Patent arterial duct

Patent arterial duct (PAD) is a congenital heart abnormality defined as persistent patency in term infants older than three months. Isolated PAD is found in around 1 in 2000 full term infants. A higher prevalence is found in preterm infants, especially those with low birth weight. The female to male ratio is 2:1. Most patients are asymptomatic when the duct is small. With a moderate-to-large duct, a characteristic continuous heart murmur (loudest in the left upper chest or infraclavicular area) is typical. The precordium may be hyperactive and peripheral pulses are bounding with a wide pulse pressure. Tachycardia, exertional dyspnoea, laboured breathing, fatigue or poor growth are common. Large shunts may lead to failure to thrive, recurrent infection of the upper respiratory tract and congestive heart failure. In the majority of cases of PAD there is no identifiable cause. Persistence of the duct is associated with chromosomal aberrations, asphyxia at birth, birth at high altitude and congenital rubella. Occasional cases are associated with specific genetic defects (trisomy 21 and 18, and the Rubinstein-Taybi and CHARGE syndromes). Familial occurrence of PAD is uncommon and the usual mechanism of inheritance is considered to be polygenic with a recurrence risk of 3%. Rare families with isolated PAD have been described in which the mode of inheritance appears to be dominant or recessive. Familial incidence of PAD has also been linked to Char syndrome, familial thoracic aortic aneurysm/dissection associated with patent arterial duct, and familial patent arterial duct and bicuspid aortic valve associated with hand abnormalities. Diagnosis is based on clinical examination and confirmed with transthoracic echocardiography. Assessment of ductal blood flow can be made using colour flow mapping and pulsed wave Doppler. Antenatal diagnosis is not possible, as PAD is a normal structure during antenatal life. Conditions with signs and symptoms of pulmonary overcirculation secondary to a left-to-right shunt must be excluded. Coronary, systemic and pulmonary arteriovenous fistula, peripheral pulmonary stenosis and ventricular septal defect with aortic regurgitation and collateral vessels must be differentiated from PAD on echocardiogram. In preterm infants with symptomatic heart failure secondary to PAD, treatment may be achieved by surgical ligation or with medical therapy blocking prostaglandin synthesis (indomethacin or ibuprofen). Transcatheter closure of the duct is usually indicated in older children. PAD in preterm and low birth weight infants is associated with significant co-morbidity and mortality due to haemodynamic instability. Asymptomatic patients with a small duct have a normal vital prognosis but have a lifetime risk of endocarditis. Patients with moderate-to-large ducts with significant haemodynamic alterations may develop irreversible changes to pulmonary vascularity and pulmonary hypertension

Approach for the classification of polliniferous vegetation using multispectral imaging and neural networks

Beekeeping has suffered a serious deterioration in the regions of the world. The possibility of nectar-polliniferous resources has decreased and, therefore, the feeding of bees, with the consequent decrease in production. There is, therefore, a need to improve marketing and diversification systems and to update production techniques and the management of the production process by beekeepers to obtain the quality of honey required by the market [1]. This work proposes the use of spectral information to identify the different pollen-producing plants using remote vision, image processing, and artificial neural networks

Donor‐Dependent and Other Nondefined Factors Have Greater Influence on the Hepatic Phenotype Than the Starting Cell Type in Induced Pluripotent Stem Cell Derived Hepatocyte‐Like Cells

Drug‐induced liver injury is the greatest cause of post‐marketing drug withdrawal; therefore, substantial resources are directed toward triaging potentially dangerous new compounds at all stages of drug development. One of the major factors preventing effective screening of new compounds is the lack of a predictive in vitro model of hepatotoxicity. Primary human hepatocytes offer a metabolically relevant model for which the molecular initiating events of hepatotoxicity can be examined; however, these cells vary greatly between donors and dedifferentiate rapidly in culture. Induced pluripotent stem cell (iPSC)‐derived hepatocyte‐like cells (HLCs) offer a reproducible, physiologically relevant and genotypically normal model cell; however, current differentiation protocols produce HLCs with a relatively immature phenotype. During the reprogramming of somatic cells, the epigenome undergoes dramatic changes; however, this “resetting” is a gradual process, resulting in an altered differentiation propensity, skewed toward the lineage of origin, particularly in early passage cultures. We, therefore, performed a comparison of human hepatocyte‐ and dermal fibroblast‐derived iPSCs, assessing the impact of epigenetic memory at all stages of HLC differentiation. These results provide the first isogenic assessment of the starting cell type in human iPSC‐derived HLCs. Despite a trend toward improvement in hepatic phenotype in albumin secretion and gene expression, few significant differences in hepatic differentiation capacity were found between hepatocyte and fibroblast‐derived iPSCs. We conclude that the donor and inter‐clonal differences have a greater influence on the hepatocyte phenotypic maturity than the starting cell type. Therefore, it is not necessary to use human hepatocytes for generating iPSC‐derived HLCs. Stem Cells Translational Medicine 2017;6:1321–133

MicroRNA-155 mediates multiple gene regulations pertinent to the role of human adipose-derived mesenchymal stem cells in skin regeneration

Introduction: The role of Adipose-derived mesenchymal stem cells (AD-MSCs) in skin wound healing remains to be fully characterized. This study aims to evaluate the regenerative potential of autologous AD-MSCs in a non-healing porcine wound model, in addition to elucidate key miRNA-mediated epigenetic regulations that underlie the regenerative potential of AD-MSCs in wounds.Methods: The regenerative potential of autologous AD-MSCs was evaluated in porcine model using histopathology and spatial frequency domain imaging. Then, the correlations between miRNAs and proteins of AD-MSCs were evaluated using an integration analysis in primary human AD-MSCs in comparison to primary human keratinocytes. Transfection study of AD-MSCs was conducted to validate the bioinformatics data.Results: Autologous porcine AD-MSCs improved wound epithelialization and skin properties in comparison to control wounds. We identified 26 proteins upregulated in human AD-MSCs, including growth and angiogenic factors, chemokines and inflammatory cytokines. Pathway enrichment analysis highlighted cell signalling-associated pathways and immunomodulatory pathways. miRNA-target modelling revealed regulations related to genes encoding for 16 upregulated proteins. miR-155-5p was predicted to regulate Fibroblast growth factor 2 and 7, C-C motif chemokine ligand 2 and Vascular cell adhesion molecule 1. Transfecting human AD-MSCs cell line with anti-miR-155 showed transient gene silencing of the four proteins at 24 h post-transfection.Discussion: This study proposes a positive miR-155-mediated gene regulation of key factors involved in wound healing. The study represents a promising approach for miRNA-based and cell-free regenerative treatment for difficult-to-heal wounds. The therapeutic potential of miR-155 and its identified targets should be further explored in-vivo

Pharmaceutical electrochemistry: the electrochemical detection of aspirin utilising screen printed graphene electrodes as sensors platforms.

A sensitive electrochemical sensor was designed for acetyl salicylic acid detection using graphene modified Screen Printed Electrodes. The electrochemical response of the sensor with graphene was improved compared to Screen Printed Electrodes without graphene and displayed an excellent analytical performance for the detection of acetyl salicylic acid. The high acetyl salicylic acid loading capacity on the electrode surface and the outstanding electric conductivity of graphene were also discussed in this manuscript. When a range of different concentrations of acetyl salicylic acid from 0.1 to 100 μM into a pH 4 buffer solution (N defined as the sample size N = 9) were plotted against the oxidation peak a linear response was observed. The detection limit was found to be 0.09 μM based on (3-σ/slope). Screen Printed Graphene electrodes sensors methodology is shown to be useful for quantifying low levels of acetyl salicylic acid in a buffer solution as well as in biological matrixes such as human oral fluid. A linear response was obtained over a range of concentrations from 10 to 150 μM into a human oral fluid solution (N = 10) giving a detection limit of 8.7 μM

Enabling connectivity for tactical networks in mountainous areas by aerial relays

A general modeling framework for realistic performance evaluations of tactical mobile ad-hoc networks deployed in mountainous areas is presented. The framework is easily extensible, and can be eventually automated. It can be also used to generate data for other network simulators. The framework utilizes the freely downloadable high resolution 3D terrain data to define time dependent trajectories of network nodes. The node speeds and directions are linked to the terrain profile which extends the previously proposed mobility models. The path-loss analysis along the node trajectories revealed the need for aerial relays to enable full network connectivity at all times. The network consisting of 5 cluster heads and a single stationary relay is considered as a case study. The relay location and its antenna height are optimized to achieve the line-of-sight connectivity over the whole mission duration. The antenna radiation pattern at the relay is incorporated in the analysis. The resulting star network topology is used by the cluster heads to broadcast their packets to all other cluster heads. Several relaying schemes including the amplify-and-forward and the decode-and-forward relaying are studied together with the go-back-N retransmissions to achieve the reliable data transfer

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Cognitive effects of transcranial direct current stimulation combined with working memory training in fibromyalgia: a randomized clinical trial

Cognitive dysfunction in fibromyalgia has been reported, especially memory. Anodal transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) has been effective in enhancing this function. We tested the effects of eight sessions of tDCS and cognitive training on immediate and delayed memory, verbal fluency and working memory and its association with brain-derived neurotrophic factor (BDNF) levels. Forty females with fibromyalgia were randomized to receive eight sessions of active or sham tDCS. Anodal stimulation (2 mA) was applied over the DLPFC and online combined with a working memory training (WMT) for 20 minutes. Pre and post-treatment neurocognitive tests were administered. Data analysis on deltas considering years of education and BDNF as covariates, indicated active-tDCS + WMT significantly increased immediate memory indexed by Rey Auditory Verbal Learning Test score when compared to sham. This effect was dependent on basal BDNF levels. In addition, the model showed active stimulation increased orthographic and semantic verbal fluency scores (Controlled Oral Word Association Test) and short-term memory (Forward Digit Span). The combination of both techniques seemed to produce effects on specific cognitive functions related to short-term and long-term episodic memory and executive functions, which has clinical relevance for top-down treatment approaches in FM.financiamento: This research was supported by grants and material support from the following Brazilian agencies: Committee for the Development of Higher Education Personnel - CAPES - PNPD/CAPES and material support. National Council for Scientific and Technological Development - CNPq (grants to Dr. I.L.S. Torres, Dr. W. Caumo). Postgraduate Program in Medical Sciences at the School of Medicine of the Federal University of Rio Grande do Sul (material support). Postgraduate Research Group at the Hospital de Clinicas de Porto Alegre - FIPE HCPA (material support). Foundations for Support of Research at Rio Grande do Sul (FAPERGS) (material support)

Glucose intolerance and gestational diabetes risk in relation to sleep duration and snoring during pregnancy: a pilot study

<p>Abstract</p> <p>Background</p> <p>Insufficient sleep and poor sleep quality, considered endemic in modern society, are associated with obesity, impaired glucose tolerance and diabetes. Little, however, is known about the consequences of insufficient sleep and poor sleep quality during pregnancy on glucose tolerance and gestational diabetes.</p> <p>Methods</p> <p>A cohort of 1,290 women was interviewed during early pregnancy. We collected information about sleep duration and snoring during early pregnancy. Results from screening and diagnostic testing for gestational diabetes mellitus (GDM) were abstracted from medical records. Generalized linear models were fitted to derive relative risk (RR) and 95% confidence intervals (95% CIs) of GDM associated with sleep duration and snoring, respectively.</p> <p>Results</p> <p>After adjusting for maternal age and race/ethnicity, GDM risk was increased among women sleeping ≤ 4 hours compared with those sleeping 9 hours per night (RR = 5.56; 95% CI 1.31-23.69). The corresponding RR for lean women (<25 kg/m²) was 3.23 (95% CI 0.34-30.41) and 9.83 (95% CI 1.12-86.32) for overweight women (≥ 25 kg/m²). Overall, snoring was associated with a 1.86-fold increased risk of GDM (RR = 1.86; 95% CI 0.88-3.94). The risk of GDM was particularly elevated among overweight women who snored. Compared with lean women who did not snore, those who were overweight and snored had a 6.9-fold increased risk of GDM (95% CI 2.87-16.6).</p> <p>Conclusions</p> <p>These preliminary findings suggest associations of short sleep duration and snoring with glucose intolerance and GDM. Though consistent with studies of men and non-pregnant women, larger studies that include objective measures of sleep duration, quality and apnea are needed to obtain more precise estimates of observed associations.</p