacteria, and enterococci was determined during annual cycles in 2001 and 2002. Enteric viruses in concentrated water samples were detected by reverse transcriptase-polymerase chain reaction (RT-PCR). Coliphages were detected using the double agar layer method. Bacteria analyses of the water samples were carried out by membrane filtration.</p> <p>Results</p> <p>The presence of viruses and bacteria in the water used for irrigation showed no relationship between current bacterial indicator detection and viral presence. Coliphages showed strong association with indicator bacteria and enterovirus, but weak association with other enteric viruses. Enterovirus and rotavirus showed significant seasonal differences in water used for irrigation, although this was not clear for astrovirus.</p> <p>Conclusion</p> <p>Coliphages proved to be adequate faecal pollution indicators for the irrigation water studied. Viral presence in this tropical high-altitude system showed a similar trend to data previously reported for temperate zones.</p

Colorectal carcinomas in MUTYH-associated polyposis display histopathological similarities to microsatellite unstable carcinomas

<p>Abstract</p> <p>Background</p> <p>MUTYH-associated polyposis (MAP) is a recessively inherited disorder which predisposes biallelic carriers for a high risk of polyposis and colorectal carcinoma (CRC). Since about one third of the biallelic MAP patients in population based CRC series has no adenomas, this study aimed to identify specific clinicopathological characteristics of MAP CRCs and compare these with reported data on sporadic and Lynch CRCs.</p> <p>Methods</p> <p>From 44 MAP patients who developed ≥ 1 CRCs, 42 of 58 tumours were analyzed histologically and 35 immunohistochemically for p53 and beta-catenin. Cell densities of CD3, CD8, CD57, and granzyme B positive lymphocytes were determined. <it>KRAS2</it>, the mutation cluster region (MCR) of <it>APC, p53</it>, and <it>SMAD4 </it>were analyzed for somatic mutations.</p> <p>Results</p> <p>MAP CRCs frequently localized to the proximal colon (69%, 40/58), were mucinous in 21% (9/42), and had a conspicuous Crohn's like infiltrate reaction in 33% (13/40); all of these parameters occurred at a higher rate than reported for sporadic CRCs. Tumour infiltrating lymphocytes (TILs) were also highly prevalent in MAP CRCs. Somatic <it>APC </it>MCR mutations occurred in 14% (5/36) while 64% (23/36) had <it>KRAS2 </it>mutations (22/23 c.34G>T). G>T tranversions were found in <it>p53 </it>and <it>SMAD4</it>, although the relative frequency compared to other mutations was low.</p> <p>Conclusion</p> <p>MAP CRCs show some similarities to micro-satellite unstable cancers, with a preferential proximal location, a high rate of mucinous histotype and increased presence of TILs. These features should direct the practicing pathologist towards a MAP aetiology of CRC as an alternative for a mismatch repair deficient cause. High frequent G>T transversions in <it>APC </it>and <it>KRAS2 </it>(mutated in early tumour development) but not in <it>P53 </it>and <it>SMAD4 </it>(implicated in tumour progression) might indicate a predominant MUTYH effect in <it>early </it>carcinogenesis.</p

A group randomized trial of a complexity-based organizational intervention to improve risk factors for diabetes complications in primary care settings: study protocol

<p>Abstract</p> <p>Background</p> <p>Most patients with type 2 diabetes have suboptimal control of their glucose, blood pressure (BP), and lipids – three risk factors for diabetes complications. Although the chronic care model (CCM) provides a roadmap for improving these outcomes, developing theoretically sound implementation strategies that will work across diverse primary care settings has been challenging. One explanation for this difficulty may be that most strategies do not account for the complex adaptive system (CAS) characteristics of the primary care setting. A CAS is comprised of individuals who can learn, interconnect, self-organize, and interact with their environment in a way that demonstrates non-linear dynamic behavior. One implementation strategy that may be used to leverage these properties is practice facilitation (PF). PF creates time for learning and reflection by members of the team in each clinic, improves their communication, and promotes an individualized approach to implement a strategy to improve patient outcomes.</p> <p>Specific objectives</p> <p>The specific objectives of this protocol are to: evaluate the effectiveness and sustainability of PF to improve risk factor control in patients with type 2 diabetes across a variety of primary care settings; assess the implementation of the CCM in response to the intervention; examine the relationship between communication within the practice team and the implementation of the CCM; and determine the cost of the intervention both from the perspective of the organization conducting the PF intervention and from the perspective of the primary care practice.</p> <p>Intervention</p> <p>The study will be a group randomized trial conducted in 40 primary care clinics. Data will be collected on all clinics, with 60 patients in each clinic, using a multi-method assessment process at baseline, 12, and 24 months. The intervention, PF, will consist of a series of practice improvement team meetings led by trained facilitators over 12 months. Primary hypotheses will be tested with 12-month outcome data. Sustainability of the intervention will be tested using 24 month data. Insights gained will be included in a delayed intervention conducted in control practices and evaluated in a pre-post design.</p> <p>Primary and secondary outcomes</p> <p>To test hypotheses, the unit of randomization will be the clinic. The unit of analysis will be the repeated measure of each risk factor for each patient, nested within the clinic. The repeated measure of glycosylated hemoglobin A1c will be the primary outcome, with BP and Low Density Lipoprotein (LDL) cholesterol as secondary outcomes. To study change in risk factor level, a hierarchical or random effect model will be used to account for the nesting of repeated measurement of risk factor within patients and patients within clinics.</p> <p>This protocol follows the CONSORT guidelines and is registered per ICMJE guidelines:</p> <p>Clinical Trial Registration Number</p> <p>NCT00482768</p