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Nutraceutical interventions supporting microbiota and eliciting clinical improvements in metabolic diseases have grown significantly. Chronic stress, gut dysbiosis, and metainflammation have emerged as key factors intertwined with sleep disorders, consequently exacerbating the decline in quality of life. This study aimed to assess the effects of two nutraceutical formulations containing prebiotics (fructooligosaccharides (FOS), galactooligosaccharides (GOS), yeast β-glucans), minerals (Mg, Se, Zn), and the herbal medicine Silybum marianum L. Gaertn., Asteraceae (Milk thistle or Silymarin). These formulations, namely NSupple (without silymarin) and NSupple_Silybum (with silymarin) were tested over 180 days in overweight/obese volunteers from Brazil's southeastern region. We accessed fecal gut microbiota by partial 16S rRNA sequences; cytokines expression by CBA; anthropometrics, quality of life and sleep, as well as metabolic and hormonal parameters, at baseline (T0) and 180 days (T180) post-supplementation. Results demonstrated gut microbiota reshaping at phyla, genera, and species level post-supplementation. The Bacteroidetes phylum, Bacteroides, and Prevotella genera were positively modulated especially in the NSupple_Silybum group. Gut microbiota modulation was associated with improved sleep patterns, quality-of-life perception, cytokines expression, and anthropometric parameters post-supplementation. Our findings suggest that the nutraceutical blends positively enhance cardiometabolic and inflammatory markers. Particularly, NSupple_Silybum modulated microbiota composition, underscoring its potential significance in ameliorating metabolic dysregulation. Clinical trial registry number: NCT04810572. 23/03/2021., (© 2024. The Author(s).)

(1) Background: Patient safety culture (PSC) encompasses the values, attitudes, norms, beliefs, practices, perceptions, competencies, policies, and behaviours of professionals that determine organisational commitment to quality and patient safety. Few studies use mixed methods to analyse patient safety culture, and none offer the richness of using a mixed methodology to develop their theoretical model. This study aims to identify the factors nurses believe contextualise and influence PSC in relation to existing theoretical frameworks. (2) Methods: This study employed a sequential explanatory mixed-methods design combined with the Pillar Integration Process for data integration. (3) Results: In the final data integration process, 26 factors affecting nurses' PSC were identified. Factors nurses related to PSC not being assessed with the tool used in phase 1 were notification system, flow of patients, patient involvement, resources and infrastructure, and service characteristics. (4) Conclusions: This mixed-methods study provides an opportunity to identify the weaknesses and strengths of currently developed theoretical frameworks related to PSC and offers content for its improvement. Even though multiple studies aim to assess PSC using existing quantitative method tools, the development of this study offers a glimpse of some aspects relevant to nurses' PSC not included in the theoretical framework of the said tools, such as patient involvement, the flow of patients, and service infrastructure.

Objective: We aimed to 1) describe how the UK obesity epidemic reflects a change over time in the proportion of the population demonstrating adverse latent patterns of BMI development and 2) investigate the potential roles of maternal and paternal BMI in this secular process., Methods: We used serial BMI data between 7 and 17 years of age from 13220 boys and 12711 girls. Half the sample was born in 1958 and half in 2001. Sex-specific growth mixture models were developed. The relationships of maternal and paternal BMI and weight status with class membership were estimated using the 3-step BCH approach, with covariate adjustment., Results: The selected models had five classes. For each sex, in addition to the two largest normal weight classes, there were "normal weight increasing to overweight" (17% of boys and 20% of girls), "overweight increasing to obesity" (8% and 6%), and "overweight decreasing to normal weight" (3% and 6%) classes. More than 1-in-10 children from the 2001 birth cohort were in the "overweight increasing to obesity" class, compared to less than 1-in-30 from the 1958 birth cohort. Approximately 75% of the mothers and fathers of this class had overweight or obesity. When considered together, both maternal and paternal BMI were associated with latent class membership, with evidence of negative departure from additivity (i.e., the combined effect of maternal and paternal BMI was smaller than the sum of the individual effects). The odds of a girl belonging to the "overweight increasing to obesity" class (compared to the largest normal weight class) was 13.11 (8.74, 19.66) times higher if both parents had overweight or obesity (compared to both parents having normal weight); the equivalent estimate for boys was 9.01 (6.37, 12.75)., Conclusions: The increase in obesity rates in the UK over more than 40 years has been partly driven by the growth of a sub-population demonstrating excess BMI gain during adolescence. Our results implicate both maternal and paternal BMI as correlates of this secular process., (© 2022. The Author(s).)

Cognitive deficits are common in borderline personality disorder (BPD) and appear to be associated with psychopathology, functioning and outcome. The availability of a cognitive screening instrument could be of use in clinical settings in order to assess neurocognition in BPD patients. The Screen for Cognitive Impairment for Psychiatry (SCIP) proved to be reliable in different psychiatric populations, but it has not yet been validated in personality disorders. The purpose of this study is therefore to evaluate its psychometric properties in a sample of 58 BPD patients. The SCIP was validated against the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Trail Making Test A and B (TMT A and B). The receiver operator curve analysis displayed an acceptable convergent validity (total score AUC: 0.78, 95% CI: 0.70-0.86; Se: 75%, Sp: 72%). A cut-off total score of 80 identified 81% of patients as cognitively impaired. The exploratory factor analysis displayed a one-factor solution explaining 55.8% of the total variance. The SCIP displayed adequate psychometric properties in BPD and could be integrated in the routine clinical assessment to provide a preliminary evaluation of cognitive features for BPD., (© 2022 The Authors Personality and Mental Health Published by John Wiley & Sons Ltd.)

Background: The school environment is an ideal setting for promoting physical activity (PA). Wearable activity trackers (wearables) have previously been implemented, in research, as intervention tools within the school-environment. However, the large-scale use and acceptance of wearables, in schools, is unknown., Methods: This study distributed a cross-sectional survey to school staff to investigate the prevalence of child and adolescent wearable use in schools, including when and how they are used, and school staff's willingness to use them in the future (as implemented by school staff). This survey consisted of between 13 and 22 items, including closed-ended and open-ended questions. Closed-ended responses were displayed descriptively (wearable prevalence and characteristics), and open-ended qualitative responses were categorised using descriptive content analysis (how wearables are used)., Results: 1087 school staff provided valid responses. Of those, 896 (82.4%) had never used a wearable as a teaching or support tool for their students, and 120 (11%) currently used- and 71 (6.5%) had previously used- a wearable as a teaching or support tool for their students. When wearables were used, school staff implemented their use regularly and during physical education lessons or throughout the entire school day. Wearables were used to monitor or increase student's PA levels, or for student and staff educational purposes (e.g., academic learning, movement breaks). Most school staff were willing to use a wearable as a teaching or support tool to promote student's PA, and/or learning about PA, in the future., Conclusions: This study is the first study to explore the widescale use and acceptance of children and adolescents using wearables in the school-setting. Findings may inform the development of future school-based interventions and public health initiatives for physical activity promotion, using wearables.

Background: The family environment plays a crucial role in child physical activity (PA). Wearable activity trackers (wearables) show potential for increasing children's PA; however, few studies have explored families' acceptance of wearables. This study investigated the acceptability of using wearables in a family setting, aligning experiences with components of the Technology Acceptance Model and Theoretical Domains Framework., Methods: Twenty-four families, with children aged 5-9 years, took part in a 5-week study, where all members were provided with a Fitbit Alta HR for 4 weeks. Acceptability was measured using weekly surveys and pre-post-questionnaires. Nineteen families participated in a focus group. Quantitative and qualitative data were integrated using the Pillar Integration Process technique., Results: Pillars reflected (1) external variables impacting wearable use and PA and (2) wearable use, (3) ease of use, (4) usefulness for increasing PA and other health outcomes, (5) attitudes, and (6) intention to use a wearable, including future intervention suggestions., Conclusions: Families found the Fitbit easy to use and acceptable, but use varied, and perceived impact on PA were mixed, with external variables contributing towards this. This study provides insights into how wearables may be integrated into family-based PA interventions and highlights barriers and facilitators of family wearable use.

Very few studies have focused on the relationship between cognitive functions and clinical features in borderline personality disorder (BPD). Subjects with BPD and healthy controls were administered the Repeatable Battery for the Assessment of Neuropsychological Status, Trail Making Test A and B, and the Wisconsin Card Sorting Test. The Brief Symptom Inventory (BSI-53) was used to assess the severity of current symptoms. Attachment style was assessed with the Experiences in Close Relationship Questionnaire, identity integration with the Personality Structure Questionnaire, and other domains of personality dysfunction with the RUDE Scale for Personality Dysfunction. Patients with BPD performed significantly worse than healthy controls in all cognitive domains. Cognitive functions, particularly delayed memory and visuospatial abilities, displayed meaningful associations with trait-like clinical features, above the effect of global cognition and state psychopathology. These findings highlight the need to evaluate effects of cognitive rehabilitation on trait features among individuals with BPD.

Background: Early life adversity is increasingly prevalent and associated with greater morbidity and mortality. It is hypothesised that the link between psychosocial early life adversity and poor health in adulthood is due to abnormal hypothalamic-pituitary-adrenal (HPA) axis functioning (often measured as cortisol patterning) and inflammation (often measured via c-reactive protein (CRP)). This study aimed to investigate the relationship between early life psychosocial adversity and cortisol patterning and CRP at 60-64 years of age., Methods: The MRC National Survey of Health and Development (NSHD) was used. The analytic "cortisol sample" included 843 individuals and the "CRP sample" included 1150 individuals. Data on adversity experienced between ages 0-15 years were utilised to compose a cumulative childhood psychosocial early life adversity (ELA) score (0, 1, 2, 3+). CRP and salivary cortisol (waking, 30 min after waking, and evening) were collected at 60-64 years. Associations between the psychosocial ELA score and cortisol outcomes (cortisol awakening response (CAR), diurnal slope (DS), and evening and morning cortisol) were assessed using general linear regression. Tobit regression was used to assess the association between psychosocial ELA score and CRP. Adjustments were made for age at follow-up, sex, childhood maternal education, childhood paternal social class, childhood housing tenure, and birth weight. After testing for sex by ELA score interactions, analyses were repeated stratified by sex for the CRP sample., Results: In fully adjusted models, individuals who experienced the highest level of childhood psychosocial adversity (3+) had a 24.63 (-41.49, -7.76) % lower waking cortisol and a 7.30 (1.49, 13.12) % lower decline in cortisol across the day compared to those with a psychosocial ELA score of zero. In females, the highest level of childhood psychosocial adversity, compared to the lowest, was associated with 32.61 (2.98, 62.25) % higher CRP at 60-64 years, which attenuated to 20.38% (-9.38, 50.14) upon adjustment for measures of early life socioeconomic position. Conversely, the association between childhood psychosocial adversity and CRP in males was null., Conclusions: Our results suggest that high-levels of psychosocial adversity in childhood might result in a lower morning cortisol and flatter DS in mid-to-late-adulthood. The finding that adversity was related to higher CRP in females but not males requires replication and further investigation., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background and Aims: We investigated the associations of 20-year body mass index (BMI) and waist circumference (WC) histories with risk of being 1) metabolically unhealthy overweight/obese (MUOO) vs metabolically healthy overweight/obese (MHOO) and 2) metabolically unhealthy normal weight (MUNW) vs metabolically healthy normal weight (MHNW)., Methods and Results: Participants comprised 3018 adults (2280 males; 738 females) with BMI and WC measured, every ~5 years, in 1991-1994, 1997-1999, 2002-2004, 2007-2009, and 2012-2013. Mean age in 2012-2013 was 69.3 years, with a range of 59.7-82.2 years. Duration was defined as the number of times a person was overweight/obese (or centrally obese) across the 5 visits, severity as each person's mean BMI (or WC), and variability as the within-person standard deviation of BMI (or WC). At the 2013-2013 visit, participants were categorised based on their weight (overweight/obese or normal weight; body mass index (BMI) ≥25 kg/m 2 ) and health status (healthy or unhealthy; two or more of hypertension, low high-density lipoprotein cholesterol, high triglycerides, high glucose, and high homeostatic model assessment of insulin resistance). Logistic regression was used to estimate associations with the risk of being MUNW (reference MHNW) and MUOO (reference MHOO) at the last visit. BMI and WC severity were each related to increased risk of being unhealthy, with estimates being stronger among normal weight than overweight/obese adults. The estimates for variability exposures became null upon adjustment for severity. Individuals who were overweight/obese at all 5 time points had a 1.60 (0.96-2.67) times higher risk of being MUOO than MHOO compared to those who were only overweight/obese at one (i.e., the last) time point. The corresponding estimate for central obesity was 4.20 (2.88-6.12). Greater duration was also related to higher risk of MUNW than MHNW., Conclusion: Being overweight/obese yet healthy seems to be partially attributable to lower exposure to adiposity across 20 years of adulthood. The results highlight the importance of maintaining optimum and stable BMI and WC, both in adults who become and do not become overweight/obese., Competing Interests: Declaration of competing statement The authors declare that they have no conflict of interest., (Copyright © 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Carbapenem-resistant Enterobacteriaceae are a worldwide health problem and isolates carrying both bla KPC-2 and bla NDM-1 are unusual. Here we describe the microbiological and clinical characteristics of five cases of bloodstream infections (BSI) caused by carbapenem-resistant Klebsiella pneumoniae and Serratia marcescens having both bla KPC-2 and bla NDM-1 . Of the five blood samples, three are from hematopoietic stem cell transplantation patients, one from a renal transplant patient, and one from a surgical patient. All patients lived in low-income neighbourhoods and had no travel history. Despite antibiotic treatment, four out of five patients died. The phenotypic susceptibility assays showed that meropenem with the addition of either EDTA, phenylboronic acid (PBA), or both, increased the zone of inhibition in comparison to meropenem alone. Molecular tests showed the presence of bla KPC-2 and bla NDM-1 genes. K. pneumoniae isolates were assigned to ST258 or ST340 by whole genome sequencing. This case-series showed a high mortality among patients with BSI caused by Enterobacteriae harbouring both carbapenemases. The detection of carbapenemase-producing isolates carrying both bla KPC-2 and bla NDM-1 remains a challenge when using only phenotypic assays. Microbiology laboratories must be alert for K. pneumoniae isolates producing both KPC-2 and NDM-1., (© 2021. The Author(s).)

How noncoding transcription influences chromatin states is still unclear. The Arabidopsis floral repressor gene FLC is quantitatively regulated through an antisense-mediated chromatin silencing mechanism. The FLC antisense transcripts form a cotranscriptional R-loop that is dynamically resolved by RNA 3' processing factors (FCA and FY), and this is linked to chromatin silencing. Here, we investigate this silencing mechanism and show, using single-molecule DNA fiber analysis, that FCA and FY are required for unimpeded replication fork progression across the Arabidopsis genome. We then employ the chicken DT40 cell line system, developed to investigate sequence-dependent replication and chromatin inheritance, and find that FLC R-loop sequences have an orientation-dependent ability to stall replication forks. These data suggest a coordination between RNA 3' processing of antisense RNA and replication fork progression in the inheritance of chromatin silencing at FLC ., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

Wearable activity trackers (wearables) embed numerous behaviour change techniques (BCTs) that have previously been shown to increase adult physical activity (PA). With few children and adolescents achieving PA guidelines, it is crucial to explore ways to increase their PA. This systematic review examined the acceptability, feasibility, and effectiveness of wearables and their potential mechanisms of action for increasing PA in 5 to 19-year-olds. A systematic search of six databases was conducted, including data from the start date of each database to December 2019 (PROSPERO registration: CRD42020164506). Thirty-three studies were included. Most studies (70%) included only adolescents (10 to 19 years). There was some-but largely mixed-evidence that wearables increase steps and moderate-to-vigorous-intensity PA and reduce sedentary behaviour. There were no apparent differences in effectiveness based on the number of BCTs used and between studies using a wearable alone or as part of a multi-component intervention. Qualitative findings suggested wearables increased motivation to be physically active via self-monitoring, goal setting, feedback, and competition. However, children and adolescents reported technical difficulties and a novelty effect when using wearables, which may impact wearables' long-term use. More rigorous and long-term studies investigating the acceptability, feasibility, and effectiveness of wearables in 5 to 19-year-olds are warranted.

Several risk factors have been related to the onset and maintenance of gambling disorder (GD). The aim of this study was to explore the differences in emotion dysregulation, impulsivity, cognitive distortions, and attentional bias between online and land-based gamblers. The sample consisted of 88 treatment-seeking patients from the Behavioral Addictions Unit at the Hospital de la Santa Creu i Sant Pau, Barcelona (Spain). Patients were divided into two groups by considering their main type of gambling, i.e., online ( n = 26) and land-based gambling ( n = 62). Online gamblers were younger, more often employed, with a higher educational level than land-based gamblers. Regarding the rest of the variables, statistically significant differences were only found in Positive Urgency , one of the UPPS-P subscales, in which the land-based gambling group scored higher than the online gambling group. In this exploratory study, individuals with online and land-based GD phenotypes did not differ either in difficulties in emotion regulation or in attentional and cognitive biases. However, land-based GD patients showed a higher tendency to succumb to strong impulses under the influence of positive emotions. These preliminary findings warrant the need to continue investigating GD phenotypes in larger patient samples.

Study Question: Is there an (epi)genetic basis in patients with central precocious puberty (CPP) associated with multiple anomalies that unmasks underlying mechanisms or reveals novel genetic findings related to human pubertal control?, Summary Answer: In a group of 36 patients with CPP associated with multiple phenotypes, pathogenic or likely pathogenic (epi)genetic defects were identified in 12 (33%) patients, providing insights into the genetics of human pubertal control., What Is Known Already: A few studies have described patients with CPP associated with multiple anomalies, but without making inferences on causalities of CPP. Genetic-molecular studies of syndromic cases may reveal disease genes or mechanisms, as the presentation of such patients likely indicates a genetic disorder., Study Design, Size, Duration: This translational study was based on a genetic-molecular analysis, including genome-wide high throughput methodologies, for searching structural or sequence variants implicated in CPP and DNA methylation analysis of candidate regions., Participants/materials, Setting, Methods: A cohort of 197 patients (188 girls) with CPP without structural brain lesions was submitted to a detailed clinical evaluation, allowing the selection of 36 unrelated patients (32 girls) with CPP associated with multiple anomalies. Pathogenic allelic variants of genes known to cause monogenic CPP (KISS1R, KISS1, MKRN3 and DLK1) had been excluded in the entire cohort (197 patients). All selected patients with CPP associated with multiple anomalies (n = 36) underwent methylation analysis of candidate regions and chromosomal microarray analysis. A subset (n = 9) underwent whole-exome sequencing, due to presenting familial CPP and/or severe congenital malformations and neurocognitive abnormalities., Main Results and the Role of Chance: Among the 36 selected patients with CPP, the more prevalent associated anomalies were metabolic, growth and neurocognitive conditions. In 12 (33%) of them, rare genetic abnormalities were identified: six patients presented genetic defects in loci known to be involved with CPP (14q32.2 and 7q11.23), whereas the other six presented defects in candidate genes or regions. In detail, three patients presented hypomethylation of DLK1/MEG3:IG-DMR (14q32.2 disruption or Temple syndrome), resulting from epimutation (n = 1) or maternal uniparental disomy of chromosome 14 (n = 2). Seven patients presented pathogenic copy number variants: three with de novo 7q11.23 deletions (Williams-Beuren syndrome), three with inherited Xp22.33 deletions, and one with de novo 1p31.3 duplication. Exome sequencing revealed potential pathogenic variants in two patients: a sporadic female case with frameshift variants in TNRC6B and AREL1 and a familial male case with a missense substitution in UGT2B4 and a frameshift deletion in MKKS., Limitations, Reasons for Caution: The selection of patients was based on a retrospective clinical characterization, lacking a longitudinal inclusion of consecutive patients. In addition, future studies are needed, showing the long-term (mainly reproductive) outcomes in the included patients, as most of them are not in adult life yet., Wider Implications of the Findings: The results highlighted the relevance of an integrative clinical-genetic approach in the elucidation of mechanisms and factors involved in pubertal control. Chromosome 14q32.2 disruption indicated the loss of imprinting of DLK1 as a probable mechanism of CPP. Two other chromosomal regions (7q11.23 and Xp22.33) represented new candidate loci potentially involved in this disorder of pubertal timing., Study Funding/competing Interest(s): This work was supported by grant number 2018/03198-0 (to A.P.M.C.) and grant number 2013/08028-1 (to A.C.V.K) from the São Paulo Research Foundation (FAPESP), and grant number 403525/2016-0 (to A.C.L.) and grant number 302849/2015-7 (to A.C.L.) and grant number 141625/2016-3 (to A.C.V.K) from the National Council for Scientific and Technological Development (CNPq). The authors have nothing to disclose., Trial Registration Number: N/A., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: Rapid infant weight gain is a key risk factor for paediatric obesity, yet there is very little evidence on how healthy behaviours in childhood might modify this association. We aimed to examine how the association of infant weight gain with adolescent adiposity might be attenuated by moderate-to-vigorous physical activity (MVPA) in childhood., Methods: The sample comprised 4666 children in the UK Millennium Cohort Study. The two outcomes were BMI Z-score and % fat at 14 years. Sex-stratified regression models were developed testing for interactions between infant weight Z-score gain between 0 and 3 years (continuous or categorical) and MVPA at 7 years (continuous or binary). Models were sequentially adjusted for basic covariates, socioeconomic variables, and parental BMI levels., Results: Effect modification was observed in boys but not girls and, among boys, was stronger for % fat than BMI. In a fully adjusted model for boys, the association between infant weight Z-score gain and adolescent % fat was 1.883 (1.444, 2.322) if MVPA < 60 min/day and 1.305 (0.920, 1.689) if MVPA ≥ 60 min/day; the difference between these two estimates being -0.578 (-1.070, -0.087). Similarly, % fat was 2.981 (1.596, 4.367) units higher among boys who demonstrated rapid infant weight gain (+0.67 to +1.34 Z-score) compared to normal weight gain (-0.67 to +0.67 Z-scores), but having MVPA ≥ 60 min/day reduced this effect size by -2.259 (-3.989, -0.535) units., Conclusions: In boys, ~75% of the excess % fat at 14 years associated with rapid infant weight gain was attenuated by meeting the MVPA guideline. In boys known to have demonstrated rapid infant weight gain, increasing childhood MVPA levels, with the target of ≥60 min/day, might therefore go a long way to towards offsetting their increased risk for adolescent obesity. The lack of effect modification in girls is likely due to lower MVPA levels.

Cognitive impairments have profound implications for the management of severe mental disorders; however, they are rarely assessed in everyday clinical practice due to constraints in time, resource and expertise. Novel and short instruments, such as the Screen for Cognitive Impairment in Psychiatry (SCIP), which overcome such limitations are greatly needed. The study aims to assess the validity and reliability, among healthy subjects, of the Italian translation of the SCIP, a brief, accessible tool to detect cognitive impairments among individuals suffering from mental disorders, as the first step to validate the instrument in clinical settings. One-hundred and twenty healthy subjects completed two of the three alternative forms of the SCIP. Cronbach Alpha (0.70) supported the reliability of the SCIP scores. Correlation coefficients supported the test-retest reliability of the tool. Learning effects were observed despite the use of alternative forms. Factor analysis indicated a two-factor solution explaining 55.4% of the total variance: the first factor ("memory") loading for VLT-I and VLT-D and less for WMT; the second factor ("executive function") loading for VFT and PST and less for WMT. The study proved the validity and reliability of the Italian version of the SCIP as a reliable and simple instrument to screen for cognitive impairment in the general population.

Introduction: Depression and demoralization are highly prevalent among individuals with physical illnesses but their relationship is still unclear., Objective: To examine the relationship between clinical features of depression and demoralization with the network approach to psychopathology., Methods: Participants were recruited from the medical wards of a University Hospital in Italy. The Demoralization Scale (DS) was used to assess demoralization, while the Patient Health Questionnaire-9 (PHQ-9) to assess depressive symptoms. The structure of the depression-demoralization symptom network was examined and complemented by the analysis of topological overlap and Exploratory Graph Analysis (EGA) to identify the most relevant groupings (communities) of symptoms and their connections. The stability of network models was estimated with bootstrap procedures and results were compared with factor analysis., Results: Life feeling pointless, low mood/discouragement, hopelessness and feeling trapped were among the most central features of the network. EGA identified four communities: (1) Neurovegetative Depression, (2) Loss of purpose, (3) Frustrated Isolation and (4) Low mood and morale. Loss of purpose and low mood/morale were largely connected with other communities through anhedonia, hopelessness and items related to isolation and lack of emotional control. Results from EGA displayed good stability and were comparable to those from factor analysis., Limitations: Cross-sectional design; sample heterogeneity CONCLUSIONS: Among general hospital inpatients, features of depression and demoralization are independent, with the exception of low mood and self-reproach. The identification of symptom groupings around entrapment and helplessness may provide a basis for a dimensional characterization of depressed/demoralized patients, with possible implications for treatment., (Copyright © 2020. Published by Elsevier B.V.)

Background: Attending childcare is related to greater childhood obesity risk, but there are few long-term follow-up studies. We aimed to examine the associations of childcare type, age at start, and intensity with body mass index body mass index (BMI) trajectories from ages 10 to 42 years., Methods: The sample comprised 8234 individuals in the 1970 British Cohort Study, who had data on childcare attendance (no, yes), type (formal, informal), age at start (4-5, 3-3.99, 0-2.99 years old), and intensity (1, 2, 3, 4-5 days/week) reported at age 5 years and 32 563 BMI observations. Multilevel linear spline models were used to estimate the association of each exposure with the sample-average BMI trajectory, with covariate adjustment. A combined age at start and intensity exposure was also examined., Results: Attending vs not attending and the type of childcare (none vs formal/informal) were not strongly related to BMI trajectories. Among participants who attended childcare 1 to 2 days a week, those who started when 3 to 3.99 years old had a 0.197 (-0.004, 0.399) kg/m 2 higher BMI at age 10 years than those who started when 4 to 5 years old, and those who started when 0 to 2.99 years old had a 0.289 (0.049, 0.529) kg/m 2 higher BMI. A similar dose-response pattern for intensity was observed when holding age at start constant. By age 42 years, individuals who started childcare at age 0 to 2.99 years and attended 3 to 5 days/week had a 1.356 kg/m 2 (0.637, 2.075) higher BMI than individuals who started at age 4 to 5 years and attended 1 to 2 days/week., Conclusions: Children who start childcare earlier and/or attend more frequently may have greater long-term obesity risk., (© 2020 The Authors. Pediatric Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Hepatoblastoma is a very rare embryonal liver cancer supposed to arise from the impairment of hepatocyte differentiation during embryogenesis. In this study, we investigated by exome sequencing the burden of somatic mutations in a cohort of 10 hepatoblastomas, including a congenital case. Our data disclosed a low mutational background and pointed out to a novel set of candidate genes for hepatoblastoma biology, which were shown to impact gene expression levels. Only three recurrently mutated genes were detected: CTNNB1 and two novel candidates, CX3CL1 and CEP164 . A relevant finding was the identification of a recurrent mutation (A235G) in two hepatoblastomas at the CX3CL1 gene; evaluation of RNA and protein expression revealed upregulation of CX3CL1 in tumors. The analysis was replicated in two independents cohorts, substantiating that an activation of the CX3CL1/CX3CR1 pathway occurs in hepatoblastomas. In inflammatory regions of hepatoblastomas, CX3CL1/CX3CR1 were not detected in the infiltrated lymphocytes, in which they should be expressed in normal conditions, whereas necrotic regions exhibited negative labeling in tumor cells, but strongly positive infiltrated lymphocytes. Altogether, these data suggested that CX3CL1/CX3CR1 upregulation may be a common feature of hepatoblastomas, potentially related to chemotherapy response and progression. In addition, three mutational signatures were identified in hepatoblastomas, two of them with predominance of either the COSMIC signatures 1 and 6, found in all cancer types, or the COSMIC signature 29, mostly related to tobacco chewing habit; a third novel mutational signature presented an unspecific pattern with an increase of C>A mutations. Overall, we present here novel candidate genes for hepatoblastoma, with evidence that CX3CL1/CX3CR1 chemokine signaling pathway is likely involved with progression, besides reporting specific mutational signatures., (Copyright © 2020 Aguiar, Rivas, Costa, Maschietto, Rodrigues, Sobral de Barros, Barbosa, Valieris, Fernandes, Bertola, Cypriano, Caminada de Toledo, Major, Tojal, Apezzato, Carraro, Rosenberg, Lima da Costa, Cunha, Sarabia, Terrada and Krepischi.)

Background: Neuropsychological performance has a strong impact on real-life functioning and clinical outcomes in psychosis. However, conducting lengthy cognitive assessments may not be feasible in routine clinical practice. Brief, reliable and cost-effective tools are highly needed, but few studies are available to guide clinician choice., Methods: The purpose of this study was to compare the performance of two widely used, short instruments: the Screen for Cognitive Impairment in Psychiatry (SCIP) and the Montreal Cognitive Assessment (MoCA). These instruments were validated in a sample of patients with psychotic disorders and healthy controls, using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and other instruments to assess executive functions, as comparators., Results: Patients fared worse than controls across almost all cognitive domains, with effect sizes ranging from 0 (MoCA naming) to 2.08 (SCIP total). Receiver Operator Curve analysis of patient and control performance suggested a better convergent validity for the SCIP (total score AUC: 0.85; 95%CI: 0.79-0.90; Se: 76%, Sp: 83%, PPV: 85%, NPV: 73%) than the MoCA (AUC: 0.78; 95%CI: 0.72-0.85; Se: 69%, Sp: 76%, PPV: 78.7%, NPV 66%)., Conclusions: The Screen for Cognitive Impairment in Psychiatry seems to be a more sensitive and specific screening tool than the MoCA to identify cognitive impairment among patients with psychotic disorders., Competing Interests: Declaration of competing interest All authors declare that they have no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Evidence suggests that South Asian school-aged children and adults are less active compared to the white British population. It is unknown if this generalises to young children. We aimed to describe variability in levels of physical activity and sedentary time in a bi-ethnic sample of young children from a deprived location., Methods: This observational study included 202 South Asian and 140 white British children aged 1.5 to 5y, who provided 3181 valid days of triaxial accelerometry (Actigraph GT3X+). Variability in sedentary time and physical activity levels were analysed by linear multilevel modelling. Logistic multilevel regression was used to identify factors associated with physical inactivity (failing to perform ≥180 min of total physical activity including ≥60 min moderate-to-vigorous physical activity (MVPA) per day)., Results: There were no significant ethnic differences in the overall levels of behaviours; South Asian and white British children spent half of daily time sedentary, just over 40% in light physical activity, and the remaining 7.5 to 8% of time in MVPA. Sedentary time was lower and physical activity levels were higher in older children, and levels of MVPA and vector magnitude counts per minute (CPM) were higher on weekends compared to weekdays. In South Asian children, sedentary time was lower on weekends. Sedentary time was lower and physical activity levels were higher in spring compared to winter in white British children, and in all seasons compared to winter in South Asian children. South Asian children born at high birth weight performed more MVPA, and in both ethnicities there was some evidence that children with older mothers were more sedentary and less active. Sedentary time was higher and light physical activity was lower in South Asian children in the highest compared to the lowest income families. South Asian girls performed less MVPA, registered fewer vector magnitude CPM, and were 3.5 times more likely to be physically inactive than South Asian boys., Conclusions: Sedentary time and physical activity levels vary by socio-demographic, temporal and perinatal characteristics in young children from a deprived location. South Asian girls have the most to gain from efforts to increase physical activity levels., Trial Registration: The Pre-schoolers in the Playground (PiP) pilot randomized controlled trial is registered with the ISRCTN (ISRCTN54165860; http://www.isrctn.com).

The rising prevalence of childhood obesity is a global public health concern. Evidence suggests that exposure to non-parental childcare before age six years is associated with development of obesity, diet, and activity behaviours (physical activity, sedentary behaviour, and sleep). However, findings are inconsistent and mostly from cross-sectional studies, making it difficult to identify the direction of causation in associations. This review identified and synthesised the published research on longitudinal associations between non-parental childcare during early childhood, diet, and activity behaviours. Seven databases were searched, and results were independently double-screened through title/abstract and full-text stages. Included studies were evaluated for risk of bias. Of the 18,793 references screened, 13 met eligibility criteria and were included in the review. These presented results on 89 tested childcare/outcome associations, 63 testing diet outcomes (59% null, remainder mixed), and 26 testing activity behaviour outcomes (85% null, remainder mixed). The scarce available literature indicates little and mixed evidence of a longitudinal association. This reflects a paucity of research, rather than clear evidence of no effect. There is an urgent need for studies investigating the longitudinal associations of non-parental childcare on diet and activity behaviours to assess potential lasting effects and mechanisms; whether and how effects vary by provider; and differences by intensity, duration, and population sub-groups.

Polycomb-mediated epigenetic silencing is central to correct growth and development in higher eukaryotes. The evolutionarily conserved Polycomb repressive complex 2 (PRC2) transcriptionally silences target genes through a mechanism requiring the histone modification H3K27me3. However, we still do not fully understand what defines Polycomb targets, how their expression state is switched from epigenetically ON to OFF and how silencing is subsequently maintained through many cell divisions. An excellent system in which to dissect the sequence of events underlying an epigenetic switch is the Arabidopsis FLC locus. Exposure to cold temperatures progressively induces a PRC2-dependent switch in an increasing proportion of cells, through a mechanism that is driven by the local chromatin environment. Temporally distinct phases of this silencing mechanism have been identified. First, the locus is transcriptionally silenced in a process involving cold-induced antisense transcripts; second, nucleation at the first exon/intron boundary of a Polycomb complex containing cold-induced accessory proteins induces a metastable epigenetically silenced state; third, a Polycomb complex with a distinct composition spreads across the locus in a process requiring DNA replication to deliver long-term epigenetic silencing. Detailed understanding from this system is likely to provide mechanistic insights important for epigenetic silencing in eukaryotes generally., (© 2019 The Author(s).)

Background: Mixture modelling is a useful approach to identify subgroups in a population who share similar trajectories. We aimed to identify distinct body mass index (BMI) trajectories between 10 and 42 years and investigate how known early-life risk factors are related to trajectories., Methods: Sample: 9187 participants in the 1970 British Birth Cohort Study, with BMI observations between 10 and 42 years and data on birth weight, parental BMI, socioeconomic status, breast feeding and puberty. Latent growth mixture modelling in Mplus was used to model age-related BMI trajectories and test associations of risk factors with trajectory membership., Results: A three latent class model was most credible: (1) normative: 92%: started normal weight but gradually increased BMI to become overweight in adulthood; (2) childhood onset persistent obesity (COP): 4%: persistently high BMI from childhood; (3) adolescent and young adulthood onset obesity (AYAO): 4%: normal weight in childhood but had a steep ascending trajectory. Higher maternal and paternal BMI and early puberty increased the probability of being in either the COP or the AYAO classes compared with the normative class., Conclusion: Most individuals gradually increased BMI and became overweight in mid-adulthood. Only 8% demonstrated more severe BMI trajectories. Further research is needed to understand the underlying body composition changes and health risks in the COP and AYAO classes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

An efficient one-step procedure to reprogram fibroblasts into human induced pluripotent stem cells (hiPSC) and perform CRISPR/Cas9 gene editing simultaneously was recently reported. Here we show that such simultaneous reprogramming and gene editing can be efficiently done from erythroblasts. We successfully obtained human induced pluripotent stem cells colonies together with in frame and out of frame CAPN1 mutations in one or both alleles. We did not identify off-targets in edited cell lines. The entire process, from blood collection to mutated hiPSC took approximately 5 weeks, a much shorter period than standard multi-step methodologies using fibroblasts. Noteworthy, blood drawing is a less invasive procedure than a skin biopsy., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Acute appendicitis (AA) is the most common surgical disease, and appendectomy is the treatment of choice in the majority of cases. A correct diagnosis is key for decreasing the negative appendectomy rate. The management can become difficult in case of complicated appendicitis. The aim of this study is to describe the worldwide clinical and diagnostic work-up and management of AA in surgical departments., Methods: This prospective multicenter observational study was performed in 116 worldwide surgical departments from 44 countries over a 6-month period (April 1, 2016-September 30, 2016). All consecutive patients admitted to surgical departments with a clinical diagnosis of AA were included in the study., Results: A total of 4282 patients were enrolled in the POSAW study, 1928 (45%) women and 2354 (55%) men, with a median age of 29 years. Nine hundred and seven (21.2%) patients underwent an abdominal CT scan, 1856 (43.3%) patients an US, and 285 (6.7%) patients both CT scan and US. A total of 4097 (95.7%) patients underwent surgery; 1809 (42.2%) underwent open appendectomy and 2215 (51.7%) had laparoscopic appendectomy. One hundred eighty-five (4.3%) patients were managed conservatively. Major complications occurred in 199 patients (4.6%). The overall mortality rate was 0.28%., Conclusions: The results of the present study confirm the clinical value of imaging techniques and prognostic scores. Appendectomy remains the most effective treatment of acute appendicitis. Mortality rate is low., Competing Interests: The data was completely anonymized, and no patient or hospital information was collected in the database. The study protocol was approved by the board of the WSES, and the study was conducted under its supervision. The board of the WSES grants the proper ethical conduct of the study.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Objective: To undertake a cost-utility analysis of a motivational multicomponent lifestyle-modification intervention in a community setting (the Healthy Eating Lifestyle Programme (HELP)) compared with enhanced standard care., Design: Cost-utility analysis alongside a randomised controlled trial., Setting: Community settings in Greater London, England., Participants: 174 young people with obesity aged 12-19 years., Interventions: Intervention participants received 12 one-to-one sessions across 6 months, addressing lifestyle behaviours and focusing on motivation to change and self-esteem rather than weight change, delivered by trained graduate health workers in community settings. Control participants received a single 1-hour one-to-one nurse-delivered session providing didactic weight-management advice., Main Outcome Measures: Mean costs and quality-adjusted life years (QALYs) per participant over a 1-year period using resource use data and utility values collected during the trial. Incremental cost-effectiveness ratio (ICER) was calculated and non-parametric bootstrapping was conducted to generate a cost-effectiveness acceptability curve (CEAC)., Results: Mean intervention costs per participant were £918 for HELP and £68 for enhanced standard care. There were no significant differences between the two groups in mean resource use per participant for any type of healthcare contact. Adjusted costs were significantly higher in the intervention group (mean incremental costs for HELP vs enhanced standard care £1003 (95% CI £837 to £1168)). There were no differences in adjusted QALYs between groups (mean QALYs gained 0.008 (95% CI -0.031 to 0.046)). The ICER of the HELP versus enhanced standard care was £120 630 per QALY gained. The CEAC shows that the probability that HELP was cost-effective relative to the enhanced standard care was 0.002 or 0.046, at a threshold of £20 000 or £30 000 per QALY gained., Conclusions: We did not find evidence that HELP was more effective than a single educational session in improving quality of life in a sample of adolescents with obesity. HELP was associated with higher costs, mainly due to the extra costs of delivering the intervention and therefore is not cost-effective., Trial Registration Number: ISRCTN9984011., Competing Interests: Competing interests: AK is Director of International Public Health at Public Health England (PHE)., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objective: Approximately 7% of children and young people aged 5-15 years in the UK have obesity at a level likely to be associated with comorbidities. The majority of multicomponent lifestyle programmes have limited applicability and generalisability for British adolescents.The Healthy Eating and Lifestyle Programme (HELP) was a specific adolescent-focused intervention, designed for obese 12 to 18-year-olds seeking help to manage their weight. Participants were randomised to the 12-session HELP intervention or standard care. The primary outcome was difference in mean body mass index (BMI) (kg/m 2 ) between groups at week 26 adjusted for baseline BMI, age and sex., Subjects: 174 subjects were randomised (87 in each arm), of whom 145 (83%) provided primary outcome data at week 26., Results: At week 26 there were no significant effects of the intervention on BMI (mean change in BMI 0.18 kg/m 2 for the intervention arm, 0.25 kg/m 2 for the control arm; adjusted difference between groups: -0.11 kg/m 2 (95% CI -0.62 to 0.40), p=0.7). At weeks 26 and 52 there were no significant differences between groups in any secondary outcomes., Conclusion: At minimum this study reinforces the need for higher level, structured interventions to tackle the growing public health burden of obesity in the UK and internationally.The HELP intervention was no more effective than a single educational session for reducing BMI in a community sample of obese adolescents.Further work is needed to understand how weight management programmes can be delivered effectively to young people from diverse and deprived backgrounds in which childhood obesity is common. The study has significant implications in terms of informing public health interventions to tackle childhood obesity., Trial Registration Number: ISRCTN: ISRCTN99840111., Competing Interests: Competing interests: ASK is director of International Public Health at Public Health England (PHE). The views represented in this paper are those of the author and do not necessarily represent those of PHE. All other authors declare no competing interests., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by loss of dopaminergic neurons and localized neuroinflammation occurring in the midbrain several years before the actual onset of symptoms. Neuroinflammation leads to microglia activation and release of a large number of proinflammatory mediators. The kynurenine pathway (KP) of tryptophan catabolism is one of the major regulators of the immune response and is also likely to be implicated in the inflammatory and neurotoxic events in Parkinsonism. Several neuroactive compounds are produced through the KP that can be either a neurotoxic, neuroprotective or immunomodulator. Among these metabolites kynurenic acid (KYNA), produced by astrocytes, is considered as neuroprotective whereas quinolinic acid (QUIN), released by activated microglia, can activate the N-methyl-d-aspartate (NMDA) receptor-signalling pathway, leading to excitotoxicity and amplify the inflammatory response. Previous studies have shown that NMDA antagonists can ease symptoms and exert a neuroprotective effect in PD both in vivo and in vitro. There are to date several lines of evidence linking some of the KP intermediates and the neuropathogenesis of PD. Moreover, it is likely that some of the KP metabolites could be used as prognostic biomarkers and that pharmacological modulators of the KP enzymes could represent a new therapeutic strategy for PD., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Purpose: This study aimed to investigate associations of objectively measured physical activity (PA) and sedentary time with adiposity in a predominantly biethnic (South Asian and White British) sample of young children., Methods: The sample included 333 children age 11 months to 5 yr who provided 526 cross-sectional observations for PA and body composition. Total PA volume (vector magnitude counts per minute), daily time at multiple intensity levels (the cumulative time in activity >500, >1000, >1500, …, >6000 counts per minute), and time spent sedentary (<820 counts per minute), in light PA (820-3907 counts per minute) and in moderate-to-vigorous PA (≥3908 counts per minute) were estimated with triaxial accelerometry. Indicators of adiposity included body mass index, waist circumference, and the sum of subscapular and triceps skinfold thicknesses. Statistical analyses were performed using multilevel regression and isotemporal substitution models adjusted for confounders. Effect modification by ethnicity was examined., Results: There was no evidence for effect modification by ethnicity (P interaction ≥ 0.13). In the whole sample, the accumulated time spent above 3500 counts per minute (i.e., high light-intensity PA) was inversely associated with the sum of skinfolds (β = -0.60 mm, 95% confidence interval [CI] = -1.19 to -0.021, per 20 min·d), and the magnitude of association increased dose dependently with PA intensity (peaking for time spent >6000 counts per minute = -1.57 mm, 95% CI = -3.01 to -0.12, per 20 min·d). The substitution of 20 min·d of sedentary time with moderate-to-vigorous PA was associated with a lower sum of skinfolds (-0.77 mm, 95% CI = -1.46 to -0.084)., Conclusions: High light-intensity PA appears to be beneficial for body composition in young South Asian and White British children, but higher-intensity PA is more advantageous.

Purpose: Adequate nutrition during adolescence is important for optimal physical and cognitive development and for pregnancy either during adolescence or later life. Thinness among adolescent girls in low- and middle-income countries has been little studied., Methods: We used body mass index data from 40 countries from the Global School Health Survey to estimate the prevalence of moderate and severe thinness in 12- to 18-year-olds using the World Health Organization 2007 growth reference. Self-report data on going to bed hungry were used as a proxy for household food insecurity. We used multilevel models to assess whether national wealth (gross domestic product), income inequality (Gini index), national gender inequality (Gender Inequality Index), and food security (Global Food Security Index) were associated with undernutrition., Results: Prevalence rates of moderate and severe thinness across 61,603 girls from 40 countries were 6.30% (95% confidence interval [CI]: 5.71-6.95) and 1.34% (1.12-1.59), respectively, with higher rates in Asia. Combined moderate/severe thinness was more common among early (12-14 years) than later adolescents (15-18 years). Going to bed hungry sometimes was associated with increased risk of moderate/severe thinness (odds ratio [OR]: 1.102; 95% CI: 1.007-1.206). A significant inverse relationship was found between thinness and gross domestic product (OR: .94; 95% CI: .88-.99) and Global Food Security Index (OR: .96; 95% CI: .93-.99) but not Gini or Gender Inequality Index., Conclusion: Thinness remains prevalent in adolescent schoolgirls in low- and middle-income countries and poses a significant threat to their health and that of the next generation. Further research is needed to assess potential interventions for this group., (Copyright © 2016 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

The purpose of this study was to investigate the relationship between the childcare environment and physical activity and sedentary behavior of toddlers and preschoolers. A total of 68 toddlers (1.0-2.9 years) and 233 preschoolers (3.0-5.9 years) were recruited from 11 childcare services in 2013 within the Illawarra and Shoalhaven region of NSW, Australia. For this study analysis was conducted in 2016. The childcare environment was assessed using the Environment and Policy Assessment Observation (EPAO) instrument, and childcare services categorized as low, medium, or high based on their scores. Time spent in physical activity and sitting was assessed over one week using activPAL accelerometers. Relationship between EPAO and children's physical activity and sedentary behavior was assessed using multilevel mixed-effects linear regression. Toddlers who attended high EPAO services sat more (8.73 min [- 10.26, 27.73]) and stood less (- 13.64 min [- 29.27, 2.00]) than those who attended low EPAO services. Preschoolers who attended high EPAO services sat less than those in low and medium services (mean [95%CI] = - 7.81 min [- 26.64, 11.02]). Sub-categories of the EPAO that were associated with less time sitting were: sedentary environments for toddlers and portable play equipment for preschoolers. This study extends previous research by identifying differences between toddlers and preschooler's physical activity and sedentary behaviors in relation to childcare environments. A greater understanding of how the childcare environment relates to sitting time for both toddlers and preschool aged children is needed.

Purpose of Review: The purpose of this review was to summarize the current literature on the longitudinal relationship between non-parental childcare during infancy and later obesity., Recent Findings: Eleven studies met the inclusion criteria, comprising 74 associations relevant to the review. Studies were highly heterogeneous in terms of defining childcare, categorizing different types of childcare, assessing obesity, and age at measurement of outcome and exposure. Most of the associations were either non-significant (42 associations, 57%) or showed a significant association between increased exposure to childcare and greater obesity (30 associations, 41%). There were very few examples of associations indicating that childcare was associated with lower obesity., Summary: There is limited research on the longitudinal relationship between childcare in infancy and later obesity. Existing studies showed mixed results, similar to recent reviews reporting on cross-sectional studies and older ages. The different definitions of childcare and wide variety of measures of exposure make comparisons between studies challenging.

We report the case of a 6-year-old female patient with Ataxia Telangiectasia, an extremely rare condition, who developed in addition a left cerebellar astrocytoma and a right cerebellar infarction, considered as two independent events. Children with AT have an increased risk of developing cancer, but only few cases of glioma are reported and, at our knowledge, no other case of unrelated cerebellar glioma and cerebellar infarction in with the same AT patient have been described. The molecular analysis of ATM (Ataxia Telangiectasia Mutated) gene showed that the patient is compound heterozygote for two previously unreported mutations: c.3291delC (p.Phe1097fs) at exon 25 and c.8198A>C (p.Gln2733Pro) at exon 58. The role of the identified ATM gene mutations in the pathogenesis of Ataxia Telangiectasia and the coexisting cerebellar disorders is discussed., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Lactobacillus fermentum Lf2, an autochthonous strain isolated as a non starter culture in Cremoso cheese, produces high EPS levels (~1g/L) in optimized conditions (SDM broth, pH6.0, 30°C, 72h). Technological (texture profile and rheological analysis) and sensory properties of non-fat yogurts with 300 and 600mg EPS/L were studied at 3 and 25days after manufacture. Yogurts with different EPS concentrations showed higher hardness values than the control group at both periods of time, being the only significant difference that remained stable during time. The consistency index was also higher for the treated samples at both times evaluated, being significantly different for samples with 300mg/L of EPS extract, while the flow behavior index was lower for EPS-added yogurts. The thixotropic index was lower (P<0.05) for samples with the highest EPS extract concentration at the end of the storage time. Regarding the sensory analysis, those yogurts with 600mg/L of EPS extract presented the highest values of consistency at 3days of storage. No considerable differences for defects (milk powder, acid, bitter and cooked milk flavors) were perceived between treated and control samples at both times evaluated. Syneresis was also studied and samples with 600mg/L of EPS extract presented the lowest syneresis values at 25days of storage, which considerably decreased with the time of storage. In conclusion, the EPS from L. fermentum Lf2, used as an additive, provided yogurt with creamy consistency and increased hardness, without the presence of unwanted defects and improving the water holding capacity of the product. All the analysis done showed the potential of this extract to be used as a technofunctional natural ingredient, and it should be considered its positive impact on health, according to previous studies., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

This study presents a worked example of a stepped process to reliably estimate the habitual physical activity and sedentary time of a sample of young children. A total of 299 children (2.9 ± 0.6 years) were recruited. Outcome variables were daily minutes of total physical activity, sedentary time, moderate to vigorous physical activity and proportional values of each variable. In total, 282 (94%) provided 3 h of accelerometer data on ≥1 day and were included in a 6-step process: Step-1: determine minimum wear-time; Step-2: process 7-day-data; Step-3: determine the inclusion of a weekend day; Step-4: examine day-to-day variability; Step-5: calculate single day intraclass correlation (ICC) (2,1); Step-6: calculate number of days required to reach reliability. Following the process the results were, Step-1: 6 h was estimated as minimum wear-time of a standard day. Step-2: 98 (32%) children had ≥6 h wear on 7 days. Step-3: no differences were found between weekdays and weekend days (P ≥ 0.05). Step-4: no differences were found between day-to-day variability (P ≥ 0.05). Step-5: single day ICC's (2,1) ranged from 0.48 (total physical activity and sedentary time) to 0.53 (proportion of moderate to vigorous physical activity). Step-6: to reach reliability (ICC = 0.7), 3 days were required for all outcomes. In conclusion following a 7 day wear protocol, ≥6 h on any 3 days was found to have acceptable reliability. The stepped-process offers researchers a method to derive sample-specific wear-time criterion.

Context: Being physically active during the early years (age 0-6 years) is vital for healthy development. Identifying correlates and determinants of physical activity (PA) is crucial to guide effective interventions. This systematic review synthesized studies investigating potential correlates and determinants of PA during the early years, accounting for different types of PA assessment., Evidence Acquisition: Nine electronic databases were searched from inception year (1900) until September 2014; data were analyzed/interpreted in April 2015. The following inclusion criteria were used: written in English, published in peer-reviewed journals, participants not in statutory/school education, and an observational design investigating associations between an exposure/variable, and a quantitative measure of PA. Correlates/determinants of total, moderate to vigorous, and light PA were reported using an ecologic model., Evidence Synthesis: Of 22,045 identified studies, 130 were included. All took place in high-income countries and few (6%) were of high quality. Correlates of total PA were sex (male, ++); parental PA (+); parental support (+); and time outdoors (+). Determinants of total PA were sex (+) and time spent playing with parents (+). The only correlate of moderate to vigorous PA was sex (male, ++). No determinants of moderate to vigorous or light PA were found. PA correlates/determinants were relatively consistent between objective and subjective PA measures., Conclusions: Numerous studies investigated potential correlates and determinants of PA, but overall quality was low. A small number of demographic/biological and social/cultural factors were associated with PA. There is a need for high-quality studies exploring correlates/determinants across all domains of the ecologic model., (Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: The rising prevalence of obesity, particularly in childhood, is a global public health emergency. There is some evidence that exposure to non-parental childcare before age 6 years is associated with subsequent development of obesity and obesity-related behaviours such as physical activity, sedentary behaviour, sleep, diet and stress, although these findings are inconsistent. It is possible that the relationship between early childcare and later obesity and obesity-related behaviours depends on characteristics of childcare exposure such as type (i.e. informal versus formal care), duration (i.e. number of years spent in childcare), intensity (e.g. number of hours per week) and timing (i.e. age of onset of childcare) of care received. The relationship may also be moderated by socio-demographic characteristics of children and their families. We will conduct a systematic review exploring longitudinal associations between childcare (type, duration, intensity and timing) and measures of adiposity and body mass, physical activity, sedentary behaviour, sleep, diet and stress. We will also assess whether these relationships vary by socio-demographic factors., Methods: We will include studies that explore longitudinal associations between childcare attendance in children aged <6 years not in primary school at first assessment and body weight, adiposity, physical activity, diet, sleep and stress. We will limit studies to those involving middle- and high-income countries. Two independent reviewers will screen search results in two stages: (1) title and abstract and (2) and full text. One reviewer will extract relevant data and a second will verify this information. We will assess risk of bias of included studies using an adaption of the United States Department of Agriculture National Evidence Library Bias Assessment Tool. We will tabulate and summarise results narratively. We may conduct meta-analysis if at least five studies report comparable data., Discussion: To our knowledge, this will be the first systematic review to summarise the existing evidence on longitudinal associations between childcare and adiposity, body mass and obesity-related risk factors. The results will be of relevance to other researchers, childcare practitioners and policy makers., Systematic Review Registration: PROSPERO CRD42015027233.

Measuring physical activity (PA) and sedentary time (ST) in young children (<5 years) is complex. Objective measures have high validity but require specialist expertise, are expensive, and can be burdensome for participants. A proxy-report instrument for young children that accurately measures PA and ST is needed. The aim of this study was to assess the reliability and validity of the Early Years Physical Activity Questionnaire (EY-PAQ). In a setting where English and Urdu are the predominant languages spoken by parents of young children, a sample of 196 parents and their young children (mean age 3.2 ± 0.8 years) from Bradford, UK took part in the study. A total of 156 (79.6%) questionnaires were completed in English and 40 (20.4%) were completed in transliterated Urdu. A total of 109 parents took part in the reliability aspect of the study, which involved completion of the EY-PAQ on two occasions (7.2 days apart; standard deviation (SD) = 1.1). All 196 participants took part in the validity aspect which involved comparison of EY-PAQ scores against accelerometry. Validty anaylsis used all data and data falling with specific MVPA and ST boundaries. Reliability was assessed using intra-class correlations (ICC) and validity by Bland⁻Altman plots and rank correlation coefficients. The test re-test reliability of the EY-PAQ was moderate for ST (ICC = 0.47) and fair for moderate-to-vigorous physical activity (MVPA)(ICC = 0.35). The EY-PAQ had poor agreement with accelerometer-determined ST (mean difference = -87.5 min·day -1 ) and good agreement for MVPA (mean difference = 7.1 min·day -1 ) limits of agreement were wide for all variables. The rank correlation coefficient was non-significant for ST (rho = 0.19) and significant for MVPA (rho = 0.30). The EY-PAQ has comparable validity and reliability to other PA self-report tools and is a promising population-based measure of young children's habitual MVPA but not ST. In situations when objective methods are not possible for measurement of young children's MVPA, the EY-PAQ may be a suitable alternative but only if boundaries are applied.

Controlled cell division is central to the growth and development of all multicellular organisms. Within the proliferating zone of the Arabidopsis root, regular symmetric divisions give rise to patterns of parallel files of cells, the genetic basis of which remains unclear. We found that genotypes impaired in the TONNEAU1a (TON1a) gene display misoriented symmetric divisions in the epidermis and have no division defects in the underlying cortical tissue. The TON1a gene encodes a microtubule-associated protein. We show that in the ton1a mutant, epidermal and cortical cells do not form narrow, ring-like preprophase bands (PPBs), which are plant-specific, cytoskeletal structures that predict the position of the division plane before mitosis. The results indicate that in the cortex but not in the epidermis, division plane positioning and patterning can proceed correctly in the absence of both a functional TON1a and PPB formation. Differences between tissues in how they respond to the signals that guide symmetric division orientation during patterning might provide the basis for organised organ growth in the absence of cell movements., (© 2016. Published by The Company of Biologists Ltd.)

Background: To validate a new practical Sepsis Severity Score for patients with complicated intra-abdominal infections (cIAIs) including the clinical conditions at the admission (severe sepsis/septic shock), the origin of the cIAIs, the delay in source control, the setting of acquisition and any risk factors such as age and immunosuppression., Methods: The WISS study (WSES cIAIs Score Study) is a multicenter observational study underwent in 132 medical institutions worldwide during a four-month study period (October 2014-February 2015). Four thousand five hundred thirty-three patients with a mean age of 51.2 years (range 18-99) were enrolled in the WISS study., Results: Univariate analysis has shown that all factors that were previously included in the WSES Sepsis Severity Score were highly statistically significant between those who died and those who survived (p < 0.0001). The multivariate logistic regression model was highly significant (p < 0.0001, R2 = 0.54) and showed that all these factors were independent in predicting mortality of sepsis. Receiver Operator Curve has shown that the WSES Severity Sepsis Score had an excellent prediction for mortality. A score above 5.5 was the best predictor of mortality having a sensitivity of 89.2 %, a specificity of 83.5 % and a positive likelihood ratio of 5.4., Conclusions: WSES Sepsis Severity Score for patients with complicated Intra-abdominal infections can be used on global level. It has shown high sensitivity, specificity, and likelihood ratio that may help us in making clinical decisions.

Terminal deletion in the short arm of chromosome 1 results in a disorder described as 1p36 deletion syndrome. The resulting phenotype varies among patients including mental retardation, developmental delay, sensorineural hearing loss, seizures, heart defects, and distinct facies. In the present case, we performed array-comparative genomic hybridization in a boy with multiple congenital malformations presenting some features overlapping the 1p36 deletion phenotype for whom chromosomal analysis did not reveal a terminal deletion in 1p. Results showed complex chromosome rearrangements involving the 1p36.33-p35.3 region. While the mechanism of origin of these rearrangements is still unclear, chromothripsis-a single catastrophic event leading to shattering chromosomes or chromosome regions and rejoining of the segments-has been described to occur in a fraction of cancers. The presence of at least 12 clustered breaks at 1p and apparent lack of mosaicism in the present case suggests that a single event like chromothripsis occurred. This finding suggests that chromothripsis is responsible for some constitutive complex chromosome rearrangements.

Background: Active commuting may help to increase adults' physical activity levels. However, estimates of its energy cost are derived from a small number of studies which are laboratory-based or use self-reported measures., Methods: Adults working in Cambridge (UK) recruited through a predominantly workplace-based strategy wore combined heart rate and movement sensors and global positioning system (GPS) devices for one week, and completed synchronous day-by-day travel diaries in 2010 and 2011. Commuting journeys were delineated using GPS data, and metabolic intensity (standard metabolic equivalents; MET) was derived and compared between journey types using mixed-effects linear regression., Results: 182 commuting journeys were included in the analysis. Median intensity was 1.28 MET for car journeys; 1.67 MET for bus journeys; 4.61 MET for walking journeys; 6.44 MET for cycling journeys; 1.78 MET for journeys made by car in combination with walking; and 2.21 MET for journeys made by car in combination with cycling. The value for journeys made solely by car was significantly lower than those for all other journey types (p<0.04). On average, 20% of the duration of journeys incorporating any active travel (equating to 8 min) was spent in moderate-to-vigorous physical activity (MVPA)., Conclusions: We have demonstrated how GPS and activity data from a free-living sample can be used simultaneously to provide objective estimates of commuting energy expenditure. On average, incorporating walking or cycling into longer journeys provided over half the weekly recommended activity levels from the commute alone. This may be an efficient way of achieving physical activity guidelines and improving population health., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The reported lower physical activity (PA) levels of British South Asians (SA) are suggested as a key influence in their increased risk of non-communicable diseases compared to their White British peers. Differences in objectively measured PA and sedentary behaviour (SB) between these ethnic groups have been observed during childhood (ages: 8-10 years). However, no information exists on objectively measured PA/SB in younger children, or how early in life differences in these behaviours emerge. Assessing PA/SB in the Born in Bradford (BIB) cohort study provides an opportunity to address such gaps in the literature, but previous studies have found recruiting and retaining SA participants challenging, and the feasibility of using accelerometers with SA children and parents is unknown. This study investigated the feasibility of recruiting and objectively measuring the habitual PA/SB of 2-3 year old SA and White British children and parents from the BIB study., Methods: Families were informed about the study during routine BIB assessments. Consenting families were visited at home for anthropometry measurements, interviews, material delivery and collection. Participants (child and parents) were instructed to wear the ActiGraph GT3X+ for 8 days. Descriptive statistics were computed, and ethnic differences tested (Chi-square) for recruitment uptake and compliance., Results: 160 families (30 % SA) provided contact details, and 97 (22 % SA) agreed to enter the study. White British families showed lower refusal and higher intake into the study than SA (p = 0.006). Of 89 children issued with an accelerometer, 34 % complied with the 8-day protocol (significantly less SA; p = 0.015) and 75 % provided enough days (≥ 3) to assess habitual PA/SB (no ethnic differences). Parental rates of compliance with the protocol did not differ between ethnicities. Issues experienced with the protocol and accelerometer use, and successful implementation strategies/procedures are presented., Conclusions: Although greater efforts may be required to recruit SA, those consenting to participate were as likely as White British to provide enough data to assess habitual PA/SB. The issues and successful strategies reported in this feasibility study represent valuable information for planning future studies, and enhance recruitment and compliance with accelerometer protocols in SA and White British toddlers and parents.

Aneuploid embryos diagnosed by FISH-based preimplantation genetic screening (PGS) have been shown to yield euploid lines of human embryonic stem cells (hESCs) with a relatively high frequency. Given that the diagnostic procedure is usually based on the analysis of 1-2 blastomeres of 5 to 10-cell cleavage-stage embryos, mosaicism has been a likely explanation for the phenomena. However, FISH-based PGS can have a significant rate of misdiagnosis, and therefore some of those lines may have been derived from euploid embryos misdiagnosed as aneuploid. More recently, coupling of trophectoderm (TE) biopsy at the blastocyst stage and array-CGH lead to a more informative form of PGS. Here we describe the establishment of a new line of hESCs from an embryo with a 43,XX,dup(9q),+12,-14,-15,-18,-21 chromosomal content based on array-CGH of TE biopsy. We show that, despite the complex chromosomal abnormality, the corresponding hESC line BR-6 is euploid (46,XX). Single nucleotide polymorphism analysis showed that the embryo's missing chromosomes were not duplicated in BR-6, suggesting the existence of extensive mosaicism in the TE lineage.