Poliserosite, artrite e doença respiratória em leitões: estudo de caso

O complexo da poliserosite em suínos é causado por múltiplos factores, em particular pelo agente Haemophilus parasuis (HPS), que tem vindo a causar vários problemas em suínos, quer ao nível respiratório, quer nas articulações. O agente HPS é o responsável pela Doença de Glässer (DG), caracterizada por uma inflamação generalizada da pleura, pericárdio, peritoneu, membranas sinoviais e meninges, acompanhada pela elevada presença de fibrina. HPS é normalmente um agente secundário causado por algum factor predisponente, como stress, pneumonias ou por algum vírus, em particular o Vírus do Síndrome Respiratório e Reprodutor Porcino (PRRSv).No caso das pneumonias verificou-se que o agente HPS é um invasor secundário oportunista e que causa doença em associação com outros agentes víricos ou bacterianos e está associado com maior prevalência de pneumonia por agentes respiratórios víricos, como o Síndrome Respiratório e Reprodutor Porcino (PRRS). Durante este estudo de caso acompanhou-se um lote de leitões desde o desmame até ao final da recria, em que foram feitas serologias e enviados leitões inteiros para laboratório de forma a isolar e identificar o agente. Foi feita a avaliação da morbilidade bem como o cálculo do índice de tosse e taxa de mortalidade nas primeiras quatro semanas de recria. Efectuaram-se necropsias dos leitões deste lote. Pretende-se, como objectivo deste estudo, definir o agente primário causador da patologia, neste caso o PRRSv, bem como a entrada da infecção bacteriana secundária causada pelo HPS. Procedeu-se à vacinação do efectivo frente ao PRRSv. Como profilaxia, devido à falha de protecção de imunidade maternal, fez-se a administração de tulatromicina a todos os leitões até todo o efectivo estar devidamente protegido frente ao PRRSv, conferindo assim uma boa imunidade maternal.The porcine polyserositis complex is caused by multiple factors, particularly by Haemophilus parasuis (HPS), which has been causing several problems in pigs, both at the respiratory and articular levels. HPS is the causative agent of Glässer's Disease (DG), characterized by a generalized inflammation of the pleura, pericardium, peritoneum, synovial membranes and meninges, toguether with an abundant presence of fibrin. HPS is usually a secondary agent enhanced by some predisposing factor, like stress, pneumonia or some viruses, such as Porcine Reproductive and Respiratory Syndrome virus (PRRSv). In pneumonia, it has been show that HPS is an opportunistic secondary invader causing disease in association with other viral or bacterial agents being PRRSv the most prevalent respiratory viral agent found together with HPS. During this study a batch of piglets was followed from weaning until the end of nursery season, when serologies were performed, samples were collected and whole piglets were sent to pathology in order to isolate and identify the agent. Health condition was evaluated as well as the calculation of cough index and mortality rate in the first four weeks of nursery. Necropsies of the piglets of this batch were also carried out.The objective of this study was to define the primary agent causing disease (in this case PRRSv), as well as the factors that predisposed to secondary bacterial infections caused by HPS. Following these findings all herd was vaccinated against PRRSv. Due to lack of protective maternal immunity, tulathromycin was administered in pigs, as prophylactic measure until all sows were adequately protected against PRRSv, thus conferring good maternal immunity to their offspring

Cardiovascular outcomes and hospitalizations in Asian patients receiving immune checkpoint inhibitors: a population-based study.

Immune checkpoint inhibitors (ICI) have known associations with cardiotoxicity. However, a representative quantification of the adverse cardiovascular events and cardiovascular attendances amongst Asian users of ICI has been lacking. This retrospective cohort study identified all ICI users in Hong Kong, China, between 2013-2021. All patients were followed up until the end of 2021 for the primary outcome of major adverse cardiovascular event (MACE; a composite of cardiovascular mortality, myocardial infarction, heart failure, and stroke). Patients with prior diagnosis of any component of MACE were excluded from all MACE analyses. In total, 4324 patients were analysed (2905 (67.2%) males; median age 63.5 years old (interquartile range 55.4-70.7 years old); median follow-up 1.0 year (interquartile range 0.4-2.3 years)), of whom 153 were excluded from MACE analyses due to prior events. MACE occurred in 116 (2.8%) with an incidence rate (IR) of 1.7 [95% confidence interval: 1.4, 2.0] events per 100 patient-years; IR was higher within the first year of follow-up (2.9 [2.3, 3.5] events per 100 patient-years). Cardiovascular hospitalization(s) occurred in 188 (4.4%) with 254 episodes (0.5% of all episodes) and 1555 days of hospitalization (1.3% of all hospitalized days), for whom the IR of cardiovascular hospitalization was 5.6 [4.6, 6.9] episodes per 100 person-years with 52.9 [39.8, 70.3] days' stay per 100 person-years. Amongst Asian users of ICI, MACE was uncommon, and a small proportion of hospitalizations was cardiovascular in nature. Most MACE and cardiovascular hospitalizations occurred during the first year after initiating ICI. [Abstract copyright: Copyright © 2022. Published by Elsevier Inc.

Control of Cyclin D1 and Breast Tumorigenesis by the EglN2 Prolyl Hydroxylase

Summary2-Oxoglutarate-dependent dioxygenases, including the EglN prolyl hydroxylases that regulate HIF, can be inhibited with drug-like molecules. EglN2 is estrogen inducible in breast carcinoma cells and the lone Drosophila EglN interacts genetically with Cyclin D1. Although EglN2 is a nonessential gene, we found that EglN2 inactivation decreases Cyclin D1 levels and suppresses mammary gland proliferation in vivo. Regulation of Cyclin D1 is a specific attribute of EglN2 among the EglN proteins and is HIF independent. Loss of EglN2 catalytic activity inhibits estrogen-dependent breast cancer tumorigenesis and can be rescued by exogenous Cyclin D1. EglN2 depletion also impairs the fitness of lung, brain, and hematopoietic cancer lines. These findings support the exploration of EglN2 inhibitors as therapeutics for estrogen-dependent breast cancer and other malignancies

Sulfonylurea is associated with higher risks of ventricular arrhythmia or sudden cardiac death compared with metformin: A population-based cohort study

Background Commonly prescribed diabetic medications such as metformin and sulfonylurea may be associated with different arrhythmogenic risks. This study compared the risk of ventricular arrhythmia or sudden cardiac death between metformin and sulfonylurea users in patients with type 2 diabetes. Methods and Results Patients aged ≥40 years who were diagnosed with type 2 diabetes or prescribed antidiabetic agents in Hong Kong between January 1, 2009, and December 31, 2009, were included and followed up until December 31, 2019. Patients prescribed with both metformin and sulfonylurea or had prior myocardial infarction were excluded. The study outcome was a composite of ventricular arrhythmia or sudden cardiac death. Metformin users and sulfonylurea users were matched at a 1:1 ratio by propensity score matching. The matched cohort consisted of 16 596 metformin users (47.70% men; age, 68±11 years; mean follow‐up, 4.92±2.55 years) and 16 596 sulfonylurea users (49.80% men; age, 70±11 years; mean follow‐up, 4.93±2.55 years). Sulfonylurea was associated with higher risk of ventricular arrhythmia or sudden cardiac death than metformin hazard ratio (HR, 1.90 [95% CI, 1.73–2.08]). Such difference was consistently observed in subgroup analyses stratifying for insulin usage or known coronary heart disease. Conclusions Sulfonylurea use is associated with higher risk of ventricular arrhythmia or sudden cardiac death than metformin in patients with type 2 diabetes

Cardiovascular outcomes and hospitalizations in Asian patients receiving immune checkpoint inhibitors: A population-based study

Immune checkpoint inhibitors (ICI) have known associations with cardiotoxicity. However, a representative quantification of the adverse cardiovascular events and cardiovascular attendances amongst Asian users of ICI has been lacking. This retrospective cohort study identified all ICI users in Hong Kong, China, between 2013 and 2021. All patients were followed up until the end of 2021 for the primary outcome of major adverse cardiovascular event (MACE; a composite of cardiovascular mortality, myocardial infarction, heart failure, and stroke). Patients with prior diagnosis of any component of MACE were excluded from all MACE analyses. In total, 4324 patients were analyzed (2905 (67.2%) males; median age 63.5 years old (interquartile range 55.4-70.7 years old); median follow-up 1.0 year (interquartile range 0.4-2.3 years)), of whom 153 were excluded from MACE analyses due to prior events. MACE occurred in 116 (2.8%) with an incidence rate (IR) of 1.7 [95% confidence interval: 1.4, 2.0] events per 100 patient-years; IR was higher within the first year of follow-up (2.9 [2.3, 3.5] events per 100 patient-years). Cardiovascular hospitalization(s) occurred in 188 (4.4%) with 254 episodes (0.5% of all episodes) and 1555 days of hospitalization (1.3% of all hospitalized days), for whom the IR of cardiovascular hospitalization was 5.6 [4.6, 6.9] episodes per 100 person-years with 52.9 [39.8, 70.3] days’ stay per 100 person-years. Amongst Asian users of ICI, MACE was uncommon, and a small proportion of hospitalizations were cardiovascular in nature. Most MACE and cardiovascular hospitalizations occurred during the first year after initiating ICI

Ezrin interacts with the SARS coronavirus spike protein and restrains infection at the entry stage

© 2012 Millet et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: Entry of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and its envelope fusion with host cell membrane are controlled by a series of complex molecular mechanisms, largely dependent on the viral envelope glycoprotein Spike (S). There are still many unknowns on the implication of cellular factors that regulate the entry process. Methodology/Principal Findings: We performed a yeast two-hybrid screen using as bait the carboxy-terminal endodomain of S, which faces the cytosol during and after opening of the fusion pore at early stages of the virus life cycle. Here we show that the ezrin membrane-actin linker interacts with S endodomain through the F1 lobe of its FERM domain and that both the eight carboxy-terminal amino-acids and a membrane-proximal cysteine cluster of S endodomain are important for this interaction in vitro. Interestingly, we found that ezrin is present at the site of entry of S-pseudotyped lentiviral particles in Vero E6 cells. Targeting ezrin function by small interfering RNA increased S-mediated entry of pseudotyped particles in epithelial cells. Furthermore, deletion of the eight carboxy-terminal amino acids of S enhanced S-pseudotyped particles infection. Expression of the ezrin dominant negative FERM domain enhanced cell susceptibility to infection by SARS-CoV and S pseudotyped particles and potentiated S-dependent membrane fusion. Conclusions/Significance: Ezrin interacts with SARS-CoV S endodomain and limits virus entry and fusion. Our data present a novel mechanism involving a cellular factor in the regulation of S-dependent early events of infection.This work was supported by the Research Grant Council of Hong Kong (RGC#760208)and the RESPARI project of the International Network of Pasteur Institutes

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

TOPOLOGICAL METHODS IN DATA ANALYSIS

Bachelor'sBACHELOR OF SCIENCE (HONOURS

TOPOLOGICAL METHODS IN DATA ANALYSIS

Bachelor'sBACHELOR OF SCIENCE (HONOURS

Significance of mitotic checkpoint regulatory proteins in chemosensitivity of nasopharyngeal carcinoma cells

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