Multicenter, Prospective, Longitudinal Study of the Recurrence, Surgical Site Infection, and Quality of Life After Contaminated Ventral Hernia Repair Using Biosynthetic Absorbable Mesh: The COBRA Study

OBJECTIVE: The aim of the study was to evaluate biosynthetic absorbable mesh in single-staged contaminated (Centers for Disease Control class II and III) ventral hernia (CVH) repair over 24 months. BACKGROUND: CVH has an increased risk of postoperative infection. CVH repair with synthetic or biologic meshes has reported chronic biomaterial infections and high hernia recurrence rates. METHODS: Patients with a contaminated or clean-contaminated operative field and a hernia defect at least 9 cm had a biosynthetic mesh (open, sublay, retrorectus, or intraperitoneal) repair with fascial closure (n = 104). Endpoints included overall Kaplan-Meier estimates for hernia recurrence and postoperative wound infection rates at 24 months, and the EQ-5D and Short Form 12 Health Survey (SF-12). Analyses were conducted on the intent-to-treat population, and health outcome measures evaluated using paired t tests. RESULTS: Patients had a mean age of 58 years, body mass index of 28 kg/m, 77% had contaminated wounds, and 84% completed 24-months follow-up. Concomitant procedures included fistula takedown (n = 24) or removal of infected previously placed mesh (n = 29). Hernia recurrence rate was 17% (n = 16). At the time of CVH repair, intraperitoneal placement of the biosynthetic mesh significantly increased the risk of recurrences (P ≤ 0.04). Surgical site infections (19/104) led to higher risk of recurrence (P < 0.01). Mean 24-month EQ-5D (index and visual analogue) and SF-12 physical component and mental scores improved from baseline (P < 0.05). CONCLUSIONS: In this prospective longitudinal study, biosynthetic absorbable mesh showed efficacy in terms of long-term recurrence and quality of life for CVH repair patients and offers an alternative to biologic and permanent synthetic meshes in these complex situations

Smooth Muscle miRNAs Are Critical for Post-Natal Regulation of Blood Pressure and Vascular Function

Phenotypic modulation of smooth muscle cells (SMCs) plays a key role in vascular disease, including atherosclerosis. Several transcription factors have been suggested to regulate phenotypic modulation of SMCs but the decisive mechanisms remain unknown. Recent reports suggest that specific microRNAs (miRNAs) are involved in SMC differentiation and vascular disease but the global role of miRNAs in postnatal vascular SMC has not been elucidated. Thus, the objective of this study was to identify the role of Dicer-dependent miRNAs for blood pressure regulation and vascular SMC contractile function and differentiation in vivo. Tamoxifen-inducible and SMC specific deletion of Dicer was achieved by Cre-Lox recombination. Deletion of Dicer resulted in a global loss of miRNAs in aortic SMC. Furthermore, Dicer-deficient mice exhibited a dramatic reduction in blood pressure due to significant loss of vascular contractile function and SMC contractile differentiation as well as vascular remodeling. Several of these results are consistent with our previous observations in SM-Dicer deficient embryos. Therefore, miRNAs are essential for maintaining blood pressure and contractile function in resistance vessels. Although the phenotype of miR-143/145 deficient mice resembles the loss of Dicer, the phenotypes of SM-Dicer KO mice were far more severe suggesting that additional miRNAs are involved in maintaining postnatal SMC differentiation

Continuing medical education challenges in chronic fatigue syndrome

<p>Abstract</p> <p>Background</p> <p>Chronic fatigue syndrome (CFS) affects at least 4 million people in the United States, yet only 16% of people with CFS have received a diagnosis or medical care for their illness. Educating health care professionals about the diagnosis and management of CFS may help to reduce population morbidity associated with CFS.</p> <p>Methods</p> <p>This report presents findings over a 5-year period from May 2000 to June 2006 during which we developed and implemented a health care professional educational program. The objective of the program was to distribute CFS continuing education materials to providers at professional conferences, offer online continuing education credits in different formats (e.g., print, video, and online), and evaluate the number of accreditation certificates awarded.</p> <p>Results</p> <p>We found that smaller conference size (OR = 80.17; 95% CI 8.80, 730.25), CFS illness related target audiences (OR = 36.0; 95% CI 2.94, 436.34), and conferences in which CFS research was highlighted (OR = 4.15; 95% CI 1.16, 14.83) significantly contributed to higher dissemination levels, as measured by visit rates to the education booth. While print and online courses were equally requested for continuing education credit opportunities, the online course resulted in 84% of the overall award certificates, compared to 14% for the print course. This remained consistent across all provider occupations: physicians, nurses, physician assistants, and allied health professionals.</p> <p>Conclusion</p> <p>These findings suggest that educational programs promoting materials at conferences may increase dissemination efforts by targeting audiences, examining conference characteristics, and promoting online continuing education forums.</p

A multi-targeted approach to suppress tumor-promoting inflammation

Cancers harbor significant genetic heterogeneity and patterns of relapse following many therapies are due to evolved resistance to treatment. While efforts have been made to combine targeted therapies, significant levels of toxicity have stymied efforts to effectively treat cancer with multi-drug combinations using currently approved therapeutics. We discuss the relationship between tumor-promoting inflammation and cancer as part of a larger effort to develop a broad-spectrum therapeutic approach aimed at a wide range of targets to address this heterogeneity. Specifically, macrophage migration inhibitory factor, cyclooxygenase-2, transcription factor nuclear factor-κB, tumor necrosis factor alpha, inducible nitric oxide synthase, protein kinase B, and CXC chemokines are reviewed as important antiinflammatory targets while curcumin, resveratrol, epigallocatechin gallate, genistein, lycopene, and anthocyanins are reviewed as low-cost, low toxicity means by which these targets might all be reached simultaneously. Future translational work will need to assess the resulting synergies of rationally designed antiinflammatory mixtures (employing low-toxicity constituents), and then combine this with similar approaches targeting the most important pathways across the range of cancer hallmark phenotypes

Comparison of quality-of-care measures in U.S. patients with end-stage renal disease secondary to lupus nephritis vs. other causes

BACKGROUND: Patients with end-stage renal disease (ESRD) due to lupus nephritis (LN-ESRD) may be followed by multiple providers (nephrologists and rheumatologists) and have greater opportunities to receive recommended ESRD-related care. We aimed to examine whether LN-ESRD patients have better quality of ESRD care compared to other ESRD patients. METHODS: Among incident patients (7/05–9/11) with ESRD due to LN (n = 6,594) vs. other causes (n = 617,758), identified using a national surveillance cohort (United States Renal Data System), we determined the association between attributed cause of ESRD and quality-of-care measures (pre-ESRD nephrology care, placement on the deceased donor kidney transplant waitlist, and placement of permanent vascular access). Multivariable logistic and Cox proportional hazards models were used to estimate adjusted odds ratios (ORs) and hazard ratios (HRs). RESULTS: LN-ESRD patients were more likely than other ESRD patients to receive pre-ESRD care (71% vs. 66%; OR = 1.68, 95% CI 1.57-1.78) and be placed on the transplant waitlist in the first year (206 vs. 86 per 1000 patient-years; HR = 1.42, 95% CI 1.34–1.52). However, only 24% had a permanent vascular access (fistula or graft) in place at dialysis start (vs. 36%; OR = 0.63, 95% CI 0.59–0.67). CONCLUSIONS: LN-ESRD patients are more likely to receive pre-ESRD care and have better access to transplant, but are less likely to have a permanent vascular access for dialysis, than other ESRD patients. Further studies are warranted to examine barriers to permanent vascular access placement, as well as morbidity and mortality associated with temporary access, in patients with LN-ESRD

The Synoptic All-Sky Infrared (SASIR) Survey

We are proposing to conduct a multicolor, synoptic infrared (IR) imaging survey of the Northern sky with a new, dedicated 6.5-meter telescope at San Pedro M\'artir (SPM) Observatory. This initiative is being developed in partnership with astronomy institutions in Mexico and the University of California. The 4-year, dedicated survey, planned to begin in 2017, will reach more than 100 times deeper than 2MASS. The Synoptic All-Sky Infrared (SASIR) Survey will reveal the missing sample of faint red dwarf stars in the local solar neighborhood, and the unprecedented sensitivity over such a wide field will result in the discovery of thousands of z ~ 7 quasars (and reaching to z > 10), allowing detailed study (in concert with JWST and Giant Segmented Mirror Telescopes) of the timing and the origin(s) of reionization. As a time-domain survey, SASIR will reveal the dynamic infrared universe, opening new phase space for discovery. Synoptic observations of over 10^6 supernovae and variable stars will provide better distance measures than optical studies alone. SASIR also provides significant synergy with other major Astro2010 facilities, improving the overall scientific return of community investments. Compared to optical-only measurements, IR colors vastly improve photometric redshifts to z ~ 4, enhancing dark energy and dark matter surveys based on weak lensing and baryon oscillations. The wide field and ToO capabilities will enable a connection of the gravitational wave and neutrino universe - with events otherwise poorly localized on the sky - to transient electromagnetic phenomena.Comment: Revised version of submitted whitepaper to the "Optical and IR Astronomy from the Ground" Program Prioritization Panel of the Astro2010 Decadal Survey; 23 page

The direct effect of Focal Adhesion Kinase (FAK), dominant-negative FAK, FAK-CD and FAK siRNA on gene expression and human MCF-7 breast cancer cell tumorigenesis

<p>Abstract</p> <p>Background</p> <p>Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that plays an important role in survival signaling. FAK has been shown to be overexpressed in breast cancer tumors at early stages of tumorigenesis.</p> <p>Methods</p> <p>To study the direct effect of FAK on breast tumorigenesis, we developed Tet-ON (tetracycline-inducible) system of MCF-7 breast cancer cells stably transfected with FAK or dominant-negative, C-terminal domain of FAK (FAK-CD), and also FAKsiRNA with silenced FAK MCF-7 stable cell line. Increased expression of FAK in isogenic Tet-inducible MCF-7 cells caused increased cell growth, adhesion and soft agar colony formation <it>in vitro</it>, while expression of dominant-negative FAK inhibitor caused inhibition of these cellular processes. To study the role of induced FAK and FAK-CD <it>in vivo</it>, we inoculated these Tet-inducible cells in nude mice to generate tumors in the presence or absence of doxycycline in the drinking water. FAKsiRNA-MCF-7 cells were also injected into nude mice to generate xenograft tumors.</p> <p>Results</p> <p>Induction of FAK resulted in significant increased tumorigenesis, while induced FAK-CD resulted in decreased tumorigenesis. Taq Man Low Density Array assay demonstrated specific induction of FAKmRNA in MCF-7-Tet-ON-FAK cells. DMP1, encoding cyclin D binding myb-like protein 1 was one of the genes specifically affected by Tet-inducible FAK or FAK-CD in breast xenograft tumors. In addition, silencing of FAK in MCF-7 cells with FAK siRNA caused increased cell rounding, decreased cell viability <it>in vitro </it>and inhibited tumorigenesis <it>in vivo</it>. Importantly, Affymetrix microarray gene profiling analysis using Human Genome U133A GeneChips revealed >4300 genes, known to be involved in apoptosis, cell cycle, and adhesion that were significantly down- or up-regulated (p < 0.05) by FAKsiRNA.</p> <p>Conclusion</p> <p>Thus, these data for the first time demonstrate the direct effect of FAK expression and function on MCF-7 breast cancer tumorigenesis <it>in vivo </it>and reveal specific expression of genes affected by silencing of FAK.</p