194 research outputs found
Brain Ultrasound as a Diagnostic and Follow up Method of Lateral Ventricle Dilatation in Hospitalised Children at the Neurology Department – Pediatric Clinic
A child’s full development is tied closely to the full development of the human’s central nervous system, which is why there are so many cases reported with central nervous system illnesses in children. Being very familiar with a child’s normal development, a Pediatric Neurologist doctor is capable of noticing any sort of neurological deviation during the first month of child’s development which can be backed up with diagnostic methods such as: Transfontanellare Ultrasonography which is the chosen method to diagnose such anomalies and also helps keep track of them.Key words: Brain ultrasonography, ventriculomegaly, our clinical experience
The Link between Genetic Factors in Children with Febrile Convulsions Appearance
The aim of this research paper is to reflect the link between genetic factors and presenting children with febrile convulsions.Keywords: febrile seizures, genetic factor, the pediatric clinic
Synthetic lethal screening in the mammalian central nervous system identifies Gpx6 as a modulator of Huntington’s disease
Huntington’s disease, the most common inherited neurodegenerative disease, is characterized by a dramatic loss of deep-layer cortical and striatal neurons, as well as morbidity in midlife. Human genetic studies led to the identification of the causative gene, huntingtin. Recent genomic advances have also led to the identification of hundreds of potential interacting partners for huntingtin protein and many hypotheses as to the molecular mechanisms whereby mutant huntingtin leads to cellular dysfunction and death. However, the multitude of possible interacting partners and cellular pathways affected by mutant huntingtin has complicated efforts to understand the etiology of this disease, and to date no curative therapeutic exists. To address the general problem of identifying the disease-phenotype contributing genes from a large number of correlative studies, here we develop a synthetic lethal screening methodology for the mammalian central nervous system, called SLIC, for synthetic lethal in the central nervous system. Applying SLIC to the study of Huntington’s disease, we identify the age-regulated glutathione peroxidase 6 (Gpx6) gene as a modulator of mutant huntingtin toxicity and show that overexpression of Gpx6 can dramatically alleviate both behavioral and molecular phenotypes associated with a mouse model of Huntington’s disease. SLIC can, in principle, be used in the study of any neurodegenerative disease for which a mouse model exists, promising to reveal modulators of neurodegenerative disease in an unbiased fashion, akin to screens in simpler model organisms.National Institute of Neurological Disorders and Stroke (U.S.) (Award R01NS085880)William N. and Bernice E. Bumpus Foundation (Early Career Investigator Innovation Award)JPB FoundationEuropean Molecular Biology Organization (Long-term Fellowship
Loss to follow-up after pregnancy among Sub-Saharan Africa-born women living with HIV in England, Wales and Northern Ireland:results from a large national cohort
BACKGROUND: Little is known about retention in human immunodeficiency virus (HIV) care in HIV-positive women after pregnancy in the United Kingdom. We explored the association between loss to follow-up (LTFU) in the year after pregnancy, maternal place of birth and duration of UK residence, in HIV-positive women in England, Wales, and Northern Ireland. METHODS: We analyzed combined data from 2 national data sets: the National Study of HIV in Pregnancy and Childhood; and the Survey of Prevalent HIV Infections Diagnosed, including pregnancies in 2000 to 2009 in women with diagnosed HIV. Logistic regression models were fitted with robust standard errors to estimate adjusted odds ratios (AOR). RESULTS: Overall, 902 of 7211 (12.5%) women did not access HIV care in the year after pregnancy. Factors associated with LTFU included younger age, last CD4 in pregnancy of 350 cells/μL or greater and detectable HIV viral load at the end of pregnancy (all P < 0.001). On multivariable analysis, LTFU was more likely in sub-Saharan Africa-born (SSA-born) women than white UK-born women (AOR, 2.17; 95% confidence interval, 1.50–3.14; P < 0.001). The SSA-born women who had migrated to the UK during pregnancy were 3 times more likely than white UK-born women to be lost to follow-up (AOR, 3.19; 95% confidence interval, 1.94–3.23; P < 0.001). CONCLUSIONS: One in 8 HIV-positive women in England, Wales, and Northern Ireland did not return for HIV care in the year after pregnancy, with SSA-born women, especially those who migrated to the United Kingdom during pregnancy, at increased risk. Although emigration is a possible explanatory factor, disengagement from care may also play a role
Emergence of compensatory mutations reveals the importance of electrostatic interactions between HIV-1 integrase and genomic RNA
HIV-1 integrase (IN) has a noncatalytic function in virion maturation through its binding to the viral RNA genome (gRNA). Class II IN substitutions inhibit IN-gRNA binding and result in the formation of virions with aberrant morphologies marked by mislocalization of the gRNA between the capsid lattice and the lipid envelope. These viruses are noninfectious due to a block at an early reverse transcription stage in target cells. HIV-1 IN utilizes basic residues within its C-terminal domain (CTD) to bind to the gRNA; however, the molecular nature of how these residues mediate gRNA binding and whether other regions of IN are involved remain unknown. To address this, we have isolated compensatory substitutions in the background of a class II IN mutant virus bearing R269A/K273A substitutions within the IN-CTD. We found that the nearby D256N and D270N compensatory substitutions restored the ability of IN to bind gRNA and led to the formation of mature infectious virions. Reinstating the local positive charge of the IN-CTD through individual D256R, D256K, D278R, and D279R substitutions was sufficient to specifically restore IN-gRNA binding and reverse transcription for the IN R269A/K273A as well as the IN R262A/R263A class II mutants. Structural modeling suggested that compensatory substitutions in the D256 residue created an additional interaction interface for gRNA binding, whereas other substitutions acted locally within the unstructured C-terminal tail of IN. Taken together, our findings highlight the essential role of CTD in gRNA binding and reveal the importance of pliable electrostatic interactions between the IN-CTD and the gRNA
Tunable Blood Shunt for Neonates With Complex Congenital Heart Defects
Despite advancements in procedures and patient care, mortality rates for neonatal recipients of the Norwood procedure, a palliation for single ventricle congenital malformations, remain high due to the use of a fixed-diameter blood shunt. In this study, a new geometrically tunable blood shunt was investigated to address limitations of the current treatment paradigm (e.g., Modified Blalock-Taussig Shunt) by allowing for controlled modulation of blood flow through the shunt to accommodate physiological changes due to the patient’s growth. First, mathematical and computational cardiovascular models were established to investigate the hemodynamic requirements of growing neonatal patients with shunts and to inform design criteria for shunt diameter changes. Then, two stages of prototyping were performed to design, build and test responsive hydrogel systems that facilitate tuning of the shunt diameter by adjusting the hydrogel’s degree of crosslinking. We examined two mechanisms to drive crosslinking: infusion of chemical crosslinking agents and near-UV photoinitiation. The growth model showed that 15–18% increases in shunt diameter were required to accommodate growing patients’ increasing blood flow; similarly, the computational models demonstrated that blood flow magnitudes were in agreement with previous reports. These target levels of diameter increases were achieved experimentally with model hydrogel systems. We also verified that the photocrosslinkable hydrogel, composed of methacrylated dextran, was contact-nonhemolytic. These results demonstrate proof-of-concept feasibility and reflect the first steps in the development of this novel blood shunt. A tunable shunt design offers a new methodology to rebalance blood flow in this vulnerable patient population during growth and development
A simplified quantitative real-time PCR assay for monitoring SARS-CoV-2 growth in cell culture
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions within just a few months, causing severe respiratory disease and mortality. Assays to monitor SARS-CoV-2 growt
Research Blogs and the Discussion of Scholarly Information
The research blog has become a popular mechanism for the quick discussion of scholarly information. However, unlike peer-reviewed journals, the characteristics of this form of scientific discourse are not well understood, for example in terms of the spread of blogger levels of education, gender and institutional affiliations. In this paper we fill this gap by analyzing a sample of blog posts discussing science via an aggregator called ResearchBlogging.org (RB). ResearchBlogging.org aggregates posts based on peer-reviewed research and allows bloggers to cite their sources in a scholarly manner. We studied the bloggers, blog posts and referenced journals of bloggers who posted at least 20 items. We found that RB bloggers show a preference for papers from high-impact journals and blog mostly about research in the life and behavioral sciences. The most frequently referenced journal sources in the sample were: Science, Nature, PNAS and PLoS One. Most of the bloggers in our sample had active Twitter accounts connected with their blogs, and at least 90% of these accounts connect to at least one other RB-related Twitter account. The average RB blogger in our sample is male, either a graduate student or has been awarded a PhD and blogs under his own name
Amilorides inhibit SARS-CoV-2 replication in vitro by targeting RNA structures
The SARS-CoV-2 pandemic, and the likelihood of future coronavirus pandemics, emphasized the urgent need for development of novel antivirals. Small-molecule chemical probes offer both to reveal aspects of virus replication and to serve as leads for antiviral therapeutic development. Here, we report on the identification of amiloride-based small molecules that potently inhibit OC43 and SARS-CoV-2 replication through targeting of conserved structured elements within the viral 5′-end. Nuclear magnetic resonance–based structural studies revealed specific amiloride interactions with stem loops containing bulge like structures and were predicted to be strongly bound by the lead amilorides in retrospective docking studies. Amilorides represent the first antiviral small molecules that target RNA structures within the 5′ untranslated regions and proximal region of the CoV genomes. These molecules will serve as chemical probes to further understand CoV RNA biology and can pave the way for the development of specific CoV RNA–targeted antivirals
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