Echocardiographic predictors of early in-hospital heart failure during first ST-elevation acute myocardial infarction: does myocardial performance index and left atrial volume improve diagnosis over conventional parameters of left ventricular function?

<p>Abstract</p> <p>Background</p> <p>Left ventricular ejection fraction (LVEF) has been considered a major determinant of early outcome in acute myocardial infarction (AMI). Myocardial performance index (MPI) has been associated to early evolution in AMI in a heterogeneous population, including non ST-elevation or previous AMI. Left atrial volume has been related with late evolution after AMI. We evaluated the independent role of clinical and echocardiographic variables including LVEF, MPI and left atrial volume in predicting early in-hospital congestive heart failure (CHF) specifically in patients with a first isolated ST-elevation AMI.</p> <p>Methods</p> <p>Echocardiography was performed within 30 hours of chest pain in 95 patients with a first ST-elevation AMI followed during the first week of hospitalization. Several clinical and echocardiographic variables were analyzed. CHF was defined as Killip class ≥ II. Multivariate regression analysis was used to select independent predictor of in-hospital CHF.</p> <p>Results</p> <p>Early in-hospital CHF occurred in 29 (31%) of patients. LVEF ≤ 0.45 was the single independent and highly significant predictor of early CHF among other clinical and echocardiographic variables (odds ratio 17.0; [95% CI 4.1 - 70.8]; p < 0.0001). MPI alone could not predict CHF in first ST-elevation AMI patients. Left atrial volume was not associated with early CHF in such patients.</p> <p>Conclusion</p> <p>For patients with first, isolated ST-elevation AMI, LVEF assessed by echocardiography still constitutes a strong and accurate independent predictor of early in-hospital CHF, superior to isolated MPI and left atrial volume in this particular subset of patients.</p

Riluzole does not ameliorate disease caused by cytoplasmic TDP-43 in a mouse model of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease commonlytreated with riluzole, a small molecule that may act via modulation of glutamatergic neurotransmission. However, riluzole only modestly extends lifespanfor people living with ALS, and its precise mechanisms of action remainunclear. Most ALS cases are characterised by accumulation of cytoplasmicTAR DNA binding protein of 43 kDa (TDP-43), and understanding the effectsof riluzole in models that closely recapitulate TDP-43 pathology may provideinsights for development of improved therapeutics. We therefore investigatedthe effects of riluzole in female transgenic mice that inducibly express nuclearlocalisation sequence (NLS)-deficient human TDP-43 in neurons (NEFH-tTA/tetO-hTDP-43ΔNLS, rNLS8, mice). Riluzole treatment from the first day ofhTDP-43ΔNLS expression did not alter disease onset, weight loss or performance on multiple motor behavioural tasks. Riluzole treatment also did notalter TDP-43 protein levels, solubility or phosphorylation. Although we identified a significant decrease in GluA2 and GluA3 proteins in the cortex of rNLS8mice, riluzole did not ameliorate this disease-associated molecular phenotype.Likewise, riluzole did not alter the disease-associated atrophy of hindlimbmuscle in rNLS8 mice. Finally, riluzole treatment beginning after disease onset in rNLS8 mice similarly had no effect on progression of late-stage disease oranimal survival. Together, we demonstrate specific glutamatergic receptoralterations and muscle fibre-type changes reminiscent of ALS in female rNLS8mice, but riluzole had no effect on these or any other disease phenotypes.Future targeting of pathways related to accumulation of TDP-43 pathologymay be needed to develop better treatments for ALS

Airway hyper-reactivity mediated by B-1 cell immunoglobulin M antibody generating complement C5a at 1 day post-immunization in a murine hapten model of non-atopic asthma

Contact skin immunization of mice with reactive hapten antigen and subsequent airway challenge with the same hapten induces immediate airflow obstruction and subsequent airway hyper-reactivity (AHR) to methacholine challenge, which is dependent on B cells but not on T cells. This responsiveness to airway challenge with antigen is elicited as early as 1 day postimmunization and can be adoptively transferred to naïve recipients via 1-day immune cells. Responses are absent in 1-day immune B-cell-deficient JH(−/−) mice and B-1 B-cell-deficient xid male mice, as well as in recipients of 1-day immune cells depleted of cells with the B-1 cell phenotype (CD19(+) B220(+) CD5(+)). As B-1 cells produce immunoglobulin M (IgM), we sought and found significantly increased numbers of anti-hapten IgM-producing cells in the spleen and lymph nodes of 1-day immune wild-type mice, but not in xid mice. Then, we passively immunized naive mice with anti-hapten IgM monoclonal antibody and, following airway hapten challenge of the recipients, we showed both immediate airflow obstruction and AHR. In addition, AHR was absent in complement C5 and C5a receptor-deficient mice. In summary, this study of the very early elicited phase of a hapten asthma model suggests, for the first time, a role of B-1 cells in producing IgM to activate complement to rapidly mediate asthma airway reactivity only 1 day after immunization

Value chain management for commodities: a case study from the chemical industry

We present a planning model for chemical commodities related to an industry case. Commodities are standard chemicals characterized by sales and supply volatility in volume and value. Increasing and volatile prices of crude oil-dependent raw materials require coordination of sales and supply decisions by volume and value throughout the value chain to ensure profitability. Contract and spot demand differentiation with volatile and uncertain spot prices, spot sales quantity flexibility, spot sales price¿3quantity functions and variable raw material consumption rates in production are problem specifics to be considered. Existing chemical industry planning models are limited to production and distribution decisions to minimize costs or makespan. Demand-oriented models focus on uncertainty in demand quantities not in prices.We develop an integrated model to optimize profit by coordinating sales quantity, price and supply decisions throughout the value chain. A two-phase optimization approach supports robust planning ensuring minimum profitability even in case of worst-case spot sales price scenarios. Model evaluations with industry case data demonstrate the impact of elasticities, variable raw material consumption rates and price uncertainties on planned profit and volume

З вопыту выкладання дысцыпліны «Славянская міфалогія»: персанажы ніжэйшага міфалагічнага ўзроўню

The brain is well protected against microbial invasion by cellular barriers, such as the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB). In addition, cells within the central nervous system (CNS) are capable of producing an immune response against invading pathogens. Nonetheless, a range of pathogenic microbes make their way to the CNS, and the resulting infections can cause significant morbidity and mortality. Bacteria, amoebae, fungi, and viruses are capable of CNS invasion, with the latter using axonal transport as a common route of infection. In this review, we compare the mechanisms by which bacterial pathogens reach the CNS and infect the brain. In particular, we focus on recent data regarding mechanisms of bacterial translocation from the nasal mucosa to the brain, which represents a little explored pathway of bacterial invasion but has been proposed as being particularly important in explaining how infection with Burkholderia pseudomallei can result in melioidosis encephalomyelitis