Biological Aging and Immune Senescence in Children with Perinatally Acquired HIV

Chronic HIV-infected children suffer from premature aging and aging-related diseases. Viral replication induces an ongoing inflammation process, with the release of pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), the activation of the immune system, and the production of proinflammatory cytokines. Although combined highly active antiretroviral therapy (ART) has significantly modified the natural course of HIV infection, normalization of T and B cell phenotype is not completely achievable; thus, many HIV-infected children display several phenotypical alterations, including higher percentages of activated cells, that favor an accelerated telomere attrition, and higher percentages of exhausted and senescent cells. All these features ultimately lead to the clinical manifestations related to premature aging and comorbidities typically observed in older general population, including non-AIDS-related malignancies. Therefore, even under effective treatment, the premature aging process of HIV-infected children negatively impacts their quality and length of life. This review examines the available data on the impact of HIV and ART on immune and biological senescence of HIV-infected children

Behavior of listeria innocua during the manufacturing and pit-ripening of formaggio di fossa di sogliano pdo cheese

Formaggio di Fossa di Sogliano is a traditional Italian Protected Designation of Origin (PDO) cheese ripened for a minimum of 5 months, with the feature of a ripening of at least 80 to at most 100 days in pits, digged into tuffaceous rocks according to medieval tradition of Italy. In this study, a challenge test using Listeria innocua as a surrogate of Listeria monocytogenes was performed, with the aim of increasing knowledge concerning the impact of the Fossa cheese process, and especially of the traditional ripening process of this PDO, on the behaviourof L. monocytogenes. Pasteurized milk was experimentally inoculated with 4.5 log CFU/mL cocktail by three L. innocua strains, and L. innocua and Mesophilic Lactic Acid Bacteria (LAB) counts as well as the evolution of temperatures, pH and aw values were monitored throughout the manufacturing and ripening processes. Throughout the ripening in maturation room a constant temperature of 8\ub0C was observed reaching a temperature between 10 and 15.5\ub0C during ripening into pit. In the final products data for LAB concentration, pH and aw values were roughly in accordance with literature, even if some differences were, probably due to variability of artisanal cheese productions. The numbers of L. innocua showed a slight decrease but remained stable until the end of ripening in maturation room, whereas a significant reduction of the microorganism was observed in the final product, at the end of the ripening into the pit. The findings give scientific evidence that the process of this PDO prevented the L. innocua growth, allowing us to speculate a similar behaviour of L. monocytogenes. Based on this study, the recommendation to extend as much as possible the ripening into pit (from 80 to 100 days) was provided to food business operators as a risk mitigation strategy to be implemented

Size of HIV-1 reservoir is associated with telomere shortening and immunosenescence in early-treated European children with perinatally acquired HIV-1

INTRODUCTION: Persistence of HIV-1, causing chronic immune activation, is a key determinant of premature senescence. Early antiretroviral therapy (ART) has been associated with a reduced HIV-1 reservoir in children with perinatally acquired HIV-1 (PHIV), but its impact on the senescence process is an open question. We investigated the association between HIV-1 reservoir and biological and immune ageing profile in PHIV enrolled in the multicentre cross-sectional study CARMA (Child and Adolescent Reservoir Measurements on early suppressive ART) conducted within the EPIICAL (Early treated Perinatally HIV Infected individuals: Improving Children's Actual Life) consortium. METHODS: Between September 2017 and June 2018, CARMA enrolled 40 PHIV who started ART before 2 years of age and had undetectable viremia for at least 5 years before sampling date. Samples from 37 children with a median age of 13.8 years were available for this study. HIV-1 DNA copies on CD4 cells, relative telomere length (marker of cellular senescence) and levels of T-cell receptor rearrangement excision circle (TREC, marker of thymic output) on CD4 and CD8 cells were quantified by qPCR. Immunological profile was assessed by flow cytometry. Associations between molecular and phenotypic markers, HIV-1 reservoir and age at ART initiation were explored using a multivariable Poisson regression. RESULTS: Higher HIV-1 reservoir was associated (p<0.001) with telomere shortening (incidence rate ratio [IRR] = 0.15 [0.13-0.17]), immunosenescence (CD28- CD57+ , IRR = 1.23 [1.21-1.26]) and immunoactivation (CD38+ HLADR+ , IRR = 7.29 [6.58-8.09]) of CD4 cells. Late ART initiation (after 6 months of age) correlated with higher HIV-1 reservoir levels (552 [303-1001] vs. 89 [56-365] copies/106 CD4 cells, p = 0.003) and percentage of CD4 senescent cells (2.89 [1.95-6.31] vs. 1.02 [0.45-2.69, p = 0.047). TREC levels in CD8 cells were inversely associated with HIV-1 reservoir (IRR = 0.77 [0.76-0.79]) and were significantly lower in late treated PHIV (1128 [486-1671] vs. 2278 [1425-3314], p = 0.042). CONCLUSIONS: Later ART initiation is associated with higher HIV-1 reservoir size, which correlates with increased telomere shortening and senescence of CD4 cells. Timing of ART initiation in infancy has long-term consequences on the immune and biological ageing profile of children with perinatally acquired HIV-1

The efficiency of acidic electrolyzed oxidizing water to reduce spoilage microorganism load in beef

The aim of this study was to evaluate the efficacy of acid electrolysed oxidizing water (EOW) in reducing contamination by spoilage bacteria in bovine meat in order to determine if the treatment can limit microbial growth and extend the shelf life of fresh meat. Five batches of bovine meat were collected. Samples were treated with EOW, vacuum-packed and analysed to determine the mesophilic microbial load, count of Enterobacteriaceae, lactic acid bacteria, Brochothrix thermosphacta and Pseudomonas spp. during 20 days of storage at different temperatures (4\ub0, 8\ub0, 12\ub0C). Comparison between data obtained from the analysis of untreated and treated samples showed no significant difference in the samples analysed immediately after treatment and during storage. Treatment by immersion of bovine meat cuts for 45 seconds in EOW has shown to be ineffective in reducing contamination by the bacteria more frequently involved in meat spoilage

Conformational properties, membrane interaction, and antibacterial activity of the peptaibiotic chalciporin A: Multitechnique spectroscopic and biophysical investigations on the natural compound and labeled analogs

In this work, an extensive set of spectroscopic and biophysical techniques (including FT-IR absorption, CD, 2D-NMR, fluorescence, and CW/PELDOR EPR) was used to study the conformational preferences, membrane interaction, and bioactivity properties of the naturally occurring synthetic 14-mer peptaibiotic chalciporin A, characterized by a relatively low (approximate to 20%), uncommon proportion of the strongly helicogenic Aib residue. In addition to the unlabeled peptide, we gained in-depth information from the study of two labeled analogs, characterized by one or two residues of the helicogenic, nitroxyl radical-containing TOAC. All three compounds were prepared using the SPPS methodology, which was carefully modified in the course of the syntheses of TOAC-labeled analogs in view of the poorly reactive a-amino function of this very bulky residue and the specific requirements of its free-radical side chain. Despite its potentially high flexibility, our results point to a predominant, partly amphiphilic, a-helical conformation for this peptaibiotic. Therefore, not surprisingly, we found an effective membrane affinity and a remarkable penetration propensity. However, chalciporin A exhibits a selectivity in its antibacterial activity not in agreement with that typical of the other members of this peptide class

Reduction of Escherichia coli O157:H7 during manufacture and ripening of Italian semi-dry salami

In order to simulate a contamination at the processing plant, one batch of freshlyprocessed salami batter (20 kg) was inoculated (1% v:w) with 5 log colony forming unit (CFU)/g of a multi-strain cocktail of two strains of Escherichia coli O157:H7 (registered and wild strain). Another batch was inoculated (1% v:w) with sterile physiological saline solution and used to check the lactic acid bacteria (Lab) behaviour and the changes of physicochemical parameters (pH and aw). Both batches were then processed to obtain a semi-dry salami (Hungarian-style): microbiological and physico-chemical properties were monitored during 94 days of ripening. During the manufacturing process, the levels of pathogen decreased of about 2.18 log CFU/g with respect to the initial inoculated levels. The behavior of the indigenous bacteria such as Lab and the physico-chemical properties can help to determine the fate of pathogens throughout processing

Long‐term clinical, virological and immunological outcomes following planned treatment interruption in HIV‐infected children

Objectives: Planned treatment interruption (PTI) of antiretroviral therapy (ART) in adults is associated with adverse outcomes. The PENTA 11 trial randomized HIV‐infected children to continuous ART (CT) vs. CD4‐driven PTIs. We report 5 years’ follow‐up after the end of main trial. / Methods: Post‐trial, all children resumed ART. Clinical, immunological, virological and treatment data were collected annually. A sub‐study investigated more detailed immunophenotype. CT and PTI arms were compared using intention‐to‐treat. Laboratory parameters were compared using linear regression, adjusting for baseline values; mixed models were used to include all data over time. / Results: In all, 101 children (51 CT, 50 PTI) contributed a median of 7.6 years, including 5.1 years of post‐trial follow‐up. Post‐trial, there were no deaths, one pulmonary tuberculosis and no other CDC stage B/C events. At 5 years post‐trial, 90% of children in the CT vs. 82% in the PTI arm had HIV RNA < 50 copies/mL (P = 0.26). A persistent increase in CD8 cells was observed in the PTI arm. The sub‐study (54 children) suggested that both naïve and memory populations contributed to higher CD8 cells following PTI. Mean CD4/CD8 ratios at 5 years post‐trial were 1.22 and 1.08 in CT and PTI arms, respectively [difference (CT – PTI) = −0.15; 95% CI: −0.34–0.05), P = 0.14]. The sub‐study also suggested that during the trial and at early timepoints after the end of the trial, reduction in CD4 in the PTI arm was mainly from loss of CD4 memory cells. / Conclusions: Children tolerated PTI with few long‐term clinical, virological or immunological consequences