High Rates of HIV Seroconversion in Pregnant Women and Low Reported Levels of HIV Testing among Male Partners in Southern Mozambique: Results from a Mixed Methods Study

Introduction

Prevention of acute HIV infections in pregnancy is required to achieve elimination of pediatric HIV. Identification and support for HIV negative pregnant women and their partners, particularly serodiscordant couples, are critical. A mixed method study done in Southern Mozambique estimated HIV incidence during pregnancy, associated risk factors and factors influencing partner''s HIV testing.

Methods

Between April 2008 and November 2011, a prospective cohort of 1230 HIV negative pregnant women was followed during pregnancy. A structured questionnaire, HIV testing, and collection of dried blood spots were done at 2–3 scheduled visits. HIV incidence rates were calculated by repeat HIV testing and risk factors assessed by Poisson regression. A qualitative study including 37 individual interviews with men, women, and nurses and 11 focus group discussions (n = 94) with men, women and grandmothers explored motivators and barriers to uptake of male HIV testing.

Results

HIV incidence rate was estimated at 4.28/100 women-years (95%CI: 2.33–7.16). Significant risk factors for HIV acquisition were early sexual debut (RR 3.79, 95%CI: 1.04–13.78, p = 0.04) and living in Maputo Province (RR 4.35, 95%CI: 0.97–19.45, p = 0.05). Nineteen percent of women reported that their partner had tested for HIV (93% knew the result with 8/213 indicating an HIV positive partner), 56% said their partner had not tested and 19% did not know their partner test status. Of the 14 seroconversions, only one reported being in a serodiscordant relationship. Fear of discrimination or stigma was reported as a key barrier to male HIV testing, while knowing the importance of getting tested and receiving care was the main motivator.

Conclusions

HIV incidence during pregnancy is high in Southern Mozambique, but knowledge of partners'' HIV status remains low. Knowledge of both partners'' HIV status is critical for maximal effectiveness of prevention and treatment services to reach elimination of pediatric HIV/AIDS.     

The Cannabinoid Receptor Type 2 as Mediator of Mesenchymal Stromal Cell Immunosuppressive Properties

Mesenchymal stromal cells are non-hematopoietic, multipotent progenitor cells producing cytokines, chemokines, and extracellular matrix proteins that support hematopoietic stem cell survival and engraftment, influence immune effector cell development, maturation, and function, and inhibit alloreactive T-cell responses. The immunosuppressive properties of human mesenchymal stromal cells have attracted much attention from immunologists, stem cell biologists and clinicians.Recently, the presence of the endocannabinoid system in hematopoietic and neural stem cells has been demonstrated. Endocannabinoids, mainly acting through the cannabinoid receptor subtype 2, are able to modulate cytokine release and to act as immunosuppressant when added to activated T lymphocytes.In the present study, we have investigated, through a multidisciplinary approach, the involvement of the endocannabinoids in migration, viability and cytokine release of human mesenchymal stromal cells.We show, for the first time, that cultures of human mesenchymal stromal cells express all of the components of the endocannabinoid system, suggesting a potential role for the cannabinoid CB2 receptor as a mediator of anti-inflammatory properties of human mesenchymal stromal cells, as well as of their survival pathways and their capability to home and migrate towards endocannabinoid sources.     

Snakes on the Balearic Islands: An Invasion Tale with Implications for Native Biodiversity Conservation

Biological invasions are a major conservation threat for biodiversity worldwide. Islands are particularly vulnerable to invasive species, especially Mediterranean islands which have suffered human pressure since ancient times. In the Balearic archipelago, reptiles represent an outstanding case with more alien than native species. Moreover, in the last decade a new wave of alien snakes landed in the main islands of the archipelago, some of which were originally snake-free. The identification of the origin and colonization pathways of alien species, as well as the prediction of their expansion, is crucial to develop effective conservation strategies. In this study, we used molecular markers to assess the allochthonous status and the putative origin of the four introduced snake species (Hemorrhois hippocrepis, Malpolon monspessulanus, Macroprotodon mauritanicus and Rhinechis scalaris) as well as ecological niche models to infer their patterns of invasion and expansion based on current and future habitat suitability. For most species, DNA sequence data suggested the Iberian Peninsula as the potential origin of the allochthonous populations, although the shallow phylogeographic structure of these species prevented the identification of a restricted source-area. For all of them, the ecological niche models showed a current low habitat suitability in the Balearic, which is however predicted to increase significantly in the next few decades under climate change scenarios. Evidence from direct observations and spatial distribution of the first-occurrence records of alien snakes (but also lizards and worm lizards) suggest the nursery trade, and in particular olive tree importation from Iberian Peninsula, as the main pathway of introduction of alien reptiles in the Balearic islands. This trend has been reported also for recent invasions in NE Spain, thus showing that olive trees transplantation may be an effective vector for bioinvasion across the Mediterranean. The combination of molecular and ecological tools used in this study reveals a promising approach for the understanding of the complex invasion process, hence guiding conservation management actions.     

Characteristics of Hospitalized Cases of Pertussis in Catalonia and Navarra,Two Regions in the North of Spain

Pertussis causes a large number of cases and hospitalizations in Catalonia and Navarra. We made a study of household cases of pertussis during 2012 and 2013 in order to identify risk factors for hospitalization in pertussis cases. Each primary case reported triggered the study of their contacts. Close contacts at home and people who were in contact for >2 hours during the transmission period of cases were included. The adjusted OR and 95% confidence intervals (CI) was calculated using logistic regression. A total of 1124 pertussis cases were detected, of which 14.9% were hospitalized. Inspiratory whoop (aOR: 1.64; CI: 1.02–2.65), apnoea (aOR: 2.47; CI: 1.51–4.03) and cyanosis (aOR: 15.51; CI: 1.87–128.09) were more common in hospitalized than in outpatient cases. Hospitalization occurred in 8.7% of correctly-vaccinated cases, 41.1% of non-vaccinated cases and 9.4% of partially-vaccinated cases. In conclusion, inspiratory whoop, apnoea and cyanosis were associated factors to hospitalization while vaccination reduced hospitalizations due to pertussis.     

Influence of <Emphasis Type="Italic">Moraxella</Emphasis> sp. colonization on the kidney proteome of farmed gilthead sea breams (<Emphasis Type="Italic">Sparus aurata</Emphasis>, L.)

Background  

Currently, presence of Moraxella sp. in internal organs of fish is not considered detrimental for fish farming. However, bacterial colonization of internal organs can affect fish wellness and decrease growth rate, stress resistance, and immune response. Recently, there have been reports by farmers concerning slow growth, poor feed conversion, and low average weight increase of fish farmed in offshore floating sea cages, often associated with internal organ colonization by Moraxella sp. Therefore, presence of these opportunistic bacteria deserves further investigations for elucidating incidence and impact on fish metabolism.     

Guanosine inhibits CD40 receptor expression and function induced by cytokines and beta amyloid in mouse microglia cells

Growing evidence implicates CD40, a member of the TNFR superfamily, as contributing to the pathogenesis of many neurodegenerative diseases. Thus, strategies to suppress its expression may be of benefit in those disorders. To this aim, we investigated the effect of guanosine, a purine nucleoside that exerts neurotrophic and neuroprotective effects. CD40 expression and function are increased by exposure of mouse microglia cultures or the N9 microglia cell line to IFN-gamma (10 ng/ml) plus TNF-alpha (50 ng/ml) or beta amyloid (Abeta) peptide (Abeta(1-42); 500 nM). Culture pretreatment with guanosine (10-300 microM), starting 1 h before cytokine or Abeta addition, dose-dependently inhibited the CD40-induced expression as well as functional CD40 signaling by suppressing IL-6 production promoted by IFN-gamma/TNF-alpha challenge in the presence of CD40 cross-linking. Moreover, guanosine abrogated IFN-gamma-induced phosphorylation on Ser(727) and translocation of STAT-1alpha to the nucleus as well as TNF-alpha-/Abeta-induced IkappaBalpha and NF-kappaB p65/RelA subunit phosphorylation, thus inhibiting NF-kappaB-induced nuclear translocation. Guanosine effects were mediated by an increased phosphorylation of Akt, a PI3K downstream effector, as well as of ERK1/2 and p38 in the MAPK system, because culture pretreatment with selective ERK1/2, p38 MAPK, and PI3K antagonists (U0126, SB203580, or LY294002, respectively) counteracted guanosine inhibition on IFN-gamma/TNF-alpha-induced CD40 expression and function as well as on STAT-1alpha or NF-kappaB nuclear translocation. These findings suggest a role for guanosine as a potential drug in the experimental therapy of neuroinflammatory/neurodegenerative diseases, particularly Alzheimer's disease.     

Neurokinins and inflammatory cell iNOS expression in guinea pigs with chronic allergic airway inflammation

In the present study we evaluated the role of neurokinins in the modulation of inducible nitric oxide synthase (iNOS) inflammatory cell expression in guinea pigs with chronic allergic airway inflammation. In addition, we studied the acute effects of nitric oxide inhibition on this response. Animals were anesthetized and pretreated with capsaicin (50 mg/kg sc) or vehicle 10 days before receiving aerosolized ovalbumin or normal saline twice weekly for 4 wk. Animals were then anesthetized, mechanically ventilated, given normal saline or N(G)-nitro-l-arginine methyl ester (l-NAME, 50 mg/kg ic), and challenged with ovalbumin. Prechallenge exhaled NO increased in ovalbumin-exposed guinea pigs (P < 0.05 compared with controls), and capsaicin reduced this response (P < 0.001). Compared with animals inhaled with normal saline, ovalbumin-exposed animals presented increases in respiratory system resistance and elastance and numbers of total mononuclear cells and eosinophils, including those expressing iNOS (P < 0.001). Capsaicin reduced all these responses (P < 0.05) except for iNOS expression in eosinophils. Treatment with l-NAME increased postantigen challenge elastance and restored both resistance and elastance previously attenuated by capsaicin treatment. Isolated l-NAME administration also reduced total eosinophils and mononuclear cells, as well as those cells expressing iNOS (P < 0.05 compared with ovalbumin alone). Because l-NAME treatment restored lung mechanical alterations previously attenuated by capsaicin, NO and neurokinins may interact in controlling airway tone. In this experimental model, NO and neurokinins modulate eosinophil and lymphocyte infiltration in the airways.     

A homogeneous HTRF assay for the identification of inhibitors of the TWEAK-Fn14 protein interaction

The TWEAK-Fn14 pathway is upregulated in models of inflammation, autoimmune diseases, and cancer. Both TWEAK and Fn14 show increased expression also in the CNS in response to different stimuli, particularly astrocytes, microglia, and neurons, leading to activation of NF-κB and release of proinflammatory cytokines. Although neutralizing antibodies against these proteins have been shown to have therapeutic efficacy in animal models of inflammation, no small-molecule therapeutics are yet available. Here, we describe the development of a novel homogeneous time-resolved fluorescence (HTRF)-based screening assay together with several counterassays for the identification of small-molecule inhibitors of this protein-protein interaction. Recombinant HIS-TWEAK and Fn14-Fc proteins as well as FLAG-TWEAK and Fn14-FLAG proteins and an anti-Fn14 antibody were used to establish and validate these assays and to screen a library of 60 000 compounds. Two HTRF counterassays with unrelated proteins in the same assay format, an antiaggregation assay and a redox assay, were applied to filter out potential false-positive compounds. The novel assay and associated screening cascade should be useful for the discovery of small-molecule inhibitors of the TWEAK-Fn14 protein interaction.     

Oral tolerance attenuates changes in in vitro lung tissue mechanics and extracellular matrix remodeling induced by chronic allergic inflammation in guinea pigs

Recent studies emphasize the presence of alveolar tissue inflammation in asthma. Immunotherapy has been considered a possible therapeutic strategy for asthma, and its effect on lung tissue had not been previously investigated. Measurements of lung tissue resistance and elastance were obtained before and after both ovalbumin and acetylcholine challenges. Using morphometry, we assessed eosinophil and smooth muscle cell density, as well as collagen and elastic fiber content, in lung tissue from guinea pigs with chronic pulmonary allergic inflammation. Animals received seven inhalations of ovalbumin (1-5 mg/ml; OVA group) or saline (SAL group) during 4 wk. Oral tolerance (OT) was induced by offering ad libitum ovalbumin 2% in sterile drinking water starting with the 1st inhalation (OT1 group) or after the 4th (OT2 group). The ovalbumin-exposed animals presented an increase in baseline and in postchallenge resistance and elastance related to baseline, eosinophil density, and collagen and elastic fiber content in lung tissue compared with controls. Baseline and post-ovalbumin and acetylcholine elastance and resistance, eosinophil density, and collagen and elastic fiber content were attenuated in OT1 and OT2 groups compared with the OVA group. Our results show that inducing oral tolerance attenuates lung tissue mechanics, as well as eosinophilic inflammation and extracellular matrix remodeling induced by chronic inflammation.     

Optimization of extraction of high-ester pectin from passion fruit peel (Passiflora edulis flavicarpa) with citric acid by using response surface methodology

A central composite design was employed to optimize the extraction of pectin with citric acid. The independent variables were citric acid concentration (0.086–2.91% w/v) and extraction time (17–102 min). The combined effect of these variables on the degree of esterification was investigated. Results have shown that the generated regression models adequately explained the data variation and significantly represented the actual relationship between the independent variables and the responses. Besides that, the citric acid concentration was the most important factor to affect the degree of esterification, as it exerted a significant influence on the dependent variable. Lower citric acid concentration increased the pectin degree of esterification. The surface response showed the relationships between the independent variables, and thus responses were generated. Through this surface, the satisfactory condition of 0.086% w/v citric acid for 60 min was established for extraction of high-ester yellow passion fruit pectin.