The dynamic crossover in water does not require bulk water

Many of the anomalous properties of water may be explained by invoking a second critical point that terminates the coexistence line between the low- and high-density amorphous states in the liquid. Direct experimental evidence of this point, and the associated polyamorphic liquid–liquid transition, is elusive as it is necessary for liquid water to be cooled below its homogeneous-nucleation temperature. To avoid crystallization, water in the eutectic LiCl solution has been studied but then it is generally considered that “bulk” water cannot be present. However, recent computational and experimental studies observe cooperative hydration in which case it is possible that sufficient hydrogen-bonded water is present for the essential characteristics of water to be preserved. For femtosecond optical Kerr-effect and nuclear magnetic resonance measurements, we observe in each case a fractional Stokes–Einstein relation with evidence of the dynamic crossover appearing near 220 K and 250 K respectively. Spectra obtained in the glass state also confirm the complex nature of the hydrogen-bonding modes reported for neat room-temperature water and support predictions of anomalous diffusion due to “worm-hole” structure

Leishmania guyanensis parasites block the activation of the inflammasome by inhibiting maturation of IL-1β.

The various symptomatic outcomes of cutaneous leishmaniasis relates to the type and potency of its underlying inflammatory responses. Presence of the cytoplasmic javax.xml.bind.JAXBElement@52daeaa2 RNA virus-1 (LRV1) within javax.xml.bind.JAXBElement@be11ae5 , worsens lesional inflammation and parasite burden, as the viral dsRNA genome acts as a potent innate immunogen stimulating Toll-Like-Receptor-3 (TLR3). Here we investigated other innate pattern recognition receptors capable of reacting to dsRNA and potentially contributing to LRV1-mediated inflammatory pathology. We included the cytoplasmic dsRNA sensors, namely, the RIG-like receptors (RLRs) and the inflammasome-dependent and -independent Nod-like-receptors (NLRs). Our study found no role for RLRs or inflammasome-dependent NLRs in the pathology of javax.xml.bind.JAXBElement@3dfe8dc4 infection irrespective of its LRV1-status. Further, neither LRV1-bearing javax.xml.bind.JAXBElement@6e03fdb4 ( javax.xml.bind.JAXBElement@6b89952c +) nor LRV1-negative javax.xml.bind.JAXBElement@68bc8c8a ( javax.xml.bind.JAXBElement@2165acf4 ) activated the inflammasome javax.xml.bind.JAXBElement@507a0b31 . Interestingly, similarly to javax.xml.bind.JAXBElement@77fdd4e7 , javax.xml.bind.JAXBElement@7b29ce4e infection induced the up-regulation of the A20 protein, known to be involved in the evasion of inflammasome activation. Moreover, we observed that javax.xml.bind.JAXBElement@77a7dfd3 + promoted the transcription of inflammasome-independent NLRC2 (also called NOD2) and NLRC5. However, only NLRC2 showed some contribution to LRV1-dependent pathology. These data confirmed that the endosomal TLR3 pathway is the dominant route of LRV1-dependent signalling, thus excluding the cytosolic and inflammasome pathways. We postulate that avoidance of the inflammasome pathways is likely an important mechanism of virulence in javax.xml.bind.JAXBElement@77047195 infection irrespective of the LRV1-status

Mammalian Innate Immune Response to a Leishmania-Resident RNA Virus Increases Macrophage Survival to Promote Parasite Persistence.

Some strains of the protozoan parasite Leishmania guyanensis (L.g) harbor a viral endosymbiont called Leishmania RNA virus 1 (LRV1). LRV1 recognition by TLR-3 increases parasite burden and lesion swelling in vivo. However, the mechanisms by which anti-viral innate immune responses affect parasitic infection are largely unknown. Upon investigating the mammalian host's response to LRV1, we found that miR-155 was singularly and strongly upregulated in macrophages infected with LRV1+ L.g when compared to LRV1- L.g. LRV1-driven miR-155 expression was dependent on TLR-3/TRIF signaling. Furthermore, LRV1-induced TLR-3 activation promoted parasite persistence by enhancing macrophage survival through Akt activation in a manner partially dependent on miR-155. Pharmacological inhibition of Akt resulted in a decrease in LRV1-mediated macrophage survival and consequently decreased parasite persistence. Consistent with these data, miR-155-deficient mice showed a drastic decrease in LRV1-induced disease severity, and lesional macrophages from these mice displayed reduced levels of Akt phosphorylation

Bringing Together Viewpoints of Mothers and Health Workers to Enhance Monitoring and Promotion of Growth and Development of Children: A Case Study from the Republic of Congo

In 1996, the Government of the Republic of Congo launched a pilot project to improve the child growth and development component of primary healthcare. The present study was carried out (i) to explore perceptions and practices of mothers and health workers regarding child growth, health, and development, and (ii) to design culturally-appropriate tools to enhance their monitoring and promotion. The study was carried out in two randomly-selected health centres in Brazzaville. Qualitative data collected included 16 focus-group discussions with 174 mothers, two focus-group discussions with 18 health workers, and 20 individual interviews with paediatricians or psychologists. The health workers reported that the main indicator of child growth was weight, while the mothers used broader concepts for evaluating growth and development of their toddlers. A strategy encompassing anthropometrics, developmental milestones, and acquisition of social skills was elaborated to enhance communication between health workers and mothers. A new growth chart was designed, and a new calendar of systematic visits, including key tasks and messages, was established. However, these new tools derived from the formative research still need to be carefully tested

Exacerbated Leishmaniasis Caused by a Viral Endosymbiont can be Prevented by Immunization with Its Viral Capsid.

Recent studies have shown that a cytoplasmic virus called Leishmaniavirus (LRV) is present in some Leishmania species and acts as a potent innate immunogen, aggravating lesional inflammation and development in mice. In humans, the presence of LRV in Leishmania guyanensis and in L. braziliensis was significantly correlated with poor treatment response and symptomatic relapse. So far, no clinical effort has used LRV for prophylactic purposes. In this context, we designed an original vaccine strategy that targeted LRV nested in Leishmania parasites to prevent virus-related complications. To this end, C57BL/6 mice were immunized with a recombinant LRV1 Leishmania guyanensis viral capsid polypeptide formulated with a T helper 1-polarizing adjuvant. LRV1-vaccinated mice had significant reduction in lesion size and parasite load when subsequently challenged with LRV1+ Leishmania guyanensis parasites. The protection conferred by this immunization could be reproduced in naïve mice via T-cell transfer from vaccinated mice but not by serum transfer. The induction of LRV1 specific T cells secreting IFN-γ was confirmed in vaccinated mice and provided strong evidence that LRV1-specific protection arose via a cell mediated immune response against the LRV1 capsid. Our studies suggest that immunization with LRV1 capsid could be of a preventive benefit in mitigating the elevated pathology associated with LRV1 bearing Leishmania infections and possibly avoiding symptomatic relapses after an initial treatment. This novel anti-endosymbiotic vaccine strategy could be exploited to control other infectious diseases, as similar viral infections are largely prevalent across pathogenic pathogens and could consequently open new vaccine opportunities

Biological Status and Dietary Intakes of Iron, Zinc and Vitamin A among Women and Preschool Children in Rural Burkina Faso

Abstract Backgroun

Assessment of Loiasis and Outcomes of Ivermectin Masstreatment in Ijebu-North, Nigeria

A total of 286 individuals from 3 selected communities (Areedi-Aje, Ipakodo/Ojokodo, and Ijebu-Igbo) of Ijebu-North, southwestern Nigeria were examined for Loa loa microfilaremia using finger prick blood smear, between December 2008 and March 2009. Rapid assessment procedure for loiasis (RAPLOA) was used to obtain information, from 187 Ijebu-Igbo residents, on adverse reactions experienced from retrospective treatments with ivermectin and history of eye worm. Only 33.9% of the respondents reported having had a history of eye worm while 33.2% had microfilaremia. The demographic factor of gender was not significant determinants of the prevalence (P>0.05) while age was significant (P<0.05). The highest prevalence of eye worm history and microfilaremia were recorded in 61-70 and 15-20 years of age categories, respectively. Ijebu-Igbo had 27.3% eye worm history, 32.1% microfilaremia, and the highest intensity of 140 microfilariae (mf)/ml. Ipakodo area had the highest eye worm history of 54.4% and the highest intensity of 420 mf/ml. Areedi-Aje had the highest occurrence of 45.2% microfilaremia and the highest intensity of 460 mf/ml. Predictably, Areedi-Aje and Ipakodo areas were high risk communities. The low intensity of L. loa infection with an insignificant (2.1%; P>0.05) adverse reactions from 187 subjects involved in the retrospective ivermectin administration confirmed that ivermectin delivery may be considered safe. The community-directed treatment with ivermectin (CDTI) programme was most probably responsible for the low prevalence and intensity

PLoS Med

Background In 2014, the government of Togo implemented a pilot unconditional cash transfer (UCT) program in rural villages that aimed at improving children’s nutrition, health, and protection. It combined monthly UCTs (approximately US$8.40 /month) with a package of community activities (including behavior change communication [BCC] sessions, home visits, and integrated community case management of childhood illnesses and acute malnutrition [ICCM-Nut]) delivered to mother–child pairs during the first “1,000 days” of life. We primarily investigated program impact at population level on children’s height-for-age z-scores (HAZs) and secondarily on stunting (HAZ < −2) and intermediary outcomes including household’s food insecurity, mother–child pairs’ diet and health, delivery in a health facility and low birth weight (LBW), women’s knowledge, and physical intimate partner violence (IPV). Methods and findings We implemented a parallel-cluster–randomized controlled trial, in which 162 villages were randomized into either an intervention arm (UCTs + package of community activities, n = 82) or a control arm (package of community activities only, n = 80). Two different representative samples of children aged 6–29 months and their mothers were surveyed in each arm, one before the intervention in 2014 (control: n = 1,301, intervention: n = 1,357), the other 2 years afterwards in 2016 (control: n = 996, intervention: n = 1,035). Difference-in-differences (DD) estimates of impact were calculated, adjusting for clustering. Children’s average age was 17.4 (± 0.24 SE) months in the control arm and 17.6 (± 0.19 SE) months in the intervention arm at baseline. UCTs had a protective effect on HAZ (DD = +0.25 z-scores, 95% confidence interval [CI]: 0.01–0.50, p = 0.039), which deteriorated in the control arm while remaining stable in the intervention arm, but had no impact on stunting (DD = −6.2 percentage points [pp], relative odds ratio [ROR]: 0.74, 95% CI: 0.51–1.06, p = 0.097). UCTs positively impacted both mothers’ and children’s (18–23 months) consumption of animal source foods (ASFs) (respectively, DD = +4.5 pp, ROR: 2.24, 95% CI: 1.09–4.61, p = 0.029 and DD = +9.1 pp, ROR: 2.65, 95% CI: 1.01–6.98, p = 0.048) and household food insecurity (DD = −10.7 pp, ROR: 0.63, 95% CI: 0.43–0.91, p = 0.016). UCTs did not impact on reported child morbidity 2 week’s prior to report (DD = −3.5 pp, ROR: 0.80, 95% CI: 0.56–1.14, p = 0.214) but reduced the financial barrier to seeking healthcare for sick children (DD = −26.4 pp, ROR: 0.23, 95% CI: 0.08–0.66, p = 0.006). Women who received cash had higher odds of delivering in a health facility (DD = +10.6 pp, ROR: 1.53, 95% CI: 1.10–2.13, p = 0.012) and lower odds of giving birth to babies with birth weights (BWs) <2,500 g (DD = −11.8, ROR: 0.29, 95% CI: 0.10–0.82, p = 0.020). Positive effects were also found on women’s knowledge (DD = +14.8, ROR: 1.86, 95% CI: 1.32–2.62, p < 0.001) and physical IPV (DD = −7.9 pp, ROR: 0.60, 95% CI: 0.36–0.99, p = 0.048). Study limitations included the short evaluation period (24 months) and the low coverage of UCTs, which might have reduced the program’s impact. Conclusions UCTs targeting the first “1,000 days” had a protective effect on child’s linear growth in rural areas of Togo. Their simultaneous positive effects on various immediate, underlying, and basic causes of malnutrition certainly contributed to this ultimate impact. The positive impacts observed on pregnancy- and birth-related outcomes call for further attention to the conception period in nutrition-sensitive programs

Exacerbated leishmaniasis caused by a viral endosymbiont can be prevented by immunization with Its viral capsid

Recent studies have shown that a cytoplasmic virus called Leishmaniavirus (LRV) is present in some Leishmania species and acts as a potent innate immunogen, aggravating lesional inflammation and development in mice. In humans, the presence of LRV in Leishmania guyanensis and in L. braziliensis was significantly correlated with poor treatment response and symptomatic relapse. So far, no clinical effort has used LRV for prophylactic purposes. In this context, we designed an original vaccine strategy that targeted LRV nested in Leishmania parasites to prevent virus-related complications. To this end, C57BL/6 mice were immunized with a recombinant LRV1 Leishmania guyanensis viral capsid polypeptide formulated with a T helper 1-polarizing adjuvant. LRV1-vaccinated mice had significant reduction in lesion size and parasite load when subsequently challenged with LRV1+ Leishmania guyanensis parasites. The protection conferred by this immunization could be reproduced in naïve mice via T-cell transfer from vaccinated mice but not by serum transfer. The induction of LRV1 specific T cells secreting IFN-γ was confirmed in vaccinated mice and provided strong evidence that LRV1-specific protection arose via a cell mediated immune response against the LRV1 capsid. Our studies suggest that immunization with LRV1 capsid could be of a preventive benefit in mitigating the elevated pathology associated with LRV1 bearing Leishmania infections and possibly avoiding symptomatic relapses after an initial treatment. This novel anti-endosymbiotic vaccine strategy could be exploited to control other infectious diseases, as similar viral infections are largely prevalent across pathogenic pathogens and could consequently open new vaccine opportunities

Poly(ethylmethacrylate-co-diethylaminoethyl acrylate) coating improves endothelial re-population, bio-mechanical and anti-thrombogenic properties of decellularized carotid arteries for blood vessel replacement

Decellularized vascular scaffolds are promising materials for vessel replacements. However, despite the natural origin of decellularized vessels, issues such as biomechanical incompatibility, immunogenicity risks and the hazards of thrombus formation, still need to be addressed. In this study, we coated decellularized vessels obtained from porcine carotid arteries with poly (ethylmethacrylate-co-diethylaminoethylacrylate) (8g7) with the purpose of improving endothelial coverage and minimizing platelet attachment while enhancing the mechanical properties of the decellularized vascular scaffolds. The polymer facilitated binding of endothelial cells (ECs) with high affinity and also induced endothelial cell capillary tube formation. In addition, platelets showed reduced adhesion on the polymer under flow conditions. Moreover, the coating of the decellularized arteries improved biomechanical properties by increasing its tensile strength and load. In addition, after 5 days in culture, ECs seeded on the luminal surface of 8g7-coated decellularized arteries showed good regeneration of the endothelium. Overall, this study shows that polymer coating of decellularized vessels provides a new strategy to improve re-endothelialization of vascular grafts, maintaining or enhancing mechanical properties while reducing the risk of thrombogenesis. These results could have potential applications in improving tissue-engineered vascular grafts for cardiovascular therapies with small caliber vessels