Miracle-dz/UniFAR-FTUs huggingface dataset:
Live Attenuated Tetravalent Dengue Virus Host Range Vaccine Is Immunogenic in African Green Monkeys following a Single Vaccination

ABSTRACT The causative agent of dengue fever, dengue virus (DENV), is transmitted by mosquitoes, and as distribution of these insects has expanded, so has dengue-related disease. DENV is a member of the Flaviviridae family and has 4 distinct serotypes (DENV-1, -2, -3, and -4). No lasting cross protection is afforded to heterologous serotypes following infection by any one of the individual serotypes. The presence of nonneutralizing antibodies to one serotype can facilitate the occurrence of more-severe dengue hemorrhagic fever through immune enhancement upon infection with a second serotype. For this reason, the development of a safe, tetravalent vaccine to produce a balanced immune response to all four serotypes is critical. We have developed a novel approach to produce safe and effective live-attenuated vaccines for DENV and other insect-borne viruses. Host range (HR) mutants of each DENV serotype were created by truncating transmembrane domain 1 of the E protein and selecting for strains of DENV that replicated well in insect cells but not mammalian cells. These vaccine strains were tested for immunogenicity in African green monkeys (AGMs). No vaccine-related adverse events occurred. The vaccine strains were confirmed to be attenuated in vivo by infectious center assay (ICA). Analysis by 50% plaque reduction neutralization test (PRNT50) established that by day 62 postvaccination, 100% of animals seroconverted to DENV-1, -2, -3, and -4. Additionally, the DENV HR tetravalent vaccine (HR-Tet) showed a tetravalent anamnestic immune response in 100% (16/16) of AGMs after challenge with wild-type (WT) DENV strains. IMPORTANCE We have generated a live attenuated viral (LAV) vaccine capable of eliciting a strong immune response in African green monkeys (AGMs) in a single dose. This vaccine is delivered by injecting one of four attenuated serotypes into each limb of the animal. 100% of animals given the vaccine generated antibodies against all 4 serotypes, and this response was found to be balanced in nature. This is also one of the first studies of dengue in AGMs, and our study suggests that viremia and antibody response in AGMs may be similar to those seen in DENV infection in humans.
Safety, efficacy and acceptability of medical abortion with mifepristone and misoprostol in Nepalese women

Unsafe abortion is a major health issue. Therefore safe abortion services which is effective. acceptable and techniquely easy to perform should be available. Aim- To confirm effectiveness, side effects, safety and patient satisfaction with medical termination of early pregnancy. Methods- It was a prospective study 150 women who were less than 63 days pregnant and consented for medical termination of pregnancy were given! 200mg 0 Mefepristone orally and 48 hrs later 800 micro gram Misoprostol was inserted vaginally. They were followed up in 14 days. Bleeding, pain G.I symptoms any other side effects were recorded. Abortion was complete or not was confirmed clinically and by USG. Failure and success was documented depending upon need for surgical evacuation. Results- The success rate with this regime was 92.6% and failure rate was 7.3%. There were no major side effects with Mifepristone. The average bleeding after misoprostol insertion was 10 days and 80% women had more bleeding than normal period. All of them had pain. Only 13.3% needed analgesic. women (96%) were satisfied with the method. Conclusion- combination of mifepristone and misoprostol is a safe and effective of early pregnancy Keywords- medical termination, pregnancy, mifepristone, misoprostol.
A inserção da epilepsia no ensino médico (graduação)

Epilepsy as a chronic CNS disorder is often treated in its first stage by a non-neurologist. Interest in epilepsy in general practice is growing at the community-based health care services. From the neuroepidemiological point of view the epilepsy stands out as one of the most prevalent neurological disorders. This fact shows the importance of integrating epilepsy into the medical graduation curriculum. The Brazilian Epilepsy League Committee on Epilepsy Education has proposed a minimum program in the medical curriculum, as part of the Neurology Course with the basic clinical aspects such as the definitions, epidemiology, classification, semiology, etiology, physiopathology, complementary methods, treatment and medical-social aspects. This minimum program is intended to provide the future doctor with a proper and competent approach for attending the patient with epilepsy and/or epileptic seizures.
Determinants of health-related lifestyles among university students

Aims: The aim of this study was to investigate students’ health-related lifestyles and to identify barriers and social determinants of healthier lifestyles. Methods: An online survey, two focus groups and three in-depth interviews across 2014/2015. A stratified by school size and random sample (n = 468) of university students answered a 67-item questionnaire comprising six scales: Rapid Assessment of Physical Activity, Rapid Eating and Activity Assessment for Patients–Short Version, CAGE, Fagerström Test for Nicotine Dependence, Warwick–Edinburgh Mental Wellbeing Scale short version, and ad hoc scale for drug use/misuse. Stratified by gender, χ2 tests were run to test associations/estimate risks and three multivariate Logistic Regression models were adjusted. A thematic approach guided the analysis of qualitative data. Results: A total of 60% of the respondents were insufficiently physically active, 47% had an unbalanced diet and 30% had low mental wellbeing. Alcohol drinkers versus abstinent were almost equally distributed. A total of 42% of alcohol drinkers reported getting drunk at least once a month. Smokers accounted for 16% of the respondents. Identified risk factors for suboptimal physical activity were as follows: being a woman, not using the university gym and smoking. Risk factors for unbalanced diet were low mental wellbeing and drug use. Poor mental wellbeing was predicted by unbalanced diet, not feeling like shopping and cooking frequently, and a lack of help-seeking behaviour in cases of distress. Qualitative analysis revealed seven thematic categories: transition to new life, university environment and systems, finances, academic pressure, health promotion on campus and recommendations. Conclusion: This study provides robust evidence that the health-related lifestyles of the student population are worrying and suggests that the trend in chronic diseases associated with unhealthy lifestyles sustained over years might be unlikely to change in future generations. University students’ health-related lifestyle is a concern. Nine out of the identified 10 predictors of problematic physical activity, nutrition and mental wellbeing, were environmental/societal or institutional barriers. Universities must expand corporate responsibilities to include the promotion of health as part of their core values.
Structural Analysis of the Roles of Influenza A Virus Membrane-Associated Proteins in Assembly and Morphology

ABSTRACT The assembly of influenza A virus at the plasma membrane of infected cells leads to release of enveloped virions that are typically round in tissue culture-adapted strains but filamentous in strains isolated from patients. The viral proteins hemagglutinin (HA), neuraminidase (NA), matrix protein 1 (M1), and M2 ion channel all contribute to virus assembly. When expressed individually or in combination in cells, they can all, under certain conditions, mediate release of membrane-enveloped particles, but their relative roles in virus assembly, release, and morphology remain unclear. To investigate these roles, we produced membrane-enveloped particles by plasmid-derived expression of combinations of HA, NA, and M proteins (M1 and M2) or by infection with influenza A virus. We monitored particle release, particle morphology, and plasma membrane morphology by using biochemical methods, electron microscopy, electron tomography, and cryo-electron tomography. Our data suggest that HA, NA, or HANA (HA plus NA) expression leads to particle release through nonspecific induction of membrane curvature. In contrast, coexpression with the M proteins clusters the glycoproteins into filamentous membrane protrusions, which can be released as particles by formation of a constricted neck at the base. HA and NA are preferentially distributed to differently curved membranes within these particles. Both the budding intermediates and the released particles are morphologically similar to those produced during infection with influenza A virus. Together, our data provide new insights into influenza virus assembly and show that the M segment together with either of the glycoproteins is the minimal requirement to assemble and release membrane-enveloped particles that are truly virus-like. IMPORTANCE Influenza A virus is a major respiratory pathogen. It assembles membrane-enveloped virus particles whose shapes vary from spherical to filamentous. Here we examine the roles of individual viral proteins in mediating virus assembly and determining virus shape. To do this, we used a range of electron microscopy techniques to obtain and compare two- and three-dimensional images of virus particles and virus-like particles during and after assembly. The virus-like particles were produced using different combinations of viral proteins. Among our results, we found that coexpression of one or both of the viral surface proteins (hemagglutinin and neuraminidase) with the viral membrane-associated proteins encoded by the M segment results in assembly and release of filamentous virus-like particles in a manner very similar to that of the budding and release of influenza virions. These data provide novel insights into the roles played by individual viral proteins in influenza A virus assembly.
On the Cramer-Rao Bound for Direction Finding of Correlated Signals

In this paper we present compact closed form formulas for the Cramer Rao Bound corresponding to the joint estimation of the directions-of-arrival, the signal covariance matrix, and the noise variance. Using these formulas we investigate the effect of signal correlation on the achievable accuracy of direction finding system in a correlated signal environment. As expected, estimation accuracy decreases with increasing correlation magnitude. We observe that under certain conditions (small aperture, high correlation magnitude), correlation phase has a strong effect on DOA estimation accuracy.
Reply to "Comments on 'self-adaptive source separation, part I: convergence analysis of a direct linear network controled by the Herault-Jutten algorithm"

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Case Report: Using the Activities-Specific Balance Confidence Scale to Quantify the Impact of Prosthetic Knee Choice on Balance Confidence

The Activities-specific Balance Confidence Scale (ABC) is a relatively recent self-report survey instrument used to quantify balance confidence. Its use among the lower extremity amputee population has been objectively validated. However, there are currently no reports in which the ABC has been used to quantify changes in balance confidence after targeted intervention. The ABC was administered to our case subject immediately before and shortly after a significant alteration to his prosthesis in which his existing rotary hydraulic knee was replaced with a microprocessor controlled hydraulic knee. His initial ABC score of 69 was increased 30% to 89. Although larger cohort studies are needed, the ABC is suggested as an easily administered but an efficient means to quantify changes in balance confidence among the lower extremity amputee population after targeted interventions.
HIV-1 Nef and Vpu Interfere with L-Selectin (CD62L) Cell Surface Expression To Inhibit Adhesion and Signaling in Infected CD4+ T Lymphocytes

ABSTRACT Leukocyte recirculation between blood and lymphoid tissues is required for the generation and maintenance of immune responses against pathogens and is crucially controlled by the L-selectin (CD62L) leukocyte homing receptor. CD62L has adhesion and signaling functions and initiates the capture and rolling on the vascular endothelium of cells entering peripheral lymph nodes. This study reveals that CD62L is strongly downregulated on primary CD4+ T lymphocytes upon infection with human immunodeficiency virus type 1 (HIV-1). Reduced cell surface CD62L expression was attributable to the Nef and Vpu viral proteins and not due to increased shedding via matrix metalloproteases. Both Nef and Vpu associated with and sequestered CD62L in perinuclear compartments, thereby impeding CD62L transport to the plasma membrane. In addition, Nef decreased total CD62L protein levels. Importantly, infection with wild-type, but not Nef- and Vpu-deficient, HIV-1 inhibited the capacity of primary CD4+ T lymphocytes to adhere to immobilized fibronectin in response to CD62L ligation. Moreover, HIV-1 infection impaired the signaling pathways and costimulatory signals triggered in primary CD4+ T cells by CD62L ligation. We propose that HIV-1 dysregulates CD62L expression to interfere with the trafficking and activation of infected T cells. Altogether, this novel HIV-1 function could contribute to virus dissemination and evasion of host immune responses. IMPORTANCE L-selectin (CD62L) is an adhesion molecule that mediates the first steps of leukocyte homing to peripheral lymph nodes, thus crucially controlling the initiation and maintenance of immune responses to pathogens. Here, we report that CD62L is downmodulated on the surfaces of HIV-1-infected T cells through the activities of two viral proteins, Nef and Vpu, that prevent newly synthesized CD62L molecules from reaching the plasma membrane. We provide evidence that CD62L downregulation on HIV-1-infected primary T cells results in impaired adhesion and signaling functions upon CD62L triggering. Removal of cell surface CD62L may predictably keep HIV-1-infected cells away from lymph nodes, the privileged sites of both viral replication and immune response activation, with important consequences, such as systemic viral spread and evasion of host immune surveillance. Altogether, we propose that Nef- and Vpu-mediated subversion of CD62L function could represent a novel determinant of HIV-1 pathogenesis.
Hepatitis C Virus Upregulates Beclin1 for Induction of Autophagy and Activates mTOR Signaling

ABSTRACT Hepatitis C virus (HCV) induces autophagosome formation in infected human hepatocytes. We have previously reported that HCV exploits autophagic machinery in favor of virus growth and survival in host cells (S. Shrivastava et al., Hepatology 53:406–414, 2011); however, the mechanisms for autophagy induction is poorly understood. In the present study, we observed that HCV infection transcriptionally upregulates Beclin1, which forms complex with Vps34, the class III phosphatidylinositol 3-kinase, as a first step for autophagy initiation. Although Bcl-2 has an anti-autophagy effect by its association with Beclin1 in nutrient-deprived cells, our studies revealed that HCV-mediated autophagy occurs independent of Beclin1–Bcl-2 dissociation. Mammalian target of rapamycin (mTOR) is a positive regulator of cell growth and is recognized as an inhibitor of autophagy induction. Our results demonstrated that HCV infection enhances phospho-mTOR expression and its downstream target 4EBP1 activation, suggesting that mTOR is not a negative regulator of HCV-induced autophagy. On the other hand, HCV infection in autophagy-impaired cells reduced phospho-mTOR, mTOR, and phospho-4EBP1 expression. Together, these results suggested that HCV induces autophagy by upregulating Beclin1 and activates mTOR signaling pathway, which in turn may promote hepatocyte growth.
Human Immunodeficiency Virus Type 1 Protease-Correlated Cleavage Site Mutations Enhance Inhibitor Resistance

ABSTRACT Drug resistance is an important cause of antiretroviral therapy failure in human immunodeficiency virus (HIV)-infected patients. Mutations in the protease render the virus resistant to protease inhibitors (PIs). Gag cleavage sites also mutate, sometimes correlating with resistance mutations in the protease, but their contribution to resistance has not been systematically analyzed. The present study examines mutations in Gag cleavage sites that associate with protease mutations and the impact of these associations on drug susceptibilities. Significant associations were observed between mutations in the nucleocapsid-p1 (NC-p1) and p1-p6 cleavage sites and various PI resistance-associated mutations in the protease. Several patterns were frequently observed, including mutations in the NC-p1 cleavage site in combination with I50L, V82A, and I84V within the protease and mutations within the p1-p6 cleavage site in combination with D30N, I50V, and I84V within the protease. For most patterns, viruses with mutations both in the protease and in either cleavage site were significantly less susceptible to specific PIs than viruses with mutations in the protease alone. Altered PI resistance in HIV-1 was found to be associated with the presence of Gag cleavage site mutations. These studies suggest that associated cleavage site mutations may contribute to PI susceptibility in highly specific ways depending on the particular combinations of mutations and inhibitors. Thus, cleavage site mutations should be considered when assessing the level of PI resistance.
BLOOD CALCIUM AND PHOSPHORUS IN THE NEWBORN

Most investigations on the calcium and phosphorus content of the blood of newborn infants have been approached through studies of rickets and tetany. The results of such investigations revealed that the figures for total serum calcium are below the accepted normal standard in tetany but remain unchanged in rickets. These same studies have helped to establish normal values of calcium and phosphorus for the infant and to develop technics for the determination of these constituents. Many papers dealing with this subject have substantiated the findings of previous authors that the newborn child has 1 to 2 mg. more calcium per hundred cubic centimeters of serum than does the adult; this is particularly noticed in the relative values for mother and child immediately after parturition. The work presented in this paper was undertaken as part of a general study dealing with the nutritional status, particularly in relation to rickets, of preschool
Exploring facilitators and barriers to individual and organizational level capacity building: outcomes of participation in a community priority setting workshop

This article explores facilitators and barriers to individual and organizational capacity to address priority strategies for community-level chronic disease prevention. Interviews were conducted with a group of participants who previously participated in a community priority-setting workshop held in two Alberta communities. The goal of the workshop was to bring together key community stakeholders to collaboratively identify action strategies for preventing chronic diseases in their communities. While capacity building was not the specific aim of the workshop, it could be considered an unintended byproduct of bringing together community representatives around a specific issue. One purpose of this study was to examine the participants’ capacity to take action on the priority strategies identified at the workshop. Eleven one-on-one semi-structured interviews were conducted with workshop participants to examine facilitators and barriers to individual and organizational level capacity building. Findings suggest that there were several barriers identified by participants that limited their capacity to take action on the workshop strategies, specifically: (i) organizations’ lack of priorities or competing priorities; (ii) priorities secondary to the organizational mandate; (iii) disconnect between organizational and community priorities; (iv) disconnect between community organization priorities; (v) disconnect between organizations and government/funder priorities; (vi) limited resources (i.e. time, money and personnel); and, (vii) bigger community issues. The primary facilitator of individual capacity to take action or priority strategies was supportive organizations. Recognition of these elements will allow practitioners, organizations, governments/funders, and communities to focus on seeking ways to improve capacity for chronic disease prevention. (Global Health Promotion, 2010; 17(2): pp. 34—43)
Human T-Cell Leukemia Virus Type 1 (HTLV-1) bZIP Factor Requires Cellular Transcription Factor JunD To Upregulate HTLV-1 Antisense Transcription from the 3′ Long Terminal Repeat

ABSTRACT Infection with the human T-cell leukemia virus type 1 (HTLV-1) results in a variety of diseases including adult T-cell leukemia (ATL), a fatal malignancy characterized by the uncontrolled proliferation of virally infected CD4+ T cells. The HTLV-1 basic leucine zipper factor (HBZ) is believed to contribute to development and maintenance of ATL. Unlike the other HTLV-1 genes, the hbz gene is encoded on the complementary strand of the provirus and therefore is not under direct control of the promoter within the 5′ long terminal repeat (LTR) of the provirus. This promoter can undergo inactivating genetic or epigenetic changes during the course of ATL that eliminates expression of all viral genes except that of hbz. In contrast, repressive modifications are not known to occur on the hbz promoter located in the 3′ LTR, and hbz expression has been consistently detected in all ATL patient samples. Although Sp1 regulates basal transcription from the HBZ promoter, other factors that activate transcription remain undefined. In this study, we used a proviral reporter construct deleted of the 5′ LTR to show that HBZ upregulates its own expression through cooperation with JunD. Activation of antisense transcription was apparent in serum-deprived cells in which the level of JunD was elevated, and elimination of JunD expression by gene knockout or shRNA-mediated knockdown abrogated this effect. Activation through HBZ and JunD additionally required Sp1 binding at the hbz promoter. These data favor a model in which JunD is recruited to the promoter through Sp1, where it heterodimerizes with HBZ thereby enhancing its activity. Separately, hbz gene expression led to an increase in JunD abundance, and this effect correlated with emergence of features of transformed cells in immortalized fibroblasts. Overall, our results suggest that JunD represents a novel therapeutic target for the treatment of ATL.