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Objectives: Data on pancreatic exocrine secretion in the youngest children are scarce. The aim of the study was to determine the range of normal values for fecal fat concentration (FFC) and fecal fat excretion (FFE) in infants and toddlers up to 2 years of age., Methods: A total of 160 subjects aged 1 to 24 months (8 groups of 20: aged 1-3, 4-6 months, etc) were included in the study. In all children, FFC (%) and FFE (g/day) were assessed in 3-day stool collection., Results: FFC correlated with age (r = -0.50, P < 0.0001). Of infants aged 1 to 3 months 65% had FFC higher than the <5% norm proposed for older children. The values of 90th/95th FFC percentile ranged from 9.7/13.0% at 1 month to 3.1/3.2% at 24 months. FFE did not differ between age groups. It was, however, higher than 4 and 3 g/day in 7.5% and 15.0% infants, respectively. The first detailed nomogram for the assessment of FFC and FFE in children aged 1 to 24 months was created., Conclusions: Healthy infants may have higher FFC and FFE than older children. We provide reference values, which should allow for both precise and facile FFC and FFE interpretation in clinical practice.

Introduction: Cystic fibrosis (CF) involves chronic inflammation and decreased pulmonary function, which increase caloric demand. Yet, sufficient energy provision is hindered by reduced appetite and fat malabsorption. Brain-derived neurotrophic factor (BDNF), leptin, and neuropeptide Y (NPY) belong to energy balance-regulating factors. We aimed to assess their concentrations in CF patients in order to search for potential clinical correlates., Material and Methods: This was an exploratory, cross-sectional study. Patients' weight and height Z- scores, forced expiratory volume in 1 s (FEV 1 %), exocrine pancreatic status (fecal elastase-1), genotypes, and other characteristics were assessed. Serum concentrations of BDNF, leptin, NPY, IL-6, and TNF-α were measured using ELISA., Results: The study enrolled 56 patients, of whom 29 (52%) were female and 17 (30%) were younger than 16 years. Median (1 st -3 rd quartile) mass Z -score was -0.85 (-1.56-(-0.36)); median FEV 1 was 70.5% (45.0-89.5); 48 (86%) patients had exocrine pancreatic insufficiency and 8 (14%) diabetes. Overall, median concentrations were: BDNF: 33.91 ng/ml (26.40-40.43), leptin: 12.05 ng/ml (8.93-17.77), NPY: 2.86 ng/ml (1.75-4.42). None of these factors correlated with mass Z -score, FEV 1 %, IL-6 or TNF-α. Leptin and NPY correlated negatively (ρ = -0.62, p = 3 × 10 -7 ); BDNF/NPY ratio was associated with leptin (ρ = 0.54, p = 2 × 10 -5 ), BDNF/leptin ratio correlated with NPY (ρ = 0.60, p = 1 × 10 -6 ). In a multivariable regression analysis NPY was weakly, but independently, associated with FEV 1 %, and leptin with age., Conclusions: BDNF and leptin were not associated with weight Z -score or FEV 1 %. Serum NPY concentrations seemed to be lower in CF patients with reduced pulmonary function independently of malnutrition and inflammation., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2018 Termedia & Banach.)

Aim: To investigate the contribution of selected types of articles to h-indices of medical researchers., Methods: We used the Web of Science to export the publication records of various members from 26 scientific medical societies (13 European, 13 North American) associated with 13 medical specialties. Those included were presidents (n=26), heads of randomly chosen committees (n=52), and randomly selected members of those committees (n=52). Publications contributing to h-index were categorized as research articles, reviews, guidelines, meta-analyses, or other published work., Results: Overall, 3259 items authored by 129 scholars were analyzed. The median h-index was 19.5. The median contribution of research articles to h-index was 84.4%. Researchers in the upper h-index tercile (≥28.5) had a larger share of research articles that contributed to h-index in comparison with those in the lower h-index tercile (≤12.5) (median 87.3% [1st-3rd quartile: 80.0%-93.1%] vs 80.0% [50.0%-88.9%], P=0.015). We observed an analogous difference with regard to guidelines (1.1% [0%-3.7%] vs 0% [0%-0%], P=0.007)., Conclusions: Original research drives h-indices in medicine. Although guidelines contribute to h-indices in medicine, their influence is low. The specific role of randomized controlled trials in building h-index in medicine remains to be assessed.

Purpose: Mulberry (Morus alba L.) leaf tea has recently received much attention as a dietary supplement due to the wide range of putative health benefits, such as antidiabetic effects. Nevertheless, data evaluating its influence on carbohydrate metabolism in humans are scarce. The present study aims to investigate the effect of mulberry leaf extract supplementation on starch digestion and absorption in humans., Materials and Methods: The study comprised of 25 healthy subjects, aged 19-27 years. In all subjects, a starch 13 C breath test was performed twice in a crossover and single blind design. Subjects were initially randomized to ingest naturally 13 C-abundant cornflakes (50g cornflakes+100ml low fat milk) either with the mulberry leaf extract (36mg of active component-1-deoxynojirimycin) or the placebo and each subject received the opposite preparation one week later., Results: The cumulative percentage dose recovery was lower for the mulberry leaf extract test than for the placebo test (median [quartile distribution]: 13.9% [9.9-17.4] vs. 17.2% [13.3-20.6]; p=0.015). A significant decrease was detectable from minute 120 after the ingestion., Conclusions: A single dose of mulberry leaf extract taken with a test meal decreases starch digestion and absorption. These findings could possibly be translated into everyday practice for improvement of postprandial glycemic control., (Copyright © 2017 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.)

Purpose: As life expectancy in cystic fibrosis (CF) increases, questions regarding its potential impact on cardiovascular health arise. Soluble vascular cell adhesion molecule 1 (sVCAM-1), P-selectin (sP-selectin) are proposed as biomarkers of cardiovascular disease. We aimed to: compare their concentrations in clinically stable CF patients and healthy subjects (HS) and verify whether they independently correlate with CF characteristics., Methods: Serum sVCAM-1 and sP-selectin levels were measured using ELISA. CF was characterized using: forced expiratory volume in 1 s, exocrine pancreatic and CF-related liver disease status, Pseudomonas aeruginosa colonization, serum high-sensitivity C-reactive protein, and body mass index (BMI). CFTR genotypes were classified as severe (classes I and II) or other., Results: 108 CF patients and 51 healthy subjects volunteered for the study. In the CF group BMI was lower (median [IQR]: 20.5 kg/m 2 [18.4-22.2] vs. 21.6 kg/m 2 [19.9-23.4], p = 0.02) and hsCRP levels were higher (3.6 mg/L [1.1-7.1] vs. 0.5 mg/dL [0.3-1.0], p < 10 -10 ). While sVCAM-1 concentrations were greater in CF patients (1018 ng/mL [851-1279] vs. 861 ng/mL [806-979], p < 10 -4 ), sP-selectin levels did not differ (155 ng/mL [129-188] vs. 156 ng/mL [144-177], p = 0.48). None of the multivariable regression models was valid for the prediction of sVCAM-1 and sP-selectin in CF., Conclusions: We found higher sVCAM-1 concentrations in CF patients than in healthy subjects, which were not explained by CF characteristics. Further research is required to check whether sVCAM-1 is a marker of microangiopathy in CF.

INTRODUCTION Diabetes mellitus and the postmenopausal period are associated with increased risk of urinary tract infections (UTIs) in women. However, data on UTIs in postmenopausal diabetic women are scarce. OBJECTIVES The aim of this study was to determine the prevalence of UTIs in postmenopausal women with type 2 diabetes mellitus, identify the potential risk factors, describe the causative pathogens, and assess their susceptibility to quinolones.  PATIENTS AND METHODS Patients were interviewed, examined, and had their hospital records analyzed. An uncontaminated midstream urine sample was collected and cultured in selective or enriched media. Colony‑forming units were counted and susceptibility to quinolones was assessed. Univariate and multivariate logistic regression models were built.  RESULTS Forty women were included in this prospective cross‑sectional study; their median age was 64 years (range, 52-84 years). UTIs occurred in 37.5% of the patients. The major implicated pathogens were Escherichia coli (66.7%) and enterococci (20%; most often Enterococcus faecalis). Most of the pathogens (93.8%) were susceptible to all tested quinolones. Patients with UTIs had a significantly lower glomerular filtration rate (P = 0.008) and higher comorbidity index (P = 0.01) compared with patients with sterile urine. Microangiopathic complications, including retinopathy and nephropathy, were identified as independent risk factor for UTIs (adjusted odds ratio, 3.5; 95% CI, 1.2-5.5; P = 0.006). The other clinical correlates of UTIs were urinary incontinence, hyperlipidemia, and microalbuminuria. CONCLUSIONS Postmenopausal diabetic patients with microangiopathy are at high risk of UTIs and therefore should be educated and vigilantly monitored. Attention should also be paid to urinary incontinence, hyperlipidemia, and microalbuminuria as other risk factors for UTIs. Quinolones are an attractive treatment option in this group of patients in Poland.

Spt5 is a conserved and essential transcriptional regulator that binds directly to RNA polymerase and is involved in transcription elongation, polymerase pausing and various co-transcriptional processes. To investigate the role of Spt5 in non-coding transcription, we used the unicellular model Paramecium tetraurelia. In this ciliate, development is controlled by epigenetic mechanisms that use different classes of non-coding RNAs to target DNA elimination. We identified two SPT5 genes. One (STP5v) is involved in vegetative growth, while the other (SPT5m) is essential for sexual reproduction. We focused our study on SPT5m, expressed at meiosis and associated with germline nuclei during sexual processes. Upon Spt5m depletion, we observed absence of scnRNAs, piRNA-like 25 nt small RNAs produced at meiosis. The scnRNAs are a temporal copy of the germline genome and play a key role in programming DNA elimination. Moreover, Spt5m depletion abolishes elimination of all germline-limited sequences, including sequences whose excision was previously shown to be scnRNA-independent. This suggests that in addition to scnRNA production, Spt5 is involved in setting some as yet uncharacterized epigenetic information at meiosis. Our study establishes that Spt5m is crucial for developmental genome rearrangements and necessary for scnRNA production., (© The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Purpose: A lower parasympathetic activity was described in patients with the gastroesophageal reflux disease. We aimed to determine whether gastroesophageal reflux (GER) episodes are associated with a short-term parasympathetic tone variability in children., Methods: In order to address this question we performed simultaneous 24-h esophageal multichannel intraluminal impedance-pH and electrocardiographic monitoring in 16 children (age range 6-18 years), including 8 with asthma and 2 with gastroesophageal reflux disease. After describing duration, height, and acidity of 483 GER episodes we also measured parasympathetic-related heart rate variability parameters in 4 time periods: preceding, containing, following GER, and in-between GERs (control). High frequency (HF) power and root-mean square differences of successive R-R intervals (r-MSSD) were assessed in 2.5-min and 1-min periods, respectively., Results: We did not identify the searched short-term parasympathetic tone changes., Conclusions: In conclusion, GER episodes and their characteristics were not associated with short-term variability of parasympathetic activity in children., (Copyright © 2017 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.)

Background: At present, fecal elastase-1 ELISA determination is the most sensitive and specific tubeless pancreatic function test available. However, the results are not available the same day in routine clinical practice. This prospective study aims at evaluating the sensitivity and specificity of the Elastase-1 Quick™ Test by comparing the results with the ELISA test., Methods: The study was composed of three groups: the screening-diagnosed cystic fibrosis (CF) patients (n=28), the screened, but non-CF subjects (n=36) and non-screened CF patients (n=62). Pancreatic status (normal vs abnormal) was evaluated using the Pancreas Elastase-1 Quick™ Test. Fecal elastase-1 concentration was determined with a commercially available ELISA kit, used as reference. The cut-off for abnormal results was set at <200μg/g of stool., Results: The Pancreatic Elastase-1 Quick Test™ showed the following sensitivities and specificities in the studied groups: 92.8% and 96.6% in all subjects, 90.5% and 100% in screening samples, and 92.8 and 90.5% in CF patients., Conclusion: Pancreatic Elastase-1 Quick Test™ proves to be a rapid and reliable option to qualitatively evaluate pancreatic function for diagnostic purposes in a clinical setting of CF care., (Copyright © 2016. Published by Elsevier B.V.)

Objectives: New tools are needed in cystic fibrosis (CF) diagnostics in pancreatic-sufficient CF (PS-CF) patients. Secretin-enhanced magnetic resonance cholangiopancreatography (SE-MRCP) allows for improved assessment of the width of the pancreatic duct., Methods: Sixteen PS-CF patients and 17 healthy volunteers underwent SE-MRCP. The width of the pancreatic duct in the head, the body, and the tail of the pancreas was measured at the baseline and 1, 2, 3, 5, and 10 minutes after secretin administration., Results: The width of the pancreatic duct in the head of the pancreas did not differ between the groups at the baseline; after 10 minutes of secretin stimulation, it was smaller in PS-CF patients (median, 1.4 mm [first-third quartile, 1.3-2.0] vs 2.2 mm [1.7-2.4], P = 0.008). The area under the curve for discrimination between the 2 groups using this parameter was 0.77 (95% confidence interval, 0.60-0.93)., Conclusions: The SE-MRCP identified differences in the width of the pancreatic duct between PS-CF and healthy volunteers. Further improvements of the method are needed to augment its clinical utility.

Background and Aims: Although indirect methods of assessment of the exocrine pancreatic function have become the standard of care in the monitoring of pancreatic status, it still remains a current clinical challenge. Our aim was to compare the width of the pancreatic duct in pancreatic insufficient (PI) and pancreatic sufficient (PS) cystic fibrosis (CF) patients using secretin-enhanced magnetic resonance cholangiopancreatography (SE-MRCP)., Methods: Thirty-seven CF patients were enrolled for this cross-sectional study, including 21 PI and 16 PS, all of whom underwent SE-MRCP. Measurement of the diameter of the pancreatic duct was performed in the head, body, and the tail of the pancreas at the baseline and after 1, 2, 3, 5, and 10 minutes after secretin administration., Results: The diameter of the pancreatic duct in the head of the pancreas after 5 and 10 minutes of secretin injection was greater in PI than in PS patients (median = 2.0 mm [interquartile range: 1.6-3.0] vs. 2.0 mm [1.0-2.0] and 2.0 mm [1.4-2.0] vs 1.0 mm [1.0-2.0], p=0.047 and p=0.040, respectively). Areas under ROC curves for discriminating between PI and PS patients were 0.693 (95% CI 0.521-0.866) and 0.698 (95% CI 0.528-0.868), respectively. No other differences in the width of the duct were identified at the baseline or during SE-MRCP., Conclusions: The measurement of the diameter of the pancreatic duct during secretin stimulation does not allow for differentiating between PS and PI status in CF patients.

The labial minor salivary glands (LSGs) play a role in medical research and practice due to their superficial location and involvement in both systemic and localized diseases. Swept-source optical coherence tomography (OCT) is a noninvasive modality that enables in vivo, micrometer resolution, wide-field three-dimensional imaging in seconds. A purpose-built swept-source OCT instrument was employed to acquire three-dimensional datasets covering the area of 2.43 cm(2) of the mucosa of the lower lip to the depth of 3.4 mm in young (n = 14; mean age ± SD: 27 ± 3 years; body mass index [BMI] 20.4 ± 2.3 kg/m(2) ) and middle-aged women (n = 11; 54 ± 6 years; 25.5 ± 3.2 kg/m(2) ). Glandular tissue reflectivity mode (range 0-255; 86 ± 17 vs. 68 ± 12, p = 0.005), average single LSG area in tissue sample (5.26 ± 2.62 mm(2) vs. 2.87 ± 1.26 mm(2) , p = 0.011), and LSG surface filling factor (0.23 ± 0.13 vs. 0.11 ± 0.10, p = 0.027) had higher values in younger than in middle-aged women. A correlation between BMI and glandular tissue reflectivity mode (Spearman's ρ = -0.60) was found (p = 0.002). The results highlight the potential value of LSGs' OCT morphometry in research regarding ageing., (© 2015 Wiley Periodicals, Inc.)

Correct pH probe placement is vital for the precision of esophageal pH monitoring. This study aimed at finding the optimal formula for placement of pH probe in the locus proposed by the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition European Pediatric Impedance Working Group, that is, 2 vertebrae above the diaphragm. An analysis of data regarding 353 children ages 0-18 years in whom the position of the pH sensor was determined radiographically revealed that a mathematical formula (3.2 + 0.2 × body length or height, centimeter) could guide the probe to within 1/12 of thoracic spine length of the desired location in 71.7% of all of the patients.

Green tea is known worldwide for its beneficial effects on human health. However, objective data evaluating this influence in humans is scarce. The aim of the study was to assess the impact of green tea extract (GTE) on starch digestion and absorption. The study comprised of 28 healthy volunteers, aged 19 to 28 years. In all subjects, a starch (13)C breath test was performed twice. Subjects randomly ingested naturally (13)C-abundant cornflakes during the GTE test (GTE 4 g) or placebo test. The cumulative percentage dose recovery (CPDR) was significantly lower for the GTE test than for the placebo test (median [interquartile range]: 11.4% [5.5-15.5] vs. 16.1% [12.7-19.5]; p = 0.003). Likewise, CPDR expressed per hour was considerably lower in each point of the measurement. In conclusion, a single dose of green tea extract taken with a test meal decreases starch digestion and absorption.

Because of their nuclear dimorphism, ciliates provide a unique opportunity to study the role of non-coding RNAs (ncRNAs) in the communication between germline and somatic lineages. In these unicellular eukaryotes, a new somatic nucleus develops at each sexual cycle from a copy of the zygotic (germline) nucleus, while the old somatic nucleus degenerates. In the ciliate Paramecium tetraurelia, the genome is massively rearranged during this process through the reproducible elimination of repeated sequences and the precise excision of over 45,000 short, single-copy Internal Eliminated Sequences (IESs). Different types of ncRNAs resulting from genome-wide transcription were shown to be involved in the epigenetic regulation of genome rearrangements. To understand how ncRNAs are produced from the entire genome, we have focused on a homolog of the TFIIS elongation factor, which regulates RNA polymerase II transcriptional pausing. Six TFIIS-paralogs, representing four distinct families, can be found in P. tetraurelia genome. Using RNA interference, we showed that TFIIS4, which encodes a development-specific TFIIS protein, is essential for the formation of a functional somatic genome. Molecular analyses and high-throughput DNA sequencing upon TFIIS4 RNAi demonstrated that TFIIS4 is involved in all kinds of genome rearrangements, including excision of ~48% of IESs. Localization of a GFP-TFIIS4 fusion revealed that TFIIS4 appears specifically in the new somatic nucleus at an early developmental stage, before IES excision. RT-PCR experiments showed that TFIIS4 is necessary for the synthesis of IES-containing non-coding transcripts. We propose that these IES+ transcripts originate from the developing somatic nucleus and serve as pairing substrates for germline-specific short RNAs that target elimination of their homologous sequences. Our study, therefore, connects the onset of zygotic non coding transcription to the control of genome plasticity in Paramecium, and establishes for the first time a specific role of TFIIS in non-coding transcription in eukaryotes.

Introduction: In inflammatory bowel diseases (IBD) diarrhea can be caused by exacerbation and/or infectious agents. Fecal calprotectin (FC) is a well-established biomarker of intestinal inflammation in IBD. However, its usefulness in depiction of IBD exacerbation from infectious diarrhea is limited. The value of fecal pyruvate kinase isoenzyme type 2 (M2-PK) in this application remains unknown., Aim: To compare the performance of M2-PK and FC in discriminating between diarrhea caused by IBD and infectious agents., Materials and Methods: One hundred three patients were enrolled for the study, including 32 with ulcerative colitis (UC), 21 with Crohn's disease (CD), 29 with acute diarrhea caused by rotavirus (AD-RV), and 21 with acute diarrhea caused by Salmonella enteritidis (AD-SE). M2-PK and FC were measured using ELISA. Areas under receiver operating characteristic curves (AUCs), sensitivities and specificities for both tests in distinguishing between patient subgroups with moderate to severe UC and CD from AD-RV and AD-SE were calculated., Results: Differences in AUCs between M2-PK and FC for distinguishing UC [CD] from AD-RV were -0.06 (p < 0.028) [-0.10 (p < 0.0018)] and for differentiating UC [CD] from AD-SE were 0.03 (NS) [-0.19(p < 0.0011)].M2-PK sensitivities and specificities in distinguishing UC [CD] from AD-RV were 75.0%[71.4%] and 89.7% [89.7%] and for differentiation of UC [CD] from AD-SE were 56.3% [71.4%] and 95.2[57.1%]., Conclusions: The performance of M2-PK in distinguishing between children with moderate-to-severe IBD and patients with infectious gastroenteritis was inferior to FC. Neither test had sensitivity ands pecificity sufficient for everyday clinical application.

The labial minor salivary glands (LSGs) are easily accessible mucus-secreting structures of the alimentary tract that may provide new information on the basis of gastrointestinal complications of cystic fibrosis (CF). It was shown that they are destructed in the course of cystic fibrosis. We employed wide-field, micrometer resolution in vivo optical coherence tomography to assess the surface density of LSGs in 18 patients with CF and 18 healthy subjects. The median LSGs' surface densities in CF patients, and in the control group were 4.32 glands/cm2 and 6.58 glands/cm2, respectively (p = 0.006; Mann-Whitney U test). A lower LSG surface density is a previously unrecognized CF-related pathology of the alimentary tract.

It is widely accepted that type 1 diabetes mellitus (T1DM) is an autoimmune disease resulting from an interaction between immunologic, genetic and environmental factors. However, the exact mechanism leading to the development of T1DM remains incomplete. There is a large body of evidence pointing towards the important role of toll-like receptor (TLR) activation and vitamin D deficiency in T1DM pathogenesis. In this article, we review the available data on the influence of TLRs' level of activation and vitamin D status on the risk of the development of T1DM in humans and rodent models. We also summarize the current information regarding the interactions between TLRs' level of activation, vitamin D status and various environmental factors, such as enteroviral infections, the gut microbiota and breastfeeding substitution, among others. Our results stipulate that vitamin D seems to protect against T1DM by reducing the TLRs' level of activation., (© 2014 John Wiley & Sons Ltd.)

Fecal concentrations of pyruvate kinase isoform M2 (M2-PK) and calprotectin (FC) serve as biomarkers of inflammation of gastrointestinal mucosa. The value of M2-PK in discriminating between patients with viral and bacterial acute diarrhea (AD) is currently unknown. We analyzed M2-PK and FC concentrations in fifty hospitalized children with AD (29 of which were caused by rotavirus and 21 by Salmonella enteritidis) as well as 32 healthy subjects. There was no difference in the areas under the receiver operating characteristic curves plotted for the two tests in differentiating rotaviral from bacterial AD. The sensitivity and specificity of M2-PK at optimal cut-off (20 U/g) were 75.9% and 71.4%, respectively. M2-PK and FC had similar values in distinguishing between children with AD caused by rotavirus and Salmonella enteritidis. The performance of both tests in hospitalized patients did not meet the needs of everyday clinical practice. Moreover, no advantage of fecal tests over the measurement of CRP was documented.

Although vitamin K deficiency has been implicated in adult inflammatory bowel disease (IBD), its prevalence in pediatric IBD remains unknown. We carried out a cross-sectional study in 63 children with Crohn's disease (CD) and 48 with ulcerative colitis (UC) to assess the prevalence of vitamin K deficiency and to search for potential correlation between vitamin K status and pediatric IBD activity. Vitamin K status was assessed using protein induced by vitamin K absence-II (PIVKA-II; ELISA). Prevalence of vitamin K deficiency was 54.0% in CD and 43.7% in UC. Vitamin K deficiency was more common in patients with higher CD activity, in CD patients with higher mass Z-scores, and less common among children with CD treated with infliximab. Relation of vitamin K deficiency to pediatric IBD clinical course and treatment demand further research.

Aims: Accurate assessment of inflammatory bowel disease (IBD) activity is the cornerstone of effective therapy. Fecal M2 isoform of pyruvate kinase (M2-PK) and fecal calprotectin (FC) are noninvasive markers of mucosal inflammation in IBD. The aim of this study was to compare performance of M2-PK and FC in assessment of pediatric ulcerative colitis (UC) and Crohn's disease (CD) severity and activity., Materials and Methods: 121 patients with IBD, including 75 with UC and 46 with CD were recruited. Control group consisted of 35 healthy children (HS). Patients were assigned to groups depending on disease severity and activity. M2-PK and calprotectin concentration were determined in stool samples using ELISA. Areas under receiver operating characteristic curves (AUC) for FC and M2-PK with cut-off level at which M2-PK specificity was matching FC specificity were calculated and compared., Results: Performance of M2-PK at identifying patients with IBD, UC and CD among HS was inferior to FC. The differences in AUC were respectively: -0.10 (95% confidence interval [CI] [-0.13-(-0.06)], p<0.0001), -0.14 (95% CI [-0.19-(-0.09)], p<0.0001) and -0.03 (95% CI [-0.05-(-0.001)], p<0.02). M2-PK was inferior to FC in discriminating patients with mild UC from those with HS (AUC difference -0.23, 95% CI [-0.31-(-0.15)], p<0.0001)., Conclusions: FC reflects pediatric IBD severity and activity better than M2-PK. This difference is particularly pronounced when identifying patients with mild UC and UC in remission.

Three-dimensional imaging of the mucosa of the lower lip and labial minor salivary glands is demonstrated in vivo using swept source optical coherence tomography (OCT) system at 1310 nm with modified interface. Volumetric data sets of the inner surface of the lower lip covering ~230 mm(2) field are obtained from patients with Sjögren's syndrome and a control group. OCT enables high-resolution visualization of mucosal architecture using cross-sectional images as well as en-face projection images. Comprehensive morphometry of the labial minor salivary glands is performed, and statistical significance is assessed. Statistically significant differences in morphometric parameters are found when subgroups of patients with Sjögren's syndrome are analyzed.

Like all ciliates, Paramecium tetraurelia is a unicellular eukaryote that harbors two kinds of nuclei within its cytoplasm. At each sexual cycle, a new somatic macronucleus (MAC) develops from the germ line micronucleus (MIC) through a sequence of complex events, which includes meiosis, karyogamy, and assembly of the MAC genome from MIC sequences. The latter process involves developmentally programmed genome rearrangements controlled by noncoding RNAs and a specialized RNA interference machinery. We describe our first attempts to identify genes and biological processes that contribute to the progression of the sexual cycle. Given the high percentage of unknown genes annotated in the P. tetraurelia genome, we applied a global strategy to monitor gene expression profiles during autogamy, a self-fertilization process. We focused this pilot study on the genes carried by the largest somatic chromosome and designed dedicated DNA arrays covering 484 genes from this chromosome (1.2% of all genes annotated in the genome). Transcriptome analysis revealed four major patterns of gene expression, including two successive waves of gene induction. Functional analysis of 15 upregulated genes revealed four that are essential for vegetative growth, one of which is involved in the maintenance of MAC integrity and another in cell division or membrane trafficking. Two additional genes, encoding a MIC-specific protein and a putative RNA helicase localizing to the old and then to the new MAC, are specifically required during sexual processes. Our work provides a proof of principle that genes essential for meiosis and nuclear reorganization can be uncovered following genome-wide transcriptome analysis.

We examined the effects of variations in postprandial glycemia and insulinemia on subjective satiety in overweight and obese women. We altered the ingestion rate of a glucose beverage to model the postprandial effects of high- and low-glycemic meals. Fourteen women were tested in a within-subjects' design with two conditions: (1) Rapid, with a large glucose beverage consumed with breakfast and lunch and (2) Slow, with the same volume of glucose beverage consumed in eight portions (one with each meal, and the remaining seven at 20-min intervals after each meal). Meals were identical in the two conditions. Subjective appetitive sensations were measured with visual analog scales before and after meals, and hourly after each meal until 5 pm. Serum glucose and insulin were measured at similar time points. Subjects reported higher ratings of hunger and prospective consumption in the Rapid versus Slow condition at 4h after breakfast and several hours after lunch. Serum glucose was more strongly correlated with the appetitive ratings in the Rapid than the Slow condition, and explained more of the variance (20-31%) than insulin (2-4%). The results of this study support the glucostatic theory linking dynamic changes in blood glucose with appetitive sensations.

The duplication of entire genomes has long been recognized as having great potential for evolutionary novelties, but the mechanisms underlying their resolution through gene loss are poorly understood. Here we show that in the unicellular eukaryote Paramecium tetraurelia, a ciliate, most of the nearly 40,000 genes arose through at least three successive whole-genome duplications. Phylogenetic analysis indicates that the most recent duplication coincides with an explosion of speciation events that gave rise to the P. aurelia complex of 15 sibling species. We observed that gene loss occurs over a long timescale, not as an initial massive event. Genes from the same metabolic pathway or protein complex have common patterns of gene loss, and highly expressed genes are over-retained after all duplications. The conclusion of this analysis is that many genes are maintained after whole-genome duplication not because of functional innovation but because of gene dosage constraints.

Paramecium, like other ciliates, remodels its entire germline genome at each sexual generation to produce a somatic genome stripped of transposons and other multicopy elements. The germline chromosomes are fragmented by a DNA elimination process that targets heterochromatin to give a reproducible set of some 200 linear molecules 50 kb to 1 Mb in size. These chromosomes are maintained at a ploidy of 800n in the somatic macronucleus and assure all gene expression. We isolated and sequenced the largest megabase somatic chromosome in order to explore its organization and gene content. The AT-rich (72%) chromosome is compact, with very small introns (average size 25 nt), short intergenic regions (median size 202 nt), and a coding density of at least 74%, higher than that reported for budding yeast (70%) or any other free-living eukaryote. Similarity to known proteins could be detected for 57% of the 460 potential protein coding genes. Thirty-two of the proteins are shared with vertebrates but absent from yeast, consistent with the morphogenetic complexity of Paramecium, a long-standing model for differentiated functions shared with metazoans but often absent from simpler eukaryotes. Extrapolation to the whole genome suggests that Paramecium has at least 30,000 genes.