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The peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear receptor that regulates fat-cell development and glucose homeostasis and is the molecular target of a class of insulin-sensitizing agents used for the management of type 2 diabetes mellitus. PPARgamma is highly expressed in macrophage foam cells of atherosclerotic lesions and has been demonstrated in cultured macrophages to both positively and negatively regulate genes implicated in the development of atherosclerosis. We report here that the PPARgamma-specific agonists rosiglitazone and GW7845 strongly inhibited the development of atherosclerosis in LDL receptor-deficient male mice, despite increased expression of the CD36 scavenger receptor in the arterial wall. The antiatherogenic effect in male mice was correlated with improved insulin sensitivity and decreased tissue expression of TNF-alpha and gelatinase B, indicating both systemic and local actions of PPARgamma. These findings suggest that PPARgamma agonists may exert antiatherogenic effects in diabetic patients and provide impetus for efforts to develop PPARgamma ligands that separate proatherogenic activities from antidiabetic and antiatherogenic activities.

Introduction: Beta-alanine is a non-essential amino acid that has been a focus of increasing research by its role as ergogenic aid to improve muscle performance., Methods: A randomized, double-blind and controlled trial was conducted to determine the effect of a nutritional supplement of a sustained-release formulation of β-alanine in recreational trained men. The active product was an innovative sustained-release β-alanine microgranules powder blend, administered at high doses (15 g/day) divided into 3 intakes during 30 days. There were 10 participants in the experimental group and 9 in the placebo group, with a mean age of 22.5 ± 3.3 years. Participants were testing at baseline and at the end of study., Results: In the β-alanine group, there were statistically increases in serum triglycerides, LDL-cholesterol, and urea nitrogen at the end of the study as compared with baseline, although there were no differences with the control group. The occurrence of paresthesia, described above all as tickling, was the majority but presented VAS score less than 3/10 in almost all subjects., Discussion: More studies are required to evaluate the changes in blood parameters that can be caused by high intake of β-alanine during a long period of time., Clinical Trial Registration: ClinicalTrials.gov, identifier (NCT05334121)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Maestre-Hernández, Pérez-Piñero, López-Román, Andreu-Caravaca, Luque-Rubia, Ramos-Campo, Díaz-Silvestre and Ávila-Gandía.)

The analysis of outcomes from patients with severe asthma treated with omalizumab, using real-life prospective data, should contribute to future informed decisions about this treatment in Portugal. The aim of this study was to assess the clinical effect of omalizumab in Portuguese patients with severe persistent allergic asthma, considering specifically asthma control and exacerbations. This was an observational, prospective, multicentre study. Data were collected at routine care over a 12-month period. Disease control was defined by Control of Allergic Rhinitis and Asthma Test (CARAT) global score >24. All asthma patients already under treatment with omalizumab in 7 departments from 6 Portuguese hospitals were included (n=48). Most (77%) patients were female and the mean (SD) age was 51.9 (10.2) years old. During the study period, asthma was controlled in 34% of the visits and the 12-month exacerbation rate was 1.7 per patient (0.6 with unscheduled medical care). One-third of the patients needed unscheduled medical care because of asthma and 29% had to start or increase oral corticosteroid. There was still a 41% reduction in the total sum of oral corticosteroids usage from the first to the last trimester of the study. During routine treatment with omalizumab, Portuguese patients with severe asthma achieved asthma control in 1/3 of the visits and only 1/3 needed unscheduled or Emergency Room care because of asthma exacerbations. These outcomes support the maintenance of the clinical effect during treatment with omalizumab in routine care in Portugal., (Copyright © 2014 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.)

Unlabelled: Influenza surveillance is usually based on nationally organized sentinel networks of physicians and on hospital reports. This study aimed to test a different report system, based on parents' phone contact to the research team and in home collection of samples by a dedicated team. The identification of influenza and other respiratory viruses in children who attended a Hospital Emergency Department was also recorded. Real-time PCR and reverse transcription PCR were performed for influenza A and B, parainfluenza 1-4, adenovirus, human metapneumovirus, respiratory syncytial virus A and B, rhinovirus, enterovirus, group 1 coronaviruses, group 2 coronaviruses, and human bocavirus. One hundred children were included, 64 from the day care centers and 36 from the Hospital. Overall, 79 samples were positive for at least one respiratory virus. Influenza A (H3) was the virus most frequently detected: 25 cases, 20 of these in children under 5 years of age (ten from day care centers and ten who went to the hospital) which was higher than those reported by the National Influenza Surveillance Programme for this age., Conclusion: The results obtained in this study suggest that a surveillance system based on parents' reports could complement the implanted system of the National Influenza Surveillance Programme.

In this prospective study, we comparatively evaluated the accuracy of several biomarkers of acute kidney injury (AKI) on predicting its occurrence after liver transplantation (LT). The parameters evaluated were urinary tubular enzymes (γ-glutamyl transpeptidase [γGT], alkaline phosphatase, and urinary lactate dehydrogenase) and urinary neutrophil gelatinase-associated lipocalin. These parameters were evaluated both as isolated variables and divided by urinary creatinine. Samples were collected by the end of surgery (determination 1) and at 12 to 24 hours after surgery (determination 2). The study endpoint was the development of AKI. The study was performed over a 1-year period, and 61 of 77 patients were enrolled (main exclusion criteria were perioperative death, previous known renal failure, and insufficient data for analysis). Of these 61 patients, AKI was observed in 19 (group 1). The main relevant parameter to predict AKI was the absolute value of urinary γGT at determination 1 (area under the curve, 0.74; specificity, 72.5%; sensitivity, 70.3%; cutoff, 36 U/mL). Urinary neutrophil gelatinase-associated lipocalin was not as accurate; the best predicted value for this parameter was absolute value at D1 with an area under the curve of 0.5 (specificity, 84.2%; sensitivity, 35.7%; cutoff value, 44.6 ng/mL). We concluded that the absolute value of urinary γGT evaluated at the end of LT was the most accurate parameter to predict AKI in our cohort. Urinary enzyme levels must be taken into account in future analysis of this issue., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Kerion celsi is rarely associated with Microsporum audouinii infection. We report the case of a 3-year-old girl with a kerion celsi caused by M. audouinii and successfully treated with oral terbinafine. Fungi identification was made by macro and microscopical colony morphology analyses and molecular (genotypic) studies.

Fourth-generation assays for the simultaneous detection of human immunodeficiency virus (HIV) antigen and antibody that were available on the international market until now have antigen detection modules with relatively poor sensitivity and produce a higher rate of false-positive results than third-generation enzyme immunoassays (EIAs). The new Cobas Core HIV Combi EIA with an improved sensitivity for HIV p24 antigen was compared to alternative fourth- and third-generation assays, the p24 antigen test, and HIV type 1 (HIV-1) RNA reverse transcriptase PCR (RT-PCR). A total of 94 seroconversion panels (n = 709 sera), samples from the acute phase of infection after seroconversion (n = 32), anti-HIV-1-positive specimens (n = 730) from patients in different stages of the disease, 462 subtyped samples from different geographical locations, anti-HIV-2-positive sera (n = 302), dilutions of cell culture supernatants (n = 62) from cells infected with different HIV-1 subtypes, selected performance panels from Boston Biomedica Inc., 7,579 unselected samples from blood donors, 303 unselected daily routine samples, 997 specimens from hospitalized patients, and potentially interfering samples (n = 1,222) were tested with Cobas Core HIV Combi EIA. The new assay showed a sensitivity comparable to that of the Abbott HIV-1 AG Monoclonal A for early detection of HIV infection in seroconversion panels. The mean time delay of Cobas Core HIV Combi EIA (last negative sample plus 1 day) in comparison to that for HIV-1 RT-PCR for 87 panels tested with both methods was 2.75 days. The diagnostic window was reduced with Cobas Core HIV Combi EIA by between 3.6 and 5.7 days from that for third-generation assays. The specificities of Cobas Core HIV Combi EIA in blood donors were 99.84 and 99.85% (after repeated testing). Overall, 30 repeatedly reactive false-positive results out of 10,031 HIV-negative samples were obtained with Cobas Core HIV Combi EIA. Our results show that a fourth-generation assay with improved specificity such as Cobas Core HIV Combi EIA is suitable for blood donor screening because of its low number of false positives and because it detects HIV p24 antigen with a sensitivity comparable to that of single-antigen assays.

High density lipoprotein-associated cholesteryl esters (HDL CE) are taken up by many cells without parallel uptake of HDL apoproteins, a pathway we have termed "selective uptake." The first step in this pathway, the reversible incorporation of HDL CE into the plasma membrane, is the subject of the present study. To examine the role of membrane proteins, the rate of HDL CE incorporation into isolated rat liver plasma membrane was compared with the rate of incorporation into synthetic membranes devoid of protein. Both membrane systems exhibited saturable uptake of CE, and at rates that were similar (t1/2 approximately 2 h, measured with 50 micrograms of HDL protein). Addition of unlabeled HDL to "chase" CE tracer from the biological and synthetic membranes revealed two kinetically distinct CE pools (t1/2 approximately 0.5 h and t1/2 approximately 30 h). Both biological and synthetic membranes accepted similar amounts of CE into both pools, with a maximum incorporation of 2-4 mol % relative to membrane phospholipids. CE transfer between HDL and membranes was kinetically second-order, in contrast to the first-order transfer of unesterified cholesterol. There was no evidence for direct participation of any apolipoprotein in CE uptake; CE in HDL or in protein-free microemulsions of similar particle size transferred to membranes at similar rates. To examine the possibility that CE transfer requires transient fusion of the HDL amphipathic coat with the membrane outer leaflet, radiolabeled cardiolipin was incorporated into either HDL particles or into synthetic membranes as an amphipathic coat marker that does not diffuse through the aqueous phase; transfer between HDL and membranes was not observed. Thus, CE are transferred between HDL and cell membranes in a collision-mediated process that does not involve amphipathic coat fusion and is not dependent on either membrane protein or apolipoproteins.