Differential Modulation of Innate Immune Responses in Human Primary Cells by Influenza A Viruses Carrying Human or Avian Nonstructural Protein 1.

The influenza A virus (IAV) nonstructural protein 1 (NS1) contributes to disease pathogenesis through the inhibition of host innate immune responses. Dendritic cells (DCs) release interferons (IFNs) and proinflammatory cytokines and promote adaptive immunity upon viral infection. In order to characterize the strain-specific effects of IAV NS1 on human DC activation, we infected human DCs with a panel of recombinant viruses with the same backbone (A/Puerto Rico/08/1934) expressing different NS1 proteins from human and avian origin.

Systemic pharmacokinetics and safety of high doses of nebulized colistimethate sodium in critically ill patients with hospital-acquired and ventilator-associated pneumonia.

Objectives: To assess the pharmacokinetics of formed colistin in plasma and the safety of two different high doses of colistimethate sodium administered via nebulization in critically ill surgical patients with hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP).

Patients And Methods: Formed colistin plasma concentrations were measured in critically ill surgical patients with pneumonia treated with two different doses of nebulized colistimethate sodium (3 MIU/8 h versus 5 MIU/8 h). Adverse events possibly related to nebulized colistimethate sodium were recorded.

Coronary artery calcium score in female rheumatoid arthritis patients: Associations with apolipoproteins and disease biomarkers.

Aims And Methods: In rheumatoid arthritis (RA), cardiovascular (CV) comorbidities are a major cause of mortality. Coronary Calcium Score (CCS) assessed by computed tomography has been associated with RA prognosis. In this work, we aimed to assess CCS in female RA patients and determine CCS association with different clinical, laboratory and imaging disease parameters.

The PSMA8 subunit of the spermatoproteasome is essential for proper meiotic exit and mouse fertility.

The ubiquitin proteasome system regulates meiotic recombination in yeast through its association with the synaptonemal complex, a 'zipper'-like structure that holds homologous chromosome pairs in synapsis during meiotic prophase I. In mammals, the proteasome activator subunit PA200 targets acetylated histones for degradation during somatic DNA double strand break repair and during histone replacement during spermiogenesis. We investigated the role of the testis-specific proteasomal subunit α4s (PSMA8) during spermatogenesis, and found that PSMA8 was localized to and dependent on the central region of the synaptonemal complex.

Comparative study of peritoneal adhesions after intraperitoneal implantation in rats of meshes of polypropylene versus polypropylene/polyglecaprone versus polyester/porcine collagen.

Purpose: To Compare the extent and intensity of adhesions formed between the intra-abdominal organs and the intraperitoneal implants of polypropylene mesh versus polypropylene/polyglecaprone versus polyester/porcine collagen used for correction of abdominal wall defect in rats.

Methods: After the defect in the abdominal wall, thirty Wistar rats were placed in three groups (ten animals each) for intraperitoneal mesh implant: polypropylene group, polypropylene/polyglecaprone group, and polyester/porcine collagen group. The macroscopic evaluation of the extent and intensity of adhesions was performed 21 days after the implant.

iW-Net: an automatic and minimalistic interactive lung nodule segmentation deep network.

We propose iW-Net, a deep learning model that allows for both automatic and interactive segmentation of lung nodules in computed tomography images. iW-Net is composed of two blocks: the first one provides an automatic segmentation and the second one allows to correct it by analyzing 2 points introduced by the user in the nodule's boundary. For this purpose, a physics inspired weight map that takes the user input into account is proposed, which is used both as a feature map and in the system's loss function.

Phylogeography of msp4 genotypes of Anaplasma marginale in beef cattle from the Brazilian Pantanal.

The msp4 gene of A. marginale is unicodon, stable and mostly homogeneous, being considered as a useful marker for phylogeographic characterization of this bacterium. The objective of this work was to analyze the phylogeography of A.

Innate Immune Response to Influenza Virus at Single-Cell Resolution in Human Epithelial Cells Revealed Paracrine Induction of Interferon Lambda 1.

Early interactions of influenza A virus (IAV) with respiratory epithelium might determine the outcome of infection. The study of global cellular innate immune responses often masks multiple aspects of the mechanisms by which populations of cells work as organized and heterogeneous systems to defeat virus infection, and how the virus counteracts these systems. In this study, we experimentally dissected the dynamics of IAV and human epithelial respiratory cell interaction during early infection at the single-cell level.

TGF-β inhibitor therapy decreases fibrosis and stimulates cardiac improvement in a pre-clinical study of chronic Chagas' heart disease.

TGF-β involvement in Chagas disease cardiomyopathy has been clearly demonstrated. The TGF-β signaling pathway is activated in the cardiac tissue of chronic phase patients and is associated with an increase in extracellular matrix protein expression. The aim of this study was to investigate the effect of GW788388, a selective inhibitor of TβR1/ALK5, on cardiac function in an experimental model of chronic Chagas' heart disease.

Assessment of immunoglobulin capture in immobilized protein A through automatic bead injection.

The repeatable immobilization of molecular recognition elements onto particle surfaces has a strong impact on the outcomes of affinity-based assays. In this work, an automatic method for the immobilization of immunoglobulin G (IgG) onto protein A-Sepharose microbeads was established through the flow programming features of the portable lab-on-valve platform using micro-bead injection spectroscopy. The reproducible packing of protein A-microbeads between two optic fibers was feasible, allowing on-column probing of IgG retention.

Combination therapy with benznidazole and doxycycline shows no additive effect to monotherapy with benznidazole in mice infected with the VL-10 strain of the Trypanosoma cruzi.

Background: Chagas heart disease is the most important clinical manifestation of Trypanosoma cruzi infection. Pharmacological therapies have been proposed aiming to reduce inflammatory response and cardiac damage in infected hosts. In this study, we investigated the use of doxycycline (Dox), in a sub-antimicrobial dose, in monotherapy and in combination with benznidazole (Bz) during the acute phase of infection with the VL-10 strain of T.

Clinical utility of plasma-based digital next-generation sequencing in oncogene-driven non-small-cell lung cancer patients with tyrosine kinase inhibitor resistance.

Objectives: Resistance to tyrosine-kinase inhibitors (TKIs) is a clinical challenge in patients with oncogene-driven non-small-cell lung cancers (NSCLC). We have analyzed the utility of next-generation sequencing (NGS) of cell-free circulating tumor DNA (ctDNA) to impact the clinical care of patients with TKI resistance.

Materials And Methods: We conducted a multi-institutional prospective study including consecutive EGFR, ALK, or ROS1-altered NSCLC patients with TKI resistance from 12 Spanish institutions.

Characterization of swine-origin H1N1 canine influenza viruses.

Host switch events of influenza A viruses (IAVs) continuously pose a zoonotic threat to humans. In 2013, swine-origin H1N1 IAVs emerged in dogs soon after they were detected in swine in the Guangxi province of China. This host switch was followed by multiple reassortment events between these H1N1 and previously circulating H3N2 canine IAVs (IAVs-C) in dogs.

Physical training improves exercise tolerance, cardiac function and promotes changes in neurotrophins levels in chagasic mice.

Aims: To investigate the effects of moderate aerobic physical training on cardiac function and morphology as well as on the levels of glial cell-derived neurotrophic factor (GDNF), nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) of animals infected with the Y strain of Trypanosoma cruzi.

Main Methods: Twenty-eight male C57BL/6 mice were distributed into 4 groups: sedentary control (SC), trained control (TC), sedentary infected (CHC) and trained infected (CHT). The infection was performed by intraperitoneal injection of trypomastigote forms and the animals were adapted to treadmill in the week before the beginning of the training protocol, initiated 45 days post infection.

Biochemical characterization of digestive membrane-associated alkaline phosphatase from the velvet bean caterpillar Anticarsia gemmatalis.

In Brazil, the use of transgenic plants expressing the insect-toxic Bacillus thuringiensis endotoxin has been successfully used as pest control management since 2013 in transgenic soybean lineages against pest caterpillars such as Helicoverpa armigera. These toxins, endogenously expressed by the plants or sprayed over the crops, are ingested by the insect and bind to receptors in the midgut of these animals, resulting in disruption of digestion and lower insect survival rates. Here, we identified and characterized a membrane-associated alkaline phosphatase (ALP) in the midgut of Anticarsia gemmatalis, the main soybean defoliator pest in Brazil, and data suggested that it binds to Cry1Ac toxin in vitro.

Antibody conjugation to carboxyl-modified microspheres through N-hydroxysuccinimide chemistry for automated immunoassay applications: A general procedure.

Immunochemical techniques are the workhorse for sample enrichment and detection of a large variety of analytes. In contrast to classical microtiter plate-based assays, microparticles are a next generation solid support, as they promote automation of immunoassays using flow-based techniques. Antibody immobilization is a crucial step, as these reagents are expensive, and inefficient coupling can result in low sensitivities.

Automated lab-on-valve sequential injection ELISA for determination of carbamazepine.

The development of an automated miniaturized analytical system that allows for the rapid monitoring of carbamazepine (CBZ) levels in serum and wastewater is proposed. Molecular recognition of CBZ was achieved through its selective interaction with microbeads carrying anti-CBZ antibodies. The proposed method combines the advantages of the micro-bead injection spectroscopy and of the flow-based platform lab-on-valve for implementation of automatic immunosorbent renewal, rendering a new recognition surface for each sample.

Dolops carvalhoi as a vector of Epistylis sp. between cultivated and wild specimens of Oreochromis niloticus in Brazil.

Epistyliasis has been characterized as an emergent disease which has a great impact on fish farms, especially on Oreochromis niloticus production systems. Although epidemiological important, information about the dispersion of these parasites and their mechanical vectors is scarce. The present study reported the cooccurrence of Epistylis sp.

Severity-Adjusted Probability of Being Cost Effective.

Background: In the context of priority setting, a differential cost-effectiveness threshold can be used to reflect a higher societal willingness to pay for quality-adjusted life-year gains in the worse off. However, uncertainty in the estimate of severity can lead to problems when evaluating the outcomes of cost-effectiveness analyses.

Objectives: This study standardizes the assessment of severity, integrates its uncertainty with the uncertainty in cost-effectiveness results and provides decision makers with a new estimate: the severity-adjusted probability of being cost effective.

Pharmacological Profile of AZD8871 (LAS191351), a Novel Inhaled Dual M Receptor Antagonist/ -Adrenoceptor Agonist Molecule with Long-Lasting Effects and Favorable Safety Profile.

AZD8871 is a novel muscarinic antagonist and -adrenoceptor agonist in development for chronic obstructive pulmonary disease. This study describes the pharmacological profile of AZD8871 in in vitro and in vivo assays. AZD8871 is potent at the human M receptor (pIC in binding assays: 9.

Ubiquitin-specific protease 26 (USP26) is not essential for mouse gametogenesis and fertility.

Ubiquitin-specific protease 26 (USP26) is a deubiquitylating enzyme belonging to the USPs family with a transcription pattern restricted to the male germline. Since protein ubiquitination is an essential regulatory mechanism during meiosis, many efforts have been focused on elucidating the function of USP26 and its relationship with fertility. During the last decade, several studies have reported the presence of different polymorphisms in USP26 in patients with non-obstructive azoospermia (NOA) or severe oligozoospermia suggesting that this gene may be associated with human infertility.

Characterization of amylose and amylopectin fractions separated from potato, banana, corn, and cassava starches.

Analytical techniques such HPSEC, DSC, and TGA have been employed for amylose determination in starch samples, though spectrophotometry by iodine binding is most commonly used. The vast majority of these techniques require an analytical curve, using amylose and amylopectin standards with physicochemical properties similar to those found in the original starch. The current study aimed to obtain the amylose and amylopectin fractions from potato, banana, corn, and cassava starches, characterize them, and evaluate their behavior via thermogravimetric curves.

Driving the precision medicine highway: community health workers and patient navigators.

The general public is currently bombarded with direct-to-consumer advertising, real time "medical" guidance through the internet, access to digital devices that capture health information, and science-based adds that promote foods, cosmetics, and dietary supplements. Unfortunately, much of this information relies on terminology and concepts not well-understood by consumers, particularly those with lower levels of health and genomic literacy. Such constraints align with the limitations of the American public to obtain and process the basic medical information needed to make appropriate healthcare decisions.