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Zika virus is a mosquito-borne virus that is associated with neurodegenerative diseases, including Guillain–Barré syndrome1 and congenital Zika syndrome2. As Zika virus targets the nervous system, there is an urgent need to develop therapeutic strategies that inhibit Zika virus infection in the brain. Here, we have engineered a brain-penetrating peptide that works against Zika virus and other mosquito-borne viruses. We evaluated the therapeutic efficacy of the peptide in a lethal Zika virus mouse model exhibiting systemic and brain infection. Therapeutic treatment protected against mortality and markedly reduced clinical symptoms, viral loads and neuroinflammation, as well as mitigated microgliosis, neurodegeneration and brain damage. In addition to controlling systemic infection, the peptide crossed the blood–brain barrier to reduce viral loads in the brain and protected against Zika-virus-induced blood–brain barrier injury. Our findings demonstrate how engineering strategies can be applied to develop peptide therapeutics and support the potential of a brain-penetrating peptide to treat neurotropic viral infections.

Fibrous particles interact with cells and organisms in complex ways that can lead to cellular dysfunction, cell death, inflammation, and disease. The development of conductive transparent networks (CTNs) composed of metallic silver nanowires (AgNWs) for flexible touchscreen displays raises new possibilities for the intimate contact between novel fibers and human skin. Here, we report that a material property, nanowire-bending stiffness that is a function of diameter, controls the cytotoxicity of AgNWs to nonimmune cells from humans, mice, and fish without deterioration of critical CTN performance parameters: electrical conductivity and optical transparency. Both 30- and 90-nm-diameter AgNWs are readily internalized by cells, but thinner NWs are mechanically crumpled by the forces imposed during or after endocytosis, while thicker nano-wires puncture the enclosing membrane and release silver ions and lysosomal contents to the cytoplasm, thereby initiating oxidative stress. This finding extends the fiber pathology paradigm and will enable the manufacture of safer products incorporating AgNWs.

TiO2 nanoparticles (TiO2-NPs) have a wide range of industrial applications (paintings, sunscreens, food and cosmetics) and is one of the most intensively used nanomaterials worldwide. Leaching from commercial products TiO2-NPs are predicted to significantly accumulate in wastewater sludges, which are then often used as soil amendment. In this work, sludge samples from four wastewater treatment plants of the Chihuahua State in Mexico were obtained during spring and summer (2017). A comprehensive characterization study was performed by X-ray based (laboratory and synchrotron) techniques and electron microscopy. Ti was detected in all sludge samples (1810–2760 mg/kg) mainly as TiO2 particles ranging from 40 nm up to hundreds of nm. Micro-XANES data was analyzed by principal component analysis and linear combination fitting enabling the identification of three predominant Ti species: anatase, rutile and ilmenite. Micro-XANES from the smaller Ti particles was predominantly anatase (68% + 32% rutile), suggesting these TiO2-NPs originate from paintings and cosmetics. TEM imaging confirmed the presence of nanoscale Ti with smooth surface morphologies resembling engineered TiO2-NPs. The size and crystalline phase of TiO2-NPs in the sludge from this region suggest increased reactivity and potential toxicity to agro-systems. Further studies should be dedicated to evaluating this.

ObjectiveWe aim to determine the disposal site for biohazardous materials resulting from diabetes surveillance and therapy.DesignCross-sectional study.SettingFive Portuguese primary care facilities.ParticipantsWe randomly sampled diabetic patients representative of five primary care facilities. Inclusion criteria consisted in patients≥18 years old with an active diagnosis of diabetes mellitus (DM). Patients unable to provide written informed consent were excluded.Outcome measureSociodemographic variables, diabetes duration, type of treatment, medical sharps disposal practices and whether adequate disposal information were provided.ResultsA total of 1436 diabetics were included. Overall, 53.8% of diabetics conducted regular capillary glicemia measurements, although 45.3% of them had no medical indication. Statistically significant predictors of adequate disposal were not having an active professional status (p=0.011) and having a DM duration between 5 and 10 years (p=0.014). Only being professionally inactive remained an independent predictor after multivariate logistic regression. Less than a fifth of patients on injectable therapy report having been advised by healthcare staff regarding sharps disposal. Over a fifth of the latter report having received wrong advice. The majority of diabetics dispose of biohazardous materials in unsorted household waste (68.1% of needles/devices with needles and 71.6% of lancets). Other incorrect disposal sites identified were recycling bins, toilet and home accumulation. Only 19.1% of the needles/devices with needles and 13.1% of the lancets were disposed of at healthcare facilities.ConclusionsMost diabetics have unsafe disposal practices for their biohazardous materials, mostly in unsorted household waste. We identified that being unemployed independently predicts adequate disposal of medical sharps and found evidence of low patient literacy on the topic, as well as poor patient education. Therefore, educating and raising awareness among healthcare professionals is crucial to address this public health issue.

Dimethyl fumarate (DMF) has shown efficacy in reducing relapse rates in patients with multiple sclerosis (MS). However, associated adverse effects (AE) such as gastrointestinal (GI) AE, flushing and lymphopenia are the main cause of treatment discontinuation. The aim of this study was to evaluate the effectiveness of DMF, and to assess strategies to reduce treatment discontinuation rates in routine clinical practice. Ninety patients started DMF treatment between August 2015 and February 2020. Prior to DMF therapy, patients received written information regarding treatment and the management of AE, along with medical prescriptions. Clinical and analytical data were collected at clinical visits performed at least 6-monthly, and disease progression was evaluated by brain magnetic resonance imaging (MRI). Prior to DMF, 78.7% of patients had an annualized relapse rate (ARR) of 1.07 (range: 1-3) and median Expanded Disability Status Scale (EDSS) score of 1.0 (range: 0-2). At final follow-up, ARR and median EDSS scores were significantly reduced to 0.09 (range: 0-2; p< 0.001) and 0 (range: 0-1.625; p< 0.001), respectively. Just over one quarter of patients with brain MRI (26.8% of 71 patients) showed improvement in disease activity based on MRI evaluation. Lymphopenia was associated with previous treatment lines (p=0.042) and longer disease duration (p=0.032). A total of twelve patients abandoned DMF treatment, mainly due to lymphopenia (7.9%), but none did it because of GI AE or flushing. In our series, DMF showed high clinical and radiological efficacy. Providing patients with complete information prior to treatment on the management of associated AE helps them to better understand what to expect, improves tolerance and reduces clinical and telephone consultations, which may help to reduce the use and cost of healthcare resources.

In recent years, higher education has felt pressured to prepare its graduates for the highly competitive international market due to globalization. Thus, many institutions have turned to position themselves well in university rankings as a way to attract the best academic and student talent from all over the world. Our work presents a predictive model for measuring university performance in the QS world university rankings (QS-WUR). We used a ten-year dataset to build models with statistical and machine learning algorithms contained in the library Caret of the RStudio software tool, to forecast global university position in QS-WUR. With these tools, we designed a methodology to predict the university partners' Final Scores based on their historical performance, achieving errors in the range of one or two points out of 100. The modelling may be a useful aid for university officers to develop strategies for improving institutional processes to attract the best students, faculty, and funding, enhance international collaboration and outlook, and foster international university prestige.

Background Culex pipiens L. is the most widespread mosquito vector in temperate regions. This species consists of two forms, denoted molestus and pipiens, that exhibit important behavioural and physiological differences. The evolutionary relationships and taxonomic status of these forms remain unclear. In northern European latitudes molestus and pipiens populations occupy different habitats (underground vs . aboveground), a separation that most likely promotes genetic isolation between forms. However, the same does not hold in southern Europe where both forms occur aboveground in sympatry. In these southern habitats, the extent of hybridisation and its impact on the extent of genetic divergence between forms under sympatric conditions has not been clarified. For this purpose, we have used phenotypic and genetic data to characterise Cx. pipiens collected aboveground in Portugal. Our aims were to determine levels of genetic differentiation and the degree of hybridisation between forms occurring in sympatry, and to relate these with both evolutionary and epidemiological tenets of this biological group. Results Autogeny and stenogamy was evaluated in the F1 progeny of 145 individual Cx. pipiens females. Bayesian clustering analysis based on the genotypes of 13 microsatellites revealed two distinct genetic clusters that were highly correlated with the alternative traits that define pipiens and molestus. Admixture analysis yielded hybrid rate estimates of 8-10%. Higher proportions of admixture were observed in pipiens individuals suggesting that more molestus genes are being introgressed into the pipiens form than the opposite. Conclusion Both physiological/behavioural and genetic data provide evidence for the sympatric occurrence of molestus and pipiens forms of Cx. pipiens in the study area. In spite of the significant genetic differentiation between forms, hybridisation occurs at considerable levels. The observed pattern of asymmetric introgression probably relates to the different mating strategies adopted by each form. Furthermore, the differential introgression of molestus genes into the pipiens form may induce a more opportunistic biting behaviour in the latter thus potentiating its capacity to act as a bridge-vector for the transmission of arboviral infections.

Biosolids (Bs) for use in agriculture are an important way for introducing and transferring TiO2 nanoparticles (NPs) to plants and food chain. Roots of Pisum sativum L. plants grown in Bs-amended soils spiked with TiO2 800 mg/kg as rutile NPs, anatase NPs, mixture of both NPs and submicron particles (SMPs) were investigated by Transmission Electron Microscopy (TEM), synchrotron radiation based micro X-ray Fluorescence and micro X-ray Absorption Near-Edge Structure (µXRF/µXANES) and Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES). TEM analysis showed damages in cells ultrastructure of all treated samples, although a more evident effect was observed with single anatase or rutile NPs treatments. Micro-XRF and TEM evidenced the presence of nano and SMPs mainly in the cortex cells near the rhizodermis. Micro-XRF/micro-XANES analysis revealed anatase, rutile, and ilmenite as the main TiO2 polymorphs in the original soil and Bs, and the preferential anatase uptake by the roots. For all treatments Ti concentration in the roots increased by 38–56%, however plants translocation factor (TF) increased mostly with NPs treatment (261–315%) and less with SMPs (about 85%), with respect to control. In addition, all samples showed a limited transfer of TiO2 to the shoots (very low TF value). These findings evidenced a potential toxicity of TiO2 NPs present in Bs and accumulating in soil, suggesting the necessity of appropriate regulations for the occurrence of NPs in Bs used in agriculture.

Zika virus (ZIKV) infection is a global health emergency that causes significant neurodegeneration. Neurodegenerative processes may be exacerbated by N -methyl- d -aspartate receptor (NMDAR)-dependent neuronal excitoxicity. Here, we have exploited the hypothesis that ZIKV-induced neurodegeneration can be rescued by blocking NMDA overstimulation with memantine. Our results show that ZIKV actively replicates in primary neurons and that virus replication is directly associated with massive neuronal cell death. Interestingly, treatment with memantine or other NMDAR blockers, including dizocilpine (MK-801), agmatine sulfate, or ifenprodil, prevents neuronal death without interfering with the ability of ZIKV to replicate in these cells. Moreover, in vivo experiments demonstrate that therapeutic memantine treatment prevents the increase of intraocular pressure (IOP) induced by infection and massively reduces neurodegeneration and microgliosis in the brain of infected mice. Our results indicate that the blockade of NMDARs by memantine provides potent neuroprotective effects against ZIKV-induced neuronal damage, suggesting it could be a viable treatment for patients at risk for ZIKV infection-induced neurodegeneration. IMPORTANCE Zika virus (ZIKV) infection is a global health emergency associated with serious neurological complications, including microcephaly and Guillain-Barré syndrome. Infection of experimental animals with ZIKV causes significant neuronal damage and microgliosis. Treatment with drugs that block NMDARs prevented neuronal damage both in vitro and in vivo . These results suggest that overactivation of NMDARs contributes significantly to the neuronal damage induced by ZIKV infection, and this is amenable to inhibition by drug treatment. Zika virus (ZIKV) infection is a global health emergency associated with serious neurological complications, including microcephaly and Guillain-Barré syndrome. Infection of experimental animals with ZIKV causes significant neuronal damage and microgliosis. Treatment with drugs that block NMDARs prevented neuronal damage both in vitro and in vivo . These results suggest that overactivation of NMDARs contributes significantly to the neuronal damage induced by ZIKV infection, and this is amenable to inhibition by drug treatment.

Zika virus (ZIKV) only induces mild symptoms in adults; however, it can cause congenital Zika syndrome (CZS), including microcephaly. Most of the knowledge on ZIKV pathogenesis was gained using immunocompromised mouse models, which do not fully recapitulate human pathology. Moreover, the study of the host immune response to ZIKV becomes challenging in these animals. Thus, the main goal of this study was to develop an immunocompetent mouse model to study the ZIKV spread and teratogeny. FVB/NJ immune competent dams were infected intravaginally with ZIKV during the early stage of pregnancy. We found that the placentae of most fetuses were positive for ZIKV, while the virus was detected in the brain of only about 42% of the embryos. To investigate the host immune response, we measured the expression of several inflammatory factors. Embryos from ZIKV-infected dams had an increased level of inflammatory factors, as compared to Mock. Next, we compared the gene expression levels in embryos from ZIKV-infected dams that were either negative or positive for ZIKV in the brain. The mRNA levels of viral response genes and cytokines were increased in both ZIKV-positive and negative brains. Interestingly, the levels of chemokines associated with microcephaly in humans, including CCL2 and CXCL10, specifically increased in embryos harboring ZIKV in the embryo brains.