bluuebunny/crossref_metadata_2025 huggingface dataset:
Heritability of a resting heart rate in a 20-year follow-up family cohort with GWAS data: Insights from the STANISLAS cohort
Authors: Xhaard Constance , Dandine-Roulland Claire , Villemereuil Pierre de , Floch Edith Le , Bacq-Daian Delphine , Machu Jean-Loup , Ferreira Joao Pedro , Deleuze Jean-François , Zannad Faiez , Rossignol Patrick , Girerd Nicolas
Published: December 2019

Background

The association between resting heart rate (HR) and cardiovascular outcomes, especially heart failure, is now well established. However, whether HR is mainly an integrated marker of risk associated with other features, or rather a genetic origin risk marker, is still a matter for debate. Previous studies reported a heritability ranging from 14% to 65%.

Design

We assessed HR heritability in the STANISLAS family-study, based on the data of four visits performed over a 20-year period, and adjusted for most known confounding effects.

Methods

These analyses were conducted using a linear mixed model, adjusted on age, sex, tea or coffee consumption, beta-blocker use, physical activity, tobacco use, and alcohol consumption to estimate the variance captured by additive genetic effects, via average information restricted maximum likelihood analysis, with both self-reported pedigree and genetic relatedness matrix (GRM) calculated from genome-wide association study data.

Results

Based on the data of all visits, the HR heritability (h2) estimate was 23.2% with GRM and 24.5% with pedigree. However, we found a large heterogeneity of HR heritability estimations when restricting the analysis to each of the four visits (h2 from 19% to 39% using pedigree, and from 14% to 32% using GRM). Moreover, only a little part of variance was explained by the common household effect (<5%), and half of the variance remained unexplained.

Conclusion

Using a comprehensive analysis based on a family cohort, including the data of multiple visits and GRM, we found that HR variability is about 25% from genetic origin, 25% from repeated measures and 50% remains unexplained.
Targeting chronic NFAT activation with calcineurin inhibitors in diffuse large B-cell lymphoma
Authors: Bucher Philip , Erdmann Tabea , Grondona Paula , Xu Wendan , Schmitt Anja , Schürch Christoph , Zapukhlyak Myroslav , Schönfeld Caroline , Serfling Edgar , Kramer Daniela , Grau Michael , Klener Pavel , Lengerke Claudia , Schulze-Osthoff Klaus , Lenz Georg , Hailfinger Stephan
Published: December 2019

Diffuse large B-cell lymphoma (DLBCL) represents the most common adult lymphoma and can be divided into 2 major molecular subtypes: the germinal center B-cell-like and the aggressive activated B-cell-like (ABC) DLBCL. Previous studies suggested that chronic B-cell receptor signaling and increased NF-κB activation contribute to ABC DLBCL survival. Here we show that the activity of the transcription factor NFAT is chronically elevated in both DLBCL subtypes. Surprisingly, NFAT activation is independent of B-cell receptor signaling, but mediated by an increased calcium flux and calcineurin-mediated dephosphorylation of NFAT. Intriguingly, although NFAT is activated in both DLBCL subtypes, long-term calcineurin inhibition with cyclosporin A or FK506, both clinically approved drugs, triggers potent cytotoxicity specifically in ABC DLBCL cells. The antitumor effects of calcineurin inhibitors are associated with the reduced expression of c-Jun, interleukin-6, and interleukin-10, which were identified as NFAT target genes that are particularly important for the survival of ABC DLBCL. Furthermore, calcineurin blockade synergized with BCL-2 and MCL-1 inhibitors in killing ABC DLBCL cells. Collectively, these findings identify constitutive NFAT signaling as a crucial functional driver of ABC DLBCL and highlight calcineurin inhibition as a novel strategy for the treatment of this aggressive lymphoma subtype.
Identifying gene-specific subgroups: an alternative to biclustering
Authors: Branders Vincent , Schaus Pierre , Dupont Pierre
Published: December 2019

Background

Transcriptome analysis aims at gaining insight into cellular processes through discovering gene expression patterns across various experimental conditions. Biclustering is a standard approach to discover genes subsets with similar expression across subgroups of samples to be identified. The result is a set of biclusters, each forming a specific submatrix of rows (e.g. genes) and columns (e.g. samples). Relevant biclusters can, however, be missed when, due to the presence of a few outliers, they lack the assumed homogeneity of expression values among a few gene/sample combinations. The Max-Sum SubMatrix problem addresses this issue by looking at highly expressed subsets of genes and of samples, without enforcing such homogeneity.

Results

We present here the algorithm to identify K relevant submatrices. Our main contribution is to show that this approach outperforms biclustering algorithms to identify several gene subsets representative of specific subgroups of samples. Experiments are conducted on 35 gene expression datasets from human tissues and yeast samples. We report comparative results with those obtained by several biclustering algorithms, including , , , , and . Gene enrichment analysis demonstrates the benefits of the proposed approach to identify more statistically significant gene subsets. The most significant Gene Ontology terms identified with are shown consistent with the controlled conditions of each dataset. This analysis supports the biological relevance of the identified gene subsets. An additional contribution is the statistical validation protocol proposed here to assess the relative performances of biclustering algorithms and of the proposed method. It relies on a Friedman test and the Hochberg’s sequential procedure to report critical differences of ranks among all algorithms.

Conclusions

We propose here the method, a computationally efficient algorithm to identify K max-sum submatrices in a large gene expression matrix. Comparisons show that it identifies more significantly enriched subsets of genes and specific subgroups of samples which are easily interpretable by biologists. Experiments also show its ability to identify more reliable GO terms. These results illustrate the benefits of the proposed approach in terms of interpretability and of biological enrichment quality. Open implementation of this algorithm is available as an R package.
Weighted gene co-expression network analysis unveils gene networks associated with the Fusarium head blight resistance in tetraploid wheat
Authors: Sari Ehsan , Cabral Adrian L. , Polley Brittany , Tan Yifang , Hsueh Emma , Konkin David J. , Knox Ron E. , Ruan Yuefeng , Fobert Pierre R.
Published: December 2019

Background

Fusarium head blight (FHB) resistance in the durum wheat breeding gene pool is rarely reported. Triticum turgidum ssp. carthlicum line Blackbird is a tetraploid relative of durum wheat that offers partial FHB resistance. Resistance QTL were identified for the durum wheat cv. Strongfield × Blackbird population on chromosomes 1A, 2A, 2B, 3A, 6A, 6B and 7B in a previous study. The objective of this study was to identify the defense mechanisms underlying the resistance of Blackbird and report candidate regulator defense genes and single nucleotide polymorphism (SNP) markers within these genes for high-resolution mapping of resistance QTL reported for the durum wheat cv. Strongfield/Blackbird population.

Results

Gene network analysis identified five networks significantly (P < 0.05) associated with the resistance to FHB spread (Type II FHB resistance) one of which showed significant correlation with both plant height and relative maturity traits. Two gene networks showed subtle differences between Fusarium graminearum-inoculated and mock-inoculated plants, supporting their involvement in constitutive defense. The candidate regulator genes have been implicated in various layers of plant defense including pathogen recognition (mainly Nucleotide-binding Leucine-rich Repeat proteins), signaling pathways including the abscisic acid and mitogen activated protein (MAP) kinase, and downstream defense genes activation including transcription factors (mostly with dual roles in defense and development), and cell death regulator and cell wall reinforcement genes. The expression of five candidate genes measured by quantitative real-time PCR was correlated with that of RNA-seq, corroborating the technical and analytical accuracy of RNA-sequencing.

Conclusions

Gene network analysis allowed identification of candidate regulator genes and genes associated with constitutive resistance, those that will not be detected using traditional differential expression analysis. This study also shed light on the association of developmental traits with FHB resistance and partially explained the co-localization of FHB resistance with plant height and maturity QTL reported in several previous studies. It also allowed the identification of candidate hub genes within the interval of three previously reported FHB resistance QTL for the Strongfield/Blackbird population and associated SNPs for future high resolution mapping studies.
Sustained degradation of quality of life in a subgroup of lymphoma survivors: a two-year prospective survey
Authors: Compaci Gisèle , Conte Cécile , Oberic Lucie , Ysebaert Loïc , Laurent Guy , Despas Fabien
Published: December 2019

Background

Previous studies have suggested that lymphoma survivors commonly display altered Health-Related Quality of Life (HRQoL). Because these were predominantly cross-sectional studies, the dynamic of events as well as the factors which influence HRQoL remain to be determined.

Methods

We conducted a prospective study on a cohort of 204 Hodgkin and non-Hodgkin lymphoma survivors who remained disease-free 2 years after undergoing chemotherapy (referred to the M0-M12-M24 periods).

Results

We found that although Physical and Mental Component Scores (PCS and MCS) of HRQoL significantly improved from M0 to M24 in the vast majority of patients (favorable group), approximately 20% of patients displayed severe alterations in HRQoL (global SF-36 scores < 50) extending over the 2-year period (unfavorable group). Low M24 PCSs were associated with Post-Traumatic Stress Disorder (PTSD), depression, cardiovascular events and neuropathy. In contrast social determinants, comorbidity and infections, as well as several other parameters related to the disease or to the treatment itself were not associated with low M24 PCSs. Low M24 MCSs were associated with a low educational level, aggressive histology, infections, cardiovascular events and PTSS. However, the most predictive risk factor for low SF-36 scores at M24 was a low SF-36 score at M12. The unfavorable group also displayed a low incidence of return to work.

Conclusions

Although the HRQoL of lymphoma survivors generally improved over time, persistent and severe HRQoL alterations still affected approximately one fifth of patients, resulting in important social consequences. This specific group, which presents with identifiable risk factors, may benefit from early, targeted psycho-social support.
Recruitment using respondent driven sampling, risk behaviors assessment and willingness of young female sex workers (18–25 years) in Dar Es Salaam, Tanzania to participate in HIV vaccine trials
Authors: Mbunda Theodora , Tarimo Edith A. M. , Bakari Muhammad , Sandström Eric , Kulane Asli
Published: December 2019

Background

Despite the present HIV preventive and treatment programs, the prevalence of HIV is still high in eastern and southern Africa, among young women and populations at high.

risk for HIV transmission such as sex workers. There is a need to prepare a suitable population that will participate in efficacy HIV vaccine trials to determine the efficacy of HIV vaccines that had proven to be safe and immune potent.

Methods

It was a cross-sectional study that recruited 600 female sex workers using respondent-driven sampling in Dar es Salaam. The study examined recruitment approaches, risk behaviors and willingness of young female sex workers to participate in an HIV vaccine trial. Descriptive statistics described risk behaviors and willingness of the participants to participate in efficacy HIV vaccine trials. The logistic regression model computed the likelihood of willingness to participate in the trials with selected variables.

Results

The study demonstrated 53% were less than 20 years old, 96% were single, and 22% lived in brothels. Eighty percent of the participants started selling sex at the age between 15 and 19 years old, 61% used illicit drugs for the first time when they were less than 20 years old, 24% had anal sex ever. Eighty-nine percent had more than 20-lifetime sexual partners, and 56% had unprotected sexual intercourse with sex clients. Ninety-one percent expressed a willingness to participate in the HIV vaccine trial. Sixty-one percent did not need permission from anyone for participating in a trial. Ninety-one percent expressed willingness to participate in the efficacy of HIV vaccine trial. In the logistic regression model, willingness was significantly associated with the need to ask permission for participation in HIV vaccine trial from sex agent.

Conclusion

Respondent-driven sampling provided a rapid means of reaching young female sex workers who reported high-risk behaviors. The majority expressed a high level of willingness to participate in the HIV vaccine trial which was marginally correlated to the need to seek consent for participation in the trial from the sex brokers. Future HIV vaccine trials involving this population should consider involving the brokers in the trials because they form an essential part of the community for the participants.
First-degree family history of diabetes and its relationship with serum osteocalcin levels independent of liver fat content in a non-diabetic Chinese cohort
Authors: Xu Yiting , Shen Yun , Ma Xiaojing , Gu Chengchen , Wang Yufei , Bao Yuqian
Published: December 2019

Background

First-degree relatives of patients with diabetes (FDR) tend to have impaired insulin activity, which lead to the alternation of circulating cytokine levels. Liver is a main target tissue of insulin action; therefore, liver fat content (LFC) has a close relationship with insulin resistance. This study aimed to find the alteration in serum osteocalcin levels in FDR and the relationship of serum osteocalcin levels with FDR and non-alcoholic fatty liver disease (NAFLD).

Methods

In total, 1206 subjects including 413 men and 793 women from the communities, aged 59.7 (range, 54.8–64.3) years, were enrolled. An electrochemiluminescence immunoassay was performed to measure the levels of serum osteocalcin. LFC was measured using quantitative ultrasonography.

Results

A significant decrease was found in serum osteocalcin levels in subjects with NAFLD (P < 0.001) as well as in FDR (19.8 ± 5.7 ng/mL versus 20.7 ± 6.8 ng/mL, P = 0.028). Furthermore, among the subjects with NAFLD, those with FDR had lower levels of osteocalcin than those without FDR (P = 0.011). The presence of FDR remained a predictor for decreased serum osteocalcin levels after adjusting for body mass index, blood glucose, blood lipids, and LFC (standardized β = − 0.057, P = 0.028).

Conclusions

FDR had lower serum osteocalcin levels than non-FDR. The inverse association between FDR and serum osteocalcin levels was independent of metabolic factors.
Compliance with the 24-h movement guidelines and the relationship with anthropometry in Finnish preschoolers: the DAGIS study
Authors: Leppänen Marja H. , Ray Carola , Wennman Heini , Alexandrou Christina , Sääksjärvi Katri , Koivusilta Leena , Erkkola Maijaliisa , Roos Eva
Published: December 2019

Background

Recent 24-h movement guidelines for the early years established recommendations for physical activity (PA), screen time (ST), and sleep. To date, few studies have focused on compliance with meeting the guidelines and their associations with health outcomes. Thus, we aimed to investigate: 1) compliance with the 24-h movement guidelines, and 2) associations between compliance and anthropometry in Finnish preschoolers.

Methods

We utilized DAGIS survey data that were collected in 2015–2016 (N = 864). PA was assessed 24 h/day over 7 days using a waist-worn ActiGraph wGT3X-BT accelerometer. ST and sleep were reported by the parents during the same 7 days. Anthropometry was assessed using body mass index (BMI, kg/m2) and waist circumference (WC, cm). Children were classified as meeting the guidelines if they averaged ≥180 min/day of PA, which consisted of ≥60 min of moderate-to-vigorous intensity; ≤60 min/day of ST; and 10–13 h/day of sleep. In total, 778 children (51% boys, mean age: 4.7 ± 0.9 years) were included in the study. The compliance with meeting the 24-h movement guidelines was calculated for each behavior separately and in combinations. Adjusted linear regression analyses were applied to examine associations of compliance with BMI and WC.

Results

Children were physically active on average 390 (±46.2) min/day and spent 86 (±25.5) min/day in moderate-to-vigorous PA. They spent 76 (±37.4) min/day on ST and had on average 10:21 (±0:33) h:min/day of sleep. The compliance rate in meeting all three movement guidelines overall was 24%. The highest compliance rate was found for PA (85%), followed by sleep (76%) and ST (35%). Meeting guidelines separately for PA or sleep, or for both, were associated with lower WC (PA: B = -1.37, p < 0.001; Sleep: B = -0.72, p = 0.009; PA + Sleep: B = -1.03, p < 0.001). In addition, meeting guidelines for sleep or for both PA and sleep were associated with lower BMI (Sleep: B = -0.26, p = 0.027; PA + Sleep: B = -0.30, p = 0.007). There were no significant associations found regarding ST.

Conclusions

Meeting recommendations for PA and sleep may have an important role in supporting a healthy weight status in young children. However, there is still a need to improve compliance with the 24-h movement guidelines, especially for ST.
The predictors and patterns of the early recurrence of pancreatic ductal adenocarcinoma after pancreatectomy: the influence of pre- and post- operative adjuvant therapy
Authors: Suto Hironobu , Okano Keiichi , Oshima Minoru , Ando Yasuhisa , Takahashi Shigeo , Shibata Toru , Kamada Hideki , Kobara Hideki , Masaki Tsutomu , Suzuki Yasuyuki
Published: December 2019

Background

The perioperative factors predicting or influencing early pancreatic ductal adenocarcinoma recurrence are unclear. This study attempted to identify the predictive factors for early pancreatic ductal adenocarcinoma recurrence post-pancreatectomy and the influence of pre- and post- operative adjuvant therapy.

Methods

One hundred and fifteen patients undergoing curative resection for pancreatic ductal adenocarcinoma between 2000 and 2016 at our institution were retrospectively analyzed. Patients were divided into two groups: those who did (n = 34) and did not (n = 81) experience a recurrence within 6 months postoperatively.

Results

Multivariate analyses demonstrated postoperative CA19–9 de-normalization, no postoperative adjuvant chemotherapy, and serosal invasion were independent risk factors for early recurrence (P < 0.001, P = 0.001, and P = 0.010, respectively). A subgroup analysis showed patients with (n = 51) and without (n = 64) preoperative chemoradiotherapy had different predictors. Although postoperative adjuvant chemotherapy was not a significant indicator in patients with preoperative chemoradiotherapy, CA19–9 de-normalization and no postoperative adjuvant chemotherapy were significant indicators in patients without preoperative chemotherapy. Preoperative chemotherapy strongly prevented early local recurrence while postoperative adjuvant chemotherapy prevented early distant recurrence.

Conclusions

CA19–9 de-normalization was an important predictor of early recurrence of pancreatic ductal adenocarcinoma. Although postoperative adjuvant chemotherapy was an important preventive measure against early recurrence, particularly for distant recurrence, preoperative chemoradiotherapy could strongly prevent the early local recurrence of pancreatic ductal adenocarcinoma. These perioperative adjuvant therapies could have a complementary relationship.
Reliability of residents’ assessments of their postgraduate medical education learning environment: an observational study
Authors: Brand Paul L. P. , Rosingh H. Jeroen , Meijssen Maarten A. C. , Nijholt Ingrid M. , Dünnwald Saskia , Prins Jelle , Schönrock-Adema Johanna
Published: December 2019

Background

Even in anonymous evaluations of a postgraduate medical education (PGME) program, residents may be reluctant to provide an honest evaluation of their PGME program, because they fear embarrassment or repercussions from their supervisors if their anonymity as a respondent is endangered. This study was set up to test the hypothesis that current residents in a PGME program provide more positive evaluations of their PGME program than residents having completed it. We therefore compared PGME learning environment evaluations of current residents in the program to leaving residents having completed it.

Methods

This observational study used data gathered routinely in the quality cycle of PGME programs at two Dutch teaching hospitals to test our hypothesis. At both hospitals, all current PGME residents are requested to complete the Scan of Postgraduate Education Environment Domains (SPEED) annually. Residents leaving the hospital after completion of the PGME program are also asked to complete the SPEED after an exit interview with the hospital’s independent residency coordinator. All SPEED evaluations are collected and analysed anonymously. We compared the residents’ grades (on a continuous scale ranging from 0 (poor) to 10 (excellent)) on the three SPEED domains (content, atmosphere, and organization of the program) and their mean (overall department grade) between current and leaving residents.

Results

Mean (SD) overall SPEED department grades were 8.00 (0.52) for 287 current residents in 39 PGME programs and 8.07 (0.48) for 170 leaving residents in 39 programs. Neither the overall SPEED department grades (t test, p = 0.53, 95% CI for difference − 0.16 to 0.31) nor the department SPEED domain grades (MANOVA, F(3, 62) = 0.79, p = 0.51) were significantly different between current and leaving residents.

Conclusions

Residents leaving the program did not provide more critical evaluations of their PGME learning environment than current residents in the program. This suggests that current residents’ evaluations of their postgraduate learning environment were not affected by social desirability bias or fear of repercussions from faculty.
KCC2 expression levels are reduced in post mortem brain tissue of Rett syndrome patients
Authors: Hinz Lisa , Torrella Barrufet Joan , Heine Vivi M.
Published: December 2019

Rett Syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the Methyl CpG binding protein 2 (MECP2) gene. Deficient K+-Cl—co-transporter 2 (KCC2) expression is suggested to play a key role in the neurodevelopmental delay in RTT patients’ neuronal networks. KCC2 is a major player in neuronal maturation by supporting the GABAergic switch, through the regulation of neuronal chlorine homeostasis. Previous studies suggest that MeCP2 mutations lead to changed KCC2 expression levels, thereby causing a disturbance in excitation/inhibition (E/I) balance. To investigate this, we performed protein and RNA expression analysis on post mortem brain tissue from RTT patients and healthy controls. We showed that KCC2 expression, in particular the KCC2a isoform, is relatively decreased in RTT patients. The expression of Na+-K+-Cl− co-transporter 1 (NKCC1), responsible for the inward transport of chlorine, is not affected, leading to a reduced KCC2/NKCC1 ratio in RTT brains. Our report confirms KCC2 expression alterations in RTT patients in human brain tissue, which is in line with other studies, suggesting affected E/I balance could underlie neurodevelopmental defects in RTT patients.
Use and pattern of previous care received by infertile Nigerian women
Authors: Mohammed-Durosinlorun Amina , Adze Joel , Bature Stephen , Abubakar Amina , Mohammed Caleb , Taingson Matthew , Airede Lydia
Published: December 2019

Background

Prevalence of infertility in sub-Saharan Africa is high yet fertility care, its development and access is limited in resource-poor countries like Nigeria so infertile women resort to different forms of treatment. This study aimed to determine the use and pattern of previous treatments.

Methodology

This was a descriptive Cross Sectional study conducted at a tertiary hospital in North-Western Nigeria. Interviewer administered pretested questionnaires were administered to 236 consenting clients seen at their first visit to the gynaecology clinic with complaints of inability to conceive, between January 2016 to March 2018. We collected information on demographic and reproductive characteristics, previous fertility treatment and other data relevant to infertility. Descriptive analysis was done using SPSS software version 22.

Results

Two hundred and thirty six clients participated in the study and majority were 20–29 years (44.5%), with a mean age of 31.5 ± 7.4, while the mean age of their husbands was 41 ± 8.0. More clients were educated up to secondary level or above (80.9%), with more Muslims (65%) than Christians. All clients were married except one, most clients had been married for 5 years or more, 18.2% were in their second order of marriage and 28% were in polygamous marriages. Many of the clients were homemakers (46.6%) and earned an average monthly income of less than fifty thousand naira. About 59.3% of clients presented with primary infertility, with 15.7% being infertile for duration of more than 10 years. One hundred and forty six respondents (61.9%) had received previous hospital treatments before presentation to our facility, 37% had visited more than three hospitals, 70% did not have adequate investigations done, treatment was successful in 15% while 40.7% received traditional treatments. Husbands of women receiving previous treatment were slightly older (p value < 0.05).

Conclusion

Majority of woman have multiple and unnecessary visits to several hospitals for infertility care with little positive results despite time and resources spent. Quality of infertility care needs to be improved.
The adventures of psychiatric reform in Greece: 1999–2019
Authors: Madianos Michael G.
Published: December 2019

Psychiatric care in Greece has a long history of traditional in-patient treatment in large public institutions (the public asylum period), which lasted until 1983. European Economic Community (EEC) intervention in 1984 marked a transitional period (1984–1989) characterised by the beginning of the transformation of the mental healthcare system. The current reform era started in 1999 and has included new mental health law, the closure of six public mental hospitals and the establishment of several sectorised mental health services.
Psychological distress after the Great East Japan Earthquake: two multilevel 6-year prospective analyses
Authors: Goodwin Robin , Sugiyama Kemmyo , Sun Shaojing , Aida Jun , Ben-Ezra Menachem
Published: December 2019

Background

The Great East Japan Earthquake of 11 March 2011 led to the relocation of 300 000 survivors. Studies following disasters focus primarily on data collected in the immediate aftermath and neglect the influence of wider community factors.

Aims

A three-level prospective study examining associations between survivors' psychological distress and individual- and social-level factors in the 6 years following a complex disaster.

Method

We drew on two multi-wave data collections in the 6 years after the earthquake, using residents from different forms of housing. Sample 1 included six waves of private-housing residents from 2011 to 2016 (n = 1084 per wave), sample 2 five waves of residents living in prefabricated housing from 2012 to 2016 (n = 1515 per wave). We analysed prospective associations between distress and time (level 1), pre-existing disorders and disaster experiences and behaviours (level 2) and city-wide measures of support and physical activity (level 3).

Results

Multilevel models with random coefficients demonstrated greater distress in earlier waves (samples 1 and 2 respectively, adjusted β = −15 and β = −0.16, P < 0.001), among female respondents (β = 0.58, P = 0.01 and β = 1.74, P = 0.001), in those with a previous psychiatric history (β = 2.76, β = 2.06, P < 0.001) with diminished levels of activity post-earthquake (β = 1.40, β = 1.51, P < 0.001) and those lacking in social support (β = 1.95, β = 1.51, P < 0.001). Support from spouses and friends was most protective of psychological health. City-level support was negatively associated with distress, but only among those in prefabricated housing.

Conclusions

Psychological distress diminished with time, but varied across gender, psychiatric history, housing, levels of activity and availability of social support. Practitioners should consider individual- and city-level factors when devising effective interventions.
Leptin: Is It Thermogenic?
Authors: Fischer Alexander W , Cannon Barbara , Nedergaard Jan
Published: December 2019

Animals that lack the hormone leptin become grossly obese, purportedly for 2 reasons: increased food intake and decreased energy expenditure (thermogenesis). This review examines the experimental evidence for the thermogenesis component. Analysis of the data available led us to conclude that the reports indicating hypometabolism in the leptin-deficient ob/ob mice (as well as in the leptin-receptor-deficient db/db mice and fa/fa rats) derive from a misleading calculation artefact resulting from expression of energy expenditure per gram of body weight and not per intact organism. Correspondingly, the body weight-reducing effects of leptin are not augmented by enhanced thermogenesis. Congruent with this, there is no evidence that the ob/ob mouse demonstrates atrophied brown adipose tissue or diminished levels of total UCP1 mRNA or protein when the ob mutation is studied on the inbred C57BL/6 mouse background, but a reduced sympathetic nerve activity is observed. On the outbred “Aston” mouse background, brown adipose tissue atrophy is seen, but whether this is of quantitative significance for the development of obesity has not been demonstrated. We conclude that leptin is not a thermogenic hormone. Rather, leptin has effects on body temperature regulation, by opposing torpor bouts and by shifting thermoregulatory thresholds. The central pathways behind these effects are largely unexplored.
Facing compromise?
Authors: Cowley Sue
Published: December 2019

Sue Cowley drills down into the detail of the proposed, new Early Learning Goals and suggests that by aligning them more closely with KS1, the EYFS is in danger of losing its status as a unique phase.
Giving children the ability to see the REAL World
Authors: Norris Saeeda , Osmond Sharon
Published: December 2019

Two programme leads outline how training for foster carers using the Raising Early Achievement in Literacy (REAL) approach has enhanced learning for looked after children in Sandwell, West Midlands.
A case of writer's block?
Authors: Baker Charlotte
Published: December 2019

Charlotte Baker argues that depriving children of time to play too early in their education can have a long-term negative impact on their ability to think and write creatively.
Get ready for your very own magical mystery tour
Authors: Solly Kathryn
Published: December 2019

Going out into the local community can provide rich experiences and support personal, social and emotional development through real contact and engagement with people and places.
Out for the count
Authors: Williams Helen J
Published: December 2019

Is there a danger that, in squeezing in so many elements, the proposed Early Learning Goals for mathematics will be unachievable for all but a few children, leading to many being assessed as failing before they start school?
Let's see the big picture
Authors: Wright David
Published: December 2019

In line with Ian McGilchrist's theory of the ‘divided brain’, are we in danger of reducing children's education to ‘left brain thinking’, where policies are founded on expectations for their contribution to GDP, rather than their well-being, creativity and compassion?
Animal countdown
Authors: Harris Judith
Published: December 2019

Explore the books of David Walliams as a great resource to introduce key mathematical concepts, such as counting, writing numbers and comparing sizes. Making playdough snakes is guaranteed to be a hit.
From trash to treasure
Authors: Hart Karen
Published: December 2019

What goes on at your local recycling centre is often a subject of fascination for children. Karen Hart suggests ways to build on this curiosity with activities which will help them to understand the importance of managing waste and recycling unwanted objects.
‘Having a go’
Authors: Rawstrone Annette
Published: December 2019

‘Playing and exploring’ focuses on how your child is engaging in what they are investigating and experiencing firsthand. Support your child to develop these important ‘soft skills’ that will put them on the path to becoming a lifelong learner.
Vintage shopper
Authors: White Hilary
Published: December 2019

Teaching children the value of re-using and sharing their old toys by role-playing a charity shop will introduce them to the importance of staying sustainable while developing their confidence and language skills.
Come into my den
Authors: Clarke Jenni
Published: December 2019

The creation of small, cosy areas are important for allowing children to occupy private spaces, either on their own or with a friend. These secure, comfortable environments provide an ideal place to share emotions and ideas.
Understanding bioidentical hormones and their effect on quality of life
Authors: Callejas Miriam Martinez
Published: December 2019

It is important to understand the functions of the body's hormones and the options available to make the right choices for use in treating the symptoms of menopause. Bioidentical hormones are compounds that have exactly the same chemical and molecular structure as endogenous human hormones. In contrast, non-bioidentical—or synthetic—hormones are structurally dissimilar from endogenous hormones. Although it has been available for years, bioidentical compounded hormone therapy has gained popularity only recently. This article highlights the main functions of these hormones and how hormone imbalances can affect a patient's quality of life, the importance of lifestyle and diet and what bioidentical hormones are, as well as the differences in treatment in different countries and the meaning of compounding.
Getting to the root of the problem: skin picking disorder and aesthetic procedures
Authors: Gorbis Eda , Kim Carolyn
Published: December 2019

Excoriation disorder or skin picking disorder (SPD) is a chronic mental illness. It is defined by recurrent skin picking, scratching, rubbing and digging or urges to do so that goes on for extended periods of time, resulting in skin lesions and behaviour that interferes with functioning in other areas of life. The skin-picked area of the body can be smooth and healthy, and the anomaly invisible to the naked eye. Commonly, individuals with SPD seek aesthetic procedures to address perceived self-defects or to remedy their self-inflicted scarring. It is important for aesthetic practitioners to identify SPD because continuing with aesthetic interventions could worsen the illness for the sufferer. In response to this issue, aesthetic practitioners can identify individuals with SPD by administering a screening questionnaire and appropriately providing referrals to mental health professionals.
Research roundup
Authors: Mcgloin Claudia
Published: December 2019

In this regular feature, aesthetic nurse Claudia McGloin presents a brief synopsis of a range of recently published articles on medical aesthetics. Research roundup aims to provide an overview, rather than a detailed summary and critique, of the papers selected. Should you wish to look at any of the papers in more detail, a full reference is provided at the end of each study summary
Nursing is an art and a science: the year of the nurse and midwife
Authors: Peate Ian
Published: December 2019

The year 2020 is important for nurses worldwide. Not only has the World Health Organization declared it to be the year of the nurse and midwife, but it also sees the celebration of 200 years since Florence Nightingale's birth
‘Tis the season to be busy…
Authors: Hussain Corrine
Published: December 2019

As Christmas fast approaches, aesthetic clinics begin to fill with patients seeking treatments to ensure they are looking their best over the holiday season. Corrine Hussain details how clinics can make the most out of their business, while also touching on the BACN's annual conference held last month
From information to income: the five ‘I's for business success
Authors: Singh Harry
Published: December 2019

What do all successful businesses have in common? Harry Singh takes an exclusive look into the five key factors that ensure success within a business, also known as the five ‘I's, and explains how information alone is not the key
Use of accelerometer-based activity monitoring in orthopaedics: benefits, impact and practical considerations
Authors: Sliepen Maik , Lipperts Matthijs , Tjur Marianne , Mechlenburg Inger
Published: December 2019

Studies of the effectiveness of orthopaedic interventions do not generally measure physical activity (PA). Applying accelerometer-based activity monitoring in orthopaedic studies will add relevant information to the generally examined physical function and pain assessment. Accelerometer-based activity monitoring is practically feasible in orthopaedic patient populations, since current day activity sensors have battery time and memory to measure continuously for several weeks without requiring technical expertise. The ongoing development in sensor technology has made it possible to combine functional tests with activity monitoring. For clinicians, the application of accelerometer-based activity monitoring can provide a measure of PA and can be used for clinical comparisons before and after interventions. In orthopaedic rehabilitation, accelerometer-based activity monitoring may be used to help patients reach their targets for PA and to coach patients towards a more active lifestyle through direct feedback.

Cite this article: EFORT Open Rev 2019;4:678-685. DOI: 10.1302/2058-5241.4.180041
P007 Double Balloon Enteroscopy in Pediatric Crohn’s Disease for Decision Therapy and 10 Years Follow up
Authors: Oba Jane , Deboni Mariana , Toma Ricardo , Azevedo Matheus , Carlos Alexandre , Milani Luciane , Damião Adérson , Saflatle Ribeiro Adriana
Published: December 2019

BACKGROUND:

Crohn’s disease (CD) is a chronic recurrent inflammatory disease that may affect any segment of gastrointestinal tract. In 60-70% of CD may involve the small bowel (SB) and present a diagnostic challenge to decision regarding therapy. Double Balloon Enteroscopy (DBE) is one of endoscopic modality for children that allow the diagnostic and therapeutic procedures of SB disease.

Objectives:

Evaluate the feasibility, validity and safety of DBE in patients of a tertiary pediatric center with CD. In addition, we analysed its impact on treatment strategies, and established other diagnoses (malignancy, stenosis) in 10 years follow up.

METHODS:

Between 2007-10, 20 patients (age 2-20 years) with CD diagnosis, refractory to treatment were selected to undergo SB evaluation by DBE, oral route. We used general anesthesia (children < 12 y) or deep sedation with propofol (patients >13 y). Previously all had performed radiological imaging to exclude structuring. A 10-year follow up of patients was performed.

RESULTS:

Among 20 patients, 90% had SB CD in jejunum or ileum, and 10% had solely lesion in SB, which was not detected by colonoscopy. The DBE findings were: Active duodenojejunal ulcers, ulcer healing and/or pseudo polyps, sub-stenosis and mucosal granularity. Mean length of SB examined was 220 cm beyond the ligament of Treitz (range 120 to 360 cm). No significant complications were related to the procedure. Currently 14 patients are in follow up, 5 children in paediatric GI clinic and the other 9 at adult GI clinic. In 10 years follow up one patient had an extra intestinal malignancy diagnosis; one had IL-10 and/or IL-10R gene mutation and one change the diagnosis to ulcerative colitis. Curiously, the proportional number of patients in therapy, particularly biologic, had decreased.

CONCLUSION(S):

DBE is a useful tool to make differential diagnosis in SB paediatric pathologies, especially in CD who require escalating and de-escalating treatment. DBE has a good safety profile with a low index of complications when performed in reference centers.
P030 Re-Initiation of Anti TNF Agents After a Drug Holiday or Disease Relapse in Inflammatory Bowel Diseases: A Systematic Review
Authors: Hamdeh Shadi , Kalot Mohamad , Numan Laith , Alujile Yaser , Mustafa Reem , Olyaee Mojtaba
Published: December 2019

BACKGROUND:

Inflammatory bowel disease is a chronic condition that usually requires life-long treatment, with approximately one third of patients relapsing within 1 year after discontinuation of medications. It’s still not clear whether it’s safe and effective to start anti TNF agents after a drug holiday, with some studies showing benefit but others not. Therefore, we conducted a meta-analysis of studies that looked at restarting anti TNF medications after a drug holiday, to discern whether this can lead to clinical response/remission or not.

METHODS:

A comprehensive search of several databases including Ovid MEDLINE Epub Ahead of Print, Ovid Medline In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus was performed up to September 15, 2019. Two independent reviewers systematically identified trials that looked at restarting anti TNF drugs after a drug holiday. A meta-analysis was performed using a random effect model to assess the outcomes of clinical remission after re-initiation of anti TNF.

RESULTS:

Total of 17 studies with 918 patients retreated with anti TNF medications after a drug holiday (2 studies) or due to disease relapse (15 studies) met our inclusion criteria and were ultimately included in the final analysis. The remission rate of patients retreated with biologics was abstracted from 17 studies. A binary random effects model was used to pool the proportions of remission from all studies. The pooled rate for remission in those patients was 82.2% (76.7%–87.7%), however we found a serious inconsistency among studies with an i2 value of 79.3%. Additionally, although some of the estimates in individual studies do not fall within the confidence internal of the estimates in the other studies, the pooled estimate for remission ranging from 76.7% to 87.7% indicates precision in the results, as both ends of the confidence interval would lead to the same clinical decision of retreating patients after a drug holiday or relapse.

CONCLUSION(S):

Our results indicated that restarting anti TNF after a drug holiday or due to disease relapse may lead to clinical response and can be considered in clinical practice.
P073 Double Balloon Enteroscopy in Refractory Crohn's Disease: Jejunal Findings and Clinical Impact After 10 Years of Follow-Up
Authors: Facanali Marcio , Facanali Carolina , Queiroz Natália , Sobrado Carlos , Prazeres Tulio , Deboni Mariana , Filho Edesio , Oba Jane , Toma Ricardo , Nahas Sergio , Saflatle Ribeiro Adriana
Published: December 2019

BACKGROUND:

Crohn's disease (CD) is a chronic inflammatory disease that can affect all segments of the gastrointestinal tract. With various phenotypes and progressive course, it can be complicated with fistulas, abscesses or stenosis. Treatment targets includes clinical remission and mucosal healing in order to avoid complicated outcomes. Double balloon enteroscopy (DBE) allows complete evaluation of the small intestine, providing diagnoses and the possibility of interventions such as biopsies, with low complication rates. Some authors suggest that involvement of the proximal small bowel may indicate worse long-term therapeutic outcomes. This study aims to correlate jejunal endoscopic findings observed in baseline DBE with the activity of CD after 10 years of follow-up.

METHODS:

Twenty paediatric refractory CD patients (2–17 years old) performed DBE by a single experienced specialist after radiological evaluation for stenosis exclusion between 2007 and 2010. After 10 years, the degree of CD activity was assessed by the Harvey-Bradshaw Index (HBI), C-Reactive Protein (CRP) serum dosage, and current therapy through collection of electronic medical records and personal communication.

RESULTS:

Sixteen 16/20 patients (80%) completed the 10 years follow up period. Two patients (2/16) changed diagnosis (1- monogenic disease, IL-10 and / or IL10R gene mutation; 1 - ulcerative colitis). Previous findings of DBE of the 14 patients corresponded to: 2 active duodenojejunal ulcers, 4 duodenojejunal scar retractions, 1 retraction and pseudopolyps in the proximal ileum, 6 hyperemia and / or edema and / or granularity of the jejunal mucosa, and 1 without alteration. After 10 years, 6/14 patients have abnormal CRP (>5 mg/L), with 3 of them having HBI between 5 and 7, 2 between 8 and 16 and 1 of 4. All of them presented previous jejunal alterations, 5/6 are currently in use of biologic and 3/6 are steroid dependent. The 2 patients who had active ulcers in baseline DBE remain steroid dependent and with higher rates of HBI activity. Eight patients (8/14) have normal CRP, all presenting HBI lower than 5. Of these, 3 are using combined therapy with immunosuppressant and biologic, 1 with biologic monotherapy, 2 with immunosuppressant, and 2 without medication.

CONCLUSION(S):

Active jejunal disease, observed through DBE, may indicate a more severe phenotype in CD after long-term follow-up, suggesting a distinct phenotype. Evaluation of the proximal small intestine should be considered in refractory paediatric CD patients or those with diagnostic uncertainty.