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Abstract Background Disruptions of brain-gut axis have been implicated in the progression of a variety of gastrointestinal (GI) disorders and central nervous system (CNS) diseases and injuries, including traumatic brain injury (TBI). TBI is a chronic disease process characterized by persistent secondary injury processes which can be exacerbated by subsequent challenges. Enteric pathogen infection during chronic TBI worsened cortical lesion volume; however, the pathophysiological mechanisms underlying the damaging effects of enteric challenge during chronic TBI remain unknown. This preclinical study examined the effect of intestinal inflammation during chronic TBI on associated neurobehavioral and neuropathological outcomes, systemic inflammation, and dysautonomia. Methods Dextran sodium sulfate (DSS) was administered to adult male C57BL/6NCrl mice 28 days following craniotomy (Sham) or TBI for 7 days to induce intestinal inflammation, followed by a return to normal drinking water for an additional 7 to 28 days for recovery; uninjured animals (Naïve) served as an additional control group. Behavioral testing was carried out prior to, during, and following DSS administration to assess changes in motor and cognitive function, social behavior, and mood. Electrocardiography was performed to examine autonomic balance. Brains were collected for histological and molecular analyses of injury lesion, neurodegeneration, and neuroinflammation. Blood, colons, spleens, mesenteric lymph nodes (mLNs), and thymus were collected for morphometric analyses and/or immune characterization by flow cytometry. Results Intestinal inflammation 28 days after craniotomy or TBI persistently induced, or exacerbated, respectively, deficits in fine motor coordination, cognition, social behavior, and anxiety-like behavior. Behavioral changes were associated with an induction, or exacerbation, of hippocampal neuronal cell loss and microglial activation in Sham and TBI mice administered DSS, respectively. Acute DSS administration resulted in a sustained systemic immune response with increases in myeloid cells in blood and spleen, as well as myeloid cells and lymphocytes in mesenteric lymph nodes. Dysautonomia was also induced in Sham and TBI mice administered DSS, with increased sympathetic tone beginning during DSS administration and persisting through the first recovery week. Conclusion Intestinal inflammation during chronic experimental TBI causes a sustained systemic immune response and altered autonomic balance that are associated with microglial activation, increased neurodegeneration, and persistent neurological deficits.

Objectives Advances in surgical management strategies have substantially reduced fatality from congenital heart defects (CHD). Decreased infant mortality might be expected, consequentially to result in greater morbidity in older children due to complications later in childhood and adolescence. This study aims to evaluate the use of cardiovascular medication (CVM) as an indicator of disease burden in children born with CHD in the first 10 years of life.Design Population-based cohort study.Setting Six population-based registries from the European Surveillance of Congenital Anomalies (EUROCAT) network participated. Data from live born children with major congenital anomalies (CA) born from 2000 to 2014 were linked to prescription databases. Four groups of children were analysed: CA, CHD, severe CHD (sCHD) and ventricular septal defect (VSD) without sCHD. Live born children without CA were included as reference group.Participants We obtained data on 61 038 children born with a CA, including 19 678 with CHD, 3392 with sCHD, 12 728 children with VSD without sCHD, and 1 725 496 reference children.Results Children born with sCHD were the most likely to receive a CVM prescription (42.9%, 95% CI, 26.3 to 58.5) in the first year of life compared with 13.3% (6.7 to 22.0) of children with any CHD, 5.9% (3.7 to 8.7) of children with any CA and 0.1% (0.0 to 0.1) of reference children. Medication was less likely to be prescribed after the first year of life for sCHD; 18.8% (14.8 to 23.1) for children 1–4 years and 15.8% (12.0 to 20.1) 5–9 years. Children with sCHD were most likely to receive a diuretic (36.4%, 18.6 to 54.5), an antihypertensive (6.9%, 3.7 to 11.3) or a beta-blocker (5.5%, 2.9 to9.2).Conclusion Almost half of all children with sCHD were prescribed CVM in their first year of life. For all four groups of children with anomalies, the proportion of children with a CVM prescription decreased with age.

To examine the prevalence, determinants and attitude towards herbal medication (HM) use in the first trimester of pregnancy in Cameroon women. Between March to August 2015, we surveyed 795 pregnant women attending 20 randomly selected urban or rural hospitals in South West Cameroon on first trimester orthodox medication (OM) and HM use. Data was obtained by interviews using structured questionnaires. First trimester HM use was reported by 293 (36∙9%) women, 76% of whom used it in combination with OM. The most frequent indication for taking HM was prevention/treatment of anaemia (26∙3%). The HM were usually self-prescribed (33∙3%) or by family (56∙2%), and obtained from the woman's own garden (69∙3%). Twenty percent of women believed that HM was always safe to take in pregnancy, compared to 69.3% for OM. Intake of HM was significantly influenced by women's opinion on OM or HM safety-the odds of taking HM was 3 time higher among women who were unsure about the safety of OM (AOR: 3∙0, 95%CI = 1∙5-6∙1), while women who thought HM were never safe or who were unsure about its safety, were 91% or 84% respectively less likely to take HM compared to women who believed HM were always safe. We identified a high prevalence of HM use and concomitant use with OM, strongly influenced by women's perception of HM and OM safety. These findings indicate the need for WHO to specifically address safety in pregnancy in its policy to integrate traditional medicine use into existing healthcare systems in Africa.

BackgroundCongenital anomalies are a leading cause of childhood morbidity, but little is known about the long-term outcomes.ObjectiveTo quantify the burden of disease in childhood for children with congenital anomalies by assessing the risk of hospitalisation, the number of days spent in hospital and proportion of children with extended stays (≥10 days).MethodsEuropean population-based record-linkage study in 11 regions in eight countries including children with congenital anomalies (EUROCAT children) and without congenital anomalies (reference children) living in the same regions. The children were born between 1995 and 2014 and were followed to their tenth birthday or 31/12/2015. European meta-analyses of the outcome measures were performed by two age groups, Results99,416 EUROCAT children and 2,021,772 reference children were linked to hospital databases. Among EUROCAT children, 85% (95%-CI: 79-90%) were hospitalised in the first year and 56% (95%-CI: 51-61%) at ages 1-4 years, compared to 31% (95%-CI: 26-37%) and 25% (95%-CI: 19-31%) of the reference children. Median length of stay was 2-3 times longer for EUROCAT children in both age groups. The percentages of children with extended stays (≥10 days) in the first year were 24% (95%-CI: 20-29%) for EUROCAT children and 1% (95%-CI: 1-2%) for reference children. The median length of stay varied greatly between congenital anomaly subgroups, with children with gastrointestinal anomalies and congenital heart defects having the longest stays.ConclusionsChildren with congenital anomalies were more frequently hospitalised and median length of stay was longer. The outlook improves after the first year. Parents of children with congenital anomalies should be informed about the increased hospitalisations required for their child's care and the impact on family life and siblings, and they should be adequately supported.

Background Studies on medication safety in pregnancy are increasingly focusing on child neurodevelopmental outcomes. Establishing neurodevelopmental safety is complex due to the range of neurodevelopmental outcomes and the length of follow-up needed for accurate assessment. The aim of this study was to provide an inventory of European data sources for use in pharmacoepidemiologic studies investigating neurodevelopment following maternal medication exposure. Method The EUROmediSAFE inventory of data sources in Europe for evaluating perinatal and long-term childhood risks associated with in-utero exposure to medication was updated by contacting colleagues across 31 European countries, literature review and internet searches. Included data sources must record at least one neurodevelopmental outcome and maternal medication use in pregnancy must be available, either in the data source itself or through linkage with another data source. Information on the domain of neurodevelopment, measure/scale used and the approach to measurement were recorded for each data source. Results Ninety data sources were identified across 14 countries. The majority (63.3%) were created for health surveillance and research with the remaining serving administrative purposes (21.1% healthcare databases,15.6% other administrative databases). Five domains of neurodevelopment were identified—infant development (36 data sources,13 countries), child behaviour (27 data sources, 10 countries), cognition (29 data sources, 12 countries), educational achievement (20 data sources, 7 countries), and diagnostic codes for neurodevelopmental disorders (42 data sources, 11 countries). Thirty-nine data sources, in 12 countries, had information on more than one domain of neurodevelopment. Conclusion This inventory is invaluable to future studies planning to investigate the neurodevelopmental impact of medication exposures during pregnancy. Caution must be used when combining varied approaches to neurodevelopment outcome measurement, the age of children in the data source, and the sensitivity and specificity of the outcome measure selected should be borne in mind.

Aim To establish the prevalence of prescriptions dispensed in early pregnancy by maternal age and area deprivation, for women who gave birth in Northern Ireland (NI) 2011–2016. Study design Population-based linked cohort study. Methods The NI Maternity System (NIMATS) database was used to identify all births to resident mothers in NI between 2011 and 2016. Prescriptions dispensed between the last menstrual period (LMP) and the first antenatal care visit (mean 10.7 weeks) (2010–2016) were extracted from the Enhanced Prescribing Database (EPD) which records all prescriptions dispensed by pharmacists in NI. EPD data were linked to NIMATS using the mother’s Health and Care Number. Maternal deprivation based on the NI Multiple Deprivation Measure 2017 was linked using the mother’s postcode. Results The cohort included 139,687 pregnancies resulting in live or stillbirths to 106,206 women. A medication was dispensed in 63.5% of pregnancies, and in 48.7% of pregnancies excluding supplements (vitamins, iron, and folic acid). Folic acid was the most commonly dispensed medication (33.1%). Excluding supplements, the mean number of medications was 1.1, with 4.2% having ≥5 medications. The most common non-supplement medications were antibiotics (13.1%), antiemetics (8.7%), analgesics (6.9%), hormonal medications (6.9%) and antidepressants (6.1%). Younger women (Conclusion Half of all pregnant women in NI were dispensed a non-supplement medication between LMP and the first antenatal care visit. Younger and older mothers and those living in the most deprived areas were more likely to have medications dispensed. More antidepressants were dispensed in areas of social deprivation.

Aging adversely affects inflammatory processes in the brain, which has important implications in the progression of neurodegenerative disease. Following traumatic brain injury (TBI), aged animals exhibit worsened neurological function and exacerbated microglial-associated neuroinflammation. Type I Interferons (IFN-I) contribute to the development of TBI neuropathology. Further, the Cyclic GMP-AMP Synthase (cGAS) and Stimulator of Interferon Genes (STING) pathway, a key inducer of IFN-I responses, has been implicated in neuroinflammatory activity in several age-related neurodegenerative diseases. Here, we set out to investigate the effects of TBI on cGAS/STING activation, IFN-I signaling and neuroinflammation in young and aged C57Bl/6 male mice. Using a controlled cortical impact model, we evaluated transcriptomic changes in the injured cortex at 24 hours post-injury, and confirmed activation of key neuroinflammatory pathways in biochemical studies. TBI induced changes were highly enriched for transcripts that were involved in inflammatory responses to stress and host defense. Deeper analysis revealed that TBI increased expression of IFN-I related genes (e.g. Ifnb1, Irf7, Ifi204, Isg15) and IFN-I signaling in the injured cortex of aged compared to young mice. There was also a significant age-related increase in the activation of the DNA-recognition pathway, cGAS, which is a key mechanism to propagate IFN-I responses. Finally, enhanced IFN-I signaling in the aged TBI brain was confirmed by increased phosphorylation of STAT1, an important IFN-I effector molecule. This age-related activation of cGAS and IFN-I signaling may prove to be a mechanistic link between microglial-associated neuroinflammation and neurodegeneration in the aged TBI brain.

ObjectiveTo determine risk of Down syndrome (DS) in multiple relative to singleton pregnancies, and compare prenatal diagnosis rates and pregnancy outcome.DesignPopulation-based prevalence study based on EUROCAT congenital anomaly registries.SettingEight European countries.Population14.8 million births 1990-2009; 2.89% multiple births.MethodsDS cases included livebirths, fetal deaths from 20 weeks, and terminations of pregnancy for fetal anomaly (TOPFA). Zygosity is inferred from like/unlike sex for birth denominators, and from concordance for DS cases.Main outcome measuresRelative risk (RR) of DS per fetus/baby from multiple versus singleton pregnancies and per pregnancy in monozygotic/dizygotic versus singleton pregnancies. Proportion of prenatally diagnosed and pregnancy outcome.Statistical analysisPoisson and logistic regression stratified for maternal age, country and time.ResultsOverall, the adjusted (adj) RR of DS for fetus/babies from multiple versus singleton pregnancies was 0.58 (95% CI 0.53-0.62), similar for all maternal ages except for mothers over 44, for whom it was considerably lower. In 8.7% of twin pairs affected by DS, both co-twins were diagnosed with the condition. The adjRR of DS for monozygotic versus singleton pregnancies was 0.34 (95% CI 0.25-0.44) and for dizygotic versus singleton pregnancies 1.34 (95% CI 1.23-1.46). DS fetuses from multiple births were less likely to be prenatally diagnosed than singletons (adjOR 0.62 [95% CI 0.50-0.78]) and following diagnosis less likely to be TOPFA (adjOR 0.40 [95% CI 0.27-0.59]).ConclusionsThe risk of DS per fetus/baby is lower in multiple than singleton pregnancies. These estimates can be used for genetic counselling and prenatal screening.

Neuroinflammation is initiated as a result of traumatic brain injury and can exacerbate evolving tissue pathology. Immune cells respond to acute signals from damaged cells, initiate neuroinflammation, and drive the pathological consequences over time. Importantly, the mechanism(s) of injury, the location of the immune cells within the brain, and the animal species all contribute to immune cell behavior following traumatic brain injury. Understanding the signals that initiate neuroinflammation and the context in which they appear may be critical for understanding immune cell contributions to pathology and regeneration. Within this paper, we review a number of factors that could affect immune cell behavior acutely following traumatic brain injury.

Widespread resistance to QoIs, DMI and SDHIs fungicides has been reported for Brazilian populations of the wheat blast pathogen Pyricularia oryzae Triticum lineage (PoTl). A pre-existing resistance mechanism not associated with target site mutations has been indicated for resistance to DMIs and SDHIs, with strong indication that PoTl has multidrugresistance (MDR). Therefore, the main objective of this study was to test the hypothesis that resistance to DMI and SDHI fungicides detected in PoTl was due to efflux pump mediated MDR mechanism(s) by characterizing the sensitivity to antifungal efflux pump substrates. Four antifungal substrates were tested: tolnaftate (TOL), cycloheximide (CHX), rhodamine 6G (RH6G) and triphenyltin chloride (TPCL). TPCL and RH6G were considered the most relevant indicators for enhanced MDR activity. Among the 16 PoTl isolates tested, 9 were insensitive to TPCL, 1 to TOL, 16 to RH6G and 1 to CHX. The PoTl isolates were grouped into four distinct multidrug resistance phenotypes (MDRPs) based on resistance to combinations of fungicides and antifungal efflux pump substrates. Insensitivity to TPCL, RH6G and or TOL correlated well with DMI insensitivity, but MDR was not associated with SDHI resistance. The identification of multiple MDRP phenotypes associated with DMI resistance in our study warrants further research aimed at revealing the exact mechanisms of multidrug resistance in the wheat blast pathogen, including efflux pumps overexpression via transcriptomic analyses of differentially expressed genes; identification and discovery of mutations associated with changes in promoter regions or transcription factors of efflux transporters associated with multidrug resistance.

Introduction Congenital anomalies (CAs) are a major cause of infant mortality, childhood morbidity and long-term disability. Over 130 000 children born in Europe every year will have a CA. This paper describes the EUROlinkCAT study, which is investigating the health and educational outcomes of children with CAs for the first 10 years of their lives.Methods and analysis EUROCAT is a European network of population-based registries for the epidemiological surveillance of CAs. EUROlinkCAT is using the EUROCAT infrastructure to support 22 EUROCAT registries in 14 countries to link their data on births with CAs to mortality, hospital discharge, prescription and educational databases. Once linked, each registry transforms their case data into a common data model (CDM) format and they are then supplied with common STATA syntax scripts to analyse their data. The resulting aggregate tables and analysis results are submitted to a central results repository (CRR) and meta-analyses are performed to summarise the results across all registries. The CRR currently contains data on 155 594 children with a CA followed up to age 10 from a population of 6 million births from 1995 to 2014.Ethics The CA registries have the required ethics permissions for routine surveillance and transmission of anonymised data to the EUROCAT central database. Each registry is responsible for applying for and obtaining additional ethics and other permissions required for their participation in EUROlinkCAT.Dissemination The CDM and associated documentation, including linkage and standardisation procedures, will be available post-EUROlinkCAT thus facilitating future local, national and European-level analyses to improve healthcare. Recommendations to improve the accuracy of routinely collected data will be made.Findings will provide evidence to inform parents, health professionals, public health authorities and national treatment guidelines to optimise diagnosis, prevention and treatment for these children with a view to reducing health inequalities in Europe.

Aim of study: The interpretation of results of leaf analysis can be performed by nutritional balance methods, such as Kenworthy method (KW) and diagnostic levels of contents, whose achievements for cacao constitute the main objective of this work. Area of study: Bahia, Brazil. Material and methods: The database covered cacao trees in two cultivation systems: agroforestry systems and full sun. The reference populations were composed of plots with relative yield higher than the average plus half a standard deviation of each of these cultivation systems, in addition to a combined population of both systems. Main results: The norms of the KW method were compared by the t test, for mean, with 72% concordance; and F, for variance, 82% concordant. The diagnoses made based on specific norms per cultivation system and the general norm agreed on average of 91%. Potential response curves were obtained as a function of the Balanced Indices of Kenworthy (BIK) for each nutrient, by the boundary-line method, in addition to sufficiency ranges for BIK and for leaf contents for cacao. Research highlights: It is concluded that the general KW norms associated with the original Kenworthy ranges or the specific ranges for cacao are efficient in the nutritional diagnosis of cacao.

Abstract Objective The 2014 update of the Swiss law on research increases patients' protection; it adds specific requirements for emergency situations, implying an active search for patients' wishes regarding research participation; the possibility of consent waivers is not clearly stated. We explored its practical impact in a RCT on critically ill adults. Methods We considered prospectively collected consents of a multicenter trial addressing the impact of continuous EEG on survival. We assessed the proportions of consents obtained strictly according to the law, of specific waivers for this study obtained from the IRB (early death; relatives' unavailability despite repeated attempts), and the yield of retrieving statements on willingness to research participation. We compared the proportion of consent refusals with those of recent trials in similar environments, and estimated the potential impact on study results. Results Of 402 recruited patients, six had double inclusions, one died before intervention, and 27 (6.7%, alive on long‐term) were excluded following consent refusal or withdrawal, leaving 368 analyzable patients. Specific waivers allowed inclusion of 134 (36.4%) patients, while informed consents were obtained for all others. A statement of willingness to research participation was found in only 14.1%. In recent trials, consent refusal oscillated between 0%–23%, according to different waiver policies. Conclusions Consent waivers should be specifically foreseen to prevent losing a potentially relevant proportion of patients reaching endpoints, and ensure results generalizability. The yield of looking for willingness to research participation seems low; this questions its current usefulness and calls for a public awareness campaign.

EUROCAT is a European network of population-based congenital anomaly (CA) registries. Twenty-one registries agreed to participate in the EUROlinkCAT study to determine if reliable information on the survival of children born with a major CA between 1995 and 2014 can be obtained through linkage to national vital statistics or mortality records. Live birth children with a CA could be linked using personal identifiers to either their national vital statistics (including birth records, death records, hospital records) or to mortality records only, depending on the data available within each region. In total, 18 of 21 registries with data on 192,862 children born with congenital anomalies participated in the study. One registry was unable to get ethical approval to participate and linkage was not possible for two registries due to local reasons. Eleven registries linked to vital statistics and seven registries linked to mortality records only; one of the latter only had identification numbers for 78% of cases, hence it was excluded from further analysis. For registries linking to vital statistics: six linked over 95% of their cases for all years and five were unable to link at least 85% of all live born CA children in the earlier years of the study. No estimate of linkage success could be calculated for registries linking to mortality records. Irrespective of linkage method, deaths that occurred during the first week of life were over three times less likely to be linked compared to deaths occurring after the first week of life. Linkage to vital statistics can provide accurate estimates of survival of children with CAs in some European countries. Bias arises when linkage is not successful, as early neonatal deaths were less likely to be linked. Linkage to mortality records only cannot be recommended, as linkage quality, and hence bias, cannot be assessed.

Biological control is considered the only viable integrated disease management practice for controlling the widely distributed and destructive foliar blight and sudden death disease caused by the fungus Rhizoctonia solani AG-1 IA on signal grass (Urochloa brizantha) pastures. Since major signal grass varieties are highly susceptible and fungicide sprays are not labeled for grass pasture cropping systems, biological control is sought as an alternative for managing this fungal disease. In this study, 24 fluorescent Pseudomonas isolates obtained from naturally suppressive soils from the Amazon biome were bio-prospected for their role as biocontrol agents against R. solani AG-1 IA. Based on in vitro antagonism, three isolates (Amana, Poti, and Yara) were selected for further in vivo assays. Multilocus phylogenetic analysis indicated that Amana and Yara were grouped into the Pseudomonas putida group while Poti was grouped into the Pseudomonas asplenii group, and could well constitute a new Pseudomonas species. For in vivo biocontrol assays, the biocontrol agents were applied either via seed-treatment or via foliar spray. All three isolates produced siderophores and solubilized phosphate, while Amana and Poti showed protease and chitinase in vitro activity. Foliar application of P. putida Amana from Amazonian suppressive soils resulted in a significant reduction of the foliar blight disease severity on signal grass. We discuss further steps for the development and labeling of Pseudomonas-based biofungicides for managing the foliar blight disease on signal grass pastures in Brazil.

DOI: https://doi.org/10.26694/reufpi.v1i3.849 Objetivo: Estudo qualitativo que objetivou descrever a percepção das puérperas sobre o parto normal e sobre a assistência prestada pela Equipe de Saúde durante o parto. Métodos: Participaram 11 puérperas que tiveram o último parto por via vaginal em maternidade pública. A coleta dos dados foi através de entrevistas semi-estruturadas, cujos dados foram analisados utilizando a análise de conteúdo temática. Resultados: As puérperas perceberam o parto como um evento doloroso e dependente da equipe. Na assistência recebida no parto, houve puérperas que apresentaram uma percepção positiva quando receberam apoio, conforto e atenção, e houve aquelas que perceberam a falta de acolhimento por parte dos profissionais de saúde. Conclusão: Assim, ainda existe uma lacuna entre as ações preconizadas pelo Ministério da Saúde brasileiro, quanto à assistência humanizada, e às condutas dos profissionais. As práticas voltadas à humanização do parto e nascimento poderão contribuir para a segurança e o respeito à dignidade e autonomia das mulheres.

We investigated the role of maternal environmental factors in the aetiology of congenital heart disease (CHD). A population-based case-control study (242 CHD cases, 966 controls) was conducted using an iPad questionnaire for mother with linkage to maternity and first trimester prescription records. Risk of CHD was associated with low maternal education (OR adjusted for confounders 1.59; 95% confidence interval [CI], 1.02-2.49), pregestational diabetes (OR 4.04; 95% CI 1.00-16.28), self-reported maternal clotting disorders (adjOR 8.55, 95%CI 1.51-48.44), prescriptions for the anticlotting medication enoxaparin (adjOR 3.22, 95%CI 1.01-10.22) and self-reported vaginal infections (adjOR 1.69, 95%CI 1.01-2.80). There was no strong support for the hypothesis that periconceptional folic acid supplements have a protective effect, but there was a protective effect of frequent consumption of folate rich fruits (adjOR 0.64, 95%CI 0.47-0.89). Compared to the most common pre-pregnancy dietary pattern, CHD risk was associated with a poor diet low in fruit and vegetables (adjOR 1.56, 95%CI 1.05-2.34). Mothers of cases reported more pregnancy related stress (adjOR 1.69; 95% CI 1.22-2.34) and multiple stressors (adjOR 1.94, 95%CI 0.83-4.53). We found no supportive evidence for CHD risk being associated with obesity, smoking, depression or antidepressant use in this population. Our findings add to the previous evidence base to show potential for public health approaches to help prevent CHD in future by modifying environmental factors. Independent confirmation should be sought regarding elevated CHD risk associated with maternal blood clotting disorders and their treatment, since we are the first to report this.

Abstract Background There is a paucity of epidemiological data on medication use in pregnancy in Cameroon. Methods Between March and August 2015, 795 pregnant women attending 8 urban and 12 rural hospitals in Cameroon for antenatal (ANC) or other care were interviewed on first trimester medication use using structured questionnaires. Multivariate logistic regression was used to analyse the association of 18 sociodemographic factors with medication use. Results A total of 582 (73.2%) women took at least one orthodox (Western) medication during the first trimester, 543 (68.3%) women a non-pregnancy related orthodox medication, and 336 (42.3%)women a pregnancy related orthodox medication. 44% of the women took anti-infectives including antimalarials (33.6%) and antibiotics (20.8%).The other most common medications were analgesics (48.8%) and antianaemias (38.6%). Sulfadoxine/pyrimethamine, contraindicated in the first trimester of pregnancy, was the most commonly used antimalarial(13% of women).0.2% of women reported antiretroviral use. Almost 80% of all orthodox medications consumed by women were purchased from the hospital. 12.8% of the women self-prescribed. Health unit and early gestational age at ANC booking were consistent determinants of prescribing of non-pregnancy related, pregnancy related and anti-infective medications. Illness and opinion on the safety of orthodox medications were determinants of the use of non-pregnancy related medications and anti-infectives. Age and parity were associated only with non-pregnancy related medications. Conclusion This study has confirmed the observations of studies across Africa indicating the increasing use of medications during pregnancy. This is an indication that access to medicine is improving and more emphasis now must be placed on medication safety systems targeting pregnant women, especially during the first trimester when the risk of teratogenicity is highest.

Abstract Neuroinflammation is recognized as one of the obligatory pathogenic features of neurodegenerative diseases including Alzheimer’s, Parkinson’s or prion diseases. In prion diseases, space and time correlations between deposition of disease-associated, pathogenic form of the prion protein or PrPSc and microglial-mediated neuroinflammation has been established. Yet, it remains unclear whether activation of microglia is triggered directly by a contact with PrPSc, and what molecular features of PrPSc microglia sense and respond to that drive microglia to inflammatory states. The current study asked the questions whether PrPSc can directly trigger activation of microglia and whether the degree of microglia response depends on the nature of terminal carbohydrate groups on the surface of PrPSc particles. PrPSc was purified from brains of mice infected with mouse-adapted prion strain 22L or neuroblastoma N2a cells stably infected with 22L. BV2 microglial cells or primary microglia were cultured in the presence of purified 22L. We found that exposure of BV2 cells or primary microglia to purified PrPSc triggered proinflammatory responses characterized by an increase in the levels of TNFα, IL6, nitric oxide (NO) and expression of inducible Nitric Oxide Synthase (iNOS). Very similar patterns of inflammatory response were induced by PrPSc purified from mouse brains and neuroblastoma cells arguing that microglia response is independent of the source of PrPSc. To test whether the microglial response is mediated by carbohydrate epitopes on PrPSc surface, the levels of sialylation of PrPSc N-linked glycans was altered by treatment of purified PrPSc with neuraminidase. Partial cleavage of sialic acid residues was found to boost the inflammatory response of microglia to PrPSc. Moreover, transient degradation of Iκβα observed upon treatment with partially desialylated PrPSc suggests that canonical NFκB activation pathway is involved in inflammatory response. The current study is the first to demonstrate that PrPSc can directly trigger inflammatory response in microglia. In addition, this work provides direct evidence that the chemical nature of the carbohydrate groups on PrPSc surface is important for microglial activation.

Objective: Posterior cortical atrophy (PCA) is a neurodegenerative syndrome characterised by progressive impairment in visuospatial and perceptual function. Recent findings show that memory functioning can also be compromised early in the course of disease. In this study, we investigated the neural basis of memory impairment in PCA, and hypothesised that correlations would be observed with parietal cortex rather than classic medial temporal memory structures. Methods: Eighteen PCA patients, 15 typical Alzheimer's disease (tAD) patients and 21 healthy controls underwent memory testing with the Rey Auditory Verbal Learning Test (RAVLT) word list and MRI. Voxel-based morphometry (VBM) was used to identify regions in the parietal and medial temporal lobes that correlated with memory performance. Results: Compared with controls, PCA patients were impaired at learning, immediate and delayed recall and recognition of the RAVLT. Learning rate and immediate recall was significantly better in PCA compared to tAD, whereas there was no difference in delayed recall. Recognition memory also was not statistically different between patient groups, but PCA patients made significantly more false positive errors than tAD patients. VBM analysis in the PCA patients revealed a significant correlation between total learning and grey matter density in the right supramarginal gyrus, right angular gyrus and left postcentral gyrus. The left post central gyrus also significantly correlated with immediate and delayed recall and with recognition memory. No correlations were detected in the medial temporal lobe. Conclusions: The findings provide novel evidence that early verbal memory impairment is frequently observed in PCA, and is associated with damage to lateral parietal structures. The results have implications for the diagnosis and management of PCA. Keywords: Posterior cortical atrophy, Episodic memory, Attention, Alzheimer's disease

Posterior cortical atrophy is a neurodegenerative syndrome characterised by progressive disruption of visual and perceptual processing, associated with atrophy in the parieto-occipital cortex. Current diagnostic criteria describe relative sparing of episodic memory function, but recent findings suggest that anterograde memory is often impaired. Whether these deficits extend to remote memory has not been addressed. A large body of evidence suggests that the recollection of an autobiographical event from the remote past coincides with the successful retrieval of visual images. We hypothesised that the profound visual processing deficits in posterior cortical atrophy would result in impaired autobiographical memory retrieval. Fourteen posterior cortical atrophy patients, eighteen typical Alzheimer's disease patients and twenty-eight healthy controls completed the Autobiographical Interview. Autobiographical memory in posterior cortical atrophy was characterised by a striking loss of internal, episodic detail relative to controls and to same extent as typical Alzheimer's disease patients, in conjunction with an increase in external details tangential to the memory described. The memory narratives of posterior cortical atrophy patients showed a specific reduction in spatiotemporal and perceptual detail. Voxel-based morphometry analysis revealed atrophy of the parieto-occipital cortices in posterior cortical atrophy but relatively spared hippocampi bilaterally, compared with characteristic atrophy of the medial temporal lobes in typical Alzheimer's disease. Analysis of brain regions showing posterior cortical atrophy-specific atrophy revealed a correlation between perceptual details in autobiographical memory and grey matter density in the right precuneus. This study demonstrates remote memory impairment in posterior cortical atrophy despite relatively preserved medial temporal lobe structures. The results demonstrate, for the first time, profound autobiographical memory impairment in PCA and suggest that this is driven by the well-recognised deficits in higher-order visual processing. The findings are discussed in the context of posterior parietal contributions to imagery and memory, and the clinical implications of autobiographical memory impairment for diagnostic and management protocols in posterior cortical atrophy. Keywords: Posterior cortical atrophy, Autobiographical memory, Visual imagery, Alzheimer's disease

Assuring security and privacy of data is a key challenge for organizations when developing WBAN applications. The reasons for this challenge include (i) developers have limited knowledge of market-specific regulatory requirements and security standards, and (ii) there are a vast number of security controls with insufficient implementation detail. To address these challenges, we have developed a WBAN data security and privacy risk management framework. The goal of this paper is trifold. First, we present the methodology used to develop the framework. The framework was developed by considering recommendations from legislation and standards. Second, we present the findings from an initial validation of the framework’s usability and effectiveness of the security and privacy controls. Finally, we present an updated version of the framework and explain how it addresses the aforementioned challenges.

Patients with hippocampal amnesia play a central role in memory neuroscience but the neural underpinnings of amnesia are hotly debated. We hypothesized that focal hippocampal damage is associated with changes across the extended hippocampal system and that these, rather than hippocampal atrophy per se, would explain variability in memory between patients. We assessed this hypothesis in a uniquely large cohort of patients (n = 38) after autoimmune limbic encephalitis, a syndrome associated with focal structural hippocampal pathology. These patients showed impaired recall, recognition and maintenance of new information, and remote autobiographical amnesia. Besides hippocampal atrophy, we observed correlatively reduced thalamic and entorhinal cortical volume, resting-state inter-hippocampal connectivity and activity in posteromedial cortex. Associations of hippocampal volume with recall, recognition, and remote memory were fully mediated by wider network abnormalities, and were only direct in forgetting. Network abnormalities may explain the variability across studies of amnesia and speak to debates in memory neuroscience.

Introduction The Baby Hearts study aimed to investigate risk and protective factors for congenital heart disease (CHD), and to investigate the health behaviours of a representative sample of pregnant women in Northern Ireland. Objectives We describe and evaluate the population-based case-control design enhanced with data linkage to administrative health data. Methods Cases (mothers of babies with CHD, n=286) were recruited following diagnosis prenatally or postnatally. Controls (mothers of babies without CHD, n=966) were recruited at 18-22 weeks gestation, from all women attending each maternity unit during a designated month. Hybrid data collection methods were used, including a self-administered iPad/postal questionnaire, and linkage to maternity and prescription records. Results Refusal rates were low (8%). iPad questionnaire completion at clinic or home visit had high acceptability whereas postal questionnaires were poorly returned leading to a further 9-10% loss of eligible cases/controls. In total, 61% of eligible cases and 68% of eligible controls were recruited, closely representative of the Northern Ireland population, with no evidence of selection bias. Of those recruited, 97% gave consent for linkage to medical records. Thirty-three percent of women had an unplanned pregnancy and 76% suspected they were pregnant by 5 weeks gestation, with no significant differences between cases and controls. There was considerable discordance between self-report, maternity and prescription records regarding medications obtained/taken in the first trimester, but no evidence of differences between cases and controls that would indicate substantial recall bias. Although there was high concordance between self-report and maternity records regarding folic acid supplementation, cases had significantly lower concordance than controls. Conclusions Our results suggest hybrid data collection approaches are a useful way forward for aetiological studies to reduce responder burden and address and estimate recall bias, and that the Baby Hearts study protocol is suitable for replication in other populations, modified to the local context.

This paper examines the current state of the art of commercially available outdoor footfall sensor technologies and defines individually tailored solutions for the walking trails involved in an ongoing research project. Effective implementation of footfall sensors can facilitate quantitative analysis of user patterns, inform maintenance schedules and assist in achieving management objectives, such as identifying future user trends like cyclo-tourism. This paper is informed by primary research conducted for the EU funded project TrailGazersBid (hereafter referred to as TrailGazers), led by Donegal County Council, and has Sligo County Council and Causeway Coast and Glens Council (NI) among the 10 project partners. The project involves three trails in Ireland and five other trails from Europe for comparison. It incorporates the footfall capture and management experiences of trail management within the EU Atlantic area and desk-based research on current footfall technologies and data capture strategies. We have examined 6 individual types of sensor and discuss the advantages and disadvantages of each. We provide key learnings and insights that can help to inform trail managers on sensor options, along with a decision-making tool based on the key factors of the power source and mounting method. The research findings can also be applied to other outdoor footfall monitoring scenarios.

Resistance to human epidermal growth factor receptor 2 (HER2)-targeted therapies presents a major clinical problem. Although preclinical studies have identified a number of possible mechanisms, clinical validation has been difficult. This is most likely to reflect the reliance on cell-line models that do not recapitulate the complexity and heterogeneity seen in human tumours. Here, we show the utility of a genetically engineered mouse model of HER2-driven breast cancer (MMTV-NIC) to define mechanisms of resistance to the pan-HER family inhibitor AZD8931. Genetic manipulation of MMTV-NIC mice demonstrated that loss of phosphatase and tensin homologue (PTEN) conferred de novo resistance to AZD8931, and a tumour fragment transplantation model was established to assess mechanisms of acquired resistance. Using this approach, 50% of tumours developed resistance to AZD8931. Analysis of the resistant tumours showed two distinct patterns of resistance: tumours in which reduced membranous HER2 expression was associated with an epithelial-to-mesenchymal transition (EMT) and resistant tumours that retained HER2 expression and an epithelial morphology. The plasticity of the EMT phenotype was demonstrated upon re-implantation of resistant tumours that then showed a mixed epithelial and mesenchymal phenotype. Further AZD8931 treatment resulted in the generation of secondary resistant tumours that again had either undergone EMT or retained their original epithelial morphology. The data provide a strong rationale for basing therapeutic decisions on the biology of the individual resistant tumour, which can be very different from that of the primary tumour and will be specific to individual patients.

Aerial twisting techniques are preferred by trampoline coaches for their balanced landings. As these techniques are not intuitive, computer simulation has been a relevant tool to explore a variety of techniques. Up to now, twisting somersaults were mainly simulated using arm abduction/adduction only (2D). Our objective was to explore more complex (3D) but still anatomically feasible arm techniques to find innovative and robust twisting techniques. The twist rotation was maximized in a straight backward somersault performed by a model including arm abduction/adduction with and without changes in the plane of elevation. A multi-start approach was used to find a series of locally optimal performances. Six of them were retained and their robustness was assessed by adding noise to the first half of the arm kinematics and then reoptimizing the second half of the skill. We found that aerial twist performance linearly correlates with the complexity of arm trajectory. Optimal techniques share a common strategy consisting of moving the arm in a plane formed by the twisting and angular momentum axes, termed as the best tilting plane. Overall, 3D techniques are simpler and require less effort than 2D techniques for similar twist performances. Three techniques which generate ∼3 aerial twists could be used by athletes because kinematic perturbations do not compromise the performance and the landing.

Background Over 130,000 children are born in Europe every year with congenital anomalies which are a major cause of infant mortality, childhood morbidity and long-term disability. A European data linkage study (EUROlinkCAT) aims to investigate the health and educational outcomes of children up to 10 years of age with congenital anomalies, born between 1995 and 2014. While congenital anomaly data including information on potential risk factors are standardised across the EUROCAT network, information on mortality, morbidity and educational outcomes are not. Objective To create a common data model that transforms key variables in local databases to standardised formats enabling data on health and educational outcomes to be pooled and analysed across multiple registries. Method Twenty-two EUROCAT registries in fourteen countries are participating in the study. Each registry records uniformly coded data on cases of congenital anomaly registered in their local population using the EUROCAT Data Management Program. The registries will link their congenital anomaly data to their local mortality, hospital discharge, prescriptions and educational data. The linked individual case data cannot leave the local institution or “safe haven” environment, therefore verification and validation of all derived variables, data transformations and proxy variables must be performed locally. Findings Creating a common data model is challenging as there are diverse coding classification systems, languages, healthcare and educational systems in Europe. As with many administrative datasets, the common data model is based on coded data rather than the often richer “free text” information. Conclusion The use of administrative datasets across Europe enables pooling of data on rare outcomes and allows hypotheses on the health and education of children to be investigated. However, a common data model must be applied to ensure that data from multiple sites conform to a standard format.

Background The Northern Ireland (NI) Baby Hearts study aimed to investigate risk factors for congenital heart defects (CHD), and to investigate the health behaviours of a representative sample of NI pregnant women. Methods We performed a case-control study with hybrid data collection methods, including self-administered iPad questionnaire or postal questionnaire, information held in maternity records and linkage to prescription records. Cases (n=286) were recruited following diagnosis prenatally or postnatally, controls (n=966) were recruited during recruitment months in each maternity unit at 18-20 weeks gestation. Findings Refusal rates for questionnaire completion were low (7-8%). Among those recruited, consent for access and linkage to medical records was high (98%). Recruitment of both cases and controls was closely representative of the NI population in terms of age, area of residence and deprivation. There was considerable discordance between self-report questionnaires, maternity records and prescription records regarding medications taken in the first trimester, and between self-report questionnaires and maternity records regarding behaviours such as preconceptional folic acid, pregnancy planning, and smoking. However, there were no differences between cases and controls that would indicate recall bias. Conclusions Our results suggest that hybrid data collection approaches are a useful way forward for aetiological studies.

Background There is great potential to use routinely collected patient health records for research if the quality of data is sufficient for this purpose. Objective To assess the accuracy of information on medications and maternal diseases reported by the mother and recorded in the NI Maternity System (NIMATS) database compared to electronic prescriptions issued by the General Practitioner and recorded in the Enhanced Prescribing Database (EPD). Method A cross-sectional data linkage validation study was conducted through the Honest Broker Service. The NIMATS database, EPD and NI Multiple Deprivation Measure (MDM) were linked for all births in NI with a pregnancy booking interview between 1st April 2010 and 30th June 2016. Information on medications and illnesses recorded in NIMATS were compared to prescription data recorded in EPD. Findings Between April 2010 and June 2016, 139,687 pregnant women were linked to EPD and the NIMDM. In NIMATS, 94.4% (131,909) of women reported taking medications in the first trimester of pregnancy compared to 63.5% (88,693) in the EPD. The most common exposures in both databases were vitamins, folic acid and iron. Use of some medications varied by maternal age for example antibiotics were more common among younger mothers while cardiac medications were more common among older mothers. Excluding vitamins, folic acid and iron, 27.2% (14,786) of pregnancies with a medication recorded in NIMATS had a current disease recorded compared to 30.3% (20,574) of those in EPD. Conclusions Medication exposure rates differ depending on the data source used. NIMATS includes over-the-counter and hospital prescribed medications but may be subject to maternal recall bias. The EPD records prescribed medications but it is unknown if the woman took these. For both NIMATS and EPD, less than a third of pregnancies with a medication exposure have a disease recorded suggesting under recording of maternal disease in NIMATS.

BACKGROUND:Surveillance of congenital anomalies is important to identify potential teratogens. METHODS:This study analysed the prevalence of 61 congenital anomaly subgroups (excluding chromosomal) in 25 population-based EUROCAT registries (1980-2012). Live births, fetal deaths and terminations of pregnancy for fetal anomaly were analysed with multilevel random-effects Poisson regression models. RESULTS:Seventeen anomaly subgroups had statistically significant trends from 2003-2012; 12 increasing and 5 decreasing. CONCLUSIONS:The annual increasing prevalence of severe congenital heart defects, single ventricle, atrioventricular septal defects and tetralogy of Fallot of 1.4% (95% CI: 0.7% to 2.0%), 4.6% (1.0% to 8.2%), 3.4% (1.3% to 5.5%) and 4.1% (2.4% to 5.7%) respectively may reflect increases in maternal obesity and diabetes (known risk factors). The increased prevalence of cystic adenomatous malformation of the lung [6.5% (3.5% to 9.4%)] and decreased prevalence of limb reduction defects [-2.8% (-4.2% to -1.5%)] are unexplained. For renal dysplasia and maternal infections, increasing trends may be explained by increased screening, and deceases in patent ductus arteriosus at term and increases in craniosynostosis, by improved follow up period after birth and improved diagnosis. For oesophageal atresia, duodenal atresia/stenosis and ano-rectal atresia/stenosis recent changes in prevalence appeared incidental when compared with larger long term fluctuations. For microcephaly and congenital hydronephrosis trends could not be interpreted due to discrepancies in diagnostic criteria. The trends for club foot and syndactyly disappeared once registries with disparate results were excluded. No decrease in neural tube defects was detected, despite efforts at prevention through folic acid supplementation.

Microglia and macrophage cells are the primary producers of cytokines in response to neuroinflammatory processes. But these cytokines are also produced by other glial cells, endothelial cells, and neurons. It is essential to identify the cells that produce these cytokines to target their different levels of activation. We used dual RNAscope® fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) techniques to visualize the mRNA expression pattern of pro- and anti-inflammatory cytokines in microglia/macrophages cells. Using these methods, we can associate one mRNA to specific cell types when combining with different cellular markers by immunofluorescence. Results from RNAscope® probes IL-1β, TNFα, TGFβ, IL-10 or Arg1, showed colocalization with antibodies for microglia/macrophage cells. These target probes showed adequate sensitivity and specificity to detect mRNA expression. New FISH detection techniques combined with immunohistochemical techniques will help to jointly determine the protein and mRNA localization, as well as provide reliable quantification of the mRNA expression levels.

There has been a dramatic growth of individuals using online auctions especially within Consumer-to-Consumer (C2C) e-commerce coupled with increasing academic attention to behaviour in the online environments. Literature has identified the influence of attitudes, perceptions, trust and security on individual’s online auction transaction intentions and behaviours. The aim of this study, therefore, was to predict and understand individuals online auction transaction intentions and behaviours through the application of the Theory of Planned Behaviour (TPB). Three hundred and seventy-two respondents completed the survey within two geographical regions. Findings reported that attitudes, self-efficacy and trust significantly influenced intentions; while intentions and self-efficacy significantly influenced online auction behaviours. Interestingly, social pressures, perceived control and security failed to have any influence. Overall, the study provided greater insight into which salient drivers influence transaction behaviours and intentions.

To explore the predictive value of cognitive and coping resources for problem- and emotion-focused coping with age, we collected data from community-dwelling adults between 20 and 90 years old. We hypothesized that age, perceived stress, self-efficacy, working-memory capacity, and mental flexibility were predictors of coping. We collected data using French versions of the Perceived Stress Scale, General Self-Efficacy Scale, and Way of Coping Checklist. Cognitive assessments comprised the WAIS III digit-span subtest and the Trail Making Test parts A and B. In multivariate analyses, neither working-memory nor mental-flexibility deficit predicted problem-focused coping. "Age" was found to predict only problem-focused coping. "Self-efficacy" predicted problem-focused coping, and "perceived stress" predicted emotion-focused coping. Our results confirmed that use of an emotion-focused coping style would not significantly change with age. Problem-focused coping increases with age and depends primarily on participants' confidence in their ability to successfully solve problems (i.e., self-efficacy).