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Experimental intraabdominal abscesses were produced in mice by intraperitoneal injection of Bacteroides fragilis and Pseudomonas aeruginosa. The therapeutic efficacy of rifampicin and cefsulodin alone, and in combination was investigated in this in-vivo experimental mixed intraabdominal abscess model. Treatment with rifampicin at 10, and 25 mg/kg or cefsulodin at 50, and 100 mg/kg singly or in combinations prevented mortality as compared to 68% mortality rate occurring in the untreated mice. Rifampicin, at 25 mg/kg dose, was very effective in preventing abscess formation and produced bacterial eradication. It prevented abscess formation in 80% of the mice and eradicated both Bacteroides and Pseudomonas in 100% and 75% of the abscesses of the mice. Cefsulodin failed to reduce the incidence of abscess formation, and to eradicate Bact. fragilis from the abscesses, although it significantly decreased Ps. aeruginosa in the abscesses. The combination of rifampicin at 10 mg/kg and cefsulodin at 100 mg/kg was more effective than either of the antibiotics alone and was as effective as rifampicin alone at 25 mg/kg levels. This combination was bactericidal against both organisms in the infected mice. [ABSTRACT FROM AUTHOR]

The efficacy of rifampicin in treating a Bacteroides fragilis infection was investigated and compared to clindamycin and metronidazole in an experimental model of intra-abdominal abscess in mice. Rifampicin, when given subcutaneously, showed activity superior to that of clindamycin in reducing the incidence of abscess formation as well as the number of Bacteroides organisms recovered from the abscess, and rifampicin was comparable in efficacy to metronidazole when given orally at the same dose level. The comparative pharmacokinetic properties of rifampicin and clindamycin demonstrated that the peak serum and abscess levels reached with rifampicin were significantly higher than those of clindamycin. The half-life of rifampicin in serum and in the abscess was longer than that of clindamycin. [ABSTRACT FROM AUTHOR]

The in-vitro activity of cefsulodin combined with sulbactam, cefoxitin or cefotaxime was investigated against 32 strains of beta-lactamase-producing Bacteroides species. Synergy of cefsulodin-sulbactam or cefsulodin-cefoxitin could be demonstrated against 30 of 32 and 32 of 32 strains tested at the concentrations readily achievable in serum. In the presence of 1 mg/l of sulbactam or cefoxitin, more than 90% of the Bacteroides isolated were inhibited by 32 mg/l of cefsulodin. The inhibitory activity of cefsulodin-sulbactam or cefsulodin-cefoxitin combinations was bactericidal against Bact. fragilis and Bact. vulgatus. In contrast, no synergistic inhibitory or bactericidal activities can be observed by the cefsoludin-cefotaxime combination. Both sulbactam and cefoxitin were potent inhibitors of beta-lactamases produced by Bact. fragilis and Bact. melaninogenicus suggesting that this inhibitory activity might be one of the factors contributing to the synergistic combinations. [ABSTRACT FROM AUTHOR]

(1) Background . Coeliac disease (CD) often co-occurs with autoimmune conditions or genetic syndromes, but there are few studies on the co-existence of CD and immunoglobulin E (IgE)-mediated allergies. The purpose of this study was to assess sensitization to food and aero-allergens in pediatric patients with CD. (2) Methods . A multiplex ALEX ® 2 test was used to determine specific IgEs (sIgEs). (3) Results . The study included 108 children newly diagnosed with CD. Allergen extract- and/or allergen molecule-sIgEs were detected in 49.1% of children. Most children (41.5%) were sensitized to both inhalant and food allergens. The three most common aero-allergens (timothy pollen, ryegrass, silver birch) were molecules Phl p 1, Lol p 1, and Bet v 1. The most common food allergens (hazelnut, apple, and peanut) were Cor a 1, Mal d 1, and Ara h 8 molecules of the PR-10 subfamily. Patients were not sensitized to cereal allergens containing gluten. Spearman's rank correlation analysis of sensitized patients showed a significant positive relationship ( r = 0.31) between the patients' age and the occurrence of positive sIgEs (≥0.3 kU A /L) for inhalant allergen molecules ( p = 0.045). In sensitized patients, mainly symptoms of inhalant allergy were observed, such as hay fever, conjunctivitis, and bronchial asthma. (4) Conclusions . The current study indicates the co-occurrence of IgE sensitization to food and inhalant allergens in children with CD. The study highlights the need to take a closer look at the diagnosis of IgE-mediated allergy in patients with CD, which may help in their care and lead to a better understanding of the relationship between CD and IgE-mediated allergy.

Celiac disease (CD) is a chronic immune-mediated disorder triggered by the ingestion of gluten in genetically predisposed individuals, affecting about 1% of the general population in the developed world. In 2012, the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) recommendations for CD diagnoses in children and adolescents were introduced, allowing the "no-biopsy" approach if certain criteria were met. This approach was also confirmed in the revised guidelines published in 2020. Thus, the aim of this study was to assess-over a one-year period-the clinical presentations and current status of the management of children and adolescents diagnosed with CD in Poland. Medical records of children and adolescents, newly diagnosed with CD in 2022/2023 in three medical centers in Poland, were involved. Gastroenterologists completed the specific anonymous web-based forms developed in the CD SKILLS project, including data routinely assessed at individual visits about the diagnostic approach and clinical presentation of the disease. Our study assessed 100 patients (56% girls) with an age range 1.6-18.0 years. We found that 98% of patients were serologically tested prior to a CD diagnosis and 58% of patients were diagnosed using the "no-biopsy" approach. In the analyzed group, 40% belonged to a known risk group, only 22% had annual screening before the CD diagnosis (the longest for 9 years), and 19% showed no symptoms at the time of the CD diagnosis. Our research confirmed the applicability of the "no-biopsy" approach for the diagnosis of CD in children and adolescents in Poland, and also showed changes in the clinical picture of CD. Moreover, we highlight the need to introduce broad CD serological screening in risk groups of the Polish population.

In the field of immunology, a systems biology approach is crucial to understanding the immune response to infection and vaccination considering the complex interplay between genetic, epigenetic, and environmental factors. Significant progress has been made in understanding the innate immune response, including cell players and critical signaling pathways, but many questions remain unanswered, including how the innate immune response dictates host/pathogen responses and responses to vaccines. To complicate things further, it is becoming increasingly clear that the innate immune response is not a linear pathway but is formed from complex networks and interactions. To further our understanding of the crosstalk and complexities, systems-level analyses and expanded experimental technologies are now needed. In this review, we discuss the most recent immunoprofiling techniques and discuss systems approaches to studying the global innate immune landscape which will inform on the development of personalized medicine and innovative vaccine strategies.

Background: Increased intestinal permeability is considered to play a crucial role in the pathogenesis of inflammatory bowel diseases (IBD). Therefore, recently, the use of non-invasive biomarkers in both diagnosis and monitoring IBD is emphasized. The aim of this study was to investigate fecal and serum zonulin and serum I-FABP in pediatric IBD patients and their correlation with fecal calprotectin (FCP)., Methods: Seventy-one individuals: 32 Crohn's disease (CD) patients, 33 ulcerative colitis (UC) patients and 6 controls were examined for fecal and serum zonulin and plasma I-FABP. Values were correlated to FCP and to each other for all children included in the study. A stool specimen and blood samples were collected during check-up visits at hospital. Then fecal and serum zonulin, I-FABP and FCP were tested by ELISA Test. Non-parametric statistical tests were used for data analysis., Results: The level of fecal zonulin and FCP were higher in IBD patients compared to control group (CG): median for CD - 46.0 (7.0-3854) ng/mL, 252.0 (77.0-1054.2) ug/g; UC - 115.3 (50.7-418.3) ng/mL, 40 (16.0-1883.0) ug/g; CG - 60.8 (31.8-123.0) ng/mL, 41.5 (31.0-323.0) ug/g, respectively, (P<0.05). No statistically significant difference in concentrations of serum zonulin and I-FABP was reported between patients and CG (P=0.55). The only correlation that has been reported was between fecal zonulin and FCP and the strongest one was in CD: CD-R =0.73, UC-R =0.67, All-R =0.67, CG-R =0.65., Conclusions: According to our results it seems that only fecal zonulin may serve as another, next to FCP, biomarker of intestinal damage in IBD. However, both fecal and serum zonulin as well as I-FABP need further studies to assess their usefulness in diagnostics and monitoring in IBD.

Pneumonia is common in the intensive care unit (ICU), infecting 27% of all critically ill patients. Given the high prevalence of this disease state in the ICU, optimizing antimicrobial therapy while minimizing toxicities is of utmost importance. Inappropriate antimicrobial use can increase the risk of antimicrobial resistance, Clostridiodes difficile infection, allergic reaction, and other complications from antimicrobial use (e.g., QTc prolongation, thrombocytopenia). This review article aims to discuss methods to optimize antimicrobial treatment in patients with pneumonia, including the following: procalcitonin use, utilization of methicillin-resistant Staphylococcus aureus nares testing to determine need for vancomycin therapy, utilization of the Biofire ® FilmArray ® pneumonia polymerase chain reaction (PCR), and microbiology reporting techniques.

The diagnosis of celiac disease (CD) at the first diagnostic step requires the detection of specific class A antibodies to tissue transglutaminase type-2 (TG2 IgA) and the measurement of total immunoglobulin A (tIgA) to exclude IgA deficiency. The aim of the study was to evaluate the new quantitative immunoassay panel allowing for the detection of celiac-specific antibodies with the simultaneous determination of tIgA from the same sample of blood at one time. This retrospective study included 104 pediatric patients divided into groups with recognized CD and IgA deficiency (n = 20; 19%), immunocompetent children with CD (n = 28; 27%), children with IgA deficiency and without CD (n = 28; 27%), and the control group of immunocompetent children without CD (n = 28; 27%). Intestinal biopsy with histopathological evaluation (except five patients with CD who were diagnosed without biopsy) and measurement of reference celiac specific antibodies were performed in all children. Multiparametric quantitative immunoassay Polycheck ® Celiac IgA plus total IgA test was used to evaluate its usefulness in CD screening and IgA deficiency diagnosis. The statistical analysis showed the high sensitivity and specificity of both TG2 IgA and tIgA on the multiparametric panel (sensitivity 96% and 100%; specificity 100% and 79%, respectively). The accuracy and area under the ROC curve for tIgA were 0.904 and 0.955, while for TG2 IgA they were 0.982 and 1.000, respectively. Although the sensitivity of IgA antibodies against deaminated gliadin peptides was low (20%), the specificity reached 100%. The study showed that Polycheck ® Celiac IgA plus total IgA test is a specific and sensitive tool for simultaneous serological CD screening and recognition of IgA deficiency.

Every ecosystem shows multiple levels of species interactions, which are often difficult to isolate and to classify regarding their specific nature. For most of the observed interactions, it comes down to either competition or consumption. The modes of consumption are various and defined by the nature of the consumed organism, e.g., carnivory, herbivory, as well as the extent of the consumption, e.g., grazing, parasitism. While the majority of consumers are animals, carnivorous plants can also pose a threat to arthropods. Water fleas of the family Daphniidae are keystone species in many lentic ecosystems. As most abundant filter feeders, they link the primary production to higher trophic levels. As a response to the high predatory pressures, water fleas have evolved various inducible defenses against animal predators. Here we show the first example, to our knowledge, in Ceriodaphnia dubia of such inducible defenses of an animal against a coexisting plant predator, i.e., the carnivorous bladderwort ( Utricularia x neglecta Lehm, Lentibulariaceae). When the bladderwort is present, C. dubia shows changes in morphology, life history and behavior. While the morphological and behavioral adaptations improve C. dubia 's survival rate in the presence of this predator, the life-history parameters likely reflect trade-offs for the defense.

Patients with type 1 diabetes (T1D) are at increased risk for developing celiac disease (CD). The aim of the study was to assess the usefulness of celiac-specific human leukocyte antigen (HLA) haplotype and the rs3130484 variant of MSH5 gene, a previously described non-HLA variant associated with CD in the Polish population as a first-line screening for CD in T1D pediatric patients. Serological CD screening performed in the T1D group ( n = 248) and healthy controls ( n = 551) allowed for CD recognition in 20 patients (8.1%) with T1D (T1D + CD group). HLA-DQ2, HLA-DQ8 and the rs3130484 variant were genotyped with TaqMan SNP Genotyping Assays. The T1D + CD group presented a higher, but not statistically significant, frequency of HLA-DQ2 in comparison with T1D subjects. Combining the rs3130484 with HLA-DQ2/HLA-DQ8 typing significantly increased the sensitivity of HLA testing from 32.7% to 68.7%, and the accuracy of estimating CD prediction from 51.7% to 86.4% but decreased the specificity from 100% to 78.2%. The receiver operating characteristic curve analysis confirmed the best discrimination for the combination of both genetic tests with an area under curve reaching 0.735 (95% CI: 0.700-0.7690) in comparison with 0.664 (95% CI: 0.632-0.696) for HLA typing alone. Results show the low utility of HLA-DQ2/HLA-DQ8 typing for CD screening in T1D pediatric patients. Combination of the rs3130484 variant of the MSH5 gene and HLA testing increases both the sensitivity and the predictive value of the test accuracy, but still, the obtained values are not satisfactory for recommending such testing as the first-line screening for CD in T1D patients.

Patients with type 1 diabetes (T1D) are at higher risk of celiac disease (CD). Recently, intestinal fatty acid binding protein (I-FABP) has been shown to be a serological biomarker of impaired intestinal barrier in CD. Thus, the aim of this study was to verify whether I-FABP could be an early marker of CD in pediatric T1D patients. I-FABP was measured in sera of patients with T1D (n = 156), active CD (n = 38), T1D with active CD (T1D-CD, n= 51), and age-matched healthy children (n = 55). Additionally, I-FABP was determined in T1D patients with negative CD serology at least one year before CD diagnosis (T1D-CD-1, n = 22), in CD patients on a gluten-free diet (CD-GFD, n = 36), and T1D-CD patients on GFD (T1D-CD-GFD, n = 39). Sera were tested using immunoenzymatic assay. Significantly increased levels of I-FABP were found in the T1D, active CD, and T1D-CD groups (1153 ± 665, 1104 ± 916, and 1208 ± 878, respectively) in comparison to healthy with controls (485 ± 416, p < 0.05). GFD induced a significant decrease in I-FABP levels in CD and T1D-CD groups (510 ± 492 and 548 ± 439, respectively). Interestingly, in T1D-CD-1 and T1D, I-FABP levels were comparable (833 ± 369 vs. 1153 ± 665), and significantly increased in relation to healthy controls and T1D-CD values on GFD. The results indicate that the epithelial barrier is disrupted in T1D patients independently of CD development; therefore, I-FABP cannot serve as an early marker of CD in T1D patients. Although GFD can improve epithelial recovery, the question remains as to whether GFD could exert beneficial effects on the intestinal barrier in early stages of T1D.

Objectives: Wilson disease (WD) is a copper metabolism disorder with toxic copper accumulation in the liver leading to liver steatosis or fibrosis. In vitro studies suggest that fatty acid-binding protein 1 (L-FABP) and lipid droplet-associated protein 5 (PLIN5) may have an impact on both processes, but knowledge about these potential biomarkers is insufficient in the case of WD. Thus, the aim of this study was to determine L-FABP and PLIN5 levels in sera of WD patients in relation to liver steatosis/fibrosis., Methods: The final study involved 74 WD children in whom liver steatosis (WD1 subgroup, n = 28) and fibrosis (WD2 subgroup, n = 13) were assessed with the use of transient elastography. Control groups included WD children without steatosis and fibrosis (WD0 subgroup, n = 33) and healthy children (n = 75). L-FABP and PLIN5 measurements were performed in sera with the use of the immunoenzymatic method., Results: L-FABP was significantly higher in the WD2 subgroup, and the correlation between L-FABP concentration and liver fibrosis was confirmed statistically by regression analysis (P = 0.04) with Pearson's coefficient r = 0.24. L-FABP was significantly correlated with alanine aminotransferase (r = 0.42) and aspartate aminotransferase (r = 0.37) activity. PLIN5 concentration was similar in all groups and was not related to steatosis and fibrosis., Conclusions: Our results suggest that serum L-FABP could be a novel biomarker of liver fibrosis in WD children., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Vegetable processing pomace contains valuable substances such as natural colors that can be reused as functional ingredients. Due to a large amount of water, they are an unstable material. The aim of our research was to assess how the pretreatment method (thermal or nonthermal) affects the properties of powders obtained from beet juice and pomace after the freeze-drying process. The raw material was steamed or sonicated for 10 or 15 min, and then squeezed into juice and pomace. Both squeezed products were freeze-dried. The content of dry substance; L*, a*, and b* color parameters; and the content of betalain pigments were analyzed. Pretreatments increased the proportion of red and yellow in the juices. Steam and ultrasound caused a significant reduction in parameter b* in the dried pomace. A significant increase in betanin in lyophilizates was observed after pretreatment with ultrasound and steam for 15 min. As a result of all experiments, dried juices and pomaces can also be used as a colorant source. However, there is higher potential with pomaces due to their additional internal substances as well as better storage properties. After a few hours, juice was sticky and not ready to use.

Intraosseous (IO) access provides a potentially lifesaving means of vascular access in settings of trauma and advanced cardiovascular life support in which patients often require prompt and large volumes of fluid resuscitation, blood products, and medications. An additional benefit of IO access is the rare incidence of complications, with many studies reporting rates of less than 1%. The most commonly cited complications include compartment syndrome, osteomyelitis, traumatic bone fracture, and epiphyseal plate damage. To evaluate the dermatologic sequelae, we performed a retrospective chart review spanning 18 consecutive months to identify patients who underwent IO line placement, either at or en route to a large metropolitan level I trauma center in the Midwestern United States. Our review identified a complication rate of 2.7%, with complications including compartment syndrome, needle breakage, and a previously unreported cutaneous complication of traumatic bullae.

Interleukin-6 signal transducer (IL6ST) encodes the GP130 protein which transduces the proinflammatory signaling of the IL6 cytokine family through Janus kinase signal transducers and activators of transcription pathway (JAK/STAT) activation. Biallelic loss-of-function IL6ST variants cause autosomal recessive hyper-IgE syndrome or a variant of the Stuve-Wiedemann syndrome. Somatic gain-of-function IL6ST mutations, in particular, small monoallelic in-frame deletions of which the most prevalent is the IL6ST Ser187&#95;Tyr190del, are an established cause of inflammatory hepatocellular tumors, but so far, no disease caused by such mutations present constitutively has been described. Herein, we report a pediatric proband with a novel syndrome of neonatal onset immunodeficiency with autoinflammation and dysmorphy associated with the IL6ST Tyr186&#95;Tyr190del variant present constitutively. Tyr186&#95;Tyr190del was found by exome sequencing and was shown to be de novo (absent in proband's parents and siblings) and mosaic (present in approximately 15-40% of cells depending on the tissue studied-blood, urine sediment, hair bulbs and buccal swab). Functional studies were performed in the Epstein-Barr virus-immortalized patient's B cell lymphoblastoid cell line, which carried the variant in approximately 95% of the cells. Western blot showed that the patient's cells exhibited constitutive hyperphosphorylation of Tyr705 in STAT3, which is indicative of IL6-independent activation of GP130. Interestingly, the STAT3 phosphorylation could be inhibited with ruxolitinib as well as tofacitinib, which are clinically approved JAK1 and JAK3 (to lesser extent JAK2 and JAK1) inhibitors, respectively. Given our results and the recent reports of ruxolitinib and tofacitinib use for the treatment of diseases caused by direct activation of STAT3 or STAT1, we speculate that these drugs may be effective in the treatment of our patient's condition., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Probiotics seem to have promising effects in the prevention and treatment of allergic conditions including atopic dermatitis (AD) and food allergy. The purpose of this multicenter randomized placebo-controlled trial was to evaluate the effectiveness of a probiotic preparation comprising Lactobacillus rhamnosus ŁOCK 0900, Lactobacillus rhamnosus ŁOCK 0908, and Lactobacillus casei ŁOCK 0918 in children under 2 years of age with AD and a cow's milk protein (CMP) allergy. The study enrolled 151 children, who-apart from being treated with a CMP elimination diet-were randomized to receive the probiotic preparation at a daily dose of 10 9 bacteria or a placebo for three months, with a subsequent nine-month follow-up. The primary outcomes included changes in AD symptom severity assessed with the scoring AD (SCORAD) index and in the proportion of children with symptom improvement (a SCORAD score decreased by at least 30% in comparison with that at baseline). After the three-month intervention, both the probiotic and placebo groups showed a significant ( p < 0.0001) decrease in SCORAD scores, which was maintained nine months later. The percentage of children who showed improvement was significantly higher in the probiotic than in the placebo group (odds ratio (OR) 2.56; 95% confidence interval (CI) 1.13-5.8; p = 0.012) after three months. Probiotics induced SCORAD improvement mainly in allergen sensitized patients (OR 6.03; 95% CI 1.85-19.67, p = 0.001), but this positive effect was not observed after nine months. The results showed that the mixture of probiotic ŁOCK strains offers benefits for children with AD and CMP allergy. Further research is necessary to assess the effect of probiotic supplementation on the development of immune tolerance (NCT04738565).

Disruption of epithelial junctional complex (EJC), especially tight junctions (TJ), resulting in increased intestinal permeability, is supposed to activate the enhanced immune response to gluten and to induce the development of celiac disease (CD). This study is aimed to present the role of EJC in CD pathogenesis. To analyze differentially expressed genes the next-generation mRNA sequencing data from CD326+ epithelial cells isolated from non-celiac and celiac patients were involved. Ultrastructural studies with morphometry of EJC were done in potential CD, newly recognized active CD, and non-celiac controls. The transcriptional analysis suggested disturbances of epithelium and the most significant gene ontology enriched terms in epithelial cells from CD patients related to the plasma membrane, extracellular exome, extracellular region, and extracellular space. Ultrastructural analyses showed significantly tighter TJ, anomalies in desmosomes, dilatations of intercellular space, and shorter microvilli in potential and active CD compared to controls. Enterocytes of fetal-like type and significantly wider adherence junctions were observed only in active CD. In conclusion, the results do not support the hypothesis that an increased passage of gluten peptides by unsealing TJ precedes CD development. However, increased intestinal permeability due to abnormality of epithelium might play a role in CD onset.

There is evidence that children with autism spectrum disorders (ASDs) display an increased immune reactivity against gluten, which is supposed to be the effect of intestinal barrier abnormalities. The aim of study was to evaluate the relation of antibody induced by gluten to zonulin and intestinal fatty acid binding proteins (I-FABP), that is, serological markers of an impaired gut barrier. The study included 77 patients with ASDs. Zonulin, I-FABP, celiac-specific antibodies, anti-gliadin antibodies (AGA), and antibodies against neural transglutaminase 6 (TG6) of immunoglobulin (Ig) A and IgG classes were detected in sera. Celiac-specific antibodies were negative in all ASD children, four children (5.2%) had positive anti-TG6 antibodies, and increased AGA-IgG production was found in 21 patients (27.3%). Mean levels of zonulin and I-FABP in ASD patients were similar to those found in healthy controls and revealed a negative correlation with age, whereas regression analysis revealed a significant positive relationship between antibody production and the age. Serum concentrations of zonulin and I-FABP showed no statistically significant association with antibody positivity. An increased production of antibodies related to gliadin and neural TG6 in ASD children is not related to serological markers of an impaired intestinal barrier.

Aim: To evaluate the clinical utility of multi-antibody strategies in the diagnosis of coeliac disease (CD), the new quantitative Polycheck immunoassays were analysed., Methods: Polycheck Celiac Panels (PCPs) are immunoenzyme screening assays for the quantitative measurement of coeliac-specific immunoglobulin class G (IgG) or class A (IgA) in serum. Lines of relevant antigens are coated together with five IgG or IgA standard lines used for the standard curve as positive control. PCP IgA consists of human recombinant human tissue transglutaminase (tTG) and deamidated gliadin peptides (DGP) as targets to detect IgA antibodies. PCP IgG consists of tTG, DGP and IF (intrinsic factor) antigens to detect antibodies in IgG class. PCPs were performed on 50 CD patients, including 6 cases with selective IgA deficiency, and 50 non-coeliac controls. CD diagnosis was performed according to the ESPGHAN recommendations: The presence of specific anti-tTG-IgA or anti-DGP-IgG (in the case of IgA deficiency) antibodies, typical histopathological changes in duodenal mucosa described in Marsh-Oberhüber classification as at least grade 2. The diagnosis of the majority of the control subjects was functional gastrointestinal disorders. The PCP results were compared with reference EliA Celikey., Results: The usage of PCPs led to the correct identification of all CD patients. In our study, PCPs showed 100% agreement with the histopathological results. PCP IgA test showed a 98% concordance and correlated positively (R = 0.651, P = 0.0014) with EliA Celikey test. The highest specificity and positive predictive value (both 100%) were observed for the detection of Polycheck anti-tTG-IgA antibodies. The highest sensitivity and negative predictive value (both 100%) were achieved by Polycheck anti-DGP-IgG antibody detection. The best performance (98% sensitivity and negative predictive value, 100% specificity and positive predictive value, diagnostic accuracy - AU ROC 99%) was observed for the strategy of using both PCP IgA and IgG and determining positive outcomes of the test with two or more coeliac-specific antibodies detected. The majority of coeliac patients had multiple antibodies. All four antibodies were detected in 7 (14%) cases, 19 children (38%) were positive for three antibodies and 23 (46%) were positive for two antibodies., Conclusion: The present study showed that detection of coeliac-specific antibodies with multi-antibody PCPs is effective and efficacious in the diagnosis of CD.

Background: Recent advances in culture-independent approaches have enabled insights into the diversity, complexity, and individual variability of gut microbial communities., Objectives: To examine the effect of oral administration of Saccharomyces (S.) boulardii and mode of delivery on the intestinal microbial community in preterm infants., Study Design: Stool samples were collected from preterm newborns randomly divided into two groups: a probiotic-receiving group (n = 18) or a placebo group (n = 21). Samples were collected before probiotic intake (day 0), and after 2 and 6 weeks of supplementation. The composition of colonizing bacteria was assessed by 16S ribosomal RNA (rRNA) gene sequencing of fecal samples using the Ion 16S Metagenomics Kit and the Ion Torrent Personal Genome Machine platform., Results: A total of 11932257 reads were generated, and were clustered into 459, 187, and 176 operational taxonomic units at 0 days, 2 weeks, and 6 weeks, respectively. Of the 17 identified phyla, Firmicutes Actinobacteria, Proteobacteria, and Bacteroidetes were universal. The microbial community differed at day 0 compared with at 2 weeks and 6 weeks. There was a tendency for increased bacterial diversity at 2 weeks and 6 weeks compared with day 0, and infants with a gestational age of 31 weeks or higher presented increased bacterial diversity prior to S. boulardii administration. Firmicutes and Proteobacteria remained stable during the observation period, whereas Actinobacteria and Bacteroidetes increased in abundance, the latter particularly more sharply in vaginally delivered infants., Conclusion: While the mode of delivery may influence the development of a microbial community, this study had not enough power to detect statistical differences between cohorts supplemented with probiotics, and in a consequence, to speculate on S. boulardii effect on gut microbiome composition in preterm newborns.

Background: Sensitization to food allergens is a common condition in pediatric atopic dermatitis (AD). Recently, the multiple allergen simultaneous test (MAST) allowing for a comprehensive assessment of atopy has been developed, but the usefulness in young AD children is not known. The aim of this study was to determine IgE specificity in AD children using MAST and to compare the results for selected food allergens with the reference ImmunoCap system., Methods: The study enrolled 50 children up to 2 years old with a diagnosis of AD. IgE antibodies were measured with the MAST-immunoblots. Children with specific IgE levels ≥ 0.35 kU/L were identified as sensitized to allergens., Results: Most often children were sensitized to food allergens (egg white and yolk, hazelnuts, potato, cow's milk proteins, wheat flour, codfish, and soybean), but a high percentage of them also had IgE antibodies against house dust mites (12%), grass (10%), and birch (10%). Eight percent of children were sensitized to domestic animals (cats and dogs). Almost perfect (kappa index 0.8 - 1.0) and substantial (kappa index 0.6 - 0.8) agreement between MAST and ImmunoCap was found for food allergens except codfish. Pearson's analysis of antibody classes showed a very strong correlation between two methods (r = 0.8 - 1.0) for egg white, hazelnuts, potato, cow's milk proteins, wheat flour, and soybean, and a strong correlation (r = 0.6 - 0.79) was observed for peanut, egg yolk, and codfish., Conclusions: The study showed the frequent occurrence of IgE antibodies against food and airborne and animal allergens in young AD children and confirmed the usefulness of MAST-immunoblots for screening of sensitization in pediatric patients.

Assessment of non-HLA variants alongside standard HLA testing was previously shown to improve the identification of potential coeliac disease (CD) patients. We intended to identify new genetic variants associated with CD in the Polish population that would improve CD risk prediction when used alongside HLA haplotype analysis. DNA samples of 336 CD and 264 unrelated healthy controls were used to create DNA pools for a genome wide association study (GWAS). GWAS findings were validated with individual HLA tag single nucleotide polymorphism (SNP) typing of 473 patients and 714 healthy controls. Association analysis using four HLA-tagging SNPs showed that, as was found in other populations, positive predicting genotypes (HLA-DQ2.5/DQ2.5, HLA-DQ2.5/DQ2.2, and HLA-DQ2.5/DQ8) were found at higher frequencies in CD patients than in healthy control individuals in the Polish population. Both CD-associated SNPs discovered by GWAS were found in the CD susceptibility region, confirming the previously-determined association of the major histocompatibility (MHC) region with CD pathogenesis. The two most significant SNPs from the GWAS were rs9272346 (HLA-dependent; localized within 1 Kb of DQA1) and rs3130484 (HLA-independent; mapped to MSH5). Specificity of CD prediction using the four HLA-tagging SNPs achieved 92.9%, but sensitivity was only 45.5%. However, when a testing combination of the HLA-tagging SNPs and the MSH5 SNP was used, specificity decreased to 80%, and sensitivity increased to 74%. This study confirmed that improvement of CD risk prediction sensitivity could be achieved by including non-HLA SNPs alongside HLA SNPs in genetic testing.

Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a very rare autosomal recessive form of spinal muscular atrophy manifested in low birth weight, diaphragmatic palsy and distal muscular atrophy. Caused by a mutation in the IGHMBP2 gene, the disease is addressed here by reference to five Polish patients in which SMARD1 has been confirmed genetically. All presented a severe form of the disease and had evident symptoms during the second month of life; with four displaying weak cries, feeding difficulties and hypotonia from birth. Two were afflicted by severe dysfunction of the autonomic nervous system. Ultrastructural analysis of a muscle biopsy revealed progressive degeneration within the nuclei of the muscle cells and Schwann cells. Neuromuscular junctions were also defective. It proved possible to identify in our patients 6 novel IGHMBP2 mutations: three missense (c.595G>C, c.1682T>C and c.1794C>A), two nonsense (c.94C>T and c.1336C>T) and one in-frame deletion (c.1615&#95;1623del). One nonsense mutation (c.429C>T) that had been described previously was also identified. Observation of our patients makes it clear that clinical picture is still the most important factor suggesting diagnosis of SMARD1, though further investigations concerning some of the symptoms are required. As the IGHMBP2 gene is characterized by significant heterogeneity, genetic counseling of affected families is rendered more complex. IGHMBP2 protein deficiency can lead to the degeneration of nuclei, in both muscle and Schwann cells., (Copyright © 2013 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Proper nutrition offers one of the most effective and least costly ways to decrease the burden of many diseases and their associated risk factors, including obesity. Nutrition research holds the key to increasing our understanding of the causes of obesity and its related comorbidities and thus holds promise to markedly influence global health and economies. After outreach to 75 thought leaders, the American Society for Nutrition (ASN) convened a Working Group to identify the nutrition research needs whose advancement will have the greatest projected impact on the future health and well-being of global populations. ASN's Nutrition Research Needs focus on the following high priority areas: 1) variability in individual responses to diet and foods; 2) healthy growth, development, and reproduction; 3) health maintenance; 4) medical management; 5) nutrition-related behaviors; and 6) food supply/environment. ASN hopes the Nutrition Research Needs will prompt collaboration among scientists across all disciplines to advance this challenging research agenda given the high potential for translation and impact on public health. Furthermore, ASN hopes the findings from the Nutrition Research Needs will stimulate the development and adoption of new and innovative strategies that can be applied toward the prevention and treatment of nutrition-related diseases. The multidisciplinary nature of nutrition research requires stakeholders with differing areas of expertise to collaborate on multifaceted approaches to establish the evidence-based nutrition guidance and policies that will lead to better health for the global population. In addition to the identified research needs, ASN also identified 5 tools that are critical to the advancement of the Nutrition Research Needs: 1) omics, 2) bioinformatics, 3) databases, 4) biomarkers, and 5) cost-effectiveness analysis.