Health monitoring of young children with Down syndrome: A parent-report study

© 2019 John Wiley & Sons Ltd.Background: Children with Down syndrome have an increased risk of serious health conditions, particularly in early childhood. Published guidelines promote the identification and monitoring of health issues and adherence could reduce health inequalities, yet there is limited research about the extent to which health monitoring occurs as recommended. This study aimed to investigate the health monitoring of children with Down syndrome aged 0–5 years in the UK. Materials and Methods: Twenty-four parents of children with Down syndrome with a mean age of 32 months (10–65 months) participated. They completed a questionnaire about their child's healthcare usage, diagnoses of health conditions and whether health checks had been completed at birth and since birth. The results of the questionnaires were charted and compared to the schedule of checks produced by the Down Syndrome Medical Interest Group UK. Results: Children with Down syndrome had high usage of health services and reported significant health issues. There was high adherence to published guidelines for the majority of health checks at birth, although 38% of children had not received all recommended checks. Not all health domains had been monitored since birth for all children, particularly breathing and blood (excluding thyroid). With the potential exception of sleep apnoea, diagnosed conditions appeared to be monitored. Conclusions: This study suggests that health monitoring after birth and screening for nondiagnosed health conditions is variable for children with Down syndrome. Further research should examine convergence of these findings with medical records and clinicians' experiences across the UK.Peer reviewedFinal Accepted Versio

Correlation between serum ferritin and glycaemic control in patients of type 2 diabetes mellitus: a case control study

Background: Diabetes Mellitus (DM) is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. Ferritin is a ubiquitous intracellular protein complex that reflectes the iron stores of the body. Many cross-sectional studies indicate that increased body iron stores have been associated with the development of glucose intolerance, type 2 diabetes, metabolic syndrome. This study was carried out to find out the relationship between serum ferritin and type 2 diabetes and to see the influence of body iron stores on HbA1c and blood glucose.Methods: This study includes 50 patients suffering from type 2 diabetes and compared with controls at Sir T hospital, Bhavnagar. S. ferritin, Fasting Blood Sugar (FBS), Post Prandial Blood Sugar (PPBS) and HbA1c were measured.Results: Serum ferritin was significantly higher (p<0.0001) in the patients suffering from type 2 diabetes and the correlation between serum ferritin and HbA1c was positive. Patients with type 2 diabetes with increased level of serum ferritin had poor glycemic control reflected by increased levels of HBA1c (r=0.701, p<0.0001)Conclusions: There is a positive association between elevated iron stores measured by serum ferritin levels and type 2 diabetes mellitus. Ferritin levels also correlated FBS, PP2BS and HbA1c.

Effects of gravitational forces on single joint arm movements in humans

We have examined the kinematics and muscle activation patterns of single joint elbow movements made in the vertical plane. Movements of different amplitudes were performed during a visual, step-tracking task. By adjusting shoulder position, both elbow flexion and extension movements were made under three conditions: (a) in the horizontal plane, (b) in the vertical plane against gravity, and (c) in the vertical plane with gravity. Regardless of the gravitational load, all movements were characterized by time symmetric velocity profiles. In addition, no differences were found in the relationships between movement duration, peak velocity, and movement amplitude in movements with or against gravity. The pattern of muscle activation was influenced however, by the gravitational load. Both flexion and extension movements made with gravity were characterized by a reciprocally organized pattern of muscle activity in which phasic agonist activity was followed by phasic antagonist activity. Flexion and extension movements made against gravity were characterized by early phasic antagonist activity occurring at about the same time as the initial agonist burst. These findings suggest that EMG patterns are modified in order to preserve a common temporal structure in the face of different gravitational loads.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46567/1/221_2004_Article_BF00239600.pd

Genome Wide Expression Profiling Reveals Suppression of Host Defence Responses during Colonisation by Neisseria meningitides but not N. lactamica

Both Neisseria meningitidis and the closely related bacterium Neisseria lactamica colonise human nasopharyngeal mucosal surface, but only N. meningitidis invades the bloodstream to cause potentially life-threatening meningitis and septicaemia. We have hypothesised that the two neisserial species differentially modulate host respiratory epithelial cell gene expression reflecting their disease potential. Confluent monolayers of 16HBE14 human bronchial epithelial cells were exposed to live and/or dead N. meningitidis (including capsule and pili mutants) and N. lactamica, and their transcriptomes were compared using whole genome microarrays. Changes in expression of selected genes were subsequently validated using Q-RT-PCR and ELISAs. Live N. meningitidis and N. lactamica induced genes involved in host energy production processes suggesting that both bacterial species utilise host resources. N. meningitidis infection was associated with down-regulation of host defence genes. N. lactamica, relative to N. meningitidis, initiates up-regulation of proinflammatory genes. Bacterial secreted proteins alone induced some of the changes observed. The results suggest N. meningitidis and N. lactamica differentially regulate host respiratory epithelial cell gene expression through colonisation and/or protein secretion, and that this may contribute to subsequent clinical outcomes associated with these bacteria

The Moraxella adhesin UspA1 binds to its human CEACAM1 receptor by a deformable trimeric coiled-coil

Moraxella catarrhalis is a ubiquitous human-specific bacterium commonly associated with upper and lower respiratory tract infections, including otitis media, sinusitis and chronic obstructive pulmonary disease. The bacterium uses an autotransporter protein UspA1 to target an important human cellular receptor carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1). Using X-ray crystallography, we show that the CEACAM1 receptor-binding region of UspA1 unusually consists of an extended, rod-like left-handed trimeric coiled-coil. Mutagenesis and binding studies of UspA1 and the N-domain of CEACAM1 have been used to delineate the interacting surfaces between ligand and receptor and guide assembly of the complex. However, solution scattering, molecular modelling and electron microscopy analyses all indicate that significant bending of the UspA1 coiled-coil stalk also occurs. This explains how UspA1 can engage CEACAM1 at a site far distant from its head group, permitting closer proximity of the respective cell surfaces during infection

Differential Modulation of TNF-α–Induced Apoptosis by Neisseria meningitidis

Infections by Neisseria meningitidis show duality between frequent asymptomatic carriage and occasional life-threatening disease. Bacterial and host factors involved in this balance are not fully understood. Cytopathic effects and cell damage may prelude to pathogenesis of isolates belonging to hyper-invasive lineages. We aimed to analyze cell–bacteria interactions using both pathogenic and carriage meningococcal isolates. Several pathogenic isolates of the ST-11 clonal complex and carriage isolates were used to infect human epithelial cells. Cytopathic effect was determined and apoptosis was scored using several methods (FITC-Annexin V staining followed by FACS analysis, caspase assays and DNA fragmentation). Only pathogenic isolates were able to induce apoptosis in human epithelial cells, mainly by lipooligosaccharide (endotoxin). Bioactive TNF-α is only detected when cells were infected by pathogenic isolates. At the opposite, carriage isolates seem to provoke shedding of the TNF-α receptor I (TNF-RI) from the surface that protect cells from apoptosis by chelating TNF-α. Ability to induce apoptosis and inflammation may represent major traits in the pathogenesis of N. meningitidis. However, our data strongly suggest that carriage isolates of meningococci reduce inflammatory response and apoptosis induction, resulting in the protection of their ecological niche at the human nasopharynx

Do we use a priori knowledge of gravity when making elbow rotations?

In this study, we aim to investigate whether motor commands, emanating from movement planning, are customized to movement orientation relative to gravity from the first trial on. Participants made fast point-to-point elbow flexions and extensions in the transverse plane. We compared movements that had been practiced in reclined orientation either against or with gravity with the same movement relative to the body axis made in the upright orientation (neutral compared to gravity). For each movement type, five rotations from reclined to upright orientation were made. For each rotation, we analyzed the first trial in upright orientation and the directly preceding trial in reclined orientation. Additionally, we analyzed the last five trials of a 30-trial block in upright position and compared these trials with the first trials in upright orientation. Although participants moved fast, gravitational torques were substantial. The change in body orientation affected movement planning: we found a decrease in peak angular velocity and a decrease in amplitude for the first trials made in the upright orientation, regardless of whether the previous movements in reclined orientation were made against or with gravity. We found that these decreases disappeared after participants familiarized themselves with moving in upright position in a 30-trial block. These results indicate that participants used a general strategy, corresponding to the strategy observed in situations with unreliable or limited information on external conditions. From this, we conclude that during movement planning, a priori knowledge of gravity was not used to specifically customize motor commands for the neutral gravity condition

Generation of Human CEACAM1 Transgenic Mice and Binding of Neisseria Opa Protein to Their Neutrophils

Human CEACAM1 is a cell-cell adhesion molecule with multiple functions including insulin clearance in the liver, vasculogenesis in endothelial cells, lumen formation in the mammary gland, and binding of certain human pathogens.Three genomic BAC clones containing the human CEACAM1 gene were microinjected into pronuclei of fertilized FVB mouse oocytes. The embryos were implanted in the oviducts of pseudopregnant females and allowed to develop to term. DNA from newborn mice was evaluated by PCR for the presence of the human CEACAM1 gene. Feces of the PCR positive offspring screened for expression of human CEACAM1. Using this assay, one out of five PCR positive lines was positive for human CEACAM1 expression and showed stable transmission to the F1 generation with the expected transmission frequency (0.5) for heterozygotes. Liver, lung, intestine, kidney, mammary gland, and prostate were strongly positive for the dual expression of both murine and human CEACAM1 and mimic that seen in human tissue. Peripheral blood and bone marrow granulocytes stained strongly for human CEACAM1 and bound Neisseria Opa proteins similar to that in human neutrophils.These transgenic animals may serve as a model for the binding of human pathogens to human CEACAM1

Polar Invasion and Translocation of Neisseria meningitidis and Streptococcus suis in a Novel Human Model of the Blood-Cerebrospinal Fluid Barrier

Acute bacterial meningitis is a life-threatening disease in humans. Discussed as entry sites for pathogens into the brain are the blood-brain and the blood-cerebrospinal fluid barrier (BCSFB). Although human brain microvascular endothelial cells (HBMEC) constitute a well established human in vitro model for the blood-brain barrier, until now no reliable human system presenting the BCSFB has been developed. Here, we describe for the first time a functional human BCSFB model based on human choroid plexus papilloma cells (HIBCPP), which display typical hallmarks of a BCSFB as the expression of junctional proteins and formation of tight junctions, a high electrical resistance and minimal levels of macromolecular flux when grown on transwell filters. Importantly, when challenged with the zoonotic pathogen Streptococcus suis or the human pathogenic bacterium Neisseria meningitidis the HIBCPP show polar bacterial invasion only from the physiologically relevant basolateral side. Meningococcal invasion is attenuated by the presence of a capsule and translocated N. meningitidis form microcolonies on the apical side of HIBCPP opposite of sites of entry. As a functionally relevant human model of the BCSFB the HIBCPP offer a wide range of options for analysis of disease-related mechanisms at the choroid plexus epithelium, especially involving human pathogens