Macrophage activation and human immunodeficiency virus infection: HIV replication directs macrophages towards a pro-inflammatory phenotype while previous activation modulates macrophage susceptibility to infection and viral production

AbstractMacrophages are pivotal for the regulation of immune and inflammatory responses, but whether their role in HIV infection is protective or deleterious remains unclear. In this study, we investigated the effect of pro- and anti-inflammatory stimuli on macrophage sensitivity to two different aspects of HIV infection: their susceptibility to infection stricto sensu, which we measured by endpoint titration method, and their ability to support virus spread, which we measured by using an RT activity assay in infection kinetics. We show a partially protective role for pro-inflammatory agents as well as for IL-4. We also illustrate that various different stimuli display differential effects on macrophage susceptibility to HIV and on virus replication that occurs thereafter. On the other hand, HIV replication strongly repressed CD206 and CD163 expression, thus clearly orientating macrophages towards a pro-inflammatory phenotype, but independently of TNF. Taken together, our results emphasize that HIV infection of macrophages sets up inflammation at the cell level but through unexpected mechanisms. This may limit target susceptibility and participate in virus clearance but may also result in tissue damage

A Cross-Sectional Study of Prisoners in Mexico City Comparing Prevalence of Transmissible Infections and Chronic Diseases with That in the General Population.

ObjectivesTo describe patterns of transmissible infections, chronic illnesses, socio-demographic characteristics and risk behaviors in Mexico City prisons, including in comparison to the general population, to identify those currently needing healthcare and inform policy.Materials and methodsA cross-sectional study among 17,000 prisoners at 4 Mexico City prisons (June to December 2010). Participation was voluntary, confidential and based on informed consent. Participants were tested for HIV, Hepatitis B & C, syphilis, hypertension, obesity, and, if at risk, glucose and cholesterol. A subset completed a questionnaire on socio-demographic characteristics and risk behaviors. Positive results were delivered with counseling and treatment or referral.Results76.8% (15,517/20,196) of men and 92.9% (1,779/1,914) of women participated. Complete data sets were available for 98.8%. The following prevalence data were established for transmissible infections: HIV 0.7%; syphilis: Anti-TP+/VDRL+ 2.0%; Hepatitis B: HBcAb 2.8%, HBsAg 0.15%; Anti-HCV 3.2%. Obesity: 9.5% men, 33.8% women. Compared with national age- and sex-matched data, the relative prevalence was greater for HIV and syphilis among women, HIV and Hepatitis C in men, and all infections in younger participants. Obesity prevalence was similar for women and lower among male participants. The prevalence of previously diagnosed diabetes and hypertension was lower. Questionnaire data (1,934 men, 520 women) demonstrated lower educational levels, increased smoking and substance use compared to national data. High levels of non-sterile tattooing, physical abuse and histories of sexual violence were found.ConclusionThe study identified that health screening is acceptable to Mexico City prisoners and feasible on a large-scale. It demonstrated higher prevalence of HIV and other infections compared to national data, though low rates compared to international data. Individual participants benefited from earlier diagnosis, treatment and support. The data collected will also enable the formulation of improved policy for this vulnerable group

Effects of a ball-burnishing process assisted by vibrations in G10380 steel specimens

This paper explores the effects on the surface roughness, hardness and residual stress of G10380 steel specimens milled and treated with a ball-burnishing process assisted by vibrations. These vibrations are incorporated through the attachment of an induced coil module to a conventional burnishing tool, with forces transmitted through a pre-loaded spring. A positive effect of vibrations on the improvement and efficiency of the burnishing treatment is demonstrated, empirically proving that the vibrations introduce additional energy into the system that aids with displacements along the surface of the material to reallocate the crystalline structure. Significant results are found in terms of final surface roughness, which is highly improved in comparison to conventional burnishing treatments, even with fewer passes and a significant time reduction. Less robust results are observed in terms of specimen hardness and residual stress, but future improvements could be derived with a thorough development of the vibration system

Risk factors for sporadic salmonellosis: a systematic review and meta-analysis

Non-typhoidal Salmonella is an important causative agent of diarrheal illness worldwide. A systematic review and meta-analysis of case-control studies were performed to determine the main risk factors associated with sporadic salmonellosis. Suitable scientific articles published up to 2017 were identified through a systematic literature search and subject to methodological quality assessment. From each study, odds ratios (OR) were extracted or calculated, as well as study characteristics such as population type, design, type of model used and risk factor categorization. Mixed-effects meta-analytical models were adjusted by population type to appropriate data partitions. From 3858 identified references, the quality assessment stage was passed by 62 case-control studies focusing on sporadic salmonellosis which provided 1154 ORs for meta-analysis. The meta-analysis identified host-specifics factors, travel, environmental, animal and food exposures as significant risk factors of salmonellosis in the mixed population. For the mixed population, foods significantly associated with salmonellosis were eggs and egg products, composite foods, and meat (pork, red meats other than beef and poultry meats). In the child population, the main risk factors were found for person-to-person transmission, recent use of gastric anti-acids or antibiotics, contact with pets and farm animals, environmental, and food vehicles. Breastfeeding was found to be a protective factor for children. The food vehicles identified in children comprised dairy (milk formula), produce, meat and eggs products. Untreated drinking water was a risk factor for the children and mixed population. The result of the meta-analysis conducted at the international level is very important in the context of increasing international trade in foodstuffs and changes in food consumption patterns.The authors would like to thank Anses staff and the members of the Anses Working Group on Source Attribution of Foodborne Diseases: Moez Sanaa, Jean Christophe Augustin, Fr´ed´eric Carlin, Alexandre Leclercq, Nicole Pavio, Isabelle Villena, and Laurence Watier. U. Gonzales-Barron and V. Cadavez are grateful to the Foundation for Science and Technology (FCT, Portugal) for financial support through national funds FCT/MCTES to CIMO (UIDB/00690/2020). U. Gonzales- Barron acknowledges the national funding by FCT, P.I., through the institutional scientific employment program contract.info:eu-repo/semantics/publishedVersio

High Burden of Non-Influenza Viruses in Influenza-Like Illness in the Early Weeks of H1N1v Epidemic in France

BACKGROUND: Influenza-like illness (ILI) may be caused by a variety of pathogens. Clinical observations are of little help to recognise myxovirus infection and implement appropriate prevention measures. The limited use of molecular tools underestimates the role of other common pathogens. OBJECTIVES: During the early weeks of the 2009-2010 flu pandemic, a clinical and virological survey was conducted in adult and paediatric patients with ILI referred to two French University hospitals in Paris and Tours. Aims were to investigate the different pathogens involved in ILI and describe the associated symptoms. METHODS: H1N1v pandemic influenza diagnosis was performed with real time RT-PCR assay. Other viral aetiologies were investigated by the molecular multiplex assay RespiFinder19®. Clinical data were collected prospectively by physicians using a standard questionnaire. RESULTS: From week 35 to 44, endonasal swabs were collected in 413 patients. Overall, 68 samples (16.5%) were positive for H1N1v. In 13 of them, other respiratory pathogens were also detected. Among H1N1v negative samples, 213 (61.9%) were positive for various respiratory agents, 190 in single infections and 23 in mixed infections. The most prevalent viruses in H1N1v negative single infections were rhinovirus (62.6%), followed by parainfluenza viruses (24.2%) and adenovirus (5.3%). 70.6% of H1N1v cases were identified in patients under 40 years and none after 65 years. There was no difference between clinical symptoms observed in patients infected with H1N1v or with other pathogens. CONCLUSION: Our results highlight the high frequency of non-influenza viruses involved in ILI during the pre-epidemic period of a flu alert and the lack of specific clinical signs associated with influenza infections. Rapid diagnostic screening of a large panel of respiratory pathogens may be critical to define and survey the epidemic situation and to provide critical information for patient management

Refugios climáticos escolares basados en la naturaleza : evaluación desde una perspectiva interdisciplinaria

Este trabajo se basa en el proyecto Coolschools (coolschools.eu) y ha recibido financiación del programa de investigación e innovación Horizon 2020 de la Unión Europea bajo el acuerdo de subvención núm. 101003758, así como de la Agencia Española de Investigación (AEI), Innoviris (Región de Bruselas Capital), Dutch Research Council (NWO), The Research Foundation - Flanders (FWO) y Agence Nationale de la Recherche (ANR).Las soluciones basadas en la naturaleza (SbN) se definen como acciones que se apoyan en lanaturaleza para proporcionar simultáneamente beneficios ambientales y socioeconómicos de forma sostenible y resiliente. Cuando se incorporan en entornos escolares, tanto dentro de los recintos escolares como en sus alrededores, las SbN pueden contribuir a la adaptación al cambio climático a la vez que proporcionar múltiples cobeneficios a la comunidad educativa. Este artículo aporta evidencias científicas y herramientas metodológicas para una evaluación holística de los cobeneficios de las SbN en entornos escolares en términos de equidad, biodiversidad, salud, seguridad, gobernanza y educación, con una mirada hacia la población infantil como beneficiaria principal. Para ello, propone y desarrolla el concepto de refugios climáticos escolares basados en la naturaleza como una estrategia innovadora para la transición hacia ciudades más sostenibles y resilientes

Istradefylline protects from cisplatin-induced nephrotoxicity and peripheral neuropathy while preserving cisplatin antitumor effects

Cisplatin is a potent chemotherapeutic drug that is widely used in the treatment of various solid cancers. However, its clinical effectiveness is strongly limited by frequent severe adverse effects, in particular nephrotoxicity and chemotherapy-induced peripheral neuropathy. Thus, there is an urgent medical need to identify novel strategies that limit cisplatin-induced toxicity. In the present study, we show that the FDA-approved adenosine A2A receptor antagonist istradefylline (KW6002) protected from cisplatin-induced nephrotoxicity and neuropathic pain in mice with or without tumors. Moreover, we also demonstrate that the antitumoral properties of cisplatin were not altered by istradefylline in tumor-bearing mice and could even be potentiated. Altogether, our results support the use of istradefylline as a valuable preventive approach for the clinical management of patients undergoing cisplatin treatment

A targeted next-generation sequencing assay for the molecular diagnosis of genetic disorders with orodental involvement.

BACKGROUND: Orodental diseases include several clinically and genetically heterogeneous disorders that can present in isolation or as part of a genetic syndrome. Due to the vast number of genes implicated in these disorders, establishing a molecular diagnosis can be challenging. We aimed to develop a targeted next-generation sequencing (NGS) assay to diagnose mutations and potentially identify novel genes mutated in this group of disorders. METHODS: We designed an NGS gene panel that targets 585 known and candidate genes in orodental disease. We screened a cohort of 101 unrelated patients without a molecular diagnosis referred to the Reference Centre for Oro-Dental Manifestations of Rare Diseases, Strasbourg, France, for a variety of orodental disorders including isolated and syndromic amelogenesis imperfecta (AI), isolated and syndromic selective tooth agenesis (STHAG), isolated and syndromic dentinogenesis imperfecta, isolated dentin dysplasia, otodental dysplasia and primary failure of tooth eruption. RESULTS: We discovered 21 novel pathogenic variants and identified the causative mutation in 39 unrelated patients in known genes (overall diagnostic rate: 39%). Among the largest subcohorts of patients with isolated AI (50 unrelated patients) and isolated STHAG (21 unrelated patients), we had a definitive diagnosis in 14 (27%) and 15 cases (71%), respectively. Surprisingly, COL17A1 mutations accounted for the majority of autosomal-dominant AI cases. CONCLUSIONS: We have developed a novel targeted NGS assay for the efficient molecular diagnosis of a wide variety of orodental diseases. Furthermore, our panel will contribute to better understanding the contribution of these genes to orodental disease. TRIAL REGISTRATION NUMBERS: NCT01746121 and NCT02397824.journal articleresearch support, non-u.s. gov't2016 Feb2015 10 26importe

A Decision Aid Algorithm for Long-Haul Parcel Transportation based on Hierarchical Network Structure

International audienceWith the explosion of e-commerce, optimizing parcel transportation has become increasingly important. We study the long-haul stage of parcel transportation which takes place between sorting centers and delivery depots and is performed on a twolevel hierarchical network. In our case study, we describe the application framework of this industrial problem faced by a French postal company: There are two vehicle types which must be balanced over the network on a daily basis, and there are two possible sorting points for each parcel, which allows a better consolidation of parcels. These industrial constraints are formalized in the Long-Haul Parcel Transportation Problem (LHPTP). We present a Mixed Integer Linear Program (MILP) and a hierarchical algorithm with aggregation of demands which uses the MILP as a subroutine. We perform numerical experiments on large-size datasets provided by a postal company, which consist of approximately 2500 demands on a network of 225 sites. These tests enable the tuning of certain parameters resulting in a tailored heuristic for the LHPTP. Our algorithm can serve as a decision aid tool for transportation managers to build daily transportation plans, modeled on solutions produced given daily demand forecasts, and can also be used to improve the network design