Membrane TNF confers protection to acute mycobacterial infection

BACKGROUND: Tumour necrosis factor (TNF) is crucial for the control of mycobacterial infection as TNF deficient (KO) die rapidly of uncontrolled infection with necrotic pneumonia. Here we investigated the role of membrane TNF for host resistance in knock-in mice with a non-cleavable and regulated allele (mem-TNF). METHODS: C57BL/6, TNF KO and mem-TNF mice were infected with M. tuberculosis H37Rv (Mtb at 100 CFU by intranasal administration) and the survival, bacterial load, lung pathology and immunological parameters were investigated. Bone marrow and lymphocytes transfers were used to test the role of membrane TNF to confer resistance to TNF KO mice. RESULTS: While TNF-KO mice succumbed to infection within 4–5 weeks, mem-TNF mice recruited normally T cells and macrophages, developed mature granuloma in the lung and controlled acute Mtb infection. However, during the chronic phase of infection mem-TNF mice succumbed to disseminated infection with necrotic pneumonia at about 150 days. Reconstitution of irradiated TNF-KO mice with mem-TNF derived bone marrow cells, but not with lymphocytes, conferred host resistance to Mtb infection in TNF-KO mice. CONCLUSION: Membrane expressed TNF is sufficient to allow cell-cell signalling and control of acute Mtb infection. Bone marrow cells, but not lymphocytes from mem-TNF mice confer resistance to infection in TNF-KO mice. Long-term infection control with chronic inflammation likely disrupting TNF mediated cell-cell signalling, additionally requires soluble TNF

Brief review on systematic hypothermia for the protection of central nervous system during aortic arch surgery: a double-sword tool?

Antegrade selective cerebral perfusion in conjunction with hypothermia attenuate postoperative neurological injury, which in turn still remains the main cause of mortality and morbidity following aortic arch surgery. Hypothermic circulatory arrest however could be a useful tool during arch surgery, surgery for chronic thromboembolic disease, air on the arterial line during CPB, during cavotomy for extraction of renal cell carcinoma with level IV extension, or when dealing with difficult trauma to the SVC or IVC. Cerebral protective effects with hypothermic procedures including inhibition of neuron excitation, and discharge of excitable amino acids, and thereby, prevention of an increase in intercellular calcium ions, hyperoxidation of lipids in cell membranes, and free radical production

The Pathogenic Properties of a Novel and Conserved Gene Product, KerV, in Proteobacteria

Identification of novel virulence factors is essential for understanding bacterial pathogenesis and designing antibacterial strategies. In this study, we uncover such a factor, termed KerV, in Proteobacteria. Experiments carried out in a variety of eukaryotic host infection models revealed that the virulence of a Pseudomonas aeruginosa kerV null mutant was compromised when it interacted with amoebae, plants, flies, and mice. Bioinformatics analyses indicated that KerV is a hypothetical methyltransferase and is well-conserved across numerous Proteobacteria, including both well-known and emerging pathogens (e.g., virulent Burkholderia, Escherichia, Shigella, Vibrio, Salmonella, Yersinia and Brucella species). Furthermore, among the 197 kerV orthologs analyzed in this study, about 89% reside in a defined genomic neighborhood, which also possesses essential DNA replication and repair genes and detoxification gene. Finally, infection of Drosophila melanogaster with null mutants demonstrated that KerV orthologs are also crucial in Vibrio cholerae and Yersinia pseudotuberculosis pathogenesis. Our findings suggested that KerV has a novel and broad significance as a virulence factor in pathogenic Proteobacteria and it might serve as a new target for antibiotic drug design

Antiepileptic drugs’ tolerability and safety – a systematic review and meta-analysis of adverse effects in dogs

<p>Various anti-epileptic drugs (AEDs) are used for the management of idiopathic epilepsy (IE) in dogs. Their safety profile is an important consideration for regulatory bodies, owners and prescribing clinicians. However, information on their adverse effects still remains limited with most of it derived from non-blinded non-randomized uncontrolled trials and case reports.</p><p><span>This poster won third place, which was presented at the Veterinary Evidence Today conference, Edinburgh November 1-3, 2016. </span></p><br /> <img src="https://www.veterinaryevidence.org/rcvskmod/icons/oa-icon.jpg" alt="Open Access" /

Soft tissue damage after minimally invasive THA: A comparison of 5 approaches

Methods 5 surgeons each performed a total hip arthroplasty on 5 fresh frozen cadaver hips, using either a MIS anterior, MIS anterolateral, MIS 2-incision, MIS posterior, or lateral transgluteal approach. Postoperatively, the hips were dissected and muscle damage color-stained. We measured proportional muscle damage relative to the midsubstance cross-sectional surface area (MCSA) using computerized color detection. The integrity of external rotator muscles, nerves, and ligaments was assessed by direct observation. Results None of the other MIS approaches resulted in less gluteus medius muscle damage than the lateral transgluteal approach. However, the MIS anterior approach completely preserved the gluteus medius muscle in 4 cases while partial damage occurred in 1 case. Furthermore, the superior gluteal nerve was transected in 4 cases after a MIS anterolateral approach and in 1 after the lateral transgluteal approach. The lateral femoral cutaneous nerve was transected once after both the MIS anterior approach and the MIS 2-incision approach. Interpretation The MIS anterior approach may preserve the gluteus medius muscle during total hip arthroplasty, but with a risk of damaging the lateral femoral cutaneous nerv