Cytokines and Their STATs in Cutaneous and Visceral Leishmaniasis

Cytokines play a critical role in shaping the host immune response to Leishmania infection and directing the development of protective and non-protective immunities during infection. Cytokines exert their biological activities through the activation and translocation of transcription factors into the nucleus whether they drive the expression of specific cytokine-responsive genes. Signal transducer and activator of transcription (STATs) are transcription factors which play a critical role in mediating signaling downstream of cytokine receptors and are important for shaping the host immune response during Leishmania infection. Here we discuss the signature cytokines and their associated STATs involved in the host immune response during cutaneous and visceral leishmaniasis

Intervention methods to control the transmission of noroviruses and other enteric and respiratory viruses

Intervention methods to control the transmission of noroviruses and other enteric and respiratory viruses Era Tuladhar Abstract Human noroviruses are the leading cause of acute and outbreak associated gastroenteritis worldwide. The outbreaks occur often in hospitals, nursing homes, health care centers as well as in individual homes. Due to the high number of outbreaks and frequency of infection, the burden of disease is high. The virus transmission takes place from person to person directly through the fecal oral route or indirectly through contaminated surfaces or consumption of contaminated food. This study aimed to investigate methods to reduce the burden of disease caused by norovirus and focuses on reducing the transmission through hands and contaminated surfaces. Besides human norovirus, other enteric and respiratory viruses are also transmitted through these routes and were included in the study. Enteric viruses included in the study were human norovirus GI.4 and GII.4, poliovirus Sabin1, rotavirus SA11, parechovirus 1 and murine norovirus 1 (MNV1). The respiratory viruses were adenovirus type 5 and influenza A (H1N1) virus. These viruses can contaminate food through food handler-related contamination. Heating and pasteurizing is a commonly used method for inactivation of microorganisms in food. Heating at commonly used temperatures of 56°C and 73°C showed that thermo-stability of parechovirus and influenza virus was found to be similar to that of proven foodborne viruses and heating at 73°C for 3 min is sufficient to reduce the infectivity of the tested viruses > 4 log10. Not only food, contaminated hands can also transfer viruses to different surfaces, which are then sources of further transmission of the viruses. Cleaning and disinfection of contaminated surfaces are common intervention methods used in health care and kitchen facilities. The enteric and respiratory viruses showed varying susceptibility to cleaning and disinfection procedures applied. Data on infectious doses and transfer efficiencies was used to estimate a target level to which the residual contamination should be reduced and it was found that a single wipe with liquid soap followed by a wipe with 250 ppm free chlorine solution was sufficient to reduce the residual contamination to below the target level for most of the pathogens tested. Spot disinfection by 1000 ppm chlorine solution after wiping with liquid soap was sufficient to reduce the genomic copies of human norovirus GI.4 and GII.4 (> 5 log10 PCRU) completely within 10 min. In addition to manual cleaning and disinfection, non-touch disinfection of contaminated surfaces by vaporized hydrogen peroxide disinfection at 127 ppm for 1 h, as approved disinfection in the Netherlands for hospitals and health care centers, is effective against poliovirus Sabin 1, rotavirus SA11, adenovirus type 5 and MNV1 on stainless steel, framing panel (> 4 log10 infectivity reduction) and gauze (> 2 log10 infectivity reduction). Beside non-touch disinfection, immobilized biocidals have been tested for disinfection of contaminated surfaces. Immobilized quaternary ammonium compound coatings were virucidal against the influenza virus within 2 min but no virucidal effect against poliovirus was found in 6 h. Thus the coating can be used against the influenza A virus to prevent the transmission through frequently touched sites but not for non-enveloped viruses. Our study demonstrated that a norovirus contaminated hand can transfer the viruses to different surfaces, including food, even after the virus is dried. As an intervention method to prevent the transmission of the virus, washing hands with soap and water (> 5 log10 PCRU reduction) is better than using alcohol based hand disinfectants in removing noroviruses from hands. This research has delivered new insights in methods to reduce transmission of human norovirus and produced comparative quantitative data on intervention methods to control transmission of other enteric and respiratory viruses. The study has additionally contributed to a better understanding of human norovirus transmission intervention efficiency. The new insights allow for the development of science based guidelines to control norovirus and other enteric and respiratory viruses in outbreak settings and thus help to reduce the burden of illness caused by these viruses.</p

Do ultrafast exciton-polaron decoherence dynamics govern photocarrier generation efficiencies in polymer solar cells?

All-organic-based photovoltaic solar cells have attracted considerable attention because of their low-cost processing and short energy payback time. In such systems the primary dissociation of an optical excitation into a pair of photocarriers has been recently shown to be extremely rapid and efficient, but the physical reason for this remains unclear. Here, two-dimensional photocurrent excitation spectroscopy, a novel non-linear optical spectroscopy, is used to probe the ultrafast coherent decay of photoexcitations into charge-producing states in a polymer:fullerene based solar cell. The two-dimensional photocurrent spectra are interpreted by introducing a theoretical model for the description of the coupling of the electronic states of the system to an external environment and to the applied laser fields. The experimental data show no cross-peaks in the two-dimensional photocurrent spectra, as predicted by the model for coherence times between the exciton and the photocurrent producing states of 20\,fs or less

Different virucidal activities of hyperbranched quaternary ammonium coatings on poliovirus and influenza virus

Virucidal activity of immobilized quaternary ammonium compounds (IQACs) coated onto glass and plastic surfaces was tested against enveloped influenza A (H1N1) virus and nonenveloped poliovirus Sabin1. The IQACs tested were virucidal against the influenza virus within 2 min, but no virucidal effect against poliovirus was found in 6 h

Residual viral and bacterial contamination of surfaces after cleaning and disinfection

Environmental surfaces contaminated with pathogens can be sources of indirect transmission, and cleaning and disinfection are common interventions focused on reducing contamination levels. We determined the efficacy of cleaning and disinfection procedures for reducing contamination by noroviruses, rotavirus, poliovirus, parechovirus, adenovirus, influenza virus, Staphylococcus aureus, and Salmonella enterica from artificially contaminated stainless steel surfaces. After a single wipe with water, liquid soap, or 250-ppm free chlorine solution, the numbers of infective viruses and bacteria were reduced by 1 log10 for poliovirus and close to 4 log10 for influenza virus. There was no significant difference in residual contamination levels after wiping with water, liquid soap, or 250-ppm chlorine solution. When a single wipe with liquid soap was followed by a second wipe using 250- or 1,000-ppm chlorine, an extra 1- to 3-log10 reduction was achieved, and except for rotavirus and norovirus genogroup I, no significant additional effect of 1,000 ppm compared to 250 ppm was found. A reduced correlation between reduction in PCR units (PCRU) and reduction in infectious particles suggests that at least part of the reduction achieved in the second step is due to inactivation instead of removal alone. We used data on infectious doses and transfer efficiencies to estimate a target level to which the residual contamination should be reduced and found that a single wipe with liquid soap followed by a wipe with 250-ppm free chlorine solution was sufficient to reduce the residual contamination to below the target level for most of the pathogens tested

Relation between physical activity and cerebral small vessel disease: A nine-year prospective cohort study.

BACKGROUND AND AIMS: Given the unexplored potential of physical activity to reduce the progression of cerebral small vessel disease (cSVD, the purpose of this study was to prospectively (across nine-year follow-up) examine the relation between (baseline) physical activity and the (clinical and imaging) consequences of the whole spectrum of cerebral small vessel disease. METHODS: Five hundred and three patients with cerebral small vessel disease from the RUNDMC study were followed for nine years. Physical activity was assessed using a questionnaire in 2006, 2011, and 2015. Clinical events (i.e. all-cause mortality, cerebrovascular events (by stroke subtype)) were collected with a structured questionnaire. Patients underwent magnetic resonance imaging scanning for the assessment of magnetic resonance imaging markers of cerebral small vessel disease (i.e. white matter hyperintensities, lacunes, and microbleeds) and microstructural integrity of the white matter at three timepoints. RESULTS: The mean age at baseline was 66 (SD 9.0) years; 44% were women. A higher baseline physical activity level was independently associated with a lower all-cause mortality (HR: 0.69, 95%CI: 0.49-0.98, p = 0.03) and incidence of cerebrovascular disease (HR: 0.58, 95%CI: 0.36-0.96, p = 0.03). However, we found no relation between physical activity and incident lacunar stroke or progression of magnetic resonance imaging markers of cerebral small vessel disease. CONCLUSIONS: Whilst regular physical activity was not related to the progression of magnetic resonance imaging markers of cerebral small vessel disease across a nine-year follow-up, results from our study prove that high levels of physical activity in patients with cerebral small vessel disease are associated with a lower all-cause mortality and lower incidence of cerebrovascular events

SCIMP is a spatiotemporal transmembrane scaffold for Erk1/2 to direct pro-inflammatory signaling in TLR-activated macrophages

Immune cells are armed with Toll-like receptors (TLRs) for sensing and responding to pathogens and other danger cues. The role of extracellular-signal-regulated kinases 1/2 (Erk1/2) in TLR signaling remains enigmatic, with both pro- and anti-inflammatory functions described. We reveal here that the immune-specific transmembrane adaptor SCIMP is a direct scaffold for Erk1/2 in TLR pathways, with high-resolution, live-cell imaging revealing that SCIMP guides the spatial and temporal recruitment of Erk2 to membrane ruffles and macropinosomes for pro-inflammatory TLR4 signaling. SCIMP-deficient mice display defects in Erk1/2 recruitment to TLR4, c-Fos activation, and pro-inflammatory cytokine production, with these effects being phenocopied by Erk1/2 signaling inhibition. Our findings thus delineate a selective role for SCIMP as a key scaffold for the membrane recruitment of Erk1/2 kinase to initiate TLR-mediated pro-inflammatory responses in macrophages