Six topics on inscribable polytopes

Inscribability of polytopes is a classic subject but also a lively research area nowadays. We illustrate this with a selection of well-known results and recent developments on six particular topics related to inscribable polytopes. Along the way we collect a list of (new and old) open questions.Comment: 11 page

Tyrosine residues mediate supercontraction in biomimetic spider silk

Water and humidity severely affect the material properties of spider major ampullate silk, causing the fiber to become plasticized, contract, swell and undergo torsion. Several amino acid residue types have been proposed to be involved in this process, but the complex composition of the native fiber complicates detailed investigations. Here, we observe supercontraction in biomimetically produced artificial spider silk fibers composed of defined proteins. We found experimental evidence that proline is not the sole residue responsible for supercontraction and that tyrosine residues in the amorphous regions of the silk fiber play an important role. Furthermore, we show that the response of artificial silk fibers to humidity can be tuned, which is important for the development of materials for applications in wet environments, eg producing water resistant fibers with maximal strain at break and toughness modulus

Impact of Obesity on Pediatric Acute Recurrent and Chronic Pancreatitis

OBJECTIVE: The aim of this study was to assess the impact of obesity on pediatric acute recurrent pancreatitis or chronic pancreatitis (CP). METHODS: We determined body mass index (BMI) status at enrollment in INSPPIRE (INternational Study group of Pediatric Pancreatitis: In search for a cuRE) cohort using CDC criteria for pediatric-specific BMI percentiles. We used the Cochran-Armitage test to assess trends and the Jonckheere-Terpstra test to determine associations. RESULTS: Of 446 subjects (acute recurrent pancreatitis, n = 241; CP, n = 205), 22 were underweight, 258 normal weight, 75 overweight, and 91 were obese. The BMI groups were similar in sex, race, and age at presentation. Hypertriglyceridemia was more common in overweight or obese. Obese children were less likely to have CP and more likely to have acute inflammation on imaging. Compared with children with normal weight, obese or overweight children were older at first acute pancreatitis episode and diagnosed with CP at an older age. Obese or overweight children were less likely to undergo medical or endoscopic treatment, develop exocrine pancreatic insufficiency, and require total pancreatectomy with islet autotransplantation. Diabetes was similar among all groups. CONCLUSIONS: Obesity or overweight seems to delay the initial acute pancreatitis episode and diagnosis of CP compared with normal weight or underweight. The impact of obesity on pediatric CP progression and severity deserves further study

Chronic pancreatitis: Pediatric and adult cohorts show similarities in disease progress despite different risk factors

Objectives: To investigate the natural history of chronic pancreatitis (CP), patients in the North American Pancreatitis Study2 (NAPS2, adults) and INternational Study group of Pediatric Pancreatitis: In search for a cuRE (INSPPIRE, pediatric) were compared. Methods: Demographics, risk factors, disease duration, management and outcomes of 224 children and 1,063 adults were compared using appropriate statistical tests for categorical and continuous variables. Results: Alcohol was a risk in 53% of adults and 1% of children (p<0.0001); tobacco in 50% of adults and 7% of children (p<0.0001). Obstructive factors were more common in children (29% vs 19% in adults, p=0.001). Genetic risk factors were found more often in children. Exocrine pancreatic insufficiency was similar (children 26% vs adult 33%, p=0.107). Diabetes was more common in adults than children (36% vs 4% respectively, p<0.0001). Median emergency room visits, hospitalizations, and missed days of work/school were similar across the cohorts. As a secondary analysis, NAPS2 subjects with childhood onset (NAPS2-CO) were compared to INSPPIRE subjects. These two cohorts were more similar than the total INSPPIRE and NAPS2 cohorts, including for genetic risk factors. The only risk factor significantly more common in the NAPS2-CO cohort compared with the INSPPIRE cohort was alcohol (9% NAPS2-CO vs 1% INSPPIRE cohorts, p=0.011). Conclusions: Despite disparity in age of onset, children and adults with CP exhibit similarity in demographics, CP treatment, and pain. Differences between groups in radiographic findings and diabetes prevalence may be related to differences in risk factors associated with disease and length of time of CP

The K+ Channel Opener 1-EBIO Potentiates Residual Function of Mutant CFTR in Rectal Biopsies from Cystic Fibrosis Patients

BACKGROUND: The identification of strategies to improve mutant CFTR function remains a key priority in the development of new treatments for cystic fibrosis (CF). Previous studies demonstrated that the K⁺ channel opener 1-ethyl-2-benzimidazolone (1-EBIO) potentiates CFTR-mediated Cl⁻ secretion in cultured cells and mouse colon. However, the effects of 1-EBIO on wild-type and mutant CFTR function in native human colonic tissues remain unknown. METHODS: We studied the effects of 1-EBIO on CFTR-mediated Cl⁻ secretion in rectal biopsies from 47 CF patients carrying a wide spectrum of CFTR mutations and 57 age-matched controls. Rectal tissues were mounted in perfused micro-Ussing chambers and the effects of 1-EBIO were compared in control tissues, CF tissues expressing residual CFTR function and CF tissues with no detectable Cl⁻ secretion. RESULTS: Studies in control tissues demonstrate that 1-EBIO activated CFTR-mediated Cl⁻ secretion in the absence of cAMP-mediated stimulation and potentiated cAMP-induced Cl⁻ secretion by 39.2±6.7% (P<0.001) via activation of basolateral Ca²⁺-activated and clotrimazole-sensitive KCNN4 K⁺ channels. In CF specimens, 1-EBIO potentiated cAMP-induced Cl⁻ secretion in tissues with residual CFTR function by 44.4±11.5% (P<0.001), but had no effect on tissues lacking CFTR-mediated Cl⁻ conductance. CONCLUSIONS: We conclude that 1-EBIO potentiates Cl⁻secretion in native CF tissues expressing CFTR mutants with residual Cl⁻ channel function by activation of basolateral KCNN4 K⁺ channels that increase the driving force for luminal Cl⁻ exit. This mechanism may augment effects of CFTR correctors and potentiators that increase the number and/or activity of mutant CFTR channels at the cell surface and suggests KCNN4 as a therapeutic target for CF

Clinical and Practice Variations in Pediatric Acute Recurrent or Chronic Pancreatitis: Report From the INSPPIRE Study

Objective: The aim of the study was to determine whether clinical characteristics and management of pediatric acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) differ across INSPPIRE (INternational Study Group of Pediatric Pancreatitis: In Search for a cuRE) sites. Study design: Data were collected from INSPPIRE and analyzed per US regions and "non-US" sites. Between-group differences were compared by Pearson chi-square test. Differences in disease burden were compared by Kruskal-Wallis test. Results: Out of the 479 subjects, 121 (25%) were enrolled in West, 151 (32%) Midwest, 45 Northeast (9%), 78 (16%) South, and 84 (18%) at non-US sites. Hispanic ethnicity was more common in South (P < 0.0001); white race in Northeast (P = 0.009). CP was less common and time from diagnosis of first acute pancreatitis to CP was longer in children at non-US sites (P = 0.0002 and P = 0.011, respectively). Genetic mutations were most common among all groups; PRSS1 variants predominated in Midwest (P = 0.002). Gallstones were more frequent in South (P = 0.002). Endoscopic retrograde cholangiopancreatography (ERCP) and computed tomography (CT) imaging were more commonly utilized in United States compared with non-United States (P < 0.0001), but there were no differences in the use of MRI/MRCP. Disease burden was highest in the West and Midwest, possibly as total pancreatectomy and islet autotransplantation (TPIAT) referral sites were located in these regions. All therapies were less commonly administered in non-US sites (P < 0.0001). Conclusions: This is the first study to describe geographical variations in the INSPPIRE cohort, which possibly reflect variations in practice and referral patterns. The underlying reason behind the lower frequency of CP and fewer treatments in non-United States sites need to be further explored

Risk Factors for Rapid Progression From Acute Recurrent to Chronic Pancreatitis in Children: Report From INSPPIRE

Objective To determine the rate of progression from acute recurrent pancreatitis (ARP) to chronic pancreatitis (CP) in children and assess risk factors. Study Design Data were collected from the INternational Study group of Pediatric Pancreatitis: In search for a cuRE (INSPPIRE) cohort. Kaplan-Meier curves were constructed to calculate duration of progression from initial attack of acute pancreatitis (AP) to CP. Log-rank test was used to compare survival (non-progression) probability distribution between groups. Cox proportional hazard regression models were fitted to obtain hazard ratio (with 95% CI) of progression for each risk variable. Results Of 442 children, 251 had ARP, 191 CP. The median time of progression from initial attack of AP to CP was 3.79 years. The progression was faster in those age ≥6 years at the first episode of AP compared to those age <6 years (median time to CP: 2.91 vs 4.92 years; p=0.01). Children with pathogenic PRSS1 variants progressed more rapidly to CP compared to children without PRSS1 variants (median time to CP: 2.52 vs 4.48 years; p=0.003). Within six years after the initial AP attack, cumulative proportion with exocrine pancreatic insufficiency (EPI) was 18.0% (95% CI: 12.4%, 25.6%); diabetes mellitus was 7.7% (95% CI: 4.2%, 14.1%). Conclusions Children with ARP rapidly progress to CP, EPI and diabetes. The progression to CP is faster in children who were ≥6 years at the first episode of AP or with pathogenic PRSS1 variants. The factors that impact the aggressive disease course in childhood warrant further investigation

Pancreas Divisum in Pediatric Acute Recurrent and Chronic Pancreatitis: Report From INSPPIRE

The significance of pancreas divisum (PD) as a risk factor for pancreatitis is controversial. We analyzed the characteristics of children with PD associated with acute recurrent or chronic pancreatitis to better understand its impact. Patients and Methods: We compared children with or without PD in the well-phenotyped INSPPIRE (INternational Study group of Pediatric Pancreatitis: In search for a cuRE) cohort. Differences were analyzed using 2-sample t test or Wilcoxon rank sum test for continuous variables, Pearson χ2 or Fisher exact test for categorical variables. Results: PD was found in 52 of 359 (14.5%) subjects, a higher prevalence than the general population (∼7%). Females more commonly had PD (71% vs. 55%; P=0.02). Children with PD did not have a higher incidence of mutations in SPINK1, CFTR, CTRC compared with children with no PD. Children with PD were less likely to have PRSS1 mutations (10% vs. 34%; P<0.01) or a family history of pancreatitis (P<0.05), and more likely to have hypertriglyceridemia (11% vs. 3%; P=0.03). Children with PD underwent significantly more endoscopic procedures and pancreatic sphincterotomy. Patients with PD had fewer attacks of acute pancreatitis (P=0.03) and were less likely to develop exocrine pancreatic insufficiency (P=0.01). Therapeutic endoscopic retrograde cholangiopancreatography was considered most helpful if pancreatic duct was impacted with stones (83% helpful). Conclusions: PD is likely a risk factor for acute recurrent pancreatitis and chronic pancreatitis in children that appears to act independently of genetic risk factors. Patients with PD and stones obstructing the pancreatic duct benefit most from therapeutic endoscopic retrograde cholangiopancreatography