pinecone/core-2020-05-10-deduplication huggingface dataset:
Intestinal fibrosis is reduced by early elimination of inflammation in a mouse model of IBD: Impact of a “Top‐Down” approach to intestinal fibrosis in mice

Background:  The natural history of Crohn's disease follows a path of progression from an inflammatory to a fibrostenosing disease, with most patients requiring surgical resection of fibrotic strictures. Potent antiinflammatory therapies reduce inflammation but do not appear to alter the natural history of intestinal fibrosis. The aim of this study was to determine the relationship between intestinal inflammation and fibrogenesis and the impact of a very early “top‐down” interventional approach on fibrosis in vivo.    Methods:  In this study we removed the inflammatory stimulus from the  Salmonella typhimurium  mouse model of intestinal fibrosis by eradicating the  S. typhimurium  infection with levofloxacin at sequential timepoints during the infection. We evaluated the effect of this elimination of the inflammatory stimulus on the natural history of inflammation and fibrosis as determined by gross pathology, histopathology, mRNA expression, and protein expression.    Results:  Fibrogenesis is preceded by inflammation. Delayed eradication of the inflammatory stimulus by antibiotic treatment represses inflammation without preventing fibrosis. Early intervention significantly ameliorates but does not completely prevent subsequent fibrosis.    Conclusions:  This study demonstrates that intestinal fibrosis develops despite removal of an inflammatory stimulus and elimination of inflammation. Early intervention ameliorates but does not abolish subsequent fibrosis, suggesting that fibrosis, once initiated, is self‐propagating, suggesting that a very early top‐down interventional approach may have the most impact on fibrostenosing disease. (Inflamm Bowel Dis 2012;
Resveratrol has antiinflammatory and antifibrotic effects in the peptidoglycan‐polysaccharide rat model of Crohn's disease

Background:  Resveratrol has antiinflammatory and antifibrotic effects. Resveratrol decreases proliferation and collagen synthesis by intestinal smooth muscle cells. We hypothesized that resveratrol would decrease inflammation and fibrosis in an animal model of Crohn's disease.    Methods:  Peptidoglycan‐polysaccharide (PG‐PS) or human serum albumin (HSA) was injected into the bowel wall of Lewis rats at laparotomy. Resveratrol or vehicle was administered daily by gavage 1–27 days postinjection. On day 28, gross abdominal and histologic findings were scored. Cecal collagen content was measured by colorimetric analysis of digital images of trichrome‐stained sections. Cecal levels of procollagen, cytokine, and growth factor mRNAs were determined.    Results:  PG‐PS‐injected rats (vehicle‐treated) developed more fibrosis than HSA‐injected rats by all measurements: gross abdominal score ( P  < 0.001), cecal collagen content ( P  = 0.04), and procollagen I and III mRNAs ( P  ≤ 0.0007). PG‐PS‐injected rats treated with 40 mg/kg resveratrol showed a trend toward decreased gross abdominal score, inflammatory cytokine mRNAs, and procollagen mRNAs. PG‐PS‐injected rats treated with 100 mg/kg resveratrol had lower inflammatory cytokine mRNAs (IL‐1β [3.50 ± 1.08 vs. 10.79 ± 1.88,  P  = 0.005], IL‐6 [17.11 ± 9.22 vs. 45.64 ± 8.83,  P  = 0.03], tumor necrosis factor alpha (TNF‐α) [0.80 ± 0.14 vs. 1.89 ± 0.22,  P  = 0.002]), transforming growth factor beta 1 (TGF‐β1) mRNA (2.24 ± 0.37 vs. 4.06 ± 0.58,  P  = 0.01), and histologic fibrosis score (6.4 ± 1.1 vs. 9.8 ± 1.0;  P  = 0.035) than those treated with vehicle. There were trends toward decreased gross abdominal score and decreased cecal collagen content. Procollagen I, procollagen III, and IGF‐I mRNAs also trended downward.    Conclusions:  Resveratrol decreases inflammatory cytokines and TGF‐β1 in the PG‐PS model of Crohn's disease and demonstrates a promising trend in decreasing tissue fibrosis. These findings may have therapeutic applications in inflammatory bowel disease. (Inflamm Bowel Dis 2011;
Spironolactone and colitis: Increased mortality in rodents and in humans

Background:  Crohn's disease causes intestinal inflammation leading to intestinal fibrosis. Spironolactone is an antifibrotic medication commonly used in heart failure to reduce mortality. We examined whether spironolactone is antifibrotic in the context of intestinal inflammation.    Methods:  In vitro, spironolactone repressed fibrogenesis in transforming growth factor beta (TGF‐β)‐stimulated human colonic myofibroblasts. However, spironolactone therapy significantly increased mortality in two rodent models of inflammation‐induced intestinal fibrosis, suggesting spironolactone could be harmful during intestinal inflammation. Since inflammatory bowel disease (IBD) patients rarely receive spironolactone therapy, we examined whether spironolactone use was associated with mortality in a common cause of inflammatory colitis,  Clostridium difficile  infection (CDI).    Results:  Spironolactone use during CDI infection was associated with increased mortality in a retrospective cohort of 4008 inpatients (15.9% vs. 9.1%,  n  = 390 deaths,  P  < 0.0001). In patients without liver disease, the adjusted odds ratio (OR) for inpatient mortality associated with 80 mg spironolactone was 1.99 (95% confidence interval [CI]: 1.51–2.63) In contrast to the main effect of spironolactone mortality, multivariate modeling revealed a protective interaction between liver disease and spironolactone dose. The adjusted OR for mortality after CDI was 1.96 (95% CI: 1.50–2.55) for patients without liver disease on spironolactone vs. 1.28 (95% CI: 0.82–2.00) for patients with liver disease on spironolactone when compared to a reference group without liver disease or spironolactone use.    Conclusions:  We propose that discontinuation of spironolactone in patients without liver disease during CDI could reduce hospital mortality by 2‐fold, potentially reducing mortality from CDI by 35,000 patients annually across Europe and the U.S. (Inflamm Bowel Dis 2011;
PKR protects colonic epithelium against colitis through the unfolded protein response and prosurvival signaling

Background:  The dsRNA‐activated protein kinase (PKR) phosphorylates the α subunit of eukaryotic translation initiation factor 2 (eIF2α), a global regulator of protein synthesis in mammals. In addition, PKR activates several signal transduction pathways including STAT3 and AKT. PKR is activated by a number of inflammatory stimuli that are induced in the inflamed intestine. In this study we intended to determine the role of PKR in colonic epithelial cells during experimental colitis in mice.    Methods:  Age‐ and sex‐matched  PKR  +/+,+/−  and  PKR  −/−  littermate mice were reconstituted with wildtype bone marrow cells and subjected to dextran sodium sulfate (DSS)‐induced colitis.    Results:   PKR  −/−  mice displayed more severe clinical and histological manifestations upon DSS colitis compared with their  PKR  +/+,+/−  littermates. In response to DSS colitis, the colonic epithelial cells of  PKR  −/−  mice exhibited impaired activation of the unfolded protein response (UPR) signaling, including eIF2α phosphorylation, endoplasmic reticulum (ER) chaperone response, and ER‐associated degradation (ERAD) components, as well as antioxidative stress response. In addition, the phosphorylation of STAT3 and AKT, which are protective against epithelial cell death and colonic inflammation, was also impaired in the colonic epithelial cells of  PKR  −/−  mice upon DSS colitis.    Conclusions:  These data demonstrate that PKR is a physiologically relevant transducer of inflammatory response signaling in colonic epithelial cells. PKR may promote the homeostasis and survival of intestinal epithelial cells (IECs) through eIF2α‐mediated UPR activation, as well as the activation of STAT3 and AKT pathways. In the absence of PKR, the survival and proliferation of IECs was impaired, thus exacerbating intestinal inflammation. (Inflamm Bowel Dis 2012;
Can we identify emotion over-regulation in infancy? Associations with avoidant attachment, dyadic emotional interaction and temperament

Emotion over-regulation in infancy has seldom been the focus of empirical research. This study analysed the specificities of overregulation when compared with under-regulation (maladaptive) and adaptive regulation by testing its association with attachment, dyadic emotional interaction,  and temperament. The sample consisted of 52
low-risk mother–infant dyads. During a home visit, dyadic emotional interaction was assessed in the daily routines and free play of 10-month-old infants. The infant’s emotion regulation was assessed using the Shape Sorter Task, and a temperament questionnaire was completed by the mother.Attachmentwas assessed at 12 or 16 months using the Strange Situation. As hypothesized, (i) emotion overregulation
(versus adaptive regulation) was predicted by a lower quality of dyadic emotional interaction and marginally by avoidant attachment; (ii) over-regulation (versus under-regulation) was predicted by avoidant attachment; and (iii) the predictive role of avoidant attachment was substantiated after controlling for another measure of mother–infant interaction. Contrary to expectations, temperament did not distinguish between emotion regulation styles. The link between over-regulation and lower quality of mother–infant emotional interaction and avoidant attachment was demonstrated. There is empirical support to the claim that it is possible to identify emotion overregulation in infancy and that it is a maladaptive style of emotion regulation.Fundação para a Ciência e a Tecnologia (SFRH/BD/16524/2004/254S)Neofarmacêutic
Paternal postnatal and subsequent mental health symptoms and child socio-emotional and behavioural problems at school entry

Research on the effect of paternal mental health problems, particularly on young children, is based predominantly on clinical levels of depression. Furthermore, potential mediators such as marital discord have often been overlooked. This longitudinal community study assessed the association between paternal mental health symptoms in a community sample (N = 705) assessed at 3 months postnatally (Edinburgh Postnatal Depression Scale) and 36 months (General Health Questionnaire) and children's socio-emotional and behavioural problems at 51 months (Strengths and Difficulties Questionnaire) as reported by mother, father and teacher. Controlling for socioeconomic status and maternal mental health symptoms at 3 and 36 months, paternal postnatal depressive symptoms predicted more father-reported child problems at 51 months but, in contrast to previous findings, not mother-reported problems. Paternal mental health symptoms at 36 months predicted both maternal and paternal reports of child problems at 51 months controlling for both paternal and maternal postnatal symptoms. Paternal mental health symptoms at 3 and 36 months were not significant predictors of teacher-reported child problems. Postnatal marital discord and paternal mental health problems at 36 months both mediated the relationship between paternal postnatal symptoms and later child emotional and behavioural problems. Child gender did not moderate the relationship. Implications for interventions are discussed. Copyright © 2013 John Wiley & Sons, Ltd
Testing for Near and Far Transfer Effects with a Short, Face-to-Face Adaptive Working Memory Training Intervention in Typical Children

A relatively quick, face-to-face, adaptive working memory training intervention was assessed in 5- to 8-year-old typically developing children, randomly allocated to a six-week intervention condition, or an active control condition. All children received 18 sessions of 10 minutes, three times/week for six weeks. Assessments of six working memory skills, word reading and mathematics were administered at pre-test, post-test, and six month follow-up. Additional measures of word reading, mathematics, spelling and reading comprehension were given at a 12 month follow-up. At post-test, the trained group showed significantly larger gains than the control group on the two trained executive-loaded working memory tasks (Listening Recall, Odd One Out Span) and on two untrained working memory tasks (Word Recall, Counting Recall). These "near transfer" effects were still apparent at six month follow-up. "Far transfer" effects were less evident: there was no difference between the groups in their gains on single word reading and mathematics over 12 months, and spelling skills did not differ at 12 month follow-up. However, the trained group showed significantly higher reading comprehension scores than the control group at 12 month follow-up. Thus, improving the ability to divide attention between processing and storage may have had specific benefits for reading comprehension
Evidence for a role of executive functions in learning biology

Research examining cognition and science learning has focused on working memory but evidence implicates a broader set of executive functions. The current study examined executive functions and learning of biology in young adolescents. Fifty-six participants, aged 12-13 years, completed tasks of working memory (Spatial Working Memory), inhibition (Stop-Signal), attention set-shifting (ID/ED), and planning (Stockings of Cambridge), from the CANTAB. They also participated in a biology teaching session, practical and assessment on the topic of DNA designed specifically for the current study which measured a) memory for biology facts taught and b) understanding of information learned in the practical. Linear regression analysis revealed that planning ability predicted performance on the factual assessment and both spatial working memory and planning were predictive of performance on the conceptual assessment. The findings suggest that planning ability is important in learning biological facts but that a broader set of executive functions are important for conceptual learning, highlighting the role of executive functions in understanding and applying knowledge about what is learned within science teaching
Exploring socioeconomic differences in bedtime behaviours and sleep duration in English preschool children.

Children's sleep is critical for optimal health and development; yet sleep duration has decreased in recent decades, and many children do not have adequate sleep. Certain sleep behaviours (‘sleep hygiene’) are commonly recommended, and there is some evidence that they are associated with longer nighttime sleep. Parents of 84 British 3-year-old children were interviewed about their children's sleep and completed five-night/four-day sleep diaries documenting their children's sleep, from which daily sleep duration was estimated. Diaries were validated by actigraphy in a subgroup of children. Sleep hygiene behaviours (regular bedtime, reading at bedtime, falling asleep in bed) were associated with each other, and were more common in the high socioeconomic status compared to the low socioeconomic status group. Parents' reasons for not practicing sleep hygiene included difficulty, inability or inconvenience. Sleep hygiene behaviours were associated with significantly longer child sleep at night but not over 24 h. Longer daytime napping compensated for shorter nighttime sleep in children whose parents did not implement sleep hygiene behaviours. Parents may need to be advised that certain behaviours are associated with longer nighttime sleep and given practical advice on how to implement these behaviours
Assessment of Working Memory Capacity in Preschool Children Using the Missing Scan Task

The purpose of this study was to investigate the feasibility and validity of a modified version of Buschke's missing scan methodology, the Missing Scan Task (MST), to assess working memory capacity (WMC) and cognitive control processes in preschool children 3-6 years in age. Forty typically developing monolingual English-speaking children between 36 and 84 months in age participated in the study. The children were tested on measures of WMC (MST), verbal and nonverbal memory (NEPSY Narrative Memory and Memory for Designs subtests), and language skills (Peabody Picture Vocabulary Test, fourth edition). Children showed increased working memory capacity scores with age, as measured by the MST, with significant differences between 3- and 5-year-olds and 3- and 6-year-olds. Significant correlations were also found between the MST and language and verbal and nonverbal memory scores. MSTscores still remained significantly correlated with the other measures of memory even after age and global language were accounted for in a regression analysis, demonstrating that the MST captures unique variance related specifically to WMC and cognitive control processes used to retrieve and scan information in short-term memory (STM). The results of this study demonstrate that the MST is a feasible and valid methodology for assessing WMC in preschool children as young 3 years of age
Children with imaginary companions focus on mental characteristics when describing their real-life friends.

Relations between having an imaginary companion (IC) and (i) descriptions of a real-life friend, (ii) theory of mind performance, and (iii) reported prosocial behaviour and behavioural difficulties were investigated in a sample of 5-year-olds (N = 159). Children who had an IC were more likely than their peers without an IC to describe their best friends with reference to their mental characteristics, but IC status was unrelated to children's theory of mind performance and reported prosocial behaviour and behavioural difficulties. These findings are discussed in the context of the proposal that there is a competence–performance gap in children's mentalizing abilities
Feasibility of undertaking off-site infant eye-tracking assessments of neuro-cognitive functioning in early-intervention centres

Recent work suggests that differences in functional brain development are already identifiable in 6- to 9-month-old infants from low socio-economic status (SES) backgrounds. Investigation of early SES-related differences in neuro-cognitive functioning requires the recruitment of large and diverse samples of infants, yet it is often difficult to persuade low-SES parents to come to a university setting. One solution is to recruit infants through early intervention children’s centres (CCs). These are often located in areas of high relative deprivation to support young children. Given the increasing portability of eye-tracking equipment, assessment of large clusters of infants could be undertaken in centres by suitably trained early intervention staff. Here we report on a study involving 174 infants and their parents, carried out in partnership with CCs, exploring the feasibility of this approach, We report the processes of setting up the project and participant recruitment. We report the diversity of sample obtained on the engagement of CC staff in training and the process of assessment itself. We report the quality of the data obtained, and the levels of engagement of parents, and infants. We conclude that this approach has great potential for recruiting large and diverse samples worldwide, provides sufficiently reliable data, and is engaging to staff, parents and infants
Maternal responsive-didactic caregiving in play interactions with 10-month-olds and cognitive development at 18 months

Maternal responsive-didactic caregiving (RDC) and infant advanced object play were investigated in a sample of 400 mothers and their 10-month-old infants during video-recorded semi-structured play interactions. Three maternal behaviours: contingent response, cognitively stimulating language and autonomy promoting speech were coded and infant object play. Factor analysis confirmed the three maternal behaviours loaded onto one underlying factor, labelled RDC. Based on ecological and transactional theories of development, associations between RDC and infant (advanced object play), maternal (age, education, ethnicity and first language) and family (size and home adversity) factors were investigated. Multiple regressions (1) explored the predictors of maternal RDC; (2) tested the possible role of maternal RDC in predicting infant intellectual development at 18 months. At 10 months infants showing higher levels of play maturity experienced more maternal responsive and didactic feedback. All mother and family characteristics predicted variations in maternal RDC. Predicting 18-months cognitive development, RDC had significant effect over and above maternal education, home adversity and infant play. Mother’s first language remained significant, reflecting that RDC, in this investigation, relies heavily on language input. The findings highlight the importance of both contingent response and didactic contributions in interactions to subsequent cognitive development, as early as the first year
Five-month-old infants' discrimination of visual-tactile synchronous facial stimulation

The distinction between self and other is crucial for self-awareness and for our awareness of others. However, how human beings learn to associate the face they see in the mirror with themselves is still a matter of debate. The exploration of body-related multisensory processing with infants has demonstrated that they can detect visual-tactile contingencies, suggesting the presence of early implicit body perception simply based on the spatiotemporal matching between visual and tactile stimuli alone. In the present study, we used facial stimuli to investigate 5-month-old infants' visual preference for visual-tactile temporal synchrony. Infants watched a side-by-side video display of a peer's face being systematically stroked on the cheek with a paintbrush. During the video presentation, the infant's own cheek was stroked in synchrony with one video and in asynchrony with the other. Our result demonstrates that 5-month-old infants are able to discriminate between visual-tactile synchrony and asynchrony, by showing a visual preference for the synchronous facial stimulus
Preferences for 'Gender-typed' Toys in Boys and Girls Aged 9 to 32 Months

Many studies have found that a majority of boys and girls prefer to play with toys that are typed to their own gender but there is still uncertainty about the age at which such sex differences first appear, and under what conditions. Applying a standardized research protocol and using a selection of gender-typed toys, we observed the toy preferences of boys and girls engaged in independent play in UK nurseries, without the presence of a parent. The 101 boys and girls fell into three age groups: 9 to 17 months, when infants can first demonstrate toy preferences in independent play (N=40); 18 to 23 months, when critical advances in gender knowledge occur (N=29); and 24 to 32 months, when knowledge becomes further established (N=32). Stereotypical toy preferences were found for boys and girls in each of the age groups, demonstrating that sex differences in toy preference appear early in development. Both boys and girls showed a trend for an increasing preference with age for toys stereotyped for boys. Theoretical implications of the findings are discussed with regard to biological predispositions, cognitive development and environmental influences on toy preference