In vivo killing of Staphylococcus aureus using a light-activated antimicrobial agent

Background: The widespread problem of antibiotic resistance in pathogens such as Staphylococcus aureus has prompted the search for new antimicrobial approaches. In this study we report for the first time the use of a light-activated antimicrobial agent, methylene blue, to kill an epidemic methicillin-resistant Staphylococcus aureus (EMRSA-16) strain in two mouse wound models.Results: Following irradiation of wounds with 360 J/cm(2) of laser light (670 nm) in the presence of 100 mu g/ml of methylene blue, a 25-fold reduction in the number of viable EMRSA was seen. This was independent of the increase in temperature of the wounds associated with the treatment. Histological examination of the wounds revealed no difference between the photodynamic therapy (PDT)-treated wounds and the untreated wounds, all of which showed the same degree of inflammatory infiltration at 24 hours.Conclusion: The results of this study demonstrate that PDT is effective at reducing the total number of viable EMRSA in a wound. This approach has promise as a means of treating wound infections caused by antibiotic-resistant microbes as well as for the elimination of such organisms from carriage sites

Exome-wide association study of pancreatic cancer risk

We conducted a case-control exome-wide association study to discover germline variants in coding regions that affect risk for pancreatic cancer, combining data from 5 studies. We analyzed exome and genome sequencing data from 437 patients with pancreatic cancer (cases) and 1922 individuals not known to have cancer (controls). In the primary analysis, BRCA2 had the strongest enrichment for rare inactivating variants (17/437 cases vs 3/1922 controls) (P=3.27x10(-6); exome-wide statistical significance threshold P<2.5x10(-6)). Cases had more rare inactivating variants in DNA repair genes than controls, even after excluding 13 genes known to predispose to pancreatic cancer (adjusted odds ratio, 1.35, P=.045). At the suggestive threshold (P<.001), 6 genes were enriched for rare damaging variants (UHMK1, AP1G2, DNTA, CHST6, FGFR3, and EPHA1) and 7 genes had associations with pancreatic cancer risk, based on the sequence-kernel association test. We confirmed variants in BRCA2 as the most common high-penetrant genetic factor associated with pancreatic cancer and we also identified candidate pancreatic cancer genes. Large collaborations and novel approaches are needed to overcome the genetic heterogeneity of pancreatic cancer predisposition

Physical Conditions of Accreting Gas in T Tauri Star Systems

We present results from a low resolution (R~300) near-infrared spectroscopic variability survey of actively accreting T Tauri stars (TTS) in the Taurus-Auriga star forming region. Paschen and Brackett series H I recombination lines were detected in 73 spectra of 15 classical T Tauri systems. The values of the Pan/PaB, Brn/BrG, and BrG/Pan H I line ratios for all observations exhibit a scatter of < 20% about the weighted mean, not only from source to source, but also for epoch-to-epoch variations in the same source. A representative or `global' value was determined for each ratio in both the Paschen and Brackett series as well as the BrG/Pan line ratios. A comparison of observed line ratio values was made to those predicted by the temperature and electron density dependent models of Case B hydrogen recombination line theory. The measured line ratios are statistically well-fit by a tightly constrained range of temperatures (T < 2000 K) and electron densities 1e9 < n_e < 1e10 cm^-3. A comparison of the observed line ratio values to the values predicted by the optically thick and thin local thermodynamic equilibrium cases rules out these conditions for the emitting H I gas. Therefore, the emission is consistent with having an origin in a non-LTE recombining gas. While the range of electron densities is consistent with the gas densities predicted by existing magnetospheric accretion models, the temperature range constrained by the Case B comparison is considerably lower than that expected for accreting gas. The cooler gas temperatures will require a non-thermal excitation process (e.g., coronal/accretion-related X-rays and UV photons) to power the observed line emission.Comment: 12 pages, emulateapj format, Accepted for publication in Ap

Smartphone Medical Applications Useful for the Rural Practitioner

Like other similarly situated rural states, West Virginia’s patients and practitioners often experience access barriers to current medical expertise for multiple disciplines. This article was generated to help bridge this gap and highlights the best-rated mobile medical applications (Apps) for smartphone use. From finding drug interactions and dosing schedules to discussing patients in HIPAA-compliant formats, Apps are becoming integral to the practice of 21st Century medicine. The increased use of these Apps by physicians-in-training and established practitioners highlights the shift from reliance upon the medical library to the easy to use mobile-based technology platforms. This article provides our practitioners, physician extenders, medical trainees, and office staff a guide to access and assess the utility of some of the best rated medical and HIPAA compliant Apps

Photoactivated release of membrane impermeant sulfonates inside cells.

Photouncaging delivers compounds with high spatial and temporal control to induce or inhibit biological processes but the released compounds may diffuse out. We here demonstrate that sulfonate anions can be photocaged so that a membrane impermeable compound can enter cells, be uncaged by photoirradiation and trapped within the cell

Gene pathway development in human epicardial adipose tissue during early life

Studies in rodents and newborn humans demonstrate the influence of brown adipose tissue (BAT) in temperature control and energy balance and a critical role in the regulation of body weight. Here, we obtained samples of epicardial adipose tissue (EAT) from neonates, infants, and children in order to evaluate changes in their transcriptional landscape by applying a systems biology approach. Surprisingly, these analyses revealed that the transition to infancy is a critical stage for changes in the morphology of EAT and is reflected in unique gene expression patterns of a substantial proportion of thermogenic gene transcripts (~10%). Our results also indicated that the pattern of gene expression represents a distinct developmental stage, even after the rebound in abundance of thermogenic genes in later childhood. Using weighted gene coexpression network analyses, we found precise anthropometric-specific correlations with changes in gene expression and the decline of thermogenic capacity within EAT. In addition, these results indicate a sequential order of transcriptional events affecting cellular pathways, which could potentially explain the variation in the amount, or activity, of BAT in adulthood. Together, these results provide a resource to elucidate gene regulatory mechanisms underlying the progressive development of BAT during early life

Disruption of cells in biosolids affects E. coli dynamics in storage

Achieving microbial compliance during biosolids storage can be complicated by the unpredictable increase of Escherichia coli. Thermal treatment during anaerobic digestion (AD) and the effects of dewatering may be a significant factor contributing to indicator survival. Shear forces present during dewatering may promote cell damage, releasing nutrient for E. coli growth. The effect of cell damage on E. coli survival was assessed in laboratory-scale thermal and physical disruption experiments. E. coli growth curves for disrupted treatments were compared with control conditions and quantified using flow cytometry and membrane filtration techniques. A significant difference (p < 0.05) in the level of damaged cells between control and disrupted conditions was observed. For thermal and physical disruption treatments, the peak of E. coli concentration increased significantly by 1.8 Log and 2.4 Log (CFU (colony forming units) g−1 DS), respectively, compared with control treatments. Research findings contribute to the understanding of bacterial growth and death dynamics in biosolid