Testing for viral penetration of non-latex surgical and examination gloves: a comparison of three methods

ABSTRACTCurrently, there are no international standards based on microbiological methodology for testing the ability of medical examination or surgical gloves to prevent the passage of viruses. Three protocols for the direct examination of the viral barrier properties of non-latex gloves were compared with 1080 gloves (270 gloves from each of two surgical brands and two medical examination brands). In two of the methods, gloves were filled with and suspended in a nutrient broth solution, and bacteriophage ϕX174 was placed either inside or outside the glove, while the entire test vessel was agitated. Gloves tested using the third method were filled with a suspension of bacteriophage and allowed to rest in a vessel containing nutrient broth. Gloves were tested directly from the manufacturer's packaging, or after being punctured intentionally or subjected to a stress protocol. The passage of bacteriophage was detected with plaque assays. Significant differences in failure rates between glove brands were apparent only among gloves that had been subjected to the stress protocol. Overall, the two methods in which bacteriophage were placed inside the gloves provided more sensitivity than the method in which bacteriophage was spiked into broth outside the gloves. Thus the placement of bacteriophage inside test gloves (or the use of pressure across the glove barrier during testing), and the use of a standardised stress protocol, will improve significantly the ability of a glove test protocol to determine the relative quality of the barrier offered by medical examination and surgical gloves. Further research is needed to provide test methods that can incorporate reproducibly both the use of bacteriophage and simulated glove use in an industrial quality control setting

Nonlinear dynamics and bifurcation behavior of a 2-DOF spring resonator with end stopper for energy harvesting

In this paper, the model of a two-degree-of-freedom (2-DOF) spring resonator with end stopper for an energy harvesting application is presented. Then we characterize its nonlinear dynamical behavior by numerical simulations when some suitable parameters are varied. The system is formed by two resonators subject to external vibrational excitation and with an end stopper. We present the continuous time dynamical model of the system in the form of a switched fourth order differential equation. Harmonic vibrations are considered as the main ambient energy source for the system and its frequency response representing the RMS value of the displacement is first computed. The dynamical behavior is unveiled by computing state-space trajectories, timedomain series and FFT spectra and frequency response as the excitation amplitude is varied.Peer ReviewedPostprint (published version

A novel six3 mutation segregates with holoprosencephaly in a large family

Holoprosencephaly is the most common structural malformation of the forebrain in humans and has a complex etiology including chromosomal aberrations, single gene mutations and environmental components. Here we present the pertinent clinical findings among members of an unusually large kindred ascertained over 15 years ago following the evaluation and subsequent genetic work-up of a female infant with congenital anomalies. A genome-wide scan and linkage analysis showed only suggestive evidence of linkage to markers on chromosome 2 among the most likely of several pedigree interpretations. We now report that a novel missense mutation in the SIX3 holopro- sencephaly gene is the likely cause in this family. Molecular genetic analysis and/or clinical characterization now show that at least 15 members of this family are presumed SIX3 mutation gene carriers, with clinical manifestations ranging from pheno- typically normal adults (non-penetrance) to alobar holoprosen- cephaly incompatible with postnatal life. This particular family represents a seminal example of the variable manifestations of gene mutations in holoprosencephaly and difficulties encountered in their elucidation.Fil: Solomon, Benjamin D.. National Institutes of Health; Estados UnidosFil: Lacbawan, Felicitas. National Institutes of Health; Estados Unidos. State University of New York; Estados UnidosFil: Jain, Mahim. National Institutes of Health; Estados UnidosFil: Domene, Sabina. National Institutes of Health; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Roessler, Erich. National Institutes of Health; Estados UnidosFil: Moore, Cynthia. Indiana University School of Medicine; Estados UnidosFil: Dobyns, William B.. University of Chicago; Estados UnidosFil: Muenke, Maximilian. National Institutes of Health; Estados Unido

New missense variants in RELT causing hypomineralised amelogenesis imperfecta

Amelogenesis imperfecta (AI) is a heterogeneous group of genetic diseases characterised by dental enamel malformation. Pathogenic variants in at least 33 genes cause syndromic or non‐syndromic AI. Recently variants in RELT, encoding an orphan receptor in the tumour necrosis factor (TNF) superfamily, were found to cause recessive AI, as part of a syndrome encompassing small stature and severe childhood infections. Here we describe four additional families with autosomal recessive hypomineralised AI due to previously unreported homozygous mutations in RELT. Three families carried a homozygous missense variant in the fourth exon (c.164C > T, p.[T55I]) and a fourth family carried a homozygous missense variant in the 11th exon (c.1264C > T, p.[R422W]). We found no evidence of additional syndromic symptoms in affected individuals. Analyses of tooth microstructure with computerized tomography and scanning electron microscopy suggest a role for RELT in ameloblasts' coordination and interaction with the enamel matrix. Microsatellite genotyping in families segregating the T55I variant reveals a shared founder haplotype. These findings extend the RELT pathogenic variant spectrum, reveal a founder mutation in the UK Pakistani population and provide detailed analysis of human teeth affected by this hypomineralised phenotype, but do not support a possible syndromic presentation in all those with RELT‐variant associated AI

Heterogeneity of Invasive Ductal Carcinoma: Proposal for a Hypothetical Classification

To investigate what heterogeneity exists in breast cancer, 228 consecutive patients with operable invasive duetal carcinoma (IDC), not otherwise specified, were categorized on the basis of the horizontal progression model of carcinogenesis. Using the reversed Black's nuclear grade (RBNG) in the IDC component and the association of ductal carcinoma in situ (DCIS), the patients were classified into pure IDC (IDC de novo or ab initio) as Group I, non-high grade (RBNG 1 and 2) IDC with DCIS as Group II, and high grade (RBNG 3) IDC with DCIS as Group III. The Groups classified in the present study appeared as a prognostic factor independent of known prognostic and predictive factors in multivariate test. Group I had the worst prognosis among the three groups and was the most non-responsive to tamoxifen. After performing stratifying analyses by group, it was found that metastasis-free survival was statistically associated with the status of hormone receptors estrogen receptor and progesterone receptor and tamoxifen therapy only in Group II. In addition, the status of c-erbB-2 expression had prognostic significance only within the Group III. Our results may be used to frame an alternative hypothetical model for breast cancer evolution and will lead us to reconsider the tailoring of the comprehensive therapeutic modality used at the present time

Regulation of Monocyte Functional Heterogeneity by miR-146a and Relb

Monocytes serve as a central defense system against infection and injury but can also promote pathological inflammatory responses. Considering the evidence that monocytes exist in at least two subsets committed to divergent functions, we investigated whether distinct factors regulate the balance between monocyte subset responses in vivo. We identified a microRNA (miRNA), miR-146a, which is differentially regulated both in mouse (Ly-6C^(hi)/Ly-6C^(lo)) and human (CD14^(hi)/CD14^(lo)CD16^+) monocyte subsets. The single miRNA controlled the amplitude of the Ly-6C^(hi) monocyte response during inflammatory challenge whereas it did not affect Ly-6C^(lo) cells. miR-146a-mediated regulation was cell-intrinsic and depended on Relb, a member of the noncanonical NF-κB/Rel family, which we identified as a direct miR-146a target. These observations not only provide mechanistic insights into the molecular events that regulate responses mediated by committed monocyte precursor populations but also identify targets for manipulating Ly-6C^(hi) monocyte responses while sparing Ly-6C^(lo) monocyte activity

Twelve weeks of protracted venous infusion of fluorouracil (5-FU) is as effective as 6 months of bolus 5-FU and folinic acid as adjuvant treatment in colorectal cancer.

We performed a multicentre randomised trial to compare the efficacy and toxicity of 12 weeks of 5-fluorouracil (5-FU) delivered by protracted intravenous infusion (PVI 5-FU) against the standard bolus regimen of 5-FU and folinic acid (5-FU/FA) given for 6 months as adjuvant treatment in colorectal cancer. A total of 716 patients with curatively resected Dukes' B or C colorectal cancer were randomised to 5-FU/FA (5-FU 425 mg m(-2) i.v. and FA 20 mg m(-2) i.v. bolus days 1-5 every 28 days for 6 months) or to PVI 5-FU alone (300 mg m(-2) day for 12 weeks). With a median follow-up of 19.8 months, 133 relapses and 77 deaths have been observed. Overall survival did not differ significantly (log rank P=0.764) between patients receiving 5-FU/FA and PVI 5-FU (3-year survival 83.2 vs 87.9%, respectively). Patients in the 5-FU/FA group had significantly worse relapse-free survival (RFS, log rank P=0.023) compared to those receiving PVI 5-FU (3-year RFS, 68.6 vs 80%, respectively). Grades 3-4 neutropenia, diarrhoea, stomatitis and severe alopecia were significantly less (P<0.0001) and global quality of life scores significantly better (P&<0.001) for patients in the PVI 5-FU treatment arm. In conclusion, infused 5-FU given over 12 weeks resulted in similar survival to bolus 5-FU and FA over a 6 month period, but with significantly less toxicity

Metastatic colorectal cancer to a primary thyroid cancer

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Automated NMR relaxation dispersion data analysis using NESSY

<p>Abstract</p> <p>Background</p> <p>Proteins are dynamic molecules with motions ranging from picoseconds to longer than seconds. Many protein functions, however, appear to occur on the micro to millisecond timescale and therefore there has been intense research of the importance of these motions in catalysis and molecular interactions. Nuclear Magnetic Resonance (NMR) relaxation dispersion experiments are used to measure motion of discrete nuclei within the micro to millisecond timescale. Information about conformational/chemical exchange, populations of exchanging states and chemical shift differences are extracted from these experiments. To ensure these parameters are correctly extracted, accurate and careful analysis of these experiments is necessary.</p> <p>Results</p> <p>The software introduced in this article is designed for the automatic analysis of relaxation dispersion data and the extraction of the parameters mentioned above. It is written in Python for multi platform use and highest performance. Experimental data can be fitted to different models using the Levenberg-Marquardt minimization algorithm and different statistical tests can be used to select the best model. To demonstrate the functionality of this program, synthetic data as well as NMR data were analyzed. Analysis of these data including the generation of plots and color coded structures can be performed with minimal user intervention and using standard procedures that are included in the program.</p> <p>Conclusions</p> <p>NESSY is easy to use open source software to analyze NMR relaxation data. The robustness and standard procedures are demonstrated in this article.</p