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We evaluated phagolysosomal fusion in peripheral blood monocytes from 20 HIV-infected individuals and 40 normal controls, using a fluorescence assay with acridine orange as marker. The percentages of phagolysosomal fusion of monocytes from HIV-infected subjects, after 30 and 60 min of yeast ingestion. (mean ± standard deviation) 57.2 ± 17 and 63.2 ± 18.6, respectively, when compared to normal controls (72.4 ± 7.8 and 7.7 ± 8.1), did not differ significantly. However, there was a direct linear association between the percentages of phagolysosomal fusion and CD4+ lymphocytes (P < 0.001) or CD4/CD8 T-cell ratio (P < 0.01). These results suggest that phagolysosomal dysfunction becomes evident at late stages of HIV infection and progresses as CD4+ T-lymphocyte count and CD4/CD8 T-cell ratio decrease. On the other hand, recombinant gp120 inhibited significantly normal phagolysosomal fusion at concentrations ranging between 1 and 1000 ng/ml. Taking together the results obtained, we can conclude that gp120 could be responsible for monocyte phagolysosomal dysfunction observed in HIV infected patients. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MS) is frequently associated with an increased body mass index (BMI), and related to an adverse cardiovascular prognosis. The purpose of this study is to evaluate the prevalence and association between MS, obesity and subclinical atherosclerosis (SA). This cross-sectional study included healthy adults, allocated to normal weight (NW) when BMI <25 kg/m 2 , overweight (OW) BMI ≥25 and <30 kg/m 2 , or obese (OB) BMI ≥30 kg/m 2 groups. Presence of MS was defined according to National Cholesterol Education Program (NCEP) criteria. SA was evidenced with vascular ultrasound. Association between SA, obesity and MS, was evaluated by logistic regression models. There were 3,716 patients studied (female 66.7%, mean age 47 ± 17.5 years). According to BMI, NW represented 28.2%, OW 39.4% and OB 32.4%. MS showed a strong correspondence with BMI (NW 4.9%, OW 21.4%, OB 49.7%; p<0.001). SA was more prevalent in each group when MS was present: NW (25.4% vs. 45.1%, p<0.005), OW (43.2% vs. 58.9%, p<0.0001) and OB (44.2% vs. 57.8%, p<0.0001). Logistic-regression models showed an independent association of SA with MS criteria (arterial hypertension p<0.001; high-density lipoprotein [HDL] p<0.05; and triglycerides p<0.005) adjusted by gender, age and BMI. In conclusion, overweight and obesity are frequent and strongly linked with MS and SA. Prevalence of SA is high, and is independently associated with MS components. However, BMI could not retain statistical significance in the multivariate analyses., Competing Interests: Conflicts of interest None declared., (Copyright © 2023 Medinews (Cardiology) Limited.)

Rifaximin is a locally acting antibiotic practically insoluble in water. It presents several crystal phases characterized by different degrees of hydration. The aim of this work is to investigate the dissolution behaviour of rifaximin α, β, and amorphous forms in relation to their relative thermodynamic stability to contribute to clarifying possible solvent- or humidity-mediated conversion patterns. Kinetic and intrinsic solubility were investigated along with particle size distribution, specific surface area, and external morphology. The solution and moisture mediated conversion from metastable α and amorphous forms to stable β form were elucidated by coupling intrinsic dissolution test with chemometric analysis as well as by dynamic vapour sorption measurements. The dissolution behaviour of the α form stems mainly from the transition to β form that occurs upon exposition to relative humidity higher than 40%. The α form converted more rapidly than the amorphous form due to the smaller supersaturation ratio. It can be concluded that, due to its marked tendency to transform into β form, the dissolution test for the α form, even if conducted according to compendial procedures, needs to be accompanied by a panel of further tests that allow to uniquely identify the solid phase under investigation.

Introduction: It has been reported in different parts of the world that war veterans are more exposed to cardiovascular risk factors. The objective of this study was to establish the risk factors, the cardiometabolic profile and the prevalence of cardiovascular disease in a group of ex-combatants of the Malvinas War (HdeM)., Methods: In a case-control design, data from 799 HdeM were analyzed and compared with 799 controls matched by age. The sample was selected from the participants of the Cardiovascular Health Prevention Program of the Favaloro Foundation, between January 2017 and December 2019., Results: The average age was 56.9 ± 3.9 years. An increase in weight was observed among the HdeM (91.3 ± 16.6 kg vs. 88.2 ± 14.7 kg; p = 0.0001). A higher frequency of arterial hypertension (42% vs. 34%; p < 0.001) and diabetes mellitus (15.1% vs. 10.4%; p < 0.005) was observed in HdeM. Metabolic syndrome was also more prevalent in HdeM (49.2% vs. 39.7%; p = 0.0001). It was observed that the history of acute myocardial infarction was more frequent among the HdeM (3.6% vs. 2%; p < 0.05), with a similar prevalence of stroke (1.2% vs. 1%; p = ns), coronary angioplasty (3.2% vs. 2.1%; p = ns) or myocardial revascularization surgery (0.8% vs. 0.4%; p = ns)., Discussion: The HdeM showed an increase in the frequency of risk factors, metabolic syndrome and acute myocardial infarction. It is important to take this increased risk into account in order to maximize cardiovascular prevention strategies in ex-combatants.

An accurate and easy-to-use Q3 system for on-chip quantitative real-time Polymerase Chain Reaction (qPCR) is hereby demonstrated, and described in detail. The qPCR reactions take place inside a single-use Lab-on-a-Chip with multiple wells, each with 5 to 15 µL capacity. The same chip hosts a printed metal heater coupled with a calibrated sensor, for rapid and accurate temperature control inside the reaction mixture. The rest of the system is non-disposable and encased in a 7 × 14 × 8.5 (height) cm plastic shell weighing 300 g. Included in the non-disposable part is a fluorescence read-out system featuring up to four channels and a self-contained control and data storage system, interfacing with an external user-friendly software suite. Hereby, we illustrate the engineering details of the Q3 system and benchmark it with seamlessly ported testing protocols, showing that Q3 equals the performance of standard commercial systems. Overall, to the best of our knowledge, this is one of the most mature general-purpose systems for on-chip qPCR currently available.

Background: Dual antiplatelet therapy with aspirin and a platelet P2Y12 receptor inhibitors (clopidogrel, prasugrel, ticagrelor) is a cornerstone of antithrombotic treatment in patients with acute coronary syndromes (ACS). Clopidogrel has been the standard of care for nearly a decade; however, its clinical efficacy is influenced by a considerable inter-patient variability in response, clearly associated to cytochrome P (CYP) enzyme genetic variations. We used a novel point-of-care lab-on-chip instrument to genotype ACS patients in order to identify carriers of the ATB-binding cassette ABCB1 3435, CYP2C19*2 and CYPC2C19*17 alleles and adjust the pharmacological approach accordingly., Methods and Results: Between October 2012 and January 2013, 160 ACS patients were enrolled at the Cardiology Unit of the Ospedale Niguarda Cà Granda and genotyped at the patients' point-of-care using the newly developed Q3 portable real-time PCR instrument, which remarkably scored the CYP2C19*2, CYP2C19*17, and ABCB1 3435 alleles in a time of 70 min from DNA extraction to final genotype calls; concordance with the other gold-standard genotyping techniques was 100%., Conclusions: The Q3 instrument proved to be as reliable as the current conventional techniques. As genotyping in the ACS setting cannot be delegated to centralised clinical laboratories for reasons of time, genotyping at the patients' bedside provides an opportunity to conduct large-scale randomised trials in order to assess whether adding genotype data to clinical variables improves clinical outcomes.

We present a clinical case of antiretroviral treatment failure with appearance of mutations demonstrated by genotyping. We also show the evolution of the pattern of mutations that confers resistance to protease and reverse transcriptase inhibitors along with changes in the scheme of drugs indicated to the patient. A deletion was found in codon 67 of the TR gen, along with a novel resistance model to AZT pointing out the benefits of the detection of antiviral resistance by sequencing (genotyping).

Hyperinsulinemia and insulin-resistance are metabolic disturbances associated with obesity, essential hypertension, hypertriglyceridemia, glucose intolerance, overt non-insulin dependent diabetes mellitus, polymetabolic syndrome and atherosclerotic disease. The assessment of in vivo insulin sensitivity (SAI in vivo) changes achieved by life style modifications or drug interventions require a reproducible technique. To evaluate the day-to-day intra-individual repeatability of SAI-in vivo, we determined the variation in the SI index (calculated from the Minimal Model of Bergman modified by insulin or MMins) in 11 subjects with a wide range of insulin-resistance. SI (first study) varied from 0.82 to 8.48 x 10(-4) min-1/microU.mL (4.43 +/- 2.85 x 10(-4) min-1/microU.mL mean +/- SD) and highly correlated with SI (second study) (r = 0.89; p = 0.0002). The average interday coefficient of variation was 20.9 +/- 13.9% and was similar in subjects with low or high SI values. We also measured SAI in vivo by assessing the rate of serum glucose decline induced by human cristalline insulin 0.025 U/kg IV dose after a 12-14 hours fasting period (a modified Bonora's method or BBD) in 11 subjects. No subject presented biochemical or symptomatic hypoglycemia. SAI in vivo values determined by BBD varied from 21 a 234 mumol/ml/min (134 +/- 64.8 mumol/ml/min, mean +/- SD). We found a highly significant correlation between SI values obtained from MMins and SAI in vivo assessed by the BBD (r = 0.89, p = 0.0002). Our results suggest that the Mmins is a fairly reproducible procedure and that a BBD is an acceptable option to quantify SAI in vivo, mainly when a fast-execution practice is necessary or cost restrictions are required.

HTLV-I and HTLV-II are two related retroviruses that are transmitted by sexual contact, breast feeding, blood transfusion and needle sharing. In this study the prevalence of HTLV-I and HTLV-II was evaluated in voluntary blood donors as a measure of the infection in the general population. Samples were tested by a gelatine particle agglutination test and repeatedly reactive samples were confirmed by Western blot tests (WBT), enriched with recombinant rgp21, rgp461 y rgp4611 proteins, which differentiates HTLV-I and HTLV-II antibodies. Of 19,426 samples, 40 were repeatedly reactive by particle agglutination (0.21%). When analyzed by WBT, 6 met the criteria for HTLV-I (0.036%), 2 for HTLV-II (0.01%) and 1 for HTLV-I/II, 13 samples were indeterminate and 18 were negative. The prevalence is low and comparable to that from non endemic countries. Screening for anti HTLV-I/II antibodies is necessary to prevent transmission through blood transfusions.