Associations between developmental changes in error-related brain activity and executive functions in early childhood

Abstract

Behavioral evidence indicates that skills associated with children's cognitive control (e.g., response inhibition and attentional control) undergo rapid development during early childhood. A particularly important time is the transition to elementary school. Yet, at present, relatively little is known about developmental changes in the brain processes linked to cognitive control during this period, including those associated with error monitoring, including the error-related negativity (ERN) and the error positivity (Pe). Moreover, understanding how ERP correlates of cognitive control relate to behavioral measures of these skills over time is also limited. In the present study, repeated assessments of 4- to 6-year-old children's (N = 49, mean age = 5 years 10 months) performance on a go/no-go task were collected to examine developmental changes in error processing and response inhibition across 6 months. Data revealed the presence of both the ERN and Pe at each time point, but also showed individual differences in the test-retest associations for each component. Behavioral changes in response inhibition on the go/no-go task and a standardized measure of attentional control were associated with changes in electrophysiological measures of error processing. Additional analyses comparing children of the same age who had completed the go/no-go task once to those who participated longitudinally revealed that, with repeated assessments, children exhibited behavioral changes in performance that could be attributed to both development and to the effects of practice, such as strategic accommodation.

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Split-Dose Bowel Preparation Reduces the Need for Early Repeat Colonoscopy Without Improving Adenoma Detection Rate

Abstract

Background and Aims

Split-dose bowel preparation is associated with improved mucosal visualization and patient tolerance, becoming a standard of care. However, quality measures data associated with this preparation are limited. At our academic tertiary-care facility, we aim to study the effect of changing from single- to split-dose preparation on colonoscopy quality measures.

Methods

A retrospective cohort study with quality indicators was conducted using electronic medical record data. Cases were identified via ICD9 code V76.51, "Special screening for malignant neoplasms of colon." Single-dose preparation data was collected from 9/1/13 to 8/31/14. Split-dose preparation was implemented 11/2014, and data were collected from 1/1/15 to 8/31/15.

Results

A total of 1602 colonoscopies in the single-dose group and 1061 colonoscopies in the split-dose group were analyzed. The Boston Bowel Preparation Scale was significantly improved in the split-dose group 8.64 ± SD 1.25 versus 8.25 ± SD 1.61, p < 0.001. There was no significant difference in adenoma detection rate 40.7% (95% CI 37.8–43.7%) versus 40.5% (95% CI 38.1–42.9%), p = 0.92; however, the rate for recommending an early repeat examination due to an inadequate bowel preparation was significantly decreased to 3.9% (95% CI 2.7–5.0%) versus 8.9% (95% CI 1.52–2.97%), p < 0.001.

Conclusion

While split-dose preparation significantly improves overall bowel cleanliness, there is no significant adenoma detection rate improvement with high baseline rate, suggesting a threshold which may not improve with enhanced preparations. Split-dose preparation significantly reduces the frequency with which inadequate preparation prompts an early repeat examination, which has important clinical implications on performance, costs, and patient experience, providing further evidence supporting split-dose preparation use.

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Carbamazepine-Associated Hypersensitivity Colitis

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Outcomes of Salvage Liver Transplantation and Re-resection/Radiofrequency Ablation for Intrahepatic Recurrent Hepatocellular Carcinoma: A New Surgical Strategy Based on Recurrence Pattern

Abstract

Background

The treatment of intrahepatic recurrent hepatocellular carcinoma (HCC) has been poorly investigated, and the optimal treatment strategy remains unclear.

Aims

The aim of this study was to compare outcomes between salvage liver transplantation (SLT) and re-resection (RR)/radiofrequency ablation (RFA) for intrahepatic recurrent HCC according to recurrence pattern.

Methods

Based on postoperative histopathological examination, 122 patients with intrahepatic recurrent HCC were divided into an intrahepatic metastasis (IM, n = 75) group and a multicentric occurrence (MO, n = 47) group. The demographic, clinical, and primary and recurrent tumor characteristics of the IM group and the MO group were collected and compared. Overall survival (OS) and disease-free survival (DFS) were analyzed, and subgroup analysis according to retreatment type (SLT vs. RR/RFA) was conducted. Twenty-nine clinicopathological variables potentially related to prognostic factors affecting survival were analyzed using a Cox proportional hazard model.

Results

The patients that received SLT treatment exhibited favorable DFS compared to patients that received RR/RFA (P = 0.002). OS (P < 0.001) and DFS (P = 0.008) rates were significantly increased in the MO group compared with in the IM group. Subgroup analysis revealed that DFS was significantly improved for patients in the MO group treated with SLT compared to patients treated with RR/RFA (P = 0.017). Recurrence pattern was an independent prognostic factor for both OS [hazard ratio (HR) = 0.093, 95% confidence interval (CI): 0.026–0.337, P < 0.001] and DFS (HR = 0.318, 95% CI: 0.125–0.810, P = 0.016; HR = 3.334, 95% CI: 1.546–7.18, P = 0.002).

Conclusions

For patients with intrahepatic recurrent HCC, an MO recurrence pattern is associated with better long-term outcomes than the IM pattern. SLT is the preferred option for intrahepatic recurrent HCC, especially for MO cases.

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Inbred or Outbred? Genetic Diversity in Laboratory Rodent Colonies

Non-model rodents are widely used as subjects for both basic and applied biological research, but the genetic diversity of the study individuals is rarely quantified. University-housed colonies tend to be small and subject to founder effects and genetic drift and so may be highly inbred or show substantial genetic divergence from other colonies, even those derived from the same source. Disregard for the levels of genetic diversity in an animal colony may result in a failure to replicate results if a different colony is used to repeat an experiment, as different colonies may have fixed alternative variants. Here we use high throughput sequencing to demonstrate genetic divergence in three isolated colonies of Mongolian gerbil (Meriones unguiculatus) even though they were all established recently from the same source. We also show that genetic diversity in allegedly 'outbred' colonies of non-model rodents (gerbils, hamsters, house mice, deer mice, and rats) varies considerably from nearly no segregating diversity, to very high levels of polymorphism. We conclude that genetic divergence in isolated colonies may play an important role in the 'replication crisis'. In a more positive light, divergent rodent colonies represent an opportunity to leverage genetically distinct individuals in genetic crossing experiments. In sum, awareness of the genetic diversity of an animal colony is paramount as it allows researchers to properly replicate experiments and also to capitalize on other, genetically distinct individuals to explore the genetic basis of a trait.

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Dosage-Dependent Expression Variation Suppressed on the Drosophila Male X Chromosome

DNA copy number variation is associated with many high phenotypic heterogeneity disorders. We systematically examined the impact of Drosophila melanogaster deletions on gene expression profiles to ask if increased expression variability due to reduced gene dose might underlie this phenotypic heterogeneity. Indeed, we find that one dose genes have higher gene expression variability relative to two dose genes. We then asked if this increase in variability could be explained by intrinsic noise within cells, due to stochastic biochemical events, or if expression variability is due to extrinsic noise arising from more complex interactions. Our modeling showed that intrinsic gene expression noise averages at the organism level and thus cannot explain increased variation in one dose gene expression simply. Interestingly, expression variability was related to the magnitude of expression compensation, suggesting that gene dose reduction induced regulation is noisy. In a remarkable exception to this rule the single X chromosome of males showed reduced expression variability, even compared to two dose genes. Analysis of sex transformed flies indicates that X expression variability is independent of the male differentiation program. Instead, we uncover a correlation between occupancy of the chromatin modifying protein encoded by males absent on first (mof) and expression variability, linking noise suppression to the specialized X chromosome dosage compensation system. MOF occupancy on autosomes in both sexes lowered transcriptional noise as well. Our results demonstrate that gene deletions can lead to heterogeneous responses, which are often noisy. This has implications for understanding gene network regulatory interactions and phenotypic heterogeneity. Additionally, chromatin modification appears to play a role in dampening transcriptional noise.

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Independent association between prediabetes and future pancreatic fat accumulation: a 5-year Japanese cohort study

Abstract

Background

The association between pancreatic fat and glucose dysmetabolism has been reported in several cross-sectional studies; however, a recent longitudinal study showed that baseline pancreatic fat did not cause subsequent diabetes mellitus. We hypothesized that pancreatic fat is not a cause but a manifestation of glucose dysmetabolism and aimed to investigate the association between baseline prediabetes and future pancreatic fat accumulation.

Methods

Between 2008 and 2015, 198 nondiabetic participants, who underwent a health check-up via unenhanced computed tomography (CT) twice with CT intervals ≥ 5 years, were enrolled as prediabetes (n = 48) and non-prediabetes participants (n = 150). Prediabetes was defined as fasting plasma glucose of 100–125 mg/dl or hemoglobin A1c of 5.7–6.4%. Pancreatic fat was evaluated using a histologically validated method to measure the difference between pancreas and spleen attenuations (P–S) on CT. Pancreatic fat accumulation during follow-up was measured as P–S change from baseline. Multiple linear regression was used to evaluate the association between baseline prediabetes and future pancreatic fat accumulation with adjustment for age, sex, body mass index, physical activity, and liver fat at baseline.

Results

Mean pancreatic fat accumulation was 0.30 (SD, 5.8) Hounsfield units during follow-up. On univariate analysis, baseline prediabetes was associated with future pancreatic fat accumulation (β = 3.73; 95% CI 1.91–5.55; P < 0.001). This association remained statistically significant on multivariate analysis (β = 3.14; 95% CI 1.25–5.03; P = 0.001).

Conclusions

Prediabetes is a risk factor for future pancreatic fat accumulation. Pancreatic fat may be a manifestation of glucose dysmetabolism.

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Cryptogenic cholestasis in young and adults: ATP8B1 , ABCB11 , ABCB4 , and TJP2 gene variants analysis by high-throughput sequencing

Abstract

Background

Mutations in ATP-transporters ATPB81, ABCB11, and ABCB4 are responsible for progressive familial intrahepatic cholestasis (PFIC) 1, 2 and 3, and recently the gene for tight junction protein-2 (TJP2) has been linked to PFIC4.

Aim

As these four genes have been poorly studied in young people and adults, we investigated them in this context here.

Methods

In patients with cryptogenic cholestasis, we analyzed the presence of mutations by high-throughput sequencing. Bioinformatics analyses were performed for mechanistic and functional predictions of their consequences on biomolecular interaction interfaces.

Results

Of 108 patients, 48 whose cause of cholestasis was not established were submitted to molecular analysis. Pathogenic/likely pathogenic mutations were found in ten (21%) probands for 13 mutations: two in ATP8B 1, six in ABCB11, two in ABCB4, three in TJP2. We also identified seven variants of uncertain significance: two in ATP8B1, one in ABCB11, two in ABCB4 and two in TJP2. Finally, we identified 11 benign/likely benign variants. Patients with pathogenic/likely pathogenic mutations had higher levels of liver stiffness (measured by FibroScan^®) and bile acids, as well as higher rates of cholestatic histological features, compared to the patients without at least likely pathogenic mutations. The multivariate analysis showed that itching was the only independent factor associated with disease-causing mutations (OR 5.801, 95% CI 1.244–27.060, p = 0.025).

Conclusions

Mutations in the genes responsible for PFIC may be involved in both young and adults with cryptogenic cholestasis in a considerable number of cases, including in heterozygous status. Diagnosis should always be suspected, particularly in the presence of itching.

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Well Preserved Renal Function in Children with Untreated Chronic Liver Disease

ABSTRACT Objectives: Based on studies with hepatorenal syndrome, it is widely regarded that renal function is impacted in chronic liver disease. Therefore we investigated renal function in our children with chronic liver disease. Methods: In a retrospective study of 277 children with chronic liver disease, renal function was investigated as glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), measured as clearance of inulin and para-amino hippuric acid or clearance of iohexol. The data were analyzed with regard to different subgroups of liver disease and to the grade of damage. Results: Hyperfiltration (> +2 SD of controls) was found in the subgroups of progressive familial intrahepatic cholestasis (44%), glycogenosis (75%) and acute fulminant liver failure (60%). Patients with biliary atresia, most other patients with metabolic disease and intrahepatic cholestasis, and those with vascular anomalies and cryptogenic cirrhosis had normal renal function. Decreased renal function was found in patients with Alagille's syndrome (64% 

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Fecal Calprotectin Test Performed at Home – a Prospective Study of Pediatric Patients with Inflammatory Bowel Disease

ABSTRACT Objectives: Measuring fecal calprotectin (FC) in a laboratory is time-consuming and that is why home tests have been developed. We studied the use of an FC home test in pediatric patients with inflammatory bowel disease (PIBD) in real-life settings. Methods: The patients were asked to perform the IBDoc® FC home test monthly for six months and to report their clinical disease activity at testing. However, clinical decision-making was guided by routine FC enzyme-linked immunosorbent assay (ELISA) for patients with raised IBDoc® values. Spare frozen samples were analyzed using ELISA and IBDoc® in the laboratory. The participants completed a questionnaire about FC testing at the start and end of the study. Results: Of the 52 patients, 35 (67%) aged 5–18 years completed the study and 197 home tests were performed. Of these, 15% failed, mainly because of technical reasons. Just under half of the patients (47%) considered home testing comparable or superior to routine testing. In contrast, the parents were unsatisfied (61%), mostly because the IBDoc® results were significantly different from ELISA and they found the phone application difficult to handle. But when the IBDoc® was performed by a laboratory professional it was comparable with ELISA, suggesting that practical issues hampered home testing. Despite their reservations, more than 80% of parents felt that home testing would improve disease management. Conclusions: PIBD patients and their families were interested in FC home monitoring and willing to adopt testing as a part of their disease management, but this approach requires thorough guidance. Address correspondence and reprint requests to Maija Piekkala, M.D., PhD, Children's Hospital, P.O.B 281, 00029 Helsinki, Finland (e-mail: maija.piekkala@helsinki.fi);Kaija-LeenaKolho,Ph.D.,M.D.,HospitalforChildrenandAdolescents,UniversityofHelsinki,Helsinki,FINLAND(e-mail:kaija-leena.kolho@helsinki.fi). Received 25 September, 2017 Accepted 29 November, 2017 Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal's Web site (www.jpgn.org). Conflicts of interest and Source of Funding: There are no conflicts of interest. The study was supported by Pediatric Research Foundation (Finland) and Helsinki University Hospital Research Fund (project TYH2015405) Abbvie donated the IBDoc® tests for the study, but had no role in the study design, the collection, analysis and interpretation of the data, writing the report or the decision to submit the paper. © 2017 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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Gastrointestinal Symptoms in Children and Adolescents With Neurofibromatosis Type 1

ABSTRACT Objectives: Neurofibromatosis type 1 (NF1) is a complex genetic disorder characterized by symptoms of the skin and nervous system. A previous study indicated that constipation is common in children with NF1. The aim of the present study was to investigate the phenotype and prevalence of gastrointestinal symptoms in a population of 4-17-year-olds with NF1 compared to their unaffected siblings. Methods: Gastrointestinal symptoms were assessed with a web-based, parent or self-administered, validated, Rome® III diagnostic questionnaire. Participants were recruited from one of two Danish National Centers of Expertise for NF1. Logistic regression was used to estimate the prevalence of functional dyspepsia, irritable bowel syndrome and constipation in each group and the groups were compared using odds ratio. Results: We compared 102 NF1 patients (median age 10.3 years) and 46 of their unaffected siblings (median age 10 years). The overall likelihood of having gastrointestinal symptoms usually attributed to either functional dyspepsia, irritable bowel syndrome or constipation was 30.4% in patients vs. 10.9% in siblings, odds ratio 3.58 (95% CI: 1.30–9.79). The prevalence of constipation was 22.5% in patients and 4.3% in siblings, odds ratio 6.41 (95% CI: 1.45–28.24). The use of laxatives was 16% (n = 16) in patients and 2% (n = 1) in siblings. Conclusions: Overall, gastrointestinal symptoms attributed to functional dyspepsia, irritable bowel syndrome or constipation are more common in 4–17-year-olds with NF1 when compared to their unaffected siblings. The high prevalence indicates that gastrointestinal dysfunction in NF1 is not functional but may be part of the underlying NF1 disorder. Address correspondence and reprint requests to Cecilie Ejerskov, MD, Centre for rare diseases, Peadiatrics and adolescent medicine, Aarhus university hospital, Palle juul-jensens boulevard 99, Dk-8200 aarhus n denmark (e-mail: cecilie@ejerskov.dk). Received 2 July, 2017 Accepted 12 November, 2017 Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal's Web site (www.jpgn.org). CONFLICTS OF INTEREST AND SOURCE OF FUNDING: THE AUTHORS DECLARE THAT THEY HAVE NO CONFLICT INTERESTS. THE STUDY WAS SUPPORTED BY AARHUS UNIVERSITY, HEALTH; NF DENMARK - THE DANISH NF PATIENT ASSOCIATION AND; THE DANISH MEDICAL RESEARCH GRANT. THE FUNDING BODIES HAVE HAD NO ROLE IN THE DESIGN OF THE STUDY, COLLECTION, ANALYSIS OR INTERPRETATION OF THE DATA NOR IN THE WRITING OF THE MANUSCRIPT. © 2017 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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Referees 2017

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Pediatric High-flow Pial Arteriovenous Fistula (AVF) for Glue Embolization: An Anesthetic Challenge

No abstract available

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Closure of the cystic duct orifice in laparoscopic subtotal cholecystectomy for severe cholecystitis

Abstract

Introduction

Laparoscopic subtotal cholecystectomy (LSC) has been recognized as an alternative to conversion to laparotomy for severe cholecystitis. However, it may be associated with an increased risk of recurrent stones in the gallbladder remnant. The objective of this study was to evaluate the safety and feasibility of the complete removal of the gallbladder cavity in LSC for severe cholecystitis using the cystic duct orifice suturing (CDOS) technique.

Methods

In a consecutive series of 412 laparoscopic cholecystectomies that were performed from January 2015 to June 2017, 12 patients who underwent LSC with CDOS were enrolled in this retrospective study. In this procedure, Hartmann's pouch was carefully identified, and the infundibulum–cystic duct junction was transected while the posterior wall adherent to Calot's triangle was left behind. The clinical records, including the operative records and outcomes, were analyzed.

Results

The median operating time and blood loss were 158 min and 20 mL, respectively. In all cases, LSC with CDOS was completed without conversion to open surgery. No injuries to the bile duct or vessels were experienced. The median postoperative hospital stay was 6 days. Postoperative complications occurred in two patients (bile leakage, n = 1: common bile duct stones, n = 1) and were successfully treated by endoscopic management. A gallbladder remnant was not delineated by postoperative imaging in any of the cases.

Conclusion

These results suggest that LSC with CDOS is a promising approach that can avoid dissection of Calot's triangle and achieve the complete removal of the gallbladder cavity in patients with severe cholecystitis.

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