How multiple threats to safety affects quality of life for picky eating adults: A new explanatory model.

Picky eating describes a pattern of eating characterised by a narrow dietary range with rejection of both novel and familiar foods. Research has suggested that picky eating in adulthood is associated with several negative psychosocial outcomes including impaired quality of life. This research aimed to build and test a model explaining the relationship between picky eating and quality of life. 230 participants were recruited via online support forums for picky eating, and an undergraduate research participation scheme. Participants completed self-report measures of picky eating, sensory sensitivity, disgust, anxiety, fear of negative evaluation and eating related quality of life. Regression analysis indicated that picky eating, disgust sensitivity, anxiety, and fear of negative evaluation were all associated with impaired eating-related quality of life. A theoretical model was then devised which aimed to explain the interactions between these factors, and Path Analysis indicated that this model was a good fit for the data. This Safety in Picky Eating and Quality of life (SPEQ) model suggests that threat perception and the drive for safety underlies the relationship between picky eating and impaired quality of life. The SPEQ model provides a preliminary basis for understanding how picky eating impacts quality of life in adulthood.

Food neophobia and the evaluation of novel foods in adults; the sensory, emotional, association (SEA) model of the decision to taste a novel food.

Reluctance to eat new foods, known as food neophobia, is well researched in children but not adults. Two studies were carried out to understand the emotional, sensory, and cognitive factors associated with food neophobia in an adult sample, and to propose a preliminary explanation of the decision to taste a novel food named the SEA model (Sensory, Emotional, cognitive Association model). Participants were recruited through opportunity sampling of a university population in the Leicester region of the UK. Study one (n = 534) was a cross sectional study examining associations between self-report measures of food neophobia, emotional variables and sensory variables. In study two (n = 160), participants completed an online cognitive evaluation of 7 images of novel fruits and vegetables, rating perceived familiarity, categorisation as fruit or vegetable, cognitive associations based on appearance (what does the food look like), liking of any associated foods, and expected liking of the novel food. In study 1 it was found that tactile sensitivity and disgust sensitivity were the main sensory and emotional variables associated with food neophobia. In study 2, it was found that food neophobia and lower expected liking of novel foods were associated with disgust sensitivity, associating the novel foods with disliked foods, and lower perceived familiarity. The SEA model further proposes that underlying tendencies and automatic reactions to foods, combine with cognitive associations based on negative memories and negative beliefs about tasting new foods, to create expected disliking of a food and a decreased likelihood that it will be tried. Further work is needed to fully test the SEA model of the decision to taste a novel food, in particular to further examine how associations are formed.

OBSERVATION AND COMPARISON OF MEALTIME BEHAVIORS IN A SAMPLE OF CHILDREN WITH AVOIDANT/RESTRICTIVE FOOD INTAKE DISORDERS AND A CONTROL SAMPLE OF CHILDREN WITH TYPICAL DEVELOPMENT.

Despite widespread use of behavioral observations to evaluate child feeding behaviors in research and clinical practice, few studies have comprehensively characterized mealtimes or identified features that differentiate children with and without disordered feeding; these were the aims of the current study. Mealtime observations were conducted for 18 children with avoidant restrictive food intake disorder (ARFID) and 21 typically developing children. Observations were coded inductively, and associations between disorder and observed mealtime actions were examined. Most behaviors were observed across both clinical and nonclinical mealtimes, and many did not differ in frequency between children with and without ARFID. However, significant group differences were observed in the frequencies of behaviors relating to food intake, visual and physical engagement with feeding, and movement during mealtimes. The comparability of behaviors across clinical and nonclinical groups suggests that eating behaviors exist on a continuum from "normal" to "abnormal," with group differences relating to frequency rather than type of behavior. The behavioral differences observed in this study suggest that identification of children with ARFID should focus on child engagement with food and restlessness during mealtimes. Reliance on emotional and escape-maintained behaviors will lead to underrecognition of families in need of clinical support.

CD248/endosialin critically regulates hepatic stellate cell proliferation during chronic liver injury via a PDGF-regulated mechanism.

INTRODUCTION: CD248 (endosialin) is a stromal cell marker expressed on fibroblasts and pericytes. During liver injury, myofibroblasts are the main source of fibrotic matrix. OBJECTIVE: To determine the role of CD248 in the development of liver fibrosis in the rodent and human setting. DESIGN: CD248 expression was studied by immunostaining and quantitative PCR in both normal and diseased human and murine liver tissue and isolated hepatic stellate cells (HSCs). Hepatic fibrosis was induced in CD248(-/-) and wild-type controls with carbon tetrachloride (CCl4) treatment. RESULTS: Expression of CD248 was seen in normal liver of humans and mice but was significantly increased in liver injury using both immunostaining and gene expression assays. CD248 was co-expressed with a range of fibroblast/HSC markers including desmin, vimentin and α-smooth muscle actin (α-SMA) in murine and human liver sections. CD248 expression was restricted to isolated primary murine and human HSC. Collagen deposition and α-SMA expression, but not inflammation and neoangiogenesis, was reduced in CD248(-/-) mice compared with wild-type mice after CCl4 treatment. Isolated HSC from wild-type and CD248(-/-) mice expressed platelet-derived growth factor receptor α (PDGFR-α) and PDGFR-ß at similar levels. As expected, PDGF-BB stimulation induced proliferation of wild-type HSC, whereas CD248(-/-) HSC did not demonstrate a proliferative response to PDGF-BB. Abrogated PDGF signalling in CD248(-/-) HSC was confirmed by significantly reduced c-fos expression in CD248(-/-) HSC compared with wild-type HSC. CONCLUSIONS: Our data show that deletion of CD248 reduces susceptibility to liver fibrosis via an effect on PDGF signalling, making it an attractive clinical target for the treatment of liver injury.

RELATIVE CONTRIBUTIONS OF PARENT-PERCEIVED CHILD CHARACTERISTICS TO VARIATION IN CHILD FEEDING BEHAVIOR.

Few studies have examined the relative impact of co-occurring child characteristics on problematic feeding behavior. The aim of the current study was to assess the relative contributions of parent-perceived child characteristics in multivariable models of child feeding behavior. One hundred sixty-one mothers reported on their child's feeding behavior and a number of key child characteristics. These characteristics were entered into controlled multivariable models of child feeding behavior, using child and parent frequency domains of the Behavioral Pediatrics Feeding Assessment Scale (BPFAS; W. Crist et al., 1994) as outcome measures. Child feeding problems were positively associated with food neophobia and external behavioral and social issues, but not with most domains of temperamental difficulty or sensory sensitivity. Feeding problem frequency was associated with externalizing symptoms whereas parental perceptions of problems and coping were associated with social-interaction problems in the child. Population feeding problems appear to be external and interactive problems rather than driven by innate or internalizing factors. The association with externalizing symptoms suggests that feeding problems at this level may fall within a wider profile of challenging behavior; however, the existence of problematic feeding behaviors may constitute a challenge for parents only when the child's social interactions also are seen to be deficient.

Non-enzymatic dissociation of human mesenchymal stromal cells improves chemokine-dependent migration and maintains immunosuppressive function.

BACKGROUND AIMS: Human bone marrow-derived mesenchymal stromal cells (MSC) can suppress inflammation; therefore their therapeutic potential is being explored in clinical trials. Poor engraftment of infused MSC limits their therapeutic utility; this may be caused by MSC processing before infusion, in particular the method of their detachment from culture. METHODS: Enzymatic methods of detaching MSC (Accutase and TrypLE) were compared with non-enzymatic methods (Cell Dissociation Buffer [CDB], ethylenediamine tetra-acetic acid and scraping) for their effect on MSC viability, chemokine receptor expression, multi-potency, immunomodulation and chemokine-dependent migration. RESULTS: TrypLE detachment preserved MSC viability and tri-lineage potential compared with non-enzymatic methods; however, this resulted in near complete loss of surface chemokine receptor expression. Of the non-enzymatic methods, CDB detachment preserved the highest viability while retaining significant tri-lineage differentiation potential. Once re-plated, CDB-detached MSC regained their original morphology and reached confluence, unlike with the use of other non-enzymatic methods. Viability was significantly reduced with the use of ethylenediamine tetra-acetic acid and further reduced with the use of cell scraping. Addition of 1% serum during CDB detachment led to higher MSC numbers entering autophagy and increased MSC recovery after re-plating. TrypLE and CDB-detached MSC suppressed CD3(+)CD4(+)CD25(-) T-cell proliferation, although TrypLE-detached MSC exhibited superior suppression at 1:20 ratio. CDB detachment retained surface chemokine receptor expression and consequently increased migration to CCL22, CXCL12 and CCL4, in contrast with TrypLE-detached MSC. CONCLUSIONS: This study demonstrates that non-enzymatic detachment of MSC with the use of CDB minimizes the negative impact on cell viability, multipotency and immunomodulation while retaining chemokine-dependent migration, which may be of importance in MSC delivery and engraftment in sites of injury.

Human mesenchymal stem cells are recruited to injured liver in a ß1-integrin and CD44 dependent manner.

UNLABELLED: Human bone marrow mesenchymal stem cells (hMSCs) have shown benefit in clinical trials of patients with liver disease. Efficient delivery of cells to target organs is critical to improving their effectiveness. This requires an understanding of the mechanisms governing cellular engraftment into the liver. Binding of hMSCs to normal/injured liver tissue, purified extracellular matrices, and human hepatic sinusoidal endothelial cells (HSECs) were quantified in static and flow conditions. To define the mechanisms underpinning hMSC interactions, neutralizing adhesion molecule antibodies were used. Fluorescently labelled hMSCs were infused intraportally into CCl(4) -injured mice with and without neutralizing antibodies. hMSCs expressed high levels of CD29/ß1-integrin and CD44. Using liver tissue binding assays, hMSC adhesion was greatest in diseased human liver versus normal liver (32.2 cells/field versus 20.5 cells/field [P = 0.048]). Neutralizing antibodies against CD29 and CD44 reduced hMSC binding to diseased liver by 34% and 35%, respectively (P = 0.05). hMSCs rolled at 528 µm/second on HSECs in flow assays. This rolling was abolished by CD29 blockade on hMSCs and vascular cell adhesion molecule-1 (VCAM-1) blockade on HSECs. Firm adhesion to HSECs was reduced by CD29 (55% [P = 0.002]) and CD44 (51% [P = 0.04]) blockade. Neutralizing antibodies to CD29 and CD44 reduced hepatic engraftment of hMSCs in murine liver from 4.45 cells/field to 2.88 cells/field (P = 0.025) and 2.35 cells/field (P = 0.03), respectively. hMSCs expressed modest levels of chemokine receptors including CCR4, CCR5, and CXCR3, but these made little contribution to hMSC adhesion in this setting. CONCLUSION: hMSCs bind preferentially to injured liver. Rolling of hMSCs is regulated by CD29/VCAM-1, whereas CD29/CD44 interactions with VCAM-1, fibronectin, and hyaluronan on HSECs determine firm adhesion both in vitro and in vivo as demonstrated using a murine model of liver injury.

Screening for feeding disorders. Creating critical values using the behavioural pediatrics feeding assessment scale.

The aim of the current study was to discriminate between clinical and non-clinical samples on the Behavioural Pediatrics Feeding Assessment Scale (BPFAS). The objective was to present a cut-off value, that was derived statistically, which could be used to screen for feeding disorders. A sample of five hundred and seventy-three families with a target child ranging in age from 20 to 85 months took part in the current study. Sixty-four children had a known diagnosis of a feeding disorder and were embedded into a typically developing sample of families that had not sought professional intervention. All families completed the BPFAS in order to provide a known database to measure discriminative statistics. The Receiver Operating Characteristic (ROC) analysis indicated that the cut off value for the BPFAS was a Child Frequency score of 61 and a Child Problem score of six. This offered an 87% accuracy rate at these values. The current study offered definitive evidence that the BPFAS was accurate (both sensitive and specific) to determine differences between clinical and non-clinical samples in the United Kingdom. It is therefore advocated that BPFAS should be adopted in future studies exploring the impact of feeding disorders and problems in both clinical and research settings.

Measuring oral sensitivity in clinical practice: a quick and reliable behavioural method.

This article aims to offer a behavioural assessment strategy for oral sensitivity that can be readily applied in the clinical setting. Four children, ranging in age and with a variety of developmental and medical problems, were used as test cases for a task analysis of tolerance to touch probes in and around the mouth. In all cases, the assessment was sensitive to weekly measures of an intervention for oral sensitivity over a 3-week period. Employing an inexpensive, direct, specific to the individual, replicable, reliable, and effective measure for a specific sensory problem would fit better with the edicts of evidence-based practice. The current method offered the initial evidence towards this goal.

Bone health in adult women with ED: A longitudinal community-based study.

Although Eating Disorders (ED) are known to affect bone health and development, little is known about the longitudinal effect of ED and ED behaviours on bone health in community dwelling adult women. Women (n = 3507) enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC) participated in a two-phase prevalence study to assess lifetime ED and ED behaviours (fasting, restrictive eating, vomiting and misuse of medication). Crude and adjusted linear regression methods investigated the association between ED diagnoses and behaviours, and total body, hip, leg and arm bone mineral density (BMD) DXA scans at mean ages of 48 and 52 years. Lifetime occurrence of Anorexia Nervosa (AN) was associated with lower BMD Z-scores for the whole body (mean difference (MD) = -0.28; 95% CI: -0.49, -0.05), hip (MD = -0.45; 95% CI -0.74, -0.16), leg (MD = -0.28; 95% CI -0.52, -0.03) and arm (MD = -0.44; 95% CI -0.68, -0.19) compared to no ED. This effect was mostly accounted for by lowest ever BMI. In post-hoc analyses, Restrictive AN, but not Binge-Purge AN was associated with a lower total body BMD Z-scores (MD = -0.37; 95% CI -0.62, -0.12). Lifetime Fasting and Restrictive Eating were associated with low BMD of the total body, hip, arm and leg in adjusted analyses, all p < 0.05. Both lifetime ED diagnoses and ED behaviours in a large community sample were predictive of low BMD in mid-life. This study confirms that the effects of AN, fasting and restrictive eating, and low BMI on bone health seen in clinical samples also occur in community samples.

Pharmacological treatment options for low Bone Mineral Density and secondary osteoporosis in Anorexia Nervosa: A systematic review of the literature.

OBJECTIVE: Although there are several evidence-based treatments available to increase Bone Mineral Density (BMD) and reduce fracture risk in aging men and women, there are still uncertainties regarding which treatments are efficacious in reducing lifetime fracture risk in women with Anorexia Nervosa (AN). METHODS: Medline, PsychInfo, Embase and the Cochrane Database were searched for English Language Studies. Inclusion criteria were studies of females of any age with AN who received pharmacological treatment with the primary aim to increase BMD or reduce fracture risk. Data were extracted from each study regarding pharmacological treatment and dosage used, BMD and bone formation marker outcomes; and participant characteristics including age, Body Mass Index (BMI), duration of AN, and duration of amenorrhea. RESULTS: 675 studies were reviewed, of which 19 fit the inclusion criteria and were included in the final review, investigating a total of 1119 participants; 10 of the 19 included studies were double-blind RCTs. The remaining studies consisted of prospective observational studies, a retrospective cohort study, a case-control study and five non-randomised control trials. Bisphosphonates were effective in increasing BMD in adult women with AN, while estrogen administered transdermally resulted in significant increases in BMD in mature adolescents with AN. Administration of oral contraceptives (OC) did not significantly increase BMD in randomised or controlled trials, however, lifetime OC use was associated with higher spinal BMD. CONCLUSION: Future research should clarify the safety of long-term bisphosphonate use in adult women with AN, and verify that transdermal estrogen replacement increases BMD in women with AN.

Screening Avoidant/Restrictive Food Intake Disorder (ARFID) in children: Outcomes from utilitarian versus specialist psychometrics.

This study assessed the specificity and sensitivity of two commonly used psychometric methods to assess ARFID in children. To achieve this, a sample of 329 mothers and one father completed the Behavioral Pediatrics Feeding Assessment Scale (BPFAS) and the Child Food Neophobia Scale (CFNS). A Receiver Operating Characteristic (ROC) analysis indicated that both measures were able to successfully differentiate a known clinical sample from those of typically developing population. Although the BPFAS was more accurate at differentiating ARFID from the general population, the CFNS was acceptable and on some metrics better than its longer counterpart. The ability of a food neophobia scale to differentiate clinical and population samples, and detect gradation of food avoidance within the population sample, suggests that the multitude of psychometric measures available may be measuring similar constructs. Therefore, confidence can be expected in cross-site comparisons despite each using different psychometric measures of food avoidance in children.

Developmental differences in sensory decision making involved in deciding to try a novel fruit.

OBJECTIVES: This research compared sensory processing and personality traits involved in deciding to try a novel fruit (guava) in adults and children. DESIGN: The research employed an age, sex, and food neophobia matched between-participant design to examine sensory decision making in choosing to eat a novel fruit. METHODS: Forty-four adults (Study 1) and 68 children (Study 2) took part. In each study, participants were separated into two groups to investigate whether prior assessment of a familiar and liked fruit (apple) that shares similar visual characteristics to the target novel fruit (guava) increased the likelihood that an individual would decide to try it. All participants completed appetitive and familiarity ratings by sensory stages: vision, smell, and touch, prior to trying (tasting) the fruit. Participants (or their parents) also completed the general and food neophobia scales and adults also completed the sensation-seeking scale. RESULTS: Twenty-eight adults (64%) tried the guava and 16 did not (36%). In the second study, 22 children decided not to try the novel fruit (32%). Significant predictors of whether the adult tried the target fruit were Thrill and Adventure Seeking, Experience Seeking, General Neophobia, and 'appealing to touch'. In children, Food Neophobia, concurrent presentation of a familiar fruit alongside the target and visual assessment of the target predicted decision to try the novel fruit. CONCLUSIONS: This study suggests that touch is pertinent to adults' decision to try a novel fruit, whereas visual cues appear to be more important for children.

Identifying clinically relevant feeding problems and disorders.

This paper outlines what is currently understood, and what can be hypothesized about paediatric feeding dysfunctions. The paper highlights the current lack of awareness of psychological factors implicated in infant and child feeding, and promotes a behavioural approach to the identification, referral and treatment of non-organic derived feeding problems and disorders. Potential risk factors to poor feeding development are outlined, and characteristic child and caregiver behaviours which may signify problems with feeding are suggested. The aim of this paper is to promote early identification of these symptoms in frontline healthcare in the hope of increasing early intervention before physical complaints, medical complications and/or disorders arise.

V600EBraf induces gastrointestinal crypt senescence and promotes tumour progression through enhanced CpG methylation of p16INK4a.

The majority of human colorectal cancers (CRCs) are initiated by mutations arising in the adenomatous polyposis coli (APC) tumour suppressor gene. However, a new class of non-APC mutated CRCs has been defined that have a serrated histopathology and carry the (V600E)BRAF oncogene. Here we have investigated the pathogenesis of serrated CRCs by expressing (V600E)Braf in the proliferative cells of the mouse gastrointestinal tract. We show that the oncogene drives an initial burst of Mek-dependent proliferation, leading to the formation of hyperplastic crypts. This is associated with ß-catenin nuclear localization by a mechanism involving Mapk/Erk kinase (Mek)-dependent, Akt-independent phosphorylation of Gsk3ß. However, hyperplastic crypts remain dormant for prolonged periods due to the induction of crypt senescence accompanied by upregulation of senescence-associated ß-galactosidase and p16(Ink4a). We show that tumour progression is associated with down-regulation of p16(Ink4a) through enhanced CpG methylation of exon 1 and knockout of Cdkn2a confirms this gene is a barrier to tumour progression. Our studies identify (V600E)BRAF as an early genetic driver mutation in serrated CRCs and indicate that, unlike APC-mutated cancers, this subtype arises by the bypassing of a (V600E)Braf driven oncogene-induced senescence programme.

Implementing a comprehensive, 24-hour emergency department pharmacy program.

PURPOSE: The implementation of a comprehensive, 24-hour emergency department pharmacy program (EDPP) is described. SUMMARY: An EDPP was created at the Veterans Affairs San Diego Healthcare System to address deficiencies identified by the pharmacy service within the ED, including medication tracking, documentation of doses administered, and formulary management. The documentation system used in the EDPP, including a computerized spreadsheet and documentation cards, allowed the activities of the ED pharmacists to be tracked on a 24-hour basis. This type of data collection allowed us to evaluate the impact of the program based on the quality of patient care delivered as well as cost. During the initial six-month implementation period, the ED pharmacists recorded 9,568 interventions. The information from these interventions was used to assess the safety components and to estimate the cost avoidance of their activities. A staff satisfaction survey was also created to assess the pharmacist's impact on providers and nurses, as well as its effect on workflow within the ED. Among the many benefits realized, the EDPP improved the quality of patient care, decreased medication errors and patient wait times, improved the medication reconciliation process, enhanced formulary management, ensured prospective medication order review, and increased overall patient safety, as evidenced by the documented interventions and staff satisfaction survey. The projected cost savings for the medical center during the first year of EDPP implementation was calculated as $1,691,185. CONCLUSION: A tertiary care teaching hospital successfully implemented a 24-hour, comprehensive ED pharmacy service that enhanced the efficiency and delivery of patient care and resulted in significant cost savings.