Involution of the mouse mammary gland is associated with an immune cascade and an acute-phase response, involving LBP, CD14 and STAT3

INTRODUCTION: Involution of the mammary gland is a complex process of controlled apoptosis and tissue remodelling. The aim of the project was to identify genes that are specifically involved in this process. METHODS: We used Affymetrix oligonucleotide microarrays to perform a detailed transcript analysis on the mechanism of controlled involution after withdrawal of the pups at day seven of lactation. Some of the results were confirmed by semi-quantitative reverse transcriptase polymerase chain reaction, Western blotting or immunohistochemistry. RESULTS: We identified 145 genes that were specifically upregulated during the first 4 days of involution; of these, 49 encoded immunoglobulin genes. A further 12 genes, including those encoding the signal transducer and activator of transcription 3 (STAT3), the lipopolysaccharide receptor (CD14) and lipopolysaccharide-binding protein (LBP), were involved in the acute-phase response, demonstrating that the expression of acute-phase response genes can occur in the mammary gland itself and not only in the liver. Expression of LBP and CD14 was upregulated, at both the RNA and protein level, immediately after pup withdrawal; CD14 was strongly expressed in the luminal epithelial cells. Other genes identified suggested neutrophil activation early in involution, followed by macrophage activation late in the process. Immunohistochemistry and histological staining confirmed the infiltration of the involuting mammary tissue with neutrophils, plasma cells, macrophages and eosinophils. CONCLUSION: Oligonucleotide microarrays are a useful tool for identifying genes that are involved in the complex developmental process of mammary gland involution. The genes identified are consistent with an immune cascade, with an early acute-phase response that occurs in the mammary gland itself and resembles a wound healing process

Bacterial Infections after Burn Injuries: Impact of Multidrug Resistance

Patients who are admitted to the hospital after sustaining a large burn injury are at high risk for developing hospital-associated infections. If patients survive the initial 72 hours after a burn injury, infections are the most common cause of death. Ventilator-associated pneumonia is the most important infection in this patient population. The risk of infections caused by multidrug-resistant bacterial pathogens increases with hospital length of stay in burn patients. In the first days of the postburn hospitalization, more susceptible, Gram-positive organisms predominate, whereas later more resistant Gram-negative organisms are found. These findings impact the choice of empiric antibiotics in critically ill burn patients. A proactive infection control approach is essential in burn units. Furthermore, a multidisciplinary approach to burn patients with a team that includes an infectious disease specialist and a pharmacist in addition to the burn surgeon is highly recommended

CRISPLD1: a novel conserved target in the transition to human heart failure

Heart failure is a major health problem worldwide with a significant morbidity and mortality rate. Although studied extensively in animal models, data from patients at the compensated disease stage are lacking. We sampled myocardium biopsies from aortic stenosis patients with compensated hypertrophy and moderate heart failure and used transcriptomics to study the transition to failure. Sequencing and comparative analysis of analogous samples of mice with transverse aortic constriction identified 25 candidate genes with similar regulation in response to pressure overload, reflecting highly conserved molecular processes. The gene cysteine-rich secretory protein LCCL domain containing 1 (CRISPLD1) is upregulated in the transition to failure in human and mouse and its function is unknown. Homology to ion channel regulatory toxins suggests a role in Ca(2+) cycling. CRISPR/Cas9-mediated loss-of-function leads to dysregulated Ca(2+) handling in human-induced pluripotent stem cell-derived cardiomyocytes. The downregulation of prohypertrophic, proapoptotic and Ca(2+)-signaling pathways upon CRISPLD1-KO and its upregulation in the transition to failure implicates a contribution to adverse remodeling. These findings provide new pathophysiological data on Ca(2+) regulation in the transition to failure and novel candidate genes with promising potential for therapeutic interventions

Precise Prediction for M_W in the MSSM

We present the currently most accurate evaluation of the W boson mass, M_W, in the Minimal Supersymmetric Standard Model (MSSM). The full complex phase dependence at the one-loop level, all available MSSM two-loop corrections as well as the full Standard Model result have been included. We analyse the impact of the different sectors of the MSSM at the one-loop level with a particular emphasis on the effect of the complex phases. We discuss the prediction for M_W based on all known higher-order contributions in representative MSSM scenarios. Furthermore we obtain an estimate of the remaining theoretical uncertainty from unknown higher-order corrections.Comment: 38 pages, 25 figures. Minor corrections, additional reference

Systems-based Practice in Burn Care: Prevention, Management, and Economic Impact of Health Care–associated Infections

Health care–associated infections in burn patients, from ventilator-associated pneumonia to skin and soft tissue infections, can substantially compromise outcomes, because these complications are associated with longer lengths of stay, increased morbidity and mortality, and greater direct medical costs. Health care–associated infections are largely preventable, through surveillance, education, appropriate hand hygiene, and culture change, especially for device-related infections. Systems-based practice, which allows individuals and clinical microsystems to navigate and improve the macro health care system, may be one of the most powerful skill sets to effect change, permitting a shift in culture toward patient safety and quality improvement

Relativistic Mean Field Model with Generalized Derivative Nucleon-Meson Couplings

The quantum hadrodynamics (QHD) model with minimal nucleon-meson couplings is generalized by introducing couplings of mesons to derivatives of the nucleon field in the Lagrangian density. This approach allows an effective description of a state-dependent in-medium interaction in the mean-field approximation. Various parametrizations for the generalized couplings are developed and applied to infinite nuclear matter. In this approach, scalar and vector self-energies depend on both density and momentum similarly as in the Dirac-Brueckner theory. The Schr\"{o}diger-equivalent optical potential is much less repulsive at high nucleon energies as compared to standard relativistic mean field models and thus agrees better with experimental findings. The derivative couplings in the extended model have significant effects on properties of symmetric nuclear matter and neutron matter.Comment: 35 pages, 1 table, 10 figure

Hadronic freeze-out following a first order hadronization phase transition in ultrarelativistic heavy-ion collisions

We analyze the hadronic freeze-out in ultra-relativistic heavy ion collisions at RHIC in a transport approach which combines hydrodynamics for the early, dense, deconfined stage of the reaction with a microscopic non-equilibrium model for the later hadronic stage at which the hydrodynamic equilibrium assumptions are not valid. With this ansatz we are able to self-consistently calculate the freeze-out of the system and determine space-time hypersurfaces for individual hadron species. The space-time domains of the freeze-out for several hadron species are found to be actually four-dimensional, and differ drastically for the individual hadrons species. Freeze-out radii distributions are similar in width for most hadron species, even though the Omega-baryon is found to be emitted rather close to the phase boundary and shows the smallest freeze-out radii and times among all baryon species. The total lifetime of the system does not change by more than 10% when going from SPS to RHIC energies.Comment: 11 pages, 4 eps-figures included, revised versio