AN INVESTIGATION OF THE PHASE BEHAVIOR OF AN AQUEOUS SYSTEM THAT CONTAINS A POLYAMPHOLYTE AND POLY(ETHYLENE GLYCOL)

The phase behavior of aqueous two-phase polymer system containing poly(ethylene glycol) and a synthetic polyampholyte in 0.1 N KCl was studied as a function of pH. The top phase was poly(ethylene glycol)-rich and the bottom phase was polyampholyte-rich. The binodal curve was found to move towards lower concentrations of polymers with increasing pH as a result of decreased solubility of the polyampholyte. Phase compositions were correlated using a model based on Flory- Huggins theory. Also, a model based on excluded volume theory was used to correlate the binodal curve

Epidemiological profile of the Ebola virus disease outbreak in Nigeria, July-September 2014

Introduction: In July 2014, Nigeria experienced an outbreak of Ebola virus disease following the introduction of the disease by an ill Liberian Traveler. The Government of Nigeria with the support of Technical and Development Partners responded quickly and effectively to contain the outbreak. The epidemiological profile of the outbreak that majorly affected two States in the country in terms of person, place and time characteristics of the cases identified is hereby described. Methods: Using field  investigation technique, all confirmed and probable cases were identified, line-listed and analysed using Microsoft Excel 2007 by persons, time and place. Results: A total of 20 confirmed and probable cases; 16 in Lagos (including the index case from Liberia) and 4 in Port Harcourt were  identified. The mean age was 39.5 ± 12.4 years with over 40% within the age group 30-39 years. The most frequent exposure type was direct physical contact in 70% of all cases and 73% among health care workers. The total case-fatality was 40%; higher among healthcare workers (46%) compared with non-healthcare workers (22%). The epidemic curve initially shows a typical common source outbreak, followed by a propagated pattern. Conclusion: Investigation revealed the size and spread of the outbreak and provided information on the characteristics of persons, time and place. Enhanced surveillance measures, including contact tracing and follow-up proved very useful in early case detection and containment of the outbreak

Modeling for understanding of coronavirus disease-2019 (COVID-19) spread and design of an isolation room in a hospital

We have modeled the transmission of coronavirus 2019 in the isolation room of a patient suffering from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the Royal Brompton Hospital in London. An adaptive mesh computational fluid dynamics model was used for simulation of three-dimensional spatial distribution of SARS-CoV-2 in the room. The modeling set-up is based on data collected in the room during the patient stay. Many numerical experiments have been carried out to provide an optimal design layout of the overall isolation room. Our focus has been on (1) the location of the air extractor and filtration rates, (2) the bed location of the patient, and (3) consideration of the health and safety of the staff working in the area

Ecthyma gangrenosum on the face of a malnourished child with Pseudomonas sepsis: Simulating Cancrum oris

Introduction: Ecthyma gangrenosum (EG) is a cutaneous lesion commonly caused by Pseudomonas aeruginosa that involves mainly the lower limbs and gluteal region, seen more in immunosuppressed patients with neutropenia. Cancrum oris (Noma) is a gangrenous necrosis of the face that begins as a gingival ulcer and progresses rapidly to destroy contiguous tissues in malnourished children. Case Presentation: This article reports a case of facial EG which was similar to Noma in a malnourished child: a 16-month old girl with fever, cough, weight loss, watery stool and swelling on right cheek. She was febrile, pale, wasted with bilateral pitting pedal oedema. She had a solitary circumscribed round necrotic lesion, with surrounding hyperaemia on the right malar area which extended to destroy the right ala nasi. No intra-oral rashes but she had left ear discharge. She received blood transfusion, antibiotics, antiseptic wound care and nutritional rehabilitation. Management and Outcome: Swabs of the lesion and ear discharge both revealed Gram-negative bacilli and culture yielded P. aeruginosa. Retroviral, Mantoux and Gene Xpert tests were negative. She had moderate anaemia, normal white blood cell count, and neutropaenia. Parenteral ceftriazone was changed to ciprofloxacin based on sensitivity results and lack of clinical response. The wound healed with residual scarring and partial destruction of right ala nasi. Discussion: Although this patient had facial necrosis to suggest Noma, she did not have initial oral involvement, and clinical features such as Pseudomonas sepsis and neutropaenia suggested EG. Facial necrosis in malnourished children may be due to EG

MFG-E8 Regulates the Immunogenic Potential of Dendritic Cells Primed with Necrotic Cell-Mediated Inflammatory Signals

Dendritic cells (DC) manipulate tissue homeostasis by recognizing dying cells and controlling immune functions. However, the precise mechanisms by which DC recognize different types of dying cells and devise distinct immunologic consequences remain largely obscure. Herein, we demonstrate that Milk-fat globule-EGF VIII (MFG-E8) is a critical mediator controlling DC immunogenicity in inflammatory microenvironments. MFG-E8 restrains DC-mediated uptake and recognition of necrotic cells. The MFG-E8-mediated suppression of necrotic cell uptake by DC resulted in the decreased proinflammatory cytokines production and activated signal components such as STAT3 and A20, which are critical to maintain tolerogenic properties of DC. Furthermore, the DC-derived MFG-E8 negatively regulates the cross-priming and effector functions of antigen-specific T cells upon recognition of necrotic cells. MFG-E8 deficiency enhances an ability of necrotic cell-primed DC to stimulate antitumor immune responses against established tumors. Our findings define what we believe to a novel mechanism whereby MFG-E8 regulates the immunogenicity of DC by modulating the modes of recognition of dying cells. Manipulating MFG-E8 levels in DC may serve as a useful strategy for controlling inflammatory microenvironments caused by various pathological conditions including cancer and autoimmunity

Human T-lymphotropic virus type 1 (HTLV-1) prevalence and quantitative detection of DNA proviral load in individuals with indeterminate/positive serological results

BACKGROUND: HTLV-1 infection is currently restricted to endemic areas. To define the prevalence of HTLV-1 infection in patients living in Italy, we first carried out a retrospective serological analysis in a group of people originating from African countries referred to our hospital from January 2003 to February 2005. We subsequently applied a real time PCR on peripheral blood mononuclear cells from subjects with positive or indeterminate serological results. METHODS: All the sera were first analysed by serological methods (ELISA and/or Western Blotting) and then the peripheral blood mononuclear cells from subjects with positive or inconclusive serological results were analyzed for the presence of proviral DNA by a sensitive SYBR Green real time PCR. In addition, twenty HTLV-I ELISA negative samples were assayed by real time PCR approach as negative controls. RESULTS: Serological results disclosed serum reactivity by ELISA (absorbance values equal or greater than the cut-off value) in 9 out of 3408 individuals attending the Sexually Transmitted Diseases Clinic and/or Oncology Department, and 2 out 534 blood donors enrolled as a control population. Irrespective of positive or inconclusive serological results, all these subjects were analyzed for the presence of proviral DNA in peripheral blood mononuclear cells by SYBR real time PCR. A clear-cut positive result for the presence of HTLV-1 DNA was obtained in two subjects from endemic areas. CONCLUSION: SYBR real time PCR cut short inconclusive serological results. This rapid and inexpensive assay showed an excellent linear dynamic range, specificity and reproducibility readily revealing and quantifying the presence of virus in PBMCs. Our results highlight the need to monitor the presence of HTLV-1 in countries which have seen a large influx of immigrants in recent years. Epidemiological surveillance and correct diagnosis are recommended to verify the prevalence and incidence of a new undesirable phenomenon

HTLV-1 Tax Mediated Downregulation of miRNAs Associated with Chromatin Remodeling Factors in T Cells with Stably Integrated Viral Promoter

RNA interference (RNAi) is a natural cellular mechanism to silence gene expression and is predominantly mediated by microRNAs (miRNAs) that target messenger RNA. Viruses can manipulate the cellular processes necessary for their replication by targeting the host RNAi machinery. This study explores the effect of human T-cell leukemia virus type 1 (HTLV-1) transactivating protein Tax on the RNAi pathway in the context of a chromosomally integrated viral long terminal repeat (LTR) using a CD4+ T-cell line, Jurkat. Transcription factor profiling of the HTLV-1 LTR stably integrated T-cell clone transfected with Tax demonstrates increased activation of substrates and factors associated with chromatin remodeling complexes. Using a miRNA microarray and bioinformatics experimental approach, Tax was also shown to downregulate the expression of miRNAs associated with the translational regulation of factors required for chromatin remodeling. These observations were validated with selected miRNAs and an HTLV-1 infected T cells line, MT-2. miR-149 and miR-873 were found to be capable of directly targeting p300 and p/CAF, chromatin remodeling factors known to play critical role in HTLV-1 pathogenesis. Overall, these results are first in line establishing HTLV-1/Tax-miRNA-chromatin concept and open new avenues toward understanding retroviral latency and/or replication in a given cell type

Translating Glutamate: From Pathophysiology to Treatment

The neurotransmitter glutamate is the primary excitatory neurotransmitter in mammalian brain and is responsible for most corticocortical and corticofugal neurotransmission. Disturbances in glutamatergic function have been implicated in the pathophysiology of several neuropsychiatric disorders—including schizophrenia, drug abuse and addiction, autism, and depression—that were until recently poorly understood. Nevertheless, improvements in basic information regarding these disorders have yet to translate into Food and Drug Administration–approved treatments. Barriers to translation include the need not only for improved compounds but also for improved biomarkers sensitive to both structural and functional target engagement and for improved translational models. Overcoming these barriers will require unique collaborative arrangements between pharma, government, and academia. Here, we review a recent Institute of Medicine–sponsored meeting, highlighting advances in glutamatergic theories of neuropsychiatric illness as well as remaining barriers to treatment development.National Institute of Mental Health (U.S.) (grant R37MH49334)National Institute of Mental Health (U.S.) (Intramural Research Program)National Institute of Mental Health (U.S.) (R01DA03383)National Institute of Mental Health (U.S.) (P50MH086385)National Institutes of Health (U.S.)FRAXA Research FoundationHoward Hughes Medical InstituteSimons Foundatio