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A nonlinear hardening role that defines a yield surface translation for homogeneous frame member materials is proposed. The rule is defined as a nonlinear constitutive relationship that examines material behavior through a postelastic perspective. The gradual development of the postelastic states of a beam along its length and through its section thickness is analyzed. The model uses a hardening index parameter to guide the nonlinear stress-strain relationship, and a smooth function to model the web-flange intersection of frame members. As such, nonlinear curvature distributions with continuous derivatives are determined along the length of the member, which enables lateral displacements to be accurately predicted. Plastic hinge lengths and finite-element displacements are subsequently determined, and a nonlinear stiffness is derived. The model is formulated on a constitutive level and applies a smoothed-over cross section to derive a single internal moment expression for any postelastic state. Results are verified through experimental published literature. DOI: 10.1061/(ASCE)0733-9445(2005)131:8(1286) CE Database subject headings: Constitutive models: Degradation: Nonlinear response; Plastic hinges; Plastic deformation; Stress distribution; Stress strain relations.

The article discusses the synthesis of multiphosphorylated peptides of bovine dentine phosphophoryn (BDP) for the development of novel dental restorative material. BDP is synthesized by odontoblasts and is believed to be involved in matrix-mediated biomineralization of dentin. When immobilized on a stable support and incubated in physiological solutions of calcium and phosphate, phosphophoryn can induce the formation of hydroxyapatite (HA). Through the H NMR spectroscopy, it has been demonstrated that phosphophoryn is a uniformly flexible molecule which is consistent with the relatively featureless sequences. The results also show that phosphophoryn, due its uniform nature has the potential to be replaced by biomimetic peptide. The synthesis of the unphosphorylated Asp-Ser-Ser-Asp-Ser-Ser-Asp-Ser-Ser- Asp was carried out using standard Fmoc protocols.

Objective: A constitutional disease-causing variant (DCV) in the SMAD4 or BMPR1A genes is present in 40%-60% of patients with juvenile polyposis syndrome (JPS). The aim of this study was to characterize the clinical course and polyp burden in children with DCV-positive JPS compared to DCV-negative JPS., Methods: Demographic, clinical, genetic, and endoscopic data of children with JPS were compiled from eight international centers in the ESPHGAN/NASPGHAN polyposis working group., Results: A total of 124 children with JPS were included: 69 (56%) DCV-negative and 55 (44%) DCV-positive (53% SMAD4 and 47% BMPR1A) with a median (interquartile range) follow-up of 4 (2.8-6.4) years. DCV-positive children were diagnosed at an older age compared to DCV-negative children [12 (8-15.7) years vs. 5 (4-7) years, respectively, p < 0.001], had a higher frequency of family history of polyposis syndromes (50.9% vs. 1.4%, p < 0.001), experienced a greater frequency of extraintestinal manifestations (27.3% vs. 5.8%, p < 0.001), and underwent more gastrointestinal surgeries (16.4% vs. 1.4%, p = 0.002). The incidence rate ratio for the development of new colonic polyps was 6.15 (95% confidence interval 3.93-9.63, p < 0.001) in the DCV-positive group compared to the DCV-negative group, with an average of 12.2 versus 2 new polyps for every year of follow-up. There was no difference in the burden of polyps between patients with SMAD4 and BMPR1A mutations., Conclusions: This largest international cohort of pediatric JPS revealed that DCV-positive and DCV-negative children exhibit distinct clinical phenotype. These findings suggest a potential need of differentiated surveillance strategies based upon mutation status., (© 2024 The Author(s). Journal of Pediatric Gastroenterology and Nutrition published by Wiley Periodicals LLC on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objectives: No study has explored whether availability of endoscopic retrograde cholangiopancreatography (ERCP) is adequate and equitable across US children's hospitals. We hypothesized that ERCP availability and utilization differs by geography and patient factors., Methods: Healthcare encounter data from 2009 to 2019 on children with pancreatic and biliary diseases from the Pediatric Health Information System were analyzed. ERCP availability was defined as treatment at a hospital that performed pediatric ERCP during the year of service., Results: From 2009 to 2019, 37,946 children (88,420 encounters) had a potential pancreatic or biliary indication for ERCP; 7066 ERCPs were performed. The commonest pancreatic diagnoses leading to ERCP were chronic (47.2%) and acute pancreatitis (43.2%); biliary diagnoses were calculus (68.3%) and obstruction (14.8%). No ERCP was available for 25.0% of pancreatic encounters and 8.1% of biliary encounters. In multivariable analysis, children with public insurance, rural residence, or of Black race were less likely to have pancreatic ERCP availability; those with rural residence or Asian race were less likely to have biliary ERCP availability. Black children or those with public insurance were less likely to undergo pancreatic ERCP where available. Among encounters for calculus or obstruction, those of Black race or admitted to hospitals in the West were less likely to undergo ERCP when available., Conclusions: One-in-four children with pancreatic disorders and one-in-12 with biliary disorders may have limited access to ERCP. We identified racial and geographic disparities in availability and utilization of ERCP. Further studies are needed to understand these differences to ensure equitable care., (© 2024 The Authors. Journal of Pediatric Gastroenterology and Nutrition published by Wiley Periodicals LLC on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Tubulin, one of the most abundant cytoskeletal building blocks, has numerous isotypes in metazoans encoded by different conserved genes. Whether these distinct isotypes form cell type- and context-specific microtubule structures is poorly understood. Based on a cohort of 12 patients with primary ciliary dyskinesia as well as mouse mutants, we identified and characterized variants in the TUBB4B isotype that specifically perturbed centriole and cilium biogenesis. Distinct TUBB4B variants differentially affected microtubule dynamics and cilia formation in a dominant-negative manner. Structure-function studies revealed that different TUBB4B variants disrupted distinct tubulin interfaces, thereby enabling stratification of patients into three classes of ciliopathic diseases. These findings show that specific tubulin isotypes have distinct and nonredundant subcellular functions and establish a link between tubulinopathies and ciliopathies.

Objectives and Study: Accidental foreign body ingestion (FBI) is a common pediatric referral concern. In contrast, recurrent and intentional FBI (RIFBI) is infrequent and associated with greater endoscopic and surgical intervention in adults. Although pediatric guidelines exist for FBI, the risk and therapeutic implications of RIFBI are not addressed. An anonymous international survey on pediatric gastroenterologist experience with RIFBI was distributed., Methods: A 33-item REDCap© survey was distributed via email to pediatric gastroenterologists identified through mailing and email lists obtained from pediatric gastroenterology professional organizations., Results: During 9-12/2021 we accrued 202 completed surveys. Respondents were from 27 countries and across the career span. Eighty percent reported experience with RIFBI; 74% reported seeing ≤ 3 patients with RIFBI within the past 24 months and 4% reported seeing ≥ 6. Of those who treated RIFBI, 38% reported an average number of annual ingestions per patient was ≥5. Frequent morbidity but not mortality was reported. Half reported adherence to FBI guidelines. Later-career endoscopists treated RIFBI more aggressively than accidental ingestion. Ninety-six percent noted that patients with RIFBI had psychiatric comorbidities. Providers at academic medical centers reported referring to behavioral health more than those in other settings., Conclusion: Most gastroenterologists surveyed reported encountering RFBI several times a year and in patients with psychiatric comorbidities. Greater likelihood of adverse outcomes associated with endoscopy was reported. Most reported referral to behavioral health and few had RIFBI management protocols. A broader spectrum of psychologic comorbidities in the pediatric population with RIFBI, notably depression and autism spectrum disorder, were reported., (© 2024 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Single or multiple polyps are frequently encountered during colonoscopy among children and adolescents and may be indicative of hereditary polyposis syndrome (HPS). The management of children with single or multiple polyps is guided by the number of polyps, their distribution and the histological findings. Children with HPS carry a high risk of complications, including intestinal and extra-intestinal malignancies. The goals of surveillance in pediatric HPS are to treat symptoms, monitor the burden of polyps and prevent short- and long-term complications. Therefore, the management of children with HPS is based on therapeutic endoscopy. The strategy of therapeutic endoscopy is a careful assessment and characterization of the polyps and performing polypectomies using advanced endoscopic techniques. A multidisciplinary approach, comprising clinical, interventional endoscopy, cancer surveillance and support of familial and emotional aspects is essential in the management of children with HPS., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: The authors report no conflicts of interest.

Competing Interests: The authors report no conflicts of interest.

Antimicrobial peptides are an important class of membrane-active peptides that can provide alternatives or complements to classic antibiotics. Among the many classes of AMPs, the histidine-rich family is of particular interest since they may induce pH-sensitive interactions with cell membranes. The AMP caerin 1.1 (Cae-1), from Australian tree frogs, has three histidine residues, and thus we studied the pH dependence of its interactions with model cell membranes. Using NMR spectroscopy and molecular dynamics simulations, we showed that Cae-1 induced greater perturbation of the lipid dynamics and water penetrations within the membrane interior in an acidic environment compared with physiological conditions. Using 31 P solid-state NMR, the packing, chemical environment, and dynamics of the lipid headgroup were monitored. 2 H solid-state NMR showed that Cae-1 ordered the acyl chains of the hydrophobic core of the bilayer. These results supported the molecular dynamics data, which showed that Cae-1 was mainly inserted within the lipid bilayer for both neutral and negatively charged membranes, with the charged residues pulling the water and phosphate groups inward. This could be an early step in the mechanism of membrane disruption by histidine-rich antimicrobial peptides and indicated that Cae-1 acts via a transmembrane mechanism in bilayers of neutral and anionic phospholipid membranes, especially in acidic conditions., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

Objectives: Pediatric neurogastroenterology and motility (PNGM) disorders impose a significant impact on health-related quality of life and cost of health care in children and adolescents. The detailed understanding of its burden across demographic groups is unknown. The objective of our study is to characterize the demographic and hospitalization trends of patients undergoing PNGM tests., Methods: We used Healthcare Cost and Utilization Project (HCUP) Inpatient Database (KID) for years 2003-2016 to perform a trend analysis in US hospitalizations for International Classification of Diseases (ICD)-9 and -10 Clinical Modification (CM)-identified PNGM studies in patients (<18 years of age) with elective admission and a length of stay (LOS) <3 days. The hospitalization rates were analyzed by year, hospital region, facility type, and patient sociodemographic characteristics. Multivariable logistic regression was used to examine factors influencing the receipt of motility studies., Results: There was an overall increase trend in hospitalizations, rates of PNGM studies, and median hospital charges from 2003 to 2016. Patients with private insurance and living in the high-income zip codes were more likely to receive a PNGM study compared with those with governmental insurance and lower income area. Although the race was not found to influence the receipt of the study, a major difference in the LOS was noted across the regions., Conclusions: There are income- and insurance-based differences in the rates of inpatient PNGM studies. PNGM studies significantly add to health care burden. Standardization of PNGM practices across the country may decrease the LOS and associated expenses. Future analysis should include ambulatory PNGM services to understand combined inpatient and outpatient trends., (Copyright © 2022 by European Society for European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Alternative promoter usage generates long and short isoforms (DCLK1-L and DCLK1-S) of doublecortin-like kinase-1 (DCLK1). Tight control of Notch signaling is important to prevent and restitute inflammation in the intestine. Our aim was to investigate whether Notch1-DCLK1 axis regulates the mucosal immune responses to infection and whether this is phenocopied in human models of colitis. In the FFPE (formalin-fixed paraffin-embedded) sections prepared from the colons of ulcerative colitis (UC) and immune-mediated colitis (IRAEC) patients, expression of DCLK1 isoforms correlated positively with Notch1 and negatively with a transcriptional repressor, FoxD3 (Forkhead Box D3). DCLK1 protein staining in these sections was predominantly sub-epithelial (stromal) wherein DCLK1 co-localized with NICD, CD68, CD11c, and neutrophil elastase (NE). NE also co-stained with Citrullinated-H3 indicating the presence of neutrophil extracellular traps. In human neutrophils, elevated levels of DCLK1-S, CXCL-10, Ly6G, MPO, NE, and Notch1/2 in LPS-treated cells were inhibited when LPS was added in conjunction with Notch blocker dibenzazepine (DBZ; LPS + DBZ group). In CR-infected Rag1 -/- mice, higher levels of DCLK1 in the colonic crypts were inhibited when mice received DBZ for 10 days coincident with significant dysbiosis, barrier disruption, and colitis. Concurrently, DCLK1 immunoreactivity shifted toward the stroma in CR + DBZ mice with predominance of DCLK1-S that coincided with higher Notch1 levels. Upon antibiotic treatment, partial restoration of crypt DCLK1, reduction in MPO activity, and increased survival followed. When intestinal epithelial cell-specific Dclk1-knockout (Dclk1 ΔIEC ) or Dclk1 ΔIEC ;Rag1 -/- double knockout (DKO) mice were infected with CR and given a single dose of DBZ, they developed barrier defect and severe colitis with higher levels of stromal DCLK1-S, Ly6G, NE, and Notch1. We therefore propose that, by regulating the mucosal immune responses, the Notch-DCLK1 axis may be integral to the development of murine or human colitis.

Although foreign body ingestion (FBI) is a common pediatric referral concern, intentional or recurrent FBI (RFBI) in youth is poorly defined. In adults, several subgroups of patients with psychiatric comorbidities account for a large portion of FBIs. A similar classification system and corresponding management recommendations are yet to be outlined in pediatrics. We report 3 patients with RFBI: a 16-year-old, African American boy with 22 admissions and 27 endoscopic procedures for FBI removal; a 4-year-old, African American boy with autism spectrum disorder admitted twice after delayed presentation of ingestion of magnets; and a 15-year-old Caucasian girl with a complex mental health history who presented twice after intentional ingestion to self-harm. We also present a literature review of pediatric RFBI. Patients with RFBI require a nuanced, multidisciplinary management approach to address acute concerns and reduce subsequent ingestion. A behavioral taxonomy and treatment considerations are presented.