Influenza virus infection: an approach to identify predictors for in-hospital and 90-day mortality from patients in Vienna during the season 2017/18.

BACKGROUND: Seasonal influenza outbreaks are associated with increased mortality and hospitalisation rates. Herein we tried to identify predictors of mortality in hospitalised patients with influenza virus infection. MATERIALS/METHODS: In this exploratory retrospective observational single-centre-study we included all influenza-positive patients older than 18 years who were hospitalised and treated at the flu-isolation-ward during the influenza season 2017/18. Diagnosis was based on point-of-care-test with the Alere™ i. First we performed χ2 tests and Mann-Whitney U tests to identify predictors of mortality. Significant variables were used in a stepwise-forward-logistic-regression-model to predict in-hospital and 90-day mortality. RESULTS: Of the 396 patients who tested positive for influenza 96 (24.2%) had influenza A and 300 (75.8%) influenza B. Twenty-two (5.6%) died in hospital and the 90-day mortality rate was 9.4%. In the stepwise logistic regression older age (OR 1.1 per year 95% CI 1.03-1.17), history of atrial fibrillation (OR 5.91 95% CI 1.91-18.34), dementia (OR 3.98 95% CI 1.24-12.78), leucocyte count (OR 1.11 per G/L 95% CI 1.03-1.20), pneumonia (OR 4.39 95% CI 1.44-13.39) and acute heart failure (OR 23.15 95% CI 4.33-123.76) increased the risk of in-hospital mortality. The risk for 90-day mortality was increased by older age (OR 1.04 per year 95% CI 1.01-1.07), history of atrial fibrillation (OR 3.1, 95% CI 1.36-7.05), history of congestive heart failure (OR 4.7 95% CI 1.94-11.48), pneumonia (OR 3.2 95% CI 1.45-6.91) and decreased by statin use (OR 0.28 95% CI 0.10-0.78). CONCLUSIONS: Older age, history of atrial fibrillation and pneumonia are associated with increased risk of influenza-associated in-hospital and 90-day mortality. Statin use may decrease 90-day mortality.

Coupling Brain Perfusion Screens and Next Generation Sequencing to Identify Blood-Brain Barrier Binding Antibodies.

Antibodies that target the blood-brain barrier (BBB) in vivo are of particular interest for the treatment of neurological diseases. Here, we screened a phage display single-chain antibody (scFv) library by brain perfusion in an attempt to isolate scFv that target the rat BBB. After four rounds of screening, the resulting antibody pool remained highly complex and discrete clonal sampling did not identify any scFvs capable of binding to the rat BBB. Thus, the heavy chain CDR3 in the resulting pools was subjected to NGS, and the resulting data was used to identify 12 scFv clones that were of high abundance and/or enriched from round 3 to 4, signifying potential hits. Of these, two scFv, denoted scFv 4 and scFv 40, were identified that bound the rat BBB. Neither of these scFvs was identified by discrete sampling, motivating NGS as a tool to identify lead antibodies from complex in vivo screens.

Topology and glass structure evolution in (BaO)x((B2O3)32(SiO2)68)(100-x) ternary--evidence of rigid, intermediate, and flexible phases.

We examine variations in the glass transition temperature (T(g)(x)), molar volume (V(m)(x)), and Raman scattering of titled glasses as a function of modifier (BaO) content in the 25% < x < 48% range. Three distinct regimes of behavior are observed; at low x, 24% < x < 29% range, the modifier largely polymerizes the backbone, T(g)(x) increase, features that we identify with the stressed-rigid elastic phase. At high x, 32% < x < 48% range, the modifier depolymerizes the network by creating non-bridging oxygen (NBO) atoms; in this regime T(g)(x) decreases, and networks are viewed to be in the flexible elastic phase. In the narrow intermediate x regime, 29% < x < 32% range, T(g)(x) shows a broad global maximum almost independent of x, and Raman mode scattering strengths and mode frequencies become relatively x-independent, V(m)(x) show a global minimum, features that we associate with the isostatically rigid elastic phase, also called the intermediate phase. In this phase, medium range structures adapt as revealed by the count of Lagrangian bonding constraints and Raman mode scattering strengths.

Identifying blood-brain-barrier selective single-chain antibody fragments.

The blood-brain barrier (BBB) represents an obstacle in targeting and delivering therapeutics to the central nervous system. In order to discover new BBB-targeting molecules, we panned a phage-displayed nonimmune human single-chain antibody fragment (scFv) library against a representative BBB model comprised of hydrocortisone-treated primary rat brain endothelial cells. Parallel screens were performed with or without pre-subtraction against primary rat heart and lung endothelial cells in an effort to identify antibodies that may have binding selectivity toward brain endothelial cells. After three rounds of screening, three unique scFvs, scFv15, scFv38, and scFv29, were identified that maintained binding to primary rat brain endothelial cells, both in phage and soluble scFv format. While scFv29 and to a lesser extent, scFv15, exhibited some brain endothelial cell specificity in tissue culture, scFv29 did not appear to bind a BBB antigen in vivo. In contrast, both scFv15 and scFv38 were capable of immunolabeling rat brain vessels in vivo and displayed brain vascular selectivity with respect to all peripheral organs tested other than heart. Taken together, scFv15 and scFv38 represent two new antibodies that are capable of binding antigens that are expressed at the BBB in vivo.

Periscapular amputation as treatment for brachial plexopathy secondary to recurrent breast carcinoma: a case series and review of the literature.

AIMS: Recurrent breast carcinoma with brachial plexus involvement is often misinterpreted as a radiation- or chemotherapy-induced brachial plexopathy. We review a case series of 4 patients at our institution within a 1-year period, and describe their diagnostic workup and treatment with a palliative periscapular amputation. Our aim is to describe this entity, indications and benefits of this procedure, when required for progressive disease, with the goal of raising a collective index of suspicion to aid in earlier diagnosis. METHODS: Four patients with recurrent axillary breast cancer and symptoms consistent with a brachial plexopathy were prospectively collected over a 1-year period. A Pubmed search was conducted; pertinent articles were reviewed and reported. RESULTS: Patients presented with intractable pain and flaccid paralysis of the ipsilateral limb. All had been previously treated with surgical resection, axillary lymph node dissection, chemotherapy, and radiation therapy. Average time from breast surgery to presentation was 78.75 months (range 11-216 months.) Workup included MRI and biopsy to confirm recurrence. Periscapular amputation was performed for each patient, all of who experienced subjective pain relief postoperatively. Three of the 4 patients are still living; one patient died of disease. CONCLUSION: Breast cancer survivors presenting with a brachial plexopathy should raise suspicion for recurrent disease. Close evaluation with MRI is the best first step in diagnosis. Although periscapular amputation is an aggressive surgical treatment, it is an acceptable option when disease has progressed to neurovascular involvement and a functionless limb.

Physalis angulata L. antineoplasic activity, in vitro, evaluation fromit's stems and fruit capsules

Physalis angulata L. (genus Physalis; family Solanaceae) is an herbaceous specimen that grows plentifully at North, Northeast and Middleast Brazilian's regions1. Its fruits are edible, roots and epigeal parts are taken as tea or infusion, all through the world as traditional medicine. Despite of this usefulness not much scientific work has been done on it. This research carried out with plant material (stems and fruit capsules) has the main aim to find out anti-neoplasic activity. The obtained results are described in Table 1. The most significant inhibition values are those for fruit capsules fractions such as 97 percent mouse lymphoma; 93 percent Erlich carcinoma strains when was assayed with MGTS-1-2ai and MGTS-1-1ai respectively. In the course on going studies on the biological response and chemical constituents of P. angulata some fractions were obtained from stems and fruit capsules ethanolic and methanolic extracts. The extract prepared from roots of P. angulata is the most clinically used by physicians for treatment of human hepatic disorders, despite the substance responsible for the efficacy still a matter of argument.

Are soluble and membrane-bound rat brain acetylcholinesterase different?

Salt-soluble and detergent-soluble acetylcholinesterases (AChE) from adult rat brain were purified to homogeneity and studied with the aim to establish the differences existing between these two forms. It was found that the enzymatic activities of the purified salt-soluble AChE as well as the detergent-soluble AChE were dependent on the Triton X-100 concentration. Moreover, the interaction of salt-soluble AChE with liposomes suggests amphiphilic behaviour of this enzyme. Serum cholinesterase (ChE) did not bind to liposomes but its activity was also detergent-dependent. Detergent-soluble AChE remained in solution below critical micellar concentrations of Triton X-100. SDS polyacrylamide gel electrophoresis of purified, Biobeads-treated and iodinated detergent-soluble 11 S AChE showed, under non reducing conditions, bands of 69 kD, 130 kD and greater than 250 kD corresponding, respectively, to monomers, dimers and probably tetramers of the same polypeptide chain. Under reducing conditions, only a 69 kD band was detected. It is proposed that an amphiphilic environment stabilizes the salt-soluble forms of AChE in the brain in vivo and that detergent-soluble Biobeads-treated 11 S AChE possess hydrophobic domain(s) different from the 20 kD peptide already described.