Examining the effectiveness of place-based interventions to improve public health and reduce health inequalities: an umbrella review.

BackgroundLocally delivered, place-based public health interventions are receiving increasing attention as a way of improving health and reducing inequalities. However, there is limited evidence on their effectiveness. This umbrella review synthesises systematic review evidence of the health and health inequalities impacts of locally delivered place-based interventions across three elements of place and health: the physical, social, and economic environments.MethodsSystematic review methodology was used to identify recent published systematic reviews of the effectiveness of place-based interventions on health and health inequalities (PROGRESS+) in high-income countries. Nine databases were searched from 1st January 2008 to 1st March 2020. The quality of the included articles was determined using the Revised Assessment of Multiple Systematic Reviews tool (R-AMSTAR).ResultsThirteen systematic reviews were identified - reporting 51 unique primary studies. Fifty of these studies reported on interventions that changed the physical environment and one reported on changes to the economic environment. Only one primary study reported cost-effectiveness data. No reviews were identified that assessed the impact of social interventions. Given heterogeneity and quality issues, we found tentative evidence that the provision of housing/home modifications, improving the public realm, parks and playgrounds, supermarkets, transport, cycle lanes, walking routes, and outdoor gyms - can all have positive impacts on health outcomes - particularly physical activity. However, as no studies reported an assessment of variation in PROGRESS+ factors, the effect of these interventions on health inequalities remains unclear.ConclusionsPlace-based interventions can be effective at improving physical health, health behaviours and social determinants of health outcomes. High agentic interventions indicate greater improvements for those living in greater proximity to the intervention, which may suggest that in order for interventions to reduce inequalities, they should be implemented at a scale commensurate with the level of disadvantage. Future research needs to ensure equity data is collected, as this is severely lacking and impeding progress on identifying interventions that are effective in reducing health inequalities.Trial registrationPROSPERO CRD42019158309

Changes in CD4+ cells’ miRNA expression following exposure to HIV-1

Background: MiRNAs inhibit HIV-1 expression by either modulating host innate immunity or by directly interfering with viral mRNAs. Here, we investigated the miRNA profile that discriminates different classes of HIV-1 infected patients from multiple exposed uninfected individuals. Methods: The expression levels of 377 miRNAs were selectively analyzed in CD4+ cells isolated from whole blood of HIV-1 \ue9lite LTNP (\ue9LTNP), naive, and multiply exposed uninfected individuals (MEU). MiRNA extraction was performed by the mirVana miRNA Isolation Kit (Ambion) and their expression was subsequently examined by real-time PCR-based arrays. The expression of miRNAs was also determined in primary culture of CD4+T cells and monocyte-macrophages infected in vitro by R5 strains. Expression of Dicer and Drosha was evaluated by real-time PCR. Results: We only considered miRNAs that were expressed in the 70% of patients of at least one class and varied by at least 1 log10 from healthy controls. Out of 377 miRNAs, 26 were up-regulated, while 88 were down-regulated. Statistical analysis showed that 21 miRNAs significantly differentiated \ue9LTNP from MEU and 23 miRNAs distinguished naive from MEU, while only 1 (miR-155) discriminated \ue9LTNP from naive. By hierarchical clustering of the miRNAs according to patient class, \ue9LTNP clustered with naive whereas all MEU subjects grouped together. The Dicer and Drosha expression in the patient classes correlated with miRNA profile changes. Among miRNAs differentially expressed in patient classes, 32 were detected in in vitro infection model: the most of the up-regulated miRNAs were expressed in monocyte-macrophages, whereas the most of the down-regulated miRNAs were expressed in T lymphocytes. Conclusions: These findings support that miRNA profile could be the result not only of a productive infection, but also of the exposure to HIV products that leave a signature in immune cells. These data provide some intriguing issues relative to the development of HIV vaccines targeting viral proteins

Investigations into, and development of, a lyophilized and formulated recombinant human factor IX produced from CHO cells

Objectives: To develop a recombinant human factor IX (rFIX) formulation equivalent to commercially available products in terms of cake appearance, residual moisture, proportion of soluble aggregates and activity maintenance for 3 months at 4–8 °C. Results: NaCl and low bulking agent/cryoprotectant mass ratio had a negative impact on cake quality upon lyophilisation for a wide range of formulations tested. Particular devised formulations maintained rFIX activity after lyophilization with a similar performance when compared with the rFIX formulated using the excipients reported for a commercially available FIX formulation (Benefix). rFIX remained active after 3 months when stored at 4 °C, though this was not the case with samples stored at 40 °C. Interestingly, particular formulations had an increase in residual moisture after 3 months storage, but not above a 3% threshold. All four formulations tested were equivalent to the Benefix formulation in terms of particle size distribution and cake appearance. Conclusions: Three specific formulations, consisting of surfactant polysorbate-80, sucrose or trehalose as cryoprotectant, mannitol or glycine as bulking agent, l-histidine as buffering agent, and NaCl added in the reconstitution liquid at 0.234% (w/v) were suitable for use with a CHO cell-derived recombinant FIX

Antibody Complementarity-Determining Regions (CDRs) Can Display Differential Antimicrobial, Antiviral and Antitumor Activities

Background: Complementarity-determining regions (CDRs) are immunoglobulin (Ig) hypervariable domains that determine specific antibody (Ab) binding. We have shown that synthetic CDR-related peptides and many decapeptides spanning the variable region of a recombinant yeast killer toxin-like antiidiotypic Ab are candidacidal in vitro. An alanine-substituted decapeptide from the variable region of this Ab displayed increased cytotoxicity in vitro and/or therapeutic effects in vivo against various bacteria, fungi, protozoa and viruses. the possibility that isolated CDRs, represented by short synthetic peptides, may display antimicrobial, antiviral and antitumor activities irrespective of Ab specificity for a given antigen is addressed here.Methodology/Principal Findings: CDR-based synthetic peptides of murine and human monoclonal Abs directed to: a) a protein epitope of Candida albicans cell wall stress mannoprotein; b) a synthetic peptide containing well-characterized B-cell and T-cell epitopes; c) a carbohydrate blood group A substance, showed differential inhibitory activities in vitro, ex vivo and/or in vivo against C. albicans, HIV-1 and B16F10-Nex2 melanoma cells, conceivably involving different mechanisms of action. Antitumor activities involved peptide-induced caspase-dependent apoptosis. Engineered peptides, obtained by alanine substitution of Ig CDR sequences, and used as surrogates of natural point mutations, showed further differential increased/unaltered/decreased antimicrobial, antiviral and/or antitumor activities. the inhibitory effects observed were largely independent of the specificity of the native Ab and involved chiefly germline encoded CDR1 and CDR2 of light and heavy chains.Conclusions/Significance: the high frequency of bioactive peptides based on CDRs suggests that Ig molecules are sources of an unlimited number of sequences potentially active against infectious agents and tumor cells. the easy production and low cost of small sized synthetic peptides representing Ig CDRs and the possibility of peptide engineering and chemical optimization associated to new delivery mechanisms are expected to give rise to a new generation of therapeutic agents.Department of Education, Universities and Research, Basque GovermentFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Istituto Superiore di Sanita, National Research Project on A.I.D.S.Cariparma Banking FoundationBrazilian National Research CouncilUniv Parma, Sez Microbiol, Dipartimento Patol, I-43100 Parma, ItalyUniv Basque Country, Fac Med Odontol, Dept Inmunol, Microbiol Parasitol, Bilbao, SpainUniv Basque Country, Dept Enfermeria I, Bilbao, SpainUniv Milan, Dipartimento Sci Cliniche L Sacco, Sez Malattie Infettive Immunopatol, Milan, ItalyUniv Studi Parma, Dipartimento Clin Med, Nefrol Sci Prev, Parma, ItalyUniversidade Federal de São Paulo, Departamento Microbiol, Imunol Parasitol, Unidade Oncol Expt, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biofis, São Paulo, BrazilUniversidade Federal de São Paulo, Departamento Microbiol, Imunol Parasitol, Unidade Oncol Expt, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biofis, São Paulo, BrazilDepartment of Education, Universities and Research, Basque Goverment: IT-264-07FAPESP: 06/50634-2Istituto Superiore di Sanita, National Research Project on A.I.D.S.: 50G.30Istituto Superiore di Sanita, National Research Project on A.I.D.S.: 40D.14Cariparma Banking Foundation: 2004.0190Brazilian National Research Council: research fellowshipWeb of Scienc

Sports activities as primary prevention of youth deviant behaviours: an educational intervention research

To improve the well-being of young people in the province of Taranto (Italy), intervention research was performed to study the effects of sport and its fundamental role in the prevention of juvenile deviance. A questionnaire was administered to 174 subjects (aged 7 and 11), and data were collected that investigated the main areas of influence in the process of growth and harmonious development of the minors’ personality structure in relation to sports practice. Sport is widely recognized as a means of disseminating and transmitting positive values such as solidarity, loyalty, respect for people and the rules; in addition, sport can create a suitable environment for promoting ease and well-being in youth. The obtained results showed that the presence of and intervention by experienced and trained figures in the sports field, such as sports science graduates, is essential. The performed research showed a significant change in the organization and function of the family and sports associations because they must respond to new educational needs arising from the current phase of social culture. Both have an enormous responsibility in the prevention of youth discomfort. The performed research indicates that in addition to the family, there is a growing need for institutional figures who are trained and well-prepared such as coaches and managers of sports associations. These figures, better if they have a degree in sports sciences, have a pedagogical and strategic value for the minors because they can positively influence the conditions of growth, evolution, and harmonious development, and contrast and prevent deviant behaviours in youth

Delayed progression to AIDS in HTLV-I/HIV-1 coinfected intravenous drug users

Delayed progression to AIDS in HTLV-I/HIV-1 coinfected intravenous drug user