89 research outputs found
Abnormal structural connectivity in the brain networks of children with hydrocephalus
Increased intracranial pressure and ventriculomegaly in children with hydrocephalus are known to have adverse effects on white matter structure. This study seeks to investigate the impact of hydrocephalus on topological features of brain networks in children. The goal was to investigate structural network connectivity, at both global and regional levels, in the brains in children with hydrocephalus using graph theory analysis and diffusion tensor tractography. Three groups of children were included in the study (29 normally developing controls, 9 preoperative hydrocephalus patients, and 17 postoperative hydrocephalus patients). Graph theory analysis was applied to calculate the global network measures including small-worldness, normalized clustering coefficients, normalized characteristic path length, global efficiency, and modularity. Abnormalities in regional network parameters, including nodal degree, local efficiency, clustering coefficient, and betweenness centrality, were also compared between the two patients groups (separately) and the controls using two tailed t-test at significance level of p < 0.05 (corrected for multiple comparison). Children with hydrocephalus in both the preoperative and postoperative groups were found to have significantly lower small-worldness and lower normalized clustering coefficient than controls. Children with hydrocephalus in the postoperative group were also found to have significantly lower normalized characteristic path length and lower modularity. At regional level, significant group differences (or differences at trend level) in regional network measures were found between hydrocephalus patients and the controls in a series of brain regions including the medial occipital gyrus, medial frontal gyrus, thalamus, cingulate gyrus, lingual gyrus, rectal gyrus, caudate, cuneus, and insular. Our data showed that structural connectivity analysis using graph theory and diffusion tensor tractography is sensitive to detect abnormalities of brain network connectivity associated with hydrocephalus at both global and regional levels, thus providing a new avenue for potential diagnosis and prognosis tool for children with hydrocephalus
Gender Socialization in Chinese Kindergartens: Teachers’ Contributions
Teacher-child interactions and peer exchanges were observed once a week for 10 months in four kindergartens in Hong Kong, China. A total of 206 anecdotes/scenes considered representative of the gender-related experiences of 109 4-year-old Chinese children in these kindergartens were analyzed. Descriptive codes, generated iteratively were clustered, categorized, integrated, recoded and recategorized and led to the identification of two major themes related to the socialization practices of teachers: Gendered Kindergarten Routines and Perpetuation of Gender Stereotypes. Findings indicated that these early years’ educational contexts were not gender neutral. Teachers interacted with boys significantly more than girls. They also subtly conveyed traditional Chinese gender values through their repeated use of gendered routines in the kindergartens and their behaviors reflected gender stereotypes
The weakest link: competence and prestige as constraints to referral by isolated nurses in rural Niger
BACKGROUND: For a health district to function referral from health centres to district hospitals is critical. In many developing countries referral systems perform well below expectations. Niger is not an exception in this matter. Beyond obvious problems of cost and access this study shows to what extent the behaviour of the health worker in its interaction with the patient can be a barrier of its own. METHODS: Information was triangulated from three sources in two rural districts in Niger: first, 46 semi-structured interviews with health centre nurses; second, 42 focus group discussions with an average of 12 participants – patients, relatives of patients and others; third, 231 semi-structured interviews with referred patients. RESULTS: Passive patients without 'voice' reinforce authoritarian attitudes of health centre staff. The latter appear reluctant to refer because they see little added value in referral and fear loss of power and prestige. As a result staff communicates poorly and show little eagerness to convince reluctant patients and families to accept referral proposals. CONCLUSIONS: Diminishing referral costs and distance barriers is not enough to correct failing referral systems. There is also a need for investment in district hospitals to make referrals visibly worthwhile and for professional upgrading of the human resources at the first contact level, so as to allow for more effective referral patterns
TRAF4 is a novel phosphoinositide-binding protein modulating tight junctions and favoring cell migration
Tumor necrosis factor (TNF) receptor-associated factor 4 (TRAF4) is frequently overexpressed in carcinomas, suggesting a specific role in cancer. Although TRAF4 protein is predominantly found at tight junctions (TJs) in normal mammary epithelial cells (MECs), it accumulates in the cytoplasm of malignant MECs. How TRAF4 is recruited and functions at TJs is unclear. Here we show that TRAF4 possesses a novel phosphoinositide (PIP)-binding domain crucial for its recruitment to TJs. Of interest, this property is shared by the other members of the TRAF protein family. Indeed, the TRAF domain of all TRAF proteins (TRAF1 to TRAF6) is a bona fide PIP-binding domain. Molecular and structural analyses revealed that the TRAF domain of TRAF4 exists as a trimer that binds up to three lipids using basic residues exposed at its surface. Cellular studies indicated that TRAF4 acts as a negative regulator of TJ and increases cell migration. These functions are dependent from its ability to interact with PIPs. Our results suggest that TRAF4 overexpression might contribute to breast cancer progression by destabilizing TJs and favoring cell migration
The Brain Tumor Segmentation (BraTS) Challenge 2023: Focus on Pediatrics (CBTN-CONNECT-DIPGR-ASNR-MICCAI BraTS-PEDs)
Pediatric tumors of the central nervous system are the most common cause of
cancer-related death in children. The five-year survival rate for high-grade
gliomas in children is less than 20\%. Due to their rarity, the diagnosis of
these entities is often delayed, their treatment is mainly based on historic
treatment concepts, and clinical trials require multi-institutional
collaborations. The MICCAI Brain Tumor Segmentation (BraTS) Challenge is a
landmark community benchmark event with a successful history of 12 years of
resource creation for the segmentation and analysis of adult glioma. Here we
present the CBTN-CONNECT-DIPGR-ASNR-MICCAI BraTS-PEDs 2023 challenge, which
represents the first BraTS challenge focused on pediatric brain tumors with
data acquired across multiple international consortia dedicated to pediatric
neuro-oncology and clinical trials. The BraTS-PEDs 2023 challenge focuses on
benchmarking the development of volumentric segmentation algorithms for
pediatric brain glioma through standardized quantitative performance evaluation
metrics utilized across the BraTS 2023 cluster of challenges. Models gaining
knowledge from the BraTS-PEDs multi-parametric structural MRI (mpMRI) training
data will be evaluated on separate validation and unseen test mpMRI dataof
high-grade pediatric glioma. The CBTN-CONNECT-DIPGR-ASNR-MICCAI BraTS-PEDs 2023
challenge brings together clinicians and AI/imaging scientists to lead to
faster development of automated segmentation techniques that could benefit
clinical trials, and ultimately the care of children with brain tumors
Hormonal signaling in cnidarians : do we understand the pathways well enough to know whether they are being disrupted?
Author Posting. © The Author, 2006. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Ecotoxicology 16 (2007): 5-13, doi:10.1007/s10646-006-0121-1.Cnidarians occupy a key evolutionary position as basal metazoans and are ecologically
important as predators, prey and structure-builders. Bioregulatory molecules (e.g.,
amines, peptides and steroids) have been identified in cnidarians, but cnidarian signaling
pathways remain poorly characterized. Cnidarians, especially hydras, are regularly used
in toxicity testing, but few studies have used cnidarians in explicit testing for signal
disruption. Sublethal endpoints developed in cnidarians include budding, regeneration,
gametogenesis, mucus production and larval metamorphosis. Cnidarian genomic
databases, microarrays and other molecular tools are increasingly facilitating mechanistic
investigation of signaling pathways and signal disruption. Elucidation of cnidarian
signaling processes in a comparative context can provide insight into the evolution and
diversification of metazoan bioregulation. Characterizing signaling and signal disruption
in cnidarians may also provide unique opportunities for evaluating risk to valuable
marine resources, such as coral reefs
A new class of glycomimetic drugs to prevent free fatty acid-induced endothelial dysfunction
Background: Carbohydrates play a major role in cell signaling in many biological processes. We have developed a set of glycomimetic drugs that mimic the structure of carbohydrates and represent a novel source of therapeutics for endothelial dysfunction, a key initiating factor in cardiovascular complications. Purpose: Our objective was to determine the protective effects of small molecule glycomimetics against free fatty acidinduced endothelial dysfunction, focusing on nitric oxide (NO) and oxidative stress pathways. Methods: Four glycomimetics were synthesized by the stepwise transformation of 2,5dihydroxybenzoic acid to a range of 2,5substituted benzoic acid derivatives, incorporating the key sulfate groups to mimic the interactions of heparan sulfate. Endothelial function was assessed using acetylcholineinduced, endotheliumdependent relaxation in mouse thoracic aortic rings using wire myography. Human umbilical vein endothelial cell (HUVEC) behavior was evaluated in the presence or absence of the free fatty acid, palmitate, with or without glycomimetics (1µM). DAF2 and H2DCFDA assays were used to determine nitric oxide (NO) and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity assays were also carried out. RTPCR and western blotting were utilized to measure Akt, eNOS, Nrf2, NQO1 and HO1 expression. Results: Ex vivo endotheliumdependent relaxation was significantly improved by the glycomimetics under palmitateinduced oxidative stress. In vitro studies showed that the glycomimetics protected HUVECs against the palmitateinduced oxidative stress and enhanced NO production. We demonstrate that the protective effects of preincubation with glycomimetics occurred via upregulation of Akt/eNOS signaling, activation of the Nrf2/ARE pathway, and suppression of ROSinduced lipid peroxidation. Conclusion: We have developed a novel set of small molecule glycomimetics that protect against free fatty acidinduced endothelial dysfunction and thus, represent a new category of therapeutic drugs to target endothelial damage, the first line of defense against cardiovascular disease
The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance
INTRODUCTION
Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic.
RATIONALE
We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs).
RESULTS
Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants.
CONCLUSION
Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century
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