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Background/Objectives: Exclusive enteral nutrition (EEN) is a safe and effective treatment modality for inducing remission in paediatric Crohn's disease (CD). The primary aim of this study was to compare the outcomes of EEN to corticosteroid (CS) therapy in newly diagnosed, treatment-naïve patients with CD. A secondary aim was to describe the outcomes of EEN in a national cohort of paediatric CD patients over a 10-year period. Subjects/Methods: A retrospective chart review was conducted at the Irish national referral centre for paediatric CD. A case-matched analysis was conducted on two cohorts matched for age, gender, disease location, disease behaviour and disease activity, who received CS or EEN as their initial treatment. Subsequently, cohort analysis was conducted on all patients who undertook a course of EEN therapy between 2004 and 2013. Results: The case-matched analysis found higher remission rates after treatment with EEN (24/28, 86%) compared with those with CS (15/28, 54%; P=0.02). Dietetic contacts were found to be pivotal to the success of treatment and the attainment of remission. In total, 59 patients completed EEN at some time-point in their disease course and were included in the cohort analysis. Sixty-nine per cent of this cohort entered clinical remission (41/59). EEN was found to be most effective when used as an initial treatment (P=0.004) and less effective in patients aged under 10 years (P=0.04). Conclusions: EEN should be strongly considered as a favourable primary treatment over CS, especially in those diagnosed over the age of 10 years., Author(s): L Lafferty [sup.1] [sup.2] , M Tuohy [sup.1] [sup.2] , A Carey [sup.2] [sup.3] , S Sugrue [sup.1] , M Hurley [sup.2] , S Hussey [sup.2] [sup.3] [sup.4] [sup.5] [...]

Background: Triple Assessment Breast Clinics are designed for rapid diagnosis of symptomatic patients. When there is no concordance between clinical and radiological assessment, clinicians perform clinical core biopsies. In patients with a clinically suspicious examination (S4, S5) and normal imaging, clinically guided core biopsy should be performed as per NCCP guidelines. However, substantial research does not exist on the diagnostic value or use of clinical core biopsies in non-suspicious palpable (S3) lesions and practices differ in each health system., Aims: The aim of this research was to assess the diagnostic value of clinical core biopsies in nonsuspicious, probably benign palpable breast lesions (S3) where image guided cores were not indicated (R1/R2)., Methods: The cohort consisted of patients undergoing clinical core biopsies at a Symptomatic Breast Unit from January 2014 to 2019. Data regarding patient demographics, outcome of triple-assessment and incidence of malignancy were obtained from a prospectively maintained database and results were analysed using Minitab 2018., Results: Three hundred and sixty patients had a clinical core biopsy performed in this period. Clinical examination scores for these patients were S1/S2 (66), S3 (277), S4 (15), and S5 (2). Radiology Scores were R1/R2 (355) and R3(5). Two patients with clinical score S3 (0.6%) were diagnosed with breast cancer due to their clinical cores. Both patients had normal mass imaging. There was no association between uncertain palpable breast lesions (S3), and atypia or malignancy on biopsy results when breast imaging was normal (P = 0.43, χ 2  test)., Conclusion: Despite clinical core biopsies being used in triple assessment, there is no certainty in their value except that there is high clinical suspicion. Imaging modalities are constantly improving and are already well established. When the patient is assigned a clinical score of S3 and has normal radiology, a clinical core biopsy is not required in most cases., (© 2023. The Author(s).)

Background: Outcomes in pediatric ulcerative colitis (UC) are heterogeneous and predictors of disease course eagerly sought. Mucosal atrophy (MA) is characterized by histological abnormalities of colonic intestinal glands., Objective: To determine the prevalence of MA in a national inception cohort of pediatric UC and its impact on outcomes., Methods: Irish children < 16 years old with UC are diagnosed at a single referral center. At diagnosis, patients underwent phenotyping by Paris classification and activity assessment by Pediatric Ulcerative Colitis Activity Index. Biopsies from all colonic segments were evaluated for MA. Patients were followed prospectively. The primary outcome was corticosteroid-free remission at 1 year. Secondary outcomes included relapse, treatment escalation, and colectomy by 2 years., Results: Of 251 pediatric patients with UC (mean age 11.8 years, 55% male), 38 (15%) had MA on diagnostic biopsy. Baseline characteristics were similar between groups with/without MA and there was no difference in steroid-free remission or rates of moderate-severe UC at 1 year. Patients with MA had higher use of steroids (29% vs 15%, P = 0.04) and immunomodulators (40% vs 21%, P = 0.04) at 6 months, higher biologic use at 1 year (34% vs 16%, P = 0.03), earlier first relapse (mean ± SD 29.4 ± 26.1 vs 46.7 ± 43.4 weeks after diagnosis, P = 0.02), and higher colectomy rates by 2 years (21% vs 8%, P = 0.01)., Conclusions: Children with MA at diagnosis had higher colectomy rates despite earlier treatment escalation and similar baseline severity scores. We identify MA as a promising new prognostic marker in children with newly diagnosed UC., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Aims To examine; (a) the number of registered dietitians (RDs) with blended tube fed (BTF) patients, work setting and caseload; (b) attitudes and experiences towards BTF; (c) current BTF supports and future resources required. Methods An online survey collected information from Irish RDs over one month. Data was examined using cross-tabulations and Mann-Whitney U tests. Free-text was categorized into thematic domains. Results A significant number of RDs with HEN paediatric patients concurrently managed BTF patients (n = 27/48, 56.3%, p<0.05). The majority were based in tertiary hospitals (HEN; n = 20/48, 41.7%, BTF; n = 12/27, 44.4%). Equal numbers were willing to support BTF or on a patient-case basis (n = 36/77, 46.8%). International guidelines were most used to inform RDs (n = 40/69, 58.0%). Professional training workshops were the preferred learning method (n = 60/73, 82.2%). Conclusion Overall, BTF appears to be a growing practice. Community services, professional guidelines, training and information are needed., Competing Interests: The authors have read and understood the IMJ policy on declaration of interests and have no competing interests to declare.

Background: Diagnostic evaluation of thyroid nodules by FNA is used in the clinical management triage based on the knowledge of the rate of malignancy of each diagnostic category. The Bethesda System for Reporting Thyroid Cytopathology was published in 2007 by the National Cancer Institute (NCI). Using this classification, we studied our institution's experience in the pediatric population calculating the rate of malignancy for each diagnostic category, comparing our findings to our general patient population and that of the literature., Methods: 13,312 thyroid FNAs were performed at our institution between 1998 and 2010. 282 cases were from patients under 19 years of age. We reviewed and reclassified these cases using the new NCI categories, and pursued cytology-surgical follow-up., Results: Of the 282 FNA cases, 20.92% (59) were classified as unsatisfactory (U), 48.22, % (136) benign (B), 2.12% (6) Atypia of undetermined significance (AUS), 14.18% (40) suspicious for follicular neoplasm (FN), 2.12% (6) suspicious for malignancy (SM) and 12.41% (35) positive for malignancy (P). The U-category was further classified into nondiagnostic (ND) 12.41% (35) and cysts (C) 8.51% (24). Seventy-four children had surgical follow-up. The rates of histologically confirmed malignancy were 10% in U (1/10), 0% in B (0/17), 50% in AUS (2/4), 39% in FN (7/18), 100% in SM (4/4) and 100% in P (24/24) categories respectively. Among the U category, malignancy rate was 0% for the ND category and 25% for the C category., Conclusions: To our knowledge, this is the first study to apply the NCI categories to the pediatric population. The rate of malignancy in the U category was only seen in the specimens with cystic component. AUS and FN categories had a higher malignancy rate (50 and 39% respectively) as compared with that of the general population (15 and 30% respectively). Given that the rates of malignancy are higher for cysts and AUS, the literature recommendation to "follow-up and repeat" may not apply to the pediatric population. Surgery may be reasonable in these categories instead., (© 2015 Wiley Periodicals, Inc.)

Purpose: This study examined the body composition, nutritional knowledge, behaviors, attitudes, and educational needs of senior schoolboy rugby players in Ireland., Methods: Participants included 203 male rugby players age 15-18 yr competing at Senior School's Cup level in Leinster, Ireland. Estimation of body composition included measurement of height, weight, and percentage body fat (PBF; using bioelectrical impedance analysis, Tanita BC-418). Nutritional knowledge, behaviors, attitudes, and education needs were assessed by questionnaire., Results: The range of PBF was 5.1-25.3%. Sixty-eight percent of the players in this study had a healthy PBF (10-20%), 32 (22%) were classified as underweight (<10% body fat), and 9.7% (n = 14) were overweight. Assessment of nutritional knowledge demonstrated poor knowledge of the foods required for refueling, appropriate use of sports drinks, and the role of protein in muscle formation. Alcohol consumption and dietary supplement use were reported by 87.7% and 64.5%, respectively. A perception that greater body size enhances sport performance did not predict dietary supplement use. Nutritional advice had been previously sought by 121 players from coaches (66.9%), magazines (42.1%), Web sites (38.8%), peers (35.5%), family (28.1%), sport organizations (16.5%), and health professionals (8.2%). Nutritional knowledge was no better in these players, nor did better nutritional knowledge correlate with positive dietary behaviors or attitudes., Conclusions: Most players had a healthy PBF. Despite a positive attitude toward nutrition, poor nutritional knowledge and dietary practices were observed in many players. Young athletes' nutritional knowledge and dietary practices may benefit from appropriate nutritional education.

Pnn (PNN) is a nuclear and cell adhesion-related protein. Previous work has suggested that Pnn/DRS/memA is a potential tumor suppressor involved in the regulation of cell adhesion and cell migration. Using the ecdysone-inducible mammalian expression system, a stable inducible GFP-tagged human Pnn gene (PNNGFP) expressing 293 cell line was created (EcR293-PNNGFP). Cells induced to express PNNGFP not only exhibited increased cell-cell adhesion but also exhibited changes in cell growth and cell cycle progression. cDNA array analyses, together with real time PCR, revealed that the effects of exogenously expressed Pnn on cellular behavior may be linked to the regulation of the expression of specific subset genes. This subset includes cell cycle-related genes such as p21(cip1/waf1), CDK4, CPR2; cell migration and invasion regulatory genes such as RhoA, CDK5, TIMP-1, MMP-7, and EMMPRIN; and MIC-1. Concordant with previous observations of Pnn-induced phenotype changes, genes coding for epithelial associated processes and cell division controls were elevated, while those coding for increased cell motility and cellular reorganizations were downregulated. We utilized p21 promoter-luciferase reporter constructs and demonstrated that a marked stimulation of p21 promoter activity in 293 cells correlated with increased Pnn expression. Taken together, these data indicate that Pnn may participate in the regulation of gene expression, thereby, positively promoting cell-cell adhesion, and negatively affecting cell migration and cell proliferation.

Purpose: To determine whether the cellular distribution of cell adhesion-associated protein, pinin, is altered during corneal epithelial migration in response to debridement wounding and to determine the effect of overexpression of pinin in cultured epithelial cells., Methods: Corneas from guinea pig and embryonic (day 17) chickens were excised, wounded, and placed on organ-culture rafts. At time points from 0 to 24 hours, corneas were cryosectioned and subsequently analyzed by immunofluorescence or immunoelectron microscopy for the presence and distribution of pinin. Cultured epithelial cell line MDCK (Madin Darby canine kidney) confluent monolayers were wounded by scraping and examined by immunofluorescence for pinin and desmoplakin. MDCK cells were transfected with full-length pinin cDNA. After selection in Geneticin, clones of pinin-transfected cells were isolated. Monolayers of transfected cells were scrape-wounded and assayed for their ability to migrate., Results: Within 2 hours after wounding, although morphologically identifiable desmosomes were present on migrating epithelial cells, the association of pinin to desmosomes was greatly reduced. Finally, after completion of wound closure, pinin returned to the corneal epithelial desmosome. Wounding of confluent epithelial monolayers (MDCK) in vitro demonstrated a very similar change in the distribution of pinin, whereas desmoplakin remained cell boundary-associated. Transfection of pinin into cultured epithelial cells resulted in an overexpression of pinin. Clones of cells expressing high levels of pinin exhibited marked reduction in their ability to migrate after wounding., Conclusions: Pinin is involved in corneal epithelium migration. The localization of pinin at or near the desmosome is correlated with the epithelial quiescence. The loss of pinin from the cell boundary correlates with the transition from quiescence to actively migrating. Overexpressing pinin in cultured epithelial cells affects epithelial homeostasis and, in turn, drives the epithelial cells to a hyperstable epithelial adhesive state and inhibits the transition from quiescence to migratory.

Handwashing practices are persistently suboptimal among healthcare professionals and are also stubbornly resistant to change. The purpose of this quasi-experimental intervention trial was to assess the impact of an intervention to change organizational culture on frequency of staff handwashing (as measured by counting devices inserted into soap dispensers on four critical care units) and nosocomial infections associated with methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). All staff in one of two hospitals in the mid-Atlantic region received an intervention with multiple components designed to change organizational culture; the second hospital served as a comparison. Over a period of 8 months, 860,567 soap dispensings were recorded, with significant improvements in the study hospital after 6 months of follow-up. Rates of MRSA were not significantly different between the two hospitals, but rates of VRE were significantly reduced in the intervention hospital during implementation.

Several cell adhesion-related proteins have been shown to act as tumor-suppressors (TS) in the neoplastic progression of epithelial-derived tumors. Pinin/DRS/memA was first identified in our laboratory and it was shown to be a cell adhesion-related molecule. Our previous study demonstrated that restoration of pinin expression in transformed cells not only positively influenced cellular adhesive properties but also reversed the transformed phenotype to more epithelial-like. Here, we show by FISH analysis that the gene locus for pinin is within 14q13. The alignment of the pinin gene with STS markers localized the gene to the previously identified TS locus D14S75-D14S288. Northern analyses revealed diminished pinin mRNA in renal cell carcinomas (RCC) and certain cancer cell lines. Immunohistochemical examination of tumor samples demonstrated absent or greatly reduced pinin in transitional cell carcinoma (TCC) and RCC tumors. TCC-derived J82 cells as well as EcR-293 cells transfected with full-length pinin cDNA demonstrated inhibition of anchorage-independent growth of cells in soft agar. Furthermore, methylation analyses revealed that aberrant methylation of pinin CpG islands was correlated with decreased/absent pinin expression in a subset of tumor tissues. These data lend significant support to the hypothesis that pinin/DRS/memA may act as a tumor suppressor in certain types of cancers.

The corneal epithelium, like other stratifying epithelium, does not present a well formed junctional complex as compared to that of simple epithelia. However, the resistance barrier of the corneal epithelium is to a great extent generated by zonula occludens (ZO, tight junction), which are formed between the cells of the apical-most strata. The tight junction provides a continuous seal around the apical aspect of adjoining epithelial cells, thereby preventing the free passage of molecules between adjacent epithelial cells (paracellular pathway). We have examined rabbit corneal epithelia with monoclonal antibody against the tight junction associated protein ZO1. With this antibody, we resolved two distinct patterns of ZO1 expression, one being the lateral boundary of the apical cell, which appeared as a true zonula around these cells. The second pattern of expression for ZO1 was at a set of punctate spots that correspond to the connection of the most apical portion of the basal corneal epithelial cells, with the above wing cells. En face, confocal analyses revealed that these areas consisted of 5-6 distinct spots per basal cell at or near the contact points with the immediate wing cells above. ImmunoEM revealed that the mid-epithelial accumulations of ZO1 were not tight junctions, but rather a form of adherens junction. The expression of ZO1 in the mid-epithelial level of the cornea is neither correlated with the presence of tight junction, nor with the established barrier functions. Interestingly, these junctions in the corneal epithelium also contain paxillin, a focal adhesion associated phosphoprotein which is a target of pp125 focal adhesion kinase, erbB-2 kinase and p21Obcr/abl oncogene. We postulated that the ZO1/paxillin adherens junction within stratified epithelium, such as the corneal epithelium, may function to reinforce attachments at the level of the basal cell to wing cell junction and be regulated by reversible phosphorylation. We speculate that the regulated phosphorylation of tyrosine residues on paxillin may perform a critical role in controlling epithelial cell-cell interactions as it does in cell-matrix adhesion.