Early Appropriate Parenteral Antimicrobial Treatment of Complicated Skin and Soft Tissue Infections Caused by Methicillin-Resistant Staphylococcus aureus

Abstract Background: Complicated skin and soft tissue infections (cSSTIs) are a major clinical problem, in part because of the increasing resistance of infecting bacteria to our current antibiotic therapies. Prompt appropriate treatment of infections in hospitalized patients reduces the mortality rate. Furthermore, appropriate and timely antibiotic therapy improves outcomes for cSSTIs caused by methicillin-resistant Staphylococcus aureus (MRSA). This review delineates factors to consider in the choice of initial antibiotic treatment for cSSTIs and describes the antimicrobial agents available or under clinical development for the treatment of cSSTIs caused by MRSA. Methods: Review of the pertinent literature and recommendations. Results: The choice of antimicrobial agent for empiric treatment of cSSTIs should be guided by the site and type of infection, the presence of an immunocompromised state or neutropenia, and risk factors for hospital-acquired MRSA (HA-MRSA) or community-associated MRSA (CA-MRSA) infection. Most CA-MRSA strains remain susceptible to ciprofloxacin, clindamycin, gentamicin, and trimethoprim/sulfamethoxazole, although resistance to clindamycin can emerge during treatment. Of the agents available for the treatment of HA-MRSA cSSTIs, vancomycin has been the reference standard, but clinical failures have been reported increasingly. Alternative agents for HA-MRSA include linezolid, which has been well-studied for treatment of cSSTIs, as well as daptomycin and tigecycline. A number of antibiotic agents are undergoing clinical trials or are under development for the treatment of cSSTIs caused by MRSA. Conclusions: Severe and progressive cSSTIs should be treated promptly with appropriate antibiotic agents. The choice of agent should be guided by a number of factors, including suspected CA-MRSA or HA-MRSA infection. Available agents should be evaluated carefully for efficacy in the treatment of MRSA cSSTIs.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63135/1/sur.2008.063.supp.pd

A Spontaneous Mutation of the Rat Themis Gene Leads to Impaired Function of Regulatory T Cells Linked to Inflammatory Bowel Disease

Spontaneous or chemically induced germline mutations, which lead to Mendelian phenotypes, are powerful tools to discover new genes and their functions. Here, we report an autosomal recessive mutation that occurred spontaneously in a Brown-Norway (BN) rat colony and was identified as causing marked T cell lymphopenia. This mutation was stabilized in a new rat strain, named BNm for “BN mutated.” In BNm rats, we found that the T cell lymphopenia originated in the thymus, was intrinsic to CD4 T lymphocytes, and was associated with the development of an inflammatory bowel disease. Furthermore, we demonstrate that the suppressive activity of both peripheral and thymic CD4+ CD25bright regulatory T cells (Treg) is defective in BNm rats. Complementation of mutant animals with BN Treg decreases disease incidence and severity, thus suggesting that the impaired Treg function is involved in the development of inflammatory bowel disease in BNm rats. Moreover, the cytokine profile of effector CD4 T cells is skewed toward Th2 and Th17 phenotypes in BNm rats. Linkage analysis and genetic dissection of the CD4 T cell lymphopenia in rats issued from BNm×DA crosses allowed the localization of the mutation on chromosome 1, within a 1.5 megabase interval. Gene expression and sequencing studies identified a frameshift mutation caused by a four-nucleotide insertion in the Themis gene, leading to its disruption. This result is the first to link Themis to the suppressive function of Treg and to suggest that, in Themis-deficient animals, defect of this function is involved in intestinal inflammation. Thus, this study highlights the importance of Themis as a new target gene that could participate in the pathogenesis of immune diseases characterized by chronic inflammation resulting from a defect in the Treg compartment

Genome-Wide Identification of MicroRNAs in Response to Low Nitrate Availability in Maize Leaves and Roots

BACKGROUND: Nitrate is the major source of nitrogen available for many crop plants and is often the limiting factor for plant growth and agricultural productivity especially for maize. Many studies have been done identifying the transcriptome changes under low nitrate conditions. However, the microRNAs (miRNAs) varied under nitrate limiting conditions in maize has not been reported. MiRNAs play important roles in abiotic stress responses and nutrient deprivation. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we used the SmartArray™ and GeneChip® microarray systems to perform a genome-wide search to detect miRNAs responding to the chronic and transient nitrate limiting conditions in maize. Nine miRNA families (miR164, miR169, miR172, miR397, miR398, miR399, miR408, miR528, and miR827) were identified in leaves, and nine miRNA families (miR160, miR167, miR168, miR169, miR319, miR395, miR399, miR408, and miR528) identified in roots. They were verified by real time stem loop RT-PCR, and some with additional time points of nitrate limitation. The miRNAs identified showed overlapping or unique responses to chronic and transient nitrate limitation, as well as tissue specificity. The potential target genes of these miRNAs in maize were identified. The expression of some of these was examined by qRT-PCR. The potential function of these miRNAs in responding to nitrate limitation is described. CONCLUSIONS/SIGNIFICANCE: Genome-wide miRNAs responding to nitrate limiting conditions in maize leaves and roots were identified. This provides an insight into the timing and tissue specificity of the transcriptional regulation to low nitrate availability in maize. The knowledge gained will help understand the important roles miRNAs play in maize responding to a nitrogen limiting environment and eventually develop strategies for the improvement of maize genetics

Short-Lived Trace Gases in the Surface Ocean and the Atmosphere

The two-way exchange of trace gases between the ocean and the atmosphere is important for both the chemistry and physics of the atmosphere and the biogeochemistry of the oceans, including the global cycling of elements. Here we review these exchanges and their importance for a range of gases whose lifetimes are generally short compared to the main greenhouse gases and which are, in most cases, more reactive than them. Gases considered include sulphur and related compounds, organohalogens, non-methane hydrocarbons, ozone, ammonia and related compounds, hydrogen and carbon monoxide. Finally, we stress the interactivity of the system, the importance of process understanding for modeling, the need for more extensive field measurements and their better seasonal coverage, the importance of inter-calibration exercises and finally the need to show the importance of air-sea exchanges for global cycling and how the field fits into the broader context of Earth System Science

MicroRNAs play critical roles during plant development and in response to abiotic stresses

MicroRNAs (miRNAs) have been identified as key molecules in regulatory networks. The fine-tuning role of miRNAs in addition to the regulatory role of transcription factors has shown that molecular events during development are tightly regulated. In addition, several miRNAs play crucial roles in the response to abiotic stress induced by drought, salinity, low temperatures, and metals such as aluminium. Interestingly, several miRNAs have overlapping roles with regard to development, stress responses, and nutrient homeostasis. Moreover, in response to the same abiotic stresses, different expression patterns for some conserved miRNA families among different plant species revealed different metabolic adjustments. The use of deep sequencing technologies for the characterisation of miRNA frequency and the identification of new miRNAs adds complexity to regulatory networks in plants. In this review, we consider the regulatory role of miRNAs in plant development and abiotic stresses, as well as the impact of deep sequencing technologies on the generation of miRNA data

In Situ Localization of Small RNAs in Plants

Small RNAs have vital roles in numerous aspects of plant biology. Deciphering their precise contributions requires knowledge of a small RNA's spatiotemporal pattern of accumulation. The in situ hybridization protocol described here takes advantage of locked nucleic acid (LNA) oligonucleotide probes to visualize small RNA expression at the cellular level with high sensitivity and specificity. The procedure is optimized for paraffin-embedded plant tissue sections, is applicable to a wide range of plants and tissues, and can be completed within 2-6 days