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The article traces the impact of Czesław Miłosz’s first American stay on his image of Central Europe in Rodzinna Europa [Native Realm]. In the United States, the post-war immigrant from Vilnius learned to perceive, understand and evaluate American culture; he also gained a new perspective on his region of Europe and Slavic immigrants. This experience enabled him to adopt an American point of view in his autobiographical essay. Following William Faulkner, Miłosz carries on an analysis of Eastern and Central Europe’s history and identities. The uses Western historical and sociological glossary to describe processes that formed his “native realm.” Analogically, the poet from pre-war Vilnius reflects on American multi-ethnicity and religious diversity from a Central European perspective. In Rodzinna Europa, Miłosz takes the position of a migrant translator and a two-way mediator between East and West.

Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) is the most common congenital malformation of the upper digestive tract. This study represents the first genome-wide association study (GWAS) to identify risk loci for EA/TEF. We used a European case-control sample comprising 764 EA/TEF patients and 5,778 controls and observed genome-wide significant associations at three loci. On chromosome 10q21 within the gene CTNNA3 (p = 2.11 × 10 -8 ; odds ratio [OR] = 3.94; 95% confidence interval [CI], 3.10-5.00), on chromosome 16q24 next to the FOX gene cluster (p = 2.25 × 10 -10 ; OR = 1.47; 95% CI, 1.38-1.55) and on chromosome 17q12 next to the gene HNF1B (p = 3.35 × 10 -16 ; OR = 1.75; 95% CI, 1.64-1.87). We next carried out an esophageal/tracheal transcriptome profiling in rat embryos at four selected embryonic time points. Based on these data and on already published data, the implicated genes at all three GWAS loci are promising candidates for EA/TEF development. We also analyzed the genetic EA/TEF architecture beyond the single marker level, which revealed an estimated single-nucleotide polymorphism (SNP)-based heritability of around 37% ± 14% standard deviation. In addition, we examined the polygenicity of EA/TEF and found that EA/TEF is less polygenic than other complex genetic diseases. In conclusion, the results of our study contribute to a better understanding on the underlying genetic architecture of ET/TEF with the identification of three risk loci and candidate genes., Competing Interests: The co-author C.M.B. declares the following interests: Shire (grant recipient, Scientific Advisory Board member), Idorsia (consultant), Lundbeckfonden (grant recipient), Pearson (author, royalty recipient), and Equip Health Inc. (Clinical Advisory Board). All other co-authors declare no competing interests., (© 2022 The Authors.)

Mutations in the PRSS1 (serine protease 1) gene encoding human cationic trypsinogen cause hereditary pancreatitis or may be associated with sporadic chronic pancreatitis. The mutations exert their pathogenic effect either by increasing intra-pancreatic trypsinogen activation (trypsin pathway) or by causing proenzyme misfolding and endoplasmic reticulum stress (misfolding pathway). Here we report a novel heterozygous c.568G>A (p.Glu190Lys) variant identified in a case with chronic pancreatitis. The parents of the index patient had no history of pancreatitis but were unavailable for genetic testing. Functional characterization revealed 2.5-fold increased autoactivation of the mutant trypsinogen relative to wild type. Unlike many other clinically relevant PRSS1 mutations, p.Glu190Lys did not alter the chymotrypsin C (CTRC)-dependent degradation of trypsinogen nor did it increase CTRC-mediated processing of the trypsinogen activation peptide. Cellular secretion of the mutant protein was unchanged indicating normal folding behavior. Based on the genetic and functional evidence, we classify the p.Glu190Lys PRSS1 variant as likely pathogenic, which stimulates autoactivation of cationic trypsinogen independently of CTRC.

Objectives: Genetic studies in adults/adolescent patients with chronic pancreatitis (CP) identified chymotrypsinogen C (CTRC) genetic variants but their association with CP risk has been difficult to replicate. To evaluate the risk of CP associated with CTRC variants in CP pediatric patients-control study., Methods: The distribution of CTRC variants in CP pediatric cohort (n = 136, median age at CP onset 8 years) with no history of alcohol/smoking abuse was compared with controls (n = 401, median age 45)., Results: We showed that p.Arg254Trp (4.6%) and p.Lys247&#95;Arg254del (5.3%) heterozygous mutations are frequent and significantly associated with CP risk in pediatric patients (odds ratio [OR] = 19.1; 95% CI 2.8-160; P = 0.001 and OR = 5.5; 95% CI 1.6-19.4; P = 0.001, respectively). For the first time, we demonstrated that the c.180TT genotype of common p.Gly60Gly variant is strong, an independent CP risk factor (OR = 23; 95% CI 7.7-70; P < 0.001) with effect size comparable to p.Arg254Trp mutation. The other novel observation is that common c.493+51C>A variant, both CA and AA genotype, is significantly underrepresented in CP compared with controls (15% vs 35%; OR = 0.33; 95% CI 0.19-0.59; P < 0.001 and 2.8% vs 11%; OR = 0.24; 95% CI 0.06-0.85; P = 0.027, respectively)., Conclusions: Our study provides evidence that CTRC variants, including c.180TT (p.Gly60Gly) are strong CP risk factors. The c.493+51C>A variant may play a protective role against CP development.

Objectives: The etiological factors of chronic pancreatitis (CP) in children differ from those in adults. To date, no study has assessed the clinical course of CP in young children. The aim of our study was to evaluate the etiology and the clinical presentation of the disease in children with disease onset before 5 years of age in comparison to later-onset of CP., Methods: A total of 276 children with CP, hospitalized from 1988 to 2015, were enrolled in the study. Data on presentation, diagnostic findings, and treatment were reviewed. Two hundred sixty patients were screened for the most frequent mutations in major pancreatitis-associated genes, such as cationic trypsinogen/serine protease gene (PRSS1), serine protease inhibitor, Kazal type 1 gene (SPINK1), and cystic fibrosis transmembrane conductance regulator gene (CFTR)., Results: The disease onset before the age of 5 years occurred in 51 patients (group 1), the later onset in 225 patients (group 2). We found no significant discrepancies in distribution of the etiological factors between groups. The youngest patients (group 1) had more pancreatitis episodes (median 5.0 vs 3.00; P < 0.05) and underwent surgeries more frequently (25.5% vs 8.9%; P < 0.05). It could be associated with significantly longer follow-up in early onset group (median 6 vs 4 years; P < 0.05). There were no differences in nutritional status or exocrine and endocrine pancreatic function., Conclusions: Early- and later-onset pancreatitis have similar etiological factors with predominance of gene mutations. The most frequent mutation found was p.Asn34Ser (N34S) in SPINK1 gene. The clinical presentation differed in number of pancreatitis episodes and frequency of surgeries.

Objectives: To evaluate the diagnostic accuracy of magnetic resonance cholangiopancreatography (MRCP) in the detection of chronic pancreatitis (CP)-specific changes in the pediatric population., Methods: The study included 48 children with pancreatic disorders subjected to both endoscopic retrograde cholangiopancreatography (ERCP) and MRCP within a 1- to 4-month interval. The sensitivity, specificity, positive predictive value, and negative predictive value of MRCP in the detection of CP-specific changes were determined using ERCP as a diagnostic standard., Results: Diagnostic ERCP pancreatograms were obtained in 41 (85.4%) of 48 patients and diagnostic MRCP images in all 48 children. The sensitivity and positive predictive value of MRCP were 77.1% and 90%, respectively, and its specificity and negative predictive value amounted to 50% and 27.3%, respectively. The patients with consistent results of MRCP and ERCP (ie, true-positive and true-negative cases) and individuals with incompatible results of the tests (ie, false-positive and false-negative cases) differed in terms of their median age at MRCP (14.17 vs 10.33 years) and median CP stage according to the Cambridge Scale (4 vs 2)., Conclusions: Magnetic resonance cholangiopancreatography provides diagnostic information equivalent to ERCP in a large percentage of pediatric patients with CP and should be used as the imaging method of choice, especially if the likelihood of therapeutic intervention is low.

Background: Available data from adult patients do not reflect natural course of hereditary pancreatitis (HP) in children. To date, no study has assessed the clinical course of HP in children., Objective: To investigate the clinical course of HP in children and compare it to non-HP group with chronic pancreatitis (CP)., Methods: A group of 265 children with CP, hospitalized from 1988 to 2014, were enrolled in the study. Medical records of those patients were reviewed for data on presentation, diagnostic findings and treatment. All children were screened for mutations in major pancreatitis-associated genes, i.e. PRSS1, SPINK1, and CFTR., Results: HP was diagnosed in 41 children (15.5%). Family history was positive in 88% of children with HP. Mutations of PRSS1 gene were found in 80% (33/41) of HP patients. We detected p.R122H, p.R122C, p.N29I, and p.E79K mutation in 34% (14/41), 27% (11/41), 12% (5/41), and 7% (3/41) of HP patients, respectively. Patients with paternal inheritance had first symptoms earlier than those with maternal inheritance (5.9 vs. 9.1 years; P < 0.05). Children with HP showed more severe changes in ERCP then those from non-HP group (2.05 Cambridge grade, vs. 1.6°; P < 0.05). ESWL was performed more frequently in HP group (12.2% vs. 3.1%; P < 0.05). There was no difference in age of disease onset (7.98 vs. 8.9 years; NS), pancreatic duct stenting (46.3% vs. 33%; NS), or number of surgical interventions (12.2% vs. 14.3%; NS) between both groups., Conclusions: Children with HP reveal significantly more severe clinical presentation of the disease than non-HP patients, despite the same age of onset., (Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

The present study sought to understand how the microstructure of protein gels impacts lipolysis of gelled emulsions. The selected system consisted of an oil-in-water (o/w) emulsion embedded within gelatin gels. The gelatin-gelled emulsions consisted of a discontinuous network of aggregated emulsion droplets (mesoscale), dispersed within a continuous network of gelatin (microscale). The viscoelastic properties of the gelled emulsions were dominated by the rheological behavior of the gelatin, suggesting a gelatin continuous microstructure rather than a bicontinuous gel. A direct relationship between the speed of fat digestion and gel average mesh size was found, indicating that the digestion of fat within gelatin-gelled emulsions is controlled by the ability of the gel's microstructure to slow lipase diffusion to the interface of fat droplets. Digestion of fat was facilitated by gradual breakdown of the gelatin network, which mainly occurred via surface erosion catalyzed by proteases. Overall, this work has demonstrated that the lipolysis kinetics of gelled emulsions is driven by the microstructure of protein gels; this knowledge is key for the future development of microstructures to control fat digestion and/or the delivery of nutrients to different parts of the gastrointestinal tract.

The relationship between the physical structure of espresso coffee foam, called crema, and the above-the-cup aroma release was studied. Espresso coffee samples were produced using the Nespresso extraction system. The samples were extracted with water with different levels of mineral content, which resulted in liquid phases with similar volatile profiles but foams with different structure properties. The structure parameters foam volume, foam drainage, and lamella film thickness at the foam surface were quantified using computer-assisted microscopic image analysis and a digital caliper. The above-the-cup volatile concentration was measured online by using PTR-MS and headspace sampling. A correlation study was done between crema structure parameters and above-the-cup volatile concentration. In the first 2.5 min after the start of the coffee extraction, the presence of foam induced an increase of concentration of selected volatile markers, independently if the crema was of high or low stability. At times longer than 2.5 min, the aroma marker concentration depends on both the stability of the crema and the volatility of the specific aroma compounds. Mechanisms of above-the-cup volatile release involved gas bubble stability, evaporation, and diffusion. It was concluded that after the initial aroma burst (during the first 2-3 min after the beginning of extraction), for the present sample space a crema of high stability provides a stronger aroma barrier over several minutes.

Whey protein isolate was heat-treated at 85 degrees C for 15 min at pH ranging from 6.0 to 7.0 in the presence of NaCl in order to generate the highest possible amount of soluble aggregates before insolubility occurred. These whey protein soluble aggregates were characterized for composition, hydrodynamic diameter, apparent molecular weight, zeta-potential, surface hydrophobicity index, activated thiol group content, and microstructure. The adsorption kinetics and rheological properties (E', etad) of these soluble aggregates were probed at the air/water interface. In addition, the gas permeability of a single bubble stabilized by the whey protein soluble aggregates was determined. Finally, the foaming and foam-stabilizing properties of these aggregates were measured. The amount of whey protein soluble aggregates after heat treatment was increased from 75% to 95% from pH 6.0 to pH 7.0 by addition of 5 mM to 120 mM NaCl, respectively. These soluble aggregates involved major whey protein fractions and exhibited a maximum of activated thiol group content at pH > 6.6. The hydrodynamic radius and the surface hydrophobicity index of the soluble aggregates increased from pH 6.0 to 7.0, but the molecular weight and zeta-potential decreased. This loss of apparent density was clearly confirmed by microscopy as the soluble aggregates shifted from a spherical/compact structure at pH 6.0 to a more fibrillar/elongated structure at pH 7.0. Surface adsorption was faster for soluble aggregates formed at pH 6.8 and 7.0 in the presence of 100 and 120 mM NaCl, respectively. However, interfacial elasticity and viscosity measured at 0.01 Hz were similar from pH 6.0 to 7.0. Single bubble gas permeability significantly decreased for aggregates generated at pH > 6.6. Furthermore, these aggregates exhibited the highest foamability and foam liquid stability. Air bubble size within the foam was the lowest at pH 7.0. The coarsening exponent, alpha, fell within predicted values of 1/3 and 1/2, except for very dry foams where it was 1/5.

The electrostatic complexation between beta-lactoglobulin and acacia gum was investigated at pH 4.2 and 25 degrees C. The binding isotherm revealed a spontaneous exothermic reaction, leading to a DeltaHobs = -2108 kJ mol(-1) and a saturation protein to polysaccharide weight mixing ratio of 2:1. Soluble electrostatic complexes formed in these conditions were characterized by a hydrodynamic diameter of 119 +/- 0.6 nm and a polydispersity index of 0.097. The effect of time on the interfacial and foaming properties of these soluble complexes was investigated at a concentration of 0.1 wt % at two different times after mixing (4 min, referred as t approximately 0 h and t = 24 h). At t approximately 0 h, the mixture is mainly made of aggregating soluble electrostatic complexes, whereas after 24 h these complexes have already insolubilize to form liquid coacervates. The surface elasticity, viscosity and phase angle obtained at low frequency (0.01 Hz) using oscillating bubble tensiometry revealed higher fluidity and less rigidity in the film formed at t approximately 0 h. This observation was confirmed by diminishing bubble experiments coupled with microscopy of the thin film. It was thicker, more homogeneous and contained more water at t approximately 0 h as compared to t = 24 h (thinner film, less water). This led to very different gas permeability's of Kt approximately 0 h = 0.021 cm s(-1) and Kt=24 h) = 0.449 cm s(-1), respectively. Aqueous foams produced with the beta-lactoglobulin/acacia gum electrostatic complexes or coacervates exhibited very different stability. The former (t approximately 0 h) had a stable volume, combining low drainage rate and mainly air bubble disproportionation as the destabilization mechanism. By contrast, using coacervates aged for 24 h, the foam was significantly less stable, combining fast liquid drainage and air bubble destabilization though fast gas diffusion followed by film rupture and bubble coalescence. The strong effect of time on the air/water interfacial properties of the beta-lactoglobulin/acacia gum electrostatic complexes can be understood by their reorganization at the interface to form a coacervate phase that is more fluid/viscous at t approximately 0 h vs rigid/elastic at t = 24 h.

Aggregation of metallo-supramolecular architectures through additional coordination is explored by introducing metal-binding units onto the outside of the supramolecular architectures. This is achieved within the framework of our imine-based approach to supramolecular architecture, by replacing the pyridylimine units with pyrazylketimine units. An advantage of the design is that it retains the ease-of-synthesis which characterises our imine-based approach. Silver(I) complexes of three pyrazylketimine ligand systems are described. The complexes demonstrate that introducing pyrazine donor units does indeed allow higher-order assembly of the distinct supramolecular architectures into engineered coordination polymers. Two distinct types of aggregation are observed. In the first, the donors on the outside of one architecture bind to the metals of another to link the units into a polymeric array. In the second type, the donors on the outside of the architectures bind to separate metal centres which are themselves not part of the architectures, and these separate metal centres link the units to form the macromolecular array. The weaker donor nature of the pyrazine nitrogens (compared to pyridine) also introduces an additional element into the design; higher coordination numbers are favoured and this can lead to arrays with higher connectivity than those observed in the discrete pyridylimine architectures.

A number of lactose-binding lectins have recently been identified in the rat and mouse intestine, one of which corresponds to the C-terminal domain of IgE-binding proteins, originally identified in rat basophilic leukemia (RBL) cells and mouse 3T3 fibroblasts. In the present report, we describe the affinity purification of a rat intestinal lactose-specific lectin which binds murine IgE antibodies. This binding most likely occurs via the immunoglobulin carbohydrate chains, as it is inhibited by lactose. This intestinal lectin molecule is also immunologically related to the previously described IgE-binding protein (epsilon BP) isolated from RBL cells, since it is recognized by antibodies raised against recombinant epsilon BP. This intestinal form of epsilon BP has a molecular mass of 17.5 kDa, which is much lower than that of its RBL cell analogue (31 kDa). The attachment of IgE to the mouse intestinal epithelium was demonstrated by immunohistochemistry, along with the presence of a corresponding mouse intestinal epsilon BP. The carbohydrate-dependent nature of this attachment was established by demonstrating that IgE binding to mouse epithelium was specifically abolished by lactose (4 mM) and by a blood-group-A-active tetrasaccharide (0.2 mM), but not by mannose (10 mM). Finally, the association of IgE with the mouse intestinal epithelium was prevented by competition with the purified IgE-binding lectin isolated from rat intestine. Although the physiological function of this intestinal protein is still unknown, the finding that IgE binds to a lectin in the intestinal epithelium pinpoints a possible novel mechanism for the regulation of IgE-mediated disorders, such as food allergy.