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Journal of Pediatric Surgery Sep 2020Congenital short bowel syndrome (CSBS) is a rare gastrointestinal disorder caused by intrauterine reduction of small bowel length whose etiology is still unknown....
BACKGROUND
Congenital short bowel syndrome (CSBS) is a rare gastrointestinal disorder caused by intrauterine reduction of small bowel length whose etiology is still unknown. Chronic diarrhea, vomiting, and failure to thrive are the most important complications, arising from less absorptive intestinal surface. This review examines clinical features and outcomes of CSBS patients.
METHODS
A PubMed and EMBASE research on CSBS was performed. Inclusion criterion was congenital short bowel diagnosis in a range of ages between 33 weeks of gestational age and 15 years old (IQR 38 days). Exclusion criteria were history of atresia of any part of the gastrointestinal tract and extensive surgical bowel resections. Qualitative and quantitative variables were collected and analyzed. Data were expressed in mean and IQR.
RESULTS
Sixty-one patients were identified (38 males, 23 females) from 1969 to date. Mean bowel length was 58.24 cm (IQR 37.5). Malrotation of the midgut was seen in 98.4% of cases. Our data showed an interesting trend in improving the survival rate of these patients (from 28.5% before 2008 to 75% in the period after 2008). Sepsis was the most frequent cause of death reported (57.9%). Interestingly, 18 patients were genetically analyzed, finding mutations either in FLNA gene (38.8%) or in CLMP gene (61.1%).
CONCLUSIONS
CSBS is a condition that seems to be related to an autosomal recessive (CLMP) or an X linked (FLNA) type of inheritance. Advance in medical management seems to have improved survival of these children in recent years. Further genetic studies can better understand the causes of this disease aiming to create personalized treatment.
TYPE OF STUDY
Systematic review.
LEVEL OF EVIDENCE
Level IV.
Topics: Adolescent; Child; Child, Preschool; Coxsackie and Adenovirus Receptor-Like Membrane Protein; Female; Filamins; Humans; Infant; Intestinal Pseudo-Obstruction; Intestines; Male; Sepsis
PubMed: 32278545
DOI: 10.1016/j.jpedsurg.2020.03.009 -
Pathology, Research and Practice Dec 2019The gelsolin-like actin-capping protein (CapG) is an actin-binding protein in the gelsolin superfamily. Increasing evidence indicates that CapG is highly expressed in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The gelsolin-like actin-capping protein (CapG) is an actin-binding protein in the gelsolin superfamily. Increasing evidence indicates that CapG is highly expressed in various types of cancer. However, the role of CapG in malignant tumors is still controversial. Therefore, we conducted a meta-analysis to assess the prognostic value and clinicopathological significance of CapG in malignant tumors.
METHOD
We searched for eligible studies in the PubMed, Web of Science, Embase, and Cochrane databases. Stata SE12.0 software was used for quantitative meta-analysis. The hazard ratios (HRs) and odds ratios (ORs) with 95% CI were pooled to assess the relationship between CapG expression and overall survival (OS), as well as clinicopathological parameters.
RESULTS
Sixteen studies with a total of 1987 cancer patients were included in this meta-analysis. The results showed that higher CapG expression was statistically correlated with shorter OS (HR 1.70, 95% CI 1.43-1.97, P < 0.001), positive lymph node metastasis (OR 1.91, 95% CI 1.19-3.09, P = 0.008), advanced TNM stage (OR 1.87, 95% CI 1.17-3.00, P = 0.009), advanced T-primary stage (OR 2.54, 95% CI 1.08-6.00, P = 0.033) and male sex (OR 1.77, 95% CI 1.23-2.56, P = 0.002). However, no significant correlation was observed between increased CapG expression and advanced age, larger tumor size, differentiation, or advanced histopathologic grading (P > 0.05).
CONCLUSIONS
High CapG expression is associated with a poor prognosis and worse clinicopathological parameters in various cancers. CapG is a potential prognostic biomarker and a possible clinicopathological predictive factor for various cancers.
Topics: Biomarkers, Tumor; Female; Humans; Lymphatic Metastasis; Male; Microfilament Proteins; Middle Aged; Neoplasm Staging; Neoplasms; Nuclear Proteins; Risk Factors; Sex Factors; Signal Transduction
PubMed: 31685300
DOI: 10.1016/j.prp.2019.152683 -
Journal of Oral and Maxillofacial... 2019Oral Submucous Fibrosis (OSMF) is a chronic progressive scarring oral disease predominantly affecting people of South Asian origin. It is characterized by... (Review)
Review
Oral Submucous Fibrosis (OSMF) is a chronic progressive scarring oral disease predominantly affecting people of South Asian origin. It is characterized by juxtaepithelial inflammatory cell infiltration followed by fibrosis in the lamina propria and submucosa of the oral mucosa. The pathogenesis of the disease is not well established and a number of mechanisms have been proposed regarding the pathogenesis. A renewed interest has been shown in myofibrobasts which have been implicated to play a significant role in the pathogenesis of OSMF. The myofibroblast were initially identified by means of electron microscopy in granulation tissue of healing wounds as a modulated fibroblast exhibiting features of smooth muscle cells, with prominent bundles of microfilaments, dense bodies scattered in between, and gap junctions. The presence of myofibroblasts has successively been described in practically all fibrotic situations characterized by tissue retraction and remodeling. This review paper is an attempt to identify all the studies involving myofibroblasts and explaining the pathogenesis in a simplified manner.
PubMed: 31516233
DOI: 10.4103/jomfp.JOMFP_238_18 -
Early Human Development Apr 2019Every year, an estimated 15 million babies are born preterm (<37 weeks' gestational age [GA]) globally. These preterm infants are exposed to repeated stressful and...
BACKGROUND
Every year, an estimated 15 million babies are born preterm (<37 weeks' gestational age [GA]) globally. These preterm infants are exposed to repeated stressful and often painful procedures as part of routine life-saving care within the neonatal intensive care unit (NICU). Preterm birth continues to be a major health issue associated with increased risk of neurodevelopmental and behavioral disorders such as cerebral palsy, cognitive impairment, autism spectrum disorders and psychiatric disease.
OBJECTIVE
This paper identifies epigenetic alterations and incidence of telomere erosion that have been studied in preterm infants while in the NICU and as a long-term outcome measure. Better understanding of epigenetic alterations and telomere erosion might aid in early detection and prevention/alleviation of the negative effects of cumulative painful/stressful experiences in this population.
METHODS
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards were used to guide this review. Systematic searches of databases included PubMed, CINAHL, SCOPUS and PsychInfo.
RESULTS
Twenty-one studies were included, appraised and then synthesized into a narrative summary.
DISCUSSION
Several putative epigenetic markers were identified although there was a paucity of studies related to telomere length. The interaction of disease entity combined with therapeutic interventions intended to treat may inadvertently increase infant allostatic load or ability to adapt to stress. Future research should include not only human studies but leverage newly available large data sets to conduct additional analysis.
Topics: Angiomotins; Brain-Derived Neurotrophic Factor; Epigenesis, Genetic; Humans; Infant, Newborn; Infant, Premature; Insulin-Like Growth Factor II; Intensive Care Units, Neonatal; Intercellular Signaling Peptides and Proteins; Membrane Proteins; Microfilament Proteins; NF-KappaB Inhibitor alpha; Neurodevelopmental Disorders; Receptors, Glucocorticoid; Stress, Physiological; Tacrolimus Binding Proteins; Telomere
PubMed: 30870624
DOI: 10.1016/j.earlhumdev.2019.03.003 -
Revista Espanola de Cardiologia... Apr 2019Dilated cardiomyopathy is inherited in nearly 50% of cases. More than 90 genes have been associated with this disease, which is one of the main causes of heart...
Dilated cardiomyopathy is inherited in nearly 50% of cases. More than 90 genes have been associated with this disease, which is one of the main causes of heart transplant and has been associated with an increased risk of sudden cardiac death. Risk stratification in these patients continues to be challenging. The identification of the specific etiology of the disease is very useful for the early detection of mutation carriers. Genetic study often provides prognostic information and can determine the therapeutic approach. Wide phenotypic variability is observed depending on the mutated gene, the type of mutation, and the presence of additional genetic and environmental factors.
Topics: Adaptor Proteins, Signal Transducing; Apoptosis Regulatory Proteins; Calcium-Binding Proteins; Cardiomyopathy, Dilated; Cytoskeletal Proteins; Desmosomes; Filamins; Genes; Genes, Mitochondrial; Genetic Testing; Humans; Lysosomal-Associated Membrane Protein 2; Mutation; NAV1.5 Voltage-Gated Sodium Channel; Prognosis; RNA-Binding Proteins; Risk Assessment; Sarcomeres
PubMed: 30792015
DOI: 10.1016/j.rec.2018.10.017 -
Clinical Journal of the American... Oct 2018Per- and polyfluoroalkyl substances (PFASs) are a large group of manufactured nonbiodegradable compounds. Despite increasing awareness as global pollutants, the impact...
BACKGROUND AND OBJECTIVES
Per- and polyfluoroalkyl substances (PFASs) are a large group of manufactured nonbiodegradable compounds. Despite increasing awareness as global pollutants, the impact of PFAS exposure on human health is not well understood, and there are growing concerns for adverse effects on kidney function. Therefore, we conducted a scoping review to summarize and identify gaps in the understanding between PFAS exposure and kidney health.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
We systematically searched PubMed, EMBASE, EBSCO Global Health, World Health Organization Global Index, and Web of Science for studies published from 1990 to 2018. We included studies on the epidemiology, pharmacokinetics, or toxicology of PFAS exposure and kidney-related health, including clinical, histologic, molecular, and metabolic outcomes related to kidney disease, or outcomes related to the pharmacokinetic role of the kidneys.
RESULTS
We identified 74 studies, including 21 epidemiologic, 13 pharmacokinetic, and 40 toxicological studies. Three population-based epidemiologic studies demonstrated associations between PFAS exposure and lower kidney function. Along with toxicology studies (=10) showing tubular histologic and cellular changes from PFAS exposure, pharmacokinetic studies (=5) demonstrated the kidneys were major routes of elimination, with active proximal tubule transport. In several studies (=17), PFAS exposure altered several pathways linked to kidney disease, including oxidative stress pathways, peroxisome proliferators-activated receptor pathways, NF-E2-related factor 2 pathways, partial epithelial mesenchymal transition, and enhanced endothelial permeability through actin filament modeling.
CONCLUSIONS
A growing body of evidence portends PFASs are emerging environmental threats to kidney health; yet several important gaps in our understanding still exist.
Topics: Environmental Exposure; Environmental Pollutants; Fluorocarbon Polymers; Humans; Kidney Diseases
PubMed: 30213782
DOI: 10.2215/CJN.04670418 -
Methods in Molecular Biology (Clifton,... 2018The Rho family of GTPases are known to play pivotal roles in the regulation of fundamental cellular processes, ranging from cell migration and polarity to wound healing...
The Rho family of GTPases are known to play pivotal roles in the regulation of fundamental cellular processes, ranging from cell migration and polarity to wound healing and regulation of actin cytoskeleton. Over the past decades, accumulating experimental work has increasingly mapped out the mechanistic details and interactions between members of the family and their regulators, establishing detailed interaction circuits within the Rho GTPase signaling network. These circuits have served as a vital foundation based on which a multitude of mathematical models have been developed to explain experimental data, gain deeper insights into the biological phenomenon they describe, as well as make new testable predictions and hypotheses. Due to the diverse nature and purpose of these models, they often vary greatly in size, scope, complexity, and formulation. Here, we provide a systematic, categorical, and comprehensive account of the recent modeling studies of Rho family GTPases, with an aim to offer a broad perspective of the field. The modeling limitations and possible future research directions are also discussed.
Topics: Animals; Computer Simulation; Humans; Models, Biological; Signal Transduction; rho GTP-Binding Proteins
PubMed: 30062401
DOI: 10.1007/978-1-4939-8612-5_1 -
Developmental Neurobiology Oct 2014The functions of microtubule-associated protein 1B (MAP1B) have historically been linked to the development of the nervous system, based on its very early expression in... (Review)
Review
The functions of microtubule-associated protein 1B (MAP1B) have historically been linked to the development of the nervous system, based on its very early expression in neurons and glial cells. Moreover, mice in which MAP1B is genetically inactivated have been used extensively to show its role in axonal elongation, neuronal migration, and axonal guidance. In the last few years, it has become apparent that MAP1B has other cellular and molecular functions that are not related to its microtubule-stabilizing properties in the embryonic and adult brain. In this review, we present a systematic review of the canonical and novel functions of MAP1B and propose that, in addition to regulating the polymerization of microtubule and actin microfilaments, MAP1B also acts as a signaling protein involved in normal physiology and pathological conditions in the nervous system.
Topics: Animals; Brain; Humans; Microtubule-Associated Proteins; Myasthenia Gravis; Neurons
PubMed: 24700609
DOI: 10.1002/dneu.22178 -
BioMed Research International 2013The Ena/VASP (enabled/vasodilator stimulated phosphoprotein) family includes the binding actin proteins such as mammalian Ena (Mena), VASP, and Ena-VASP-like. It is... (Review)
Review
The Ena/VASP (enabled/vasodilator stimulated phosphoprotein) family includes the binding actin proteins such as mammalian Ena (Mena), VASP, and Ena-VASP-like. It is known that the perturbation of actin cycle could determine alteration in the mobility of cells and in consequence of organogenesis. Few recent studies have revealed that Mena protein could play a role in breast or pancreatic carcinogenesis. Based on our researches, we observed that the intensity of Mena expression increased from premalignant to malignant lesions in some organs such as large bowel, stomach, cervix, and salivary glands. These findings prove that Mena could be a marker of premalignant epithelial lesions. In premalignant lesions, it could be helpful to define more accurately the risk for malignant transformation. In malignant tumors, correlation of expression of its splice variants could indicate metastatic behavior. In conclusion, we consider that it is necessary to analyze the expression of Mena splice variants in a higher number of cases, in different epithelial lesions, and also in experimental studies to define its exact role in carcinogenesis and also its possible prognostic and predictive values.
Topics: Actins; Alternative Splicing; Carcinogenesis; DNA-Binding Proteins; Embryonic Development; Humans; Microfilament Proteins; Neoplasm Invasiveness; Protein Binding; Protein Isoforms
PubMed: 23956979
DOI: 10.1155/2013/365192 -
Journal of the American Academy of... Apr 2013The purpose of the present study was to discover the extent to which distinct DSM disorders share large, highly recurrent copy number variants (CNVs) as susceptibility... (Review)
Review
OBJECTIVE
The purpose of the present study was to discover the extent to which distinct DSM disorders share large, highly recurrent copy number variants (CNVs) as susceptibility factors. We also sought to identify gene mechanisms common to groups of diagnoses and/or specific to a given diagnosis based on associations with CNVs.
METHOD
Systematic review of 820 PubMed articles on autism spectrum disorder (ASD), intellectual disability (ID), schizophrenia, and epilepsy produced 54 CNVs associated with one or several disorders. Pathway analysis on genes implicated by CNVs in different groupings was conducted.
RESULTS
The majority of CNVs were found in ID with the other disorders somewhat subsumed, yet certain CNVs were associated with isolated or groups of disorders. Based on genes implicated by CNVs, ID encompassed 96.8% of genes in ASD, 92.8% of genes in schizophrenia, and 100.0% of genes in epilepsy. Pathway analysis revealed that synapse processes were enriched in ASD, ID, and schizophrenia. Disease-specific processes were identified in ID (actin cytoskeleton processes), schizophrenia (ubiquitin-related processes), and ASD (synaptic vesicle transport and exocytosis).
CONCLUSIONS
Intellectual disability may arise from the broadest range of genetic pathways, and specific subsets of these pathways appear to be relevant to other disorders or combinations of these disorders. It is clear that statistically significant CNVs across disorders of cognitive development are highly enriched for biological processes related to the synapse. There are also disorder-specific processes that may aid in understanding the distinct presentations and pathophysiology of these disorders.
Topics: DNA Copy Number Variations; Genetic Predisposition to Disease; Humans; Intellectual Disability; Mental Disorders
PubMed: 23582872
DOI: 10.1016/j.jaac.2013.01.003