The Experience of Implementing Urban HEART Barcelona: a Tool for Action

Urban Health Equity Assessment and Response Tool (HEART) is a tool developed by the World Health Organization whose objective is to provide evidence on urban health inequalities so as to help to decide the best interventions aimed to promote urban health equity. The aim of this paper is to describe the experience of implementing Urban HEART in Barcelona city, both the adaptation of Urban HEART to the city of Barcelona, its use as a means of identifying and monitoring health inequalities among city neighbourhoods, and the difficulties and barriers encountered throughout the process. Although ASPB public health technicians participated in the Urban HEART Advisory Group, had large experience in health inequalities analysis and research and showed interest in implementing the tool, it was not until 2015, when the city council was governed by a new left-wing party for which reducing health inequalities was a priority that Urban HEART could be used. A provisional matrix was developed, including both health and health determinant indicators, which allowed to show how some neighbourhoods in the city systematically fare worse for most of the indicators while others systematically fare better. It also allowed to identify 18 neighbourhoods—those which fared worse in most indicators—which were considered a priority for intervention, which entered the Health in the Barcelona Neighbourhoods programme and the Neighbourhoods Plan. This provisional version was reviewed and improved by the Urban HEART Barcelona Working Group. Technicians with experience in public health and/or in indicator and database management were asked to indicate suitability and relevance from a list of potential indicators. The definitive Urban HEART Barcelona version included 15 indicators from the five Urban HEART domains and improved the previous version in several requirements. Several barriers were encountered, such as having to estimate indicators in scarcely populated areas or finding adequate indicators for the physical context domain. In conclusion, the Urban HEART tool allowed to identify urban inequalities in the city of Barcelona and to include health inequalities in the public debate. It also allowed to reinforce the community health programme Health in the Barcelona Neighbourhoods as well as other city programmes aimed at reducing health inequalities. A strong political will is essential to place health inequalities in the political agenda and implement policies to tackle them.     

Impaired serotonin communication during juvenile development in rats diminishes adult sperm quality

Spermatogenesis and steroidogenesis are testicular functions regulated by gonadotrophins as well as other factors, including serotonin. Testicular serotonin acts as an autocrine regulator of testosterone secretion, but studies on its role in spermatogenesis and sperm quality are scarce. Here, we analyzed the effects of intratesticular inhibition of serotonin synthesis on gonadotrophins, testosterone, and sperm quality. Both testicles of 30-day-old rats were injected once with saline solution (SS) or distinct concentrations of p-chloroamphetamine (PCA) (0.03, 0.06, or 0.12 mg). At 65 days of age, rats were euthanized and sperm density, motility, membrane integrity, mitochondrial function, and abnormalities were evaluated in gametes from the vas deferens. Inhibition of synthesis of intratesticular serotonin by PCA diminished the concentrations of testosterone and follicle-stimulating hormone (FSH) but luteinizing hormone (LH) levels were unaltered. Sperm density was not modified in animals injected with the different concentrations of PCA. In contrast, the percentage of sperm with abnormalities increased and the sperm membrane integrity decreased in animals injected at higher PCA concentrations. The functionality of sperm mitochondria in PCA-injected animals decreased only at the highest PCA dose. Our results indicate that testicular serotonin plays a role in testosterone synthesis and in the normal development of sperm, and blocking its effects disrupts the hormonal communication between the testis and hypophysis.

Abbreviations: SS: saline solution; PCA: p-chloroamphetamine; FSH: follicle-stimulating hormone; LH: luteinizing hormone; TPH: tryptophan hydroxylase; MAO: monoamine oxidase; AC: absolute control group; PI: propidium iodide; FLICA: fluorescence inhibitor of caspase; 3β-HSD: 3β-hydroxysteroid dehydrogenase; 17-KSR: 17-ketosteroid reductase; DHT: 5-dihydrotestosterone     

Effect of a Multi-Site Trial using Short Message Service (SMS) on Infant Feeding Practices and Weight Gain in Low-Income Minorities

Objective: To test the effects of weekly SMS for improving infant feeding practices and infant weight.

Methods: This was a multi-site randomized clinical trial in a convenience sample of 202 caregivers of healthy term infants 0–2 months participating in the WIC program in Puerto Rico and Hawaii. Participants were randomized to receive SMS about infant's general health issues (control) or SMS for improving feeding practices (intervention) for four months. Weight, length and infant feeding practices were assessed at baseline and four months later.

Results: A total of 170 participants completed the study (n = 86 control and n = 84 intervention). Baseline characteristics were similar between groups. At the end, exclusive breastfeeding rates were similar between groups (67.4% control and 59.1% intervention). Introduction of other foods and beverages, addition of foods to the bottle, placing infants to sleep with milk bottles, caregiver's method and response to feeding infants and distractions while feeding infants were similar between groups. Also, weight status or rate of weight gain was similar between groups.

Conclusion: There were no significant improvements in feeding practices or in weight with the intervention. The timeline of the messages in relation to the targeted behavior may have affected the effectiveness of the intervention. Earlier dissemination of messages, higher level of intensity, longer intervention, additional contacts and inclusion of other caregivers may be needed to achieve the desired effects.     

Pilot scale production of the vaccine adjuvant Proteoliposome derived Cochleates (AFCo1) from <Emphasis Type="Italic">Neisseria meningitidis</Emphasis> serogroup B

The use of new adjuvants in vaccine formulations is a subject of current research. Only few parenteral adjuvants have been licensed. We have developed a mucosal and parenteral adjuvant known as AFCo1 (Adjuvant Finlay Cochleate 1, derived from proteoliposomes of N. meningitidis B) using a dialysis procedure to produce them on lab scale. The immunogenicity of the AFCo1 produced by dialysis has been already evaluated, but it was necessary to demonstrate the feasibility of a larger-scale manufacturing process. Therefore, we used a crossflow diafiltration system (CFS) that allows easy scale up to obtain large batches in an aseptic environment. The aim of this work was to produce AFCo1 on pilot scale, while conserving the adjuvant properties. The proteoliposomes (raw material) were resuspended in a buffer containing sodium deoxycholate and were transformed into AFCo1 under the action of a calcium forming buffer. The detergent was removed from the protein solution by diafiltration to a constant volume. In this CFS, we used a hollow fiber cartridge from Amicon (polysulfona cartridge of 10 kDa porosity, 1mm channel diameter of fiber and 0.45 m² area of filtration), allowing production of a batch of up to 20 L. AFCo1 were successfully produced by tangential filtration to pilot scale. The batch passed preliminary stability tests. Nasal immunization of BALB/c mice, induced specific saliva IgA and serum IgG. The induction of Th1 responses were demonstrated by the induction of IgG2a, IFNγ and not IL-5. The adjuvant action over Neisseria (self) antigens and with co-administered (heterologous) antigens such as ovalbumin and a synthetic peptide from haemolytic Streptococcus B was also demonstrated.     

NOTCH pathway inactivation promotes bladder cancer progression

NOTCH signaling suppresses tumor growth and proliferation in several types of stratified epithelia. Here, we show that missense mutations in NOTCH1 and NOTCH2 found in human bladder cancers result in loss of function. In murine models, genetic ablation of the NOTCH pathway accelerated bladder tumorigenesis and promoted the formation of squamous cell carcinomas, with areas of mesenchymal features. Using bladder cancer cells, we determined that the NOTCH pathway stabilizes the epithelial phenotype through its effector HES1 and, consequently, loss of NOTCH activity favors the process of epithelial-mesenchymal transition. Evaluation of human bladder cancer samples revealed that tumors with low levels of HES1 present mesenchymal features and are more aggressive. Together, our results indicate that NOTCH serves as a tumor suppressor in the bladder and that loss of this pathway promotes mesenchymal and invasive features.     

Facilitated molecular typing of Shigella isolates using ERIC-PCR

To evaluate the performance of enterobacterial repetitive intergenic sequence-based polymerase chain reaction (ERIC-PCR) typing versus the current standard for the typing of Shigella pulsed gel electrophoresis (PFGE), we typed 116 Shigella isolates from a village in an endemic setting over a 20-month period using both methods. PFGE identified 37 pulse types and had a discrimination index of 0.925 (95% confidence interval = 0.830-1.00), whereas ERIC-PCR identified 42 types and had a discrimination index of 0.961 (95% confidence interval = 0.886-1.00). PFGE and ERIC-PCR showed a 90.4% correlation in the designation of isolates as clonal or non-clonal in pairwise comparisons. Both systems were highly reproducible and provided highly similar and supplementary data compared with serotyping regarding the transmission dynamics of shigellosis in this community. ERIC-PCR is considerably more rapid and inexpensive than PFGE and may have a complementary role to PFGE for initial investigations of hypothesized outbreaks in resource-limited settings.     

An insight into the Phlebotomus perniciosus saliva by a proteomic approach

Sand fly saliva is known to play an important role in the establishment of Leishmania spp. infection. As a consequence, identifying antigenic salivary proteins of different leishmaniasis vectors has currently become a major task in the field of anti-Leishmania vaccine development. The purpose of this work was to improve the knowledge of Phlebotomus perniciosus salivary proteins by combining two-dimensional gel electrophoresis (2DE) methodology, mass spectrometry and Western blotting (WB). Salivary protein profiles of three P. perniciosus colonies from different geographic origins in Spain were compared through SDS-PAGE, leading to a similar pattern with no qualitatively noticeable differences. A gradual increase of the protein content was significantly detected with the age of sand flies, reaching the complete salivary protein profiles at day four. The 2DE revealed a reproducible protein profile that matched the classic monodimensional SDS-PAGE pattern (1DE). More spots rather than protein bands (19 versus 11) were visualized by 2DE and 1DE, respectively, suggesting the presence of either protein isoforms or posttranslational modifications. Sera of mice and hamsters immunized through exposure to sand fly bites following different immunization schedules showed elevated anti-saliva IgG levels. These sera allowed the detection of 5 bands and 16 immunogenic spots in 1DE and 2DE, respectively, followed by WB. These antigens were identified by MALDITOF/TOF as SP03, SP03B, SP08, SP01, SP01B, SP04, SP04B, SP02, Phlebotomus ariasi SP16, and Phlebotomus argentipes SP13. This work is assumed to be the first attempt to establish 2DE proteomic maps of P. perniciosus saliva. All spots were identified as salivary proteins, confirming this technology as an interesting tool to improve sand fly salivary knowledge.     

Lack of effect of glycoprotein IIb/IIIa blockade on myocardial platelet or polymorphonuclear leukocyte accumulation and on infarct size after transient coronary occlusion in pigs.

OBJECTIVES: We sought to assess the effect of glycoprotein (GP) IIb/IIIa blockade on myocardial platelet and polymorphonuclear leukocyte accumulation and on infarct size after coronary injury and transient coronary occlusion (CO) in pigs. BACKGROUND: It has been suggested that platelet GP IIb/IIIa blockade might reduce the severity of microvascular damage after reperfusion. METHODS: Sixteen thiopental-anesthetized, open-chest pigs, in whom platelets had been labeled with technetium-99m (99mTc) on the previous day, were submitted to catheter-induced left anterior descending coronary artery (LAD) injury followed by 55 min of CO and 5 h of reperfusion. Five minutes before reflow, the animals were blindly allocated to receive lamifiban (intravenous bolus of 250 microg/kg body weight and continuous infusion of 3 microg/kg per min) or saline. RESULTS: Lamifiban had a rapid and potent platelet anti-aggregatory effect, as demonstrated by significant prolongation of the bleeding time and profound (approximately 90%) inhibition of ex vivo platelet aggregation, and completely prevented the development of cyclic flow reductions of the LAD (0 vs. 5 +/- 1, one of them followed by re-occlusion, in control animals, p = 0.005). However, compared with animals receiving placebo, those treated with lamifiban had a similar (p = NS) content of (99m)Tc platelets in the reperfused myocardium (288 +/- 40% vs. 205 +/- 27% of the value in the control region, respectively) and similar myeloperoxidase activity (0.50 +/- 0.17 U/g vs. 0.47 +/- 0.17 U/g, respectively) and infarct size (46.8 +/- 12.0% vs. 49.8 +/- 10.5% of the area at risk, respectively). Arteriolar platelet thromboemboli were very rarely seen on histologic analysis. Lamifiban did not modify platelet P-selectin expression in additional studies. CONCLUSIONS: Platelet GP IIb/IIIa blockade has a potent antithrombotic effect at the culprit lesion, but does not significantly reduce the magnitude of microvascular platelet accumulation or myocardial damage after transient CO.