Heparin prevents Zika virus induced-cytopathic effects in human neural progenitor cells

The recent Zika virus (ZIKV) outbreak, which mainly affected Brazil and neighbouring states, demonstrated the paucity of information concerning the epidemiology of several flaviruses, but also highlighted the lack of available agents with which to treat such emerging diseases. Here, we show that heparin, a widely used anticoagulant, while exerting a modest inhibitory effect on Zika Virus replication, fully prevents virus-induced cell death of human neural progenitor cells (NPCs)

Crude Heparin Preparations Unveil the Presence of Structurally Diverse Oversulfated Contaminants

Nowadays, pharmaceutical heparin is purified from porcine and bovine intestinal mucosa. In the past decade there has been an ongoing concern about the safety of heparin, since in 2008, adverse effects associated with the presence of an oversulfated chondroitin sulfate (OSCS) were observed in preparations of pharmaceutical porcine heparin, which led to the death of patients, causing a global public health crisis. However, it has not been clarified whether OSCS has been added to the purified heparin preparation, or whether it has already been introduced during the production of the raw heparin. Using a combination of different analytical methods, we investigate both crude and final heparin products and we are able to demonstrate that the sulfated contaminants are intentionally introduced in the initial steps of heparin preparation. Furthermore, the results show that the oversulfated compounds are not structurally homogeneous. In addition, we show that these contaminants are able to bind to cells in using well known heparin binding sites. Together, the data highlights the importance of heparin quality control even at the initial stages of its production

Nitrogen-limited mangrove ecosystems conserve N through dissimilatory nitrate reduction to ammonium

Earlier observations in mangrove sediments of Goa, India have shown denitrification to be a major pathway for N loss1. However, percentage of total nitrate transformed through complete denitrification accounted for <0–72% of the pore water nitrate reduced. Here, we show that up to 99% of nitrate removal in mangrove sediments is routed through dissimilatory nitrate reduction to ammonium (DNRA). The DNRA process was 2x higher at the relatively pristine site Tuvem compared to the anthropogenically-influenced Divar mangrove ecosystem. In systems receiving low extraneous nutrient inputs, this mechanism effectively conserves and re-circulates N minimizing nutrient loss that would otherwise occur through denitrification. In a global context, the occurrence of DNRA in mangroves has important implications for maintaining N levels and sustaining ecosystem productivity. For the first time, this study also highlights the significance of DNRA in buffering the climate by modulating the production of the greenhouse gas nitrous oxide

Neuroprogenitor Cells From Patients With TBCK Encephalopathy Suggest Deregulation of Early Secretory Vesicle Transport

Biallelic pathogenic variants in TBCK cause encephaloneuropathy, infantile hypotonia with psychomotor retardation, and characteristic facies 3 (IHPRF3). The molecular mechanisms underlying its neuronal phenotype are largely unexplored. In this study, we reported two sisters, who harbored biallelic variants in TBCK and met diagnostic criteria for IHPRF3. We provided evidence that TBCK may play an important role in the early secretory pathway in neuroprogenitor cells (iNPC) differentiated from induced pluripotent stem cells (iPSC). Lack of functional TBCK protein in iNPC is associated with impaired endoplasmic reticulum-to-Golgi vesicle transport and autophagosome biogenesis, as well as altered cell cycle progression and severe impairment in the capacity of migration. Alteration in these processes, which are crucial for neurogenesis, neuronal migration, and cytoarchitecture organization, may represent an important causative mechanism of both neurodevelopmental and neurodegenerative phenotypes observed in IHPRF3. Whether reduced mechanistic target of rapamycin (mTOR) signaling is secondary to impaired TBCK function over other secretory transport regulators still needs further investigation.</jats:p

Evaluating the health and economic impact of osteoarthritis pain in the workforce: results from the National Health and Wellness Survey

<p>Abstract</p> <p>Background</p> <p>There has been increasing recognition that osteoarthritis (OA) affects younger individuals who are still participants in the workforce, but there are only limited data on the contribution of OA pain to work productivity and other outcomes in an employed population. This study evaluated the impact of OA pain on healthcare resource utilization, productivity and costs in employed individuals.</p> <p>Methods</p> <p>Data were derived from the 2009 National Health and Wellness Survey. Univariable and multivariable analyses were used to characterize employed individuals (full-time, part-time, or self-employed) ≥20 years of age who were diagnosed with OA and had arthritis pain in the past month relative to employed individuals not diagnosed with OA or not experiencing arthritis pain in the past month. Work productivity was assessed using the Work Productivity and Activity Impairment (WPAI) questionnaire; health status was assessed using the physical (PCS) and mental component summary (MCS) scores from the SF-12v2 Health Survey and SF-6D health utilities; and healthcare utilization was evaluated by type and number of resources within the past 6 months. Direct and indirect costs were estimated and compared between the two cohorts.</p> <p>Results</p> <p>Individuals with OA pain were less likely to be employed. Relative to workers without OA pain (n = 37,599), the OA pain cohort (n = 2,173) was significantly older (mean age 52.1 ± 11.5 years vs 41.4 ± 13.2 years; <it>P </it>< 0.0001) and with a greater proportion of females (58.2% vs 45.9%; <it>P </it>< 0.0001). OA pain resulted in greater work impairment than among workers without OA pain (34.4% versus 17.8%; <it>P </it>< 0.0001), and was primarily due to presenteeism (impaired activity while at work). Health status, assessed both by the SF-12v2 and the SF-6D was significantly poorer among workers with OA pain (<it>P </it>< 0.0001), and healthcare resource utilization was significantly higher (<it>P </it>< 0.0001) than workers without OA pain. Total costs were higher in the OA pain cohort ($15,047 versus$8,175; <it>P </it>< 0.0001), driven by indirect costs that accounted for approximately 75% of total costs.</p> <p>Conclusions</p> <p>A substantial proportion of workers suffer from OA pain. After controlling for confounders, the impact of OA pain was significant, resulting in lower productivity and higher costs.</p

Duffy blood group gene polymorphisms among malaria vivax patients in four areas of the Brazilian Amazon region

<p>Abstract</p> <p>Background</p> <p>Duffy blood group polymorphisms are important in areas where <it>Plasmodium vivax </it>predominates, because this molecule acts as a receptor for this protozoan. In the present study, Duffy blood group genotyping in <it>P. vivax </it>malaria patients from four different Brazilian endemic areas is reported, exploring significant associations between blood group variants and susceptibility or resistance to malaria.</p> <p>Methods</p> <p>The <it>P. vivax </it>identification was determined by non-genotypic and genotypic screening tests. The Duffy blood group was genotyped by PCR/RFLP in 330 blood donors and 312 malaria patients from four Brazilian Amazon areas. In order to assess the variables significance and to obtain independence among the proportions, the Fisher's exact test was used.</p> <p>Results</p> <p>The data show a high frequency of the <it>FYA/FYB </it>genotype, followed by <it>FYB/FYB, FYA/FYA</it>, <it>FYA/FYB-33 </it>and <it>FYB/FYB-33</it>. Low frequencies were detected for the <it>FYA/FY</it>^<it>X</it>, <it>FYB/FY</it>^<it>X</it>, <it>FYX/FY</it>^{<it>X </it>}and <it>FYB-33/FYB-33 </it>genotypes. Negative Duffy genotype (<it>FYB-33/FYB-33</it>) was found in both groups: individuals infected and non-infected (blood donors). No individual carried the <it>FY</it>^<it>X</it><it>/FYB-33 </it>genotype. Some of the Duffy genotypes frequencies showed significant differences between donors and malaria patients.</p> <p>Conclusion</p> <p>The obtained data suggest that individuals with the <it>FYA/FYB </it>genotype have higher susceptibility to malaria. The presence of the <it>FYB-33 </it>allele may be a selective advantage in the population, reducing the rate of infection by <it>P. vivax </it>in this region. Additional efforts may contribute to better elucidate the physiopathologic differences in this parasite/host relationship in regions endemic for <it>P. vivax </it>malaria, in particular the Brazilian Amazon region.</p