Is Schimmelpenning Syndrome Associated with Intracranial Tumors? A Case Report.

Schimmelpenning syndrome is a rare, well-defined constellation of clinical phenotypes associated with the presence of nevus sebaceous and multisystem abnormalities most commonly manifested as cerebral, ocular, and skeletal defects [1]. A single nucleotide mutation in the HRAS or KRAS genes resulting in genetic mosaicism is responsible for the clinical manifestations of this syndrome in the majority of cases. We report a case of an adolescent boy with Schimmelpenning syndrome with a multifocal pilocytic astrocytoma. No HRAS or KRAS gene mutations were noted in the tumor on genetic sequencing. However, glial tumors have been associated with genetic mutations of RAS upregulation, which may imply a common pathway.

Serum Proteomics in African American Female Patients With Irritable Bowel Syndrome: An Exploratory Study.

BACKGROUND: Sex and subtype differences within patients with irritable bowel syndrome (IBS) complicate the understanding of disorder pathogenesis and hinder the design of efficacious, therapeutic interventions. OBJECTIVES: The aims of this study were to harness the power of shotgun proteomic analysis, identify circulating proteins that differentiate African American female patients with IBS from healthy controls (HC), and gain biological insight on symptomatology. METHODS: Serum proteome analysis was performed upon a cohort of overweight, African American female participants with constipation predominant IBS symptoms (n = 5) and HC (n = 5), matched on age, sex, years of education, body mass index, and 11 physiological markers. Tandem mass tags for multiplexed proteomic analysis were performed, incorporating reverse-phase liquid chromatography and liquid chromatography-tandem mass spectrometry. RESULTS: Participants with IBS did not differ from HC in demographics, clinical characteristics, or initial proteomic analysis. Nested case control analysis of six samples (IBS: n = 3, HC: n = 3), hierarchically clustered into two main groups, with 12 out of 1,317 proteins significantly different in levels of expression: TGFß1, PF4V1, PF4, APP, MMP9, PPBP, CTGF, SRGN, THBS1, WRN, LTBP1 (Isoform 3), and IGLV5-48. Top associations of identified proteins in DAVID and STRING resources (upregulated in HC vs. IBS) involve platelet alpha granule lumen, platelet activation/degranulation, extracellular region, and secretion by cell. DISCUSSION: Differentially expressed proteins between participants with IBS and HC involving platelet-related associations prompt inquiry as to differences in serotonergic signaling, inflammatory or immunomodulatory mechanisms underlying IBS symptomatology. Although preliminary and requiring validation in larger cohorts, these findings bear relevance to understanding pathogenic processes of IBS and biological effects of the disorder.

Endoscopic Therapy With Lumen-apposing Metal Stents Is Safe and Effective for Patients With Pancreatic Walled-off Necrosis.

BACKGROUND & AIMS: Endoscopic ultrasound-guided transmural drainage and necrosectomy have become the standard treatment for patients with pancreatic walled-off necrosis (WON). Lumen-apposing metal stents (LAMS) have shown success in the management of pancreatic fluid collections. However, there are few data on their specific roles in management of WON. We investigated the efficacy and safety of LAMS in treatment of WON. METHODS: We performed a retrospective multicenter case series of 124 patients with WON who underwent endoscopic transmural drainage by using LAMS at 17 tertiary care centers from January 2014 through May 2015. Patients underwent endoscopic ultrasound-guided cystogastrostomy or cystoenterostomy with placement of an LAMS into the WON collection. At the discretion of the endoscopist, we performed direct endoscopic necrosectomy, irrigation with hydrogen peroxide, and/or nasocystic drain placement. We performed endoscopic retrograde cholangiopancreatography with pancreatic duct stent placement when indicated. Concomitant therapies included direct endoscopic debridement (n = 78), pancreatic duct stent placement for leak (n = 19), hydrogen peroxide-assisted necrosectomy (n = 38), and nasocystic irrigation (n = 22). We collected data for a median time of 4 months (range, 1-34 months) after the LAMS placement. The primary outcomes were rates of technical success (successful placement of the LAMS), clinical success (resolution of WON, on the basis of image analysis, without need for further intervention via surgery or interventional radiology), and adverse events. RESULTS: The median size of the WON was 9.5 cm (range, 4-30 cm). Eight patients had 2 LAMS placed for multiport access, all with technical success (100%). Clinical success was achieved in 107 patients (86.3%) after 3 months of follow-up. Thirteen patients required a percutaneous drain, and 3 required a surgical intervention to manage their WON. The stents remained patent in 94% of patients (117 of 124) and migrated in 5.6% of patients (7 of 124). The median number of endoscopic interventions was 2 (range, 1-9 interventions). CONCLUSIONS: On the basis of a retrospective analysis of 124 patients, endoscopic therapy of WON by using LAMS is safe and effective. Creation of a large and sustained cystogastrostomy or cystoenterostomy tract is effective in the drainage and treatment of WON.

Endoscopic gallbladder drainage compared with percutaneous drainage.

BACKGROUND: High-risk patients with cholecystitis have conventionally been offered percutaneous gallbladder drainage (PGBD) for treatment. A growing experience of endoscopic gallbladder drainage (EGBD) has been reported to be effective and safe. OBJECTIVE: To compare the short- and long-term outcomes of EGBD and PGBD. DESIGN: A retrospective review. SETTING: Single academic tertiary care center. PATIENTS: Inpatients diagnosed with cholecystitis. INTERVENTIONS: Any patient deemed a nonsurgical candidate and who has undergone either PGBD or EGBD was included in the analysis. MAIN OUTCOME MEASUREMENTS: Patient demographics along with procedural and clinical outcomes were recorded for each group. RESULTS: Forty-three patients underwent PGBD and 30 underwent EGBD (24 transpapillary, 6 transmural). Technical (97.6% vs 100%) and clinical (97.6% vs 86.7%) success rates of PGBD and EGBD were similar. However, postprocedure hospital length of stay (16.3 vs 7.6 days), time to clinical resolution (4.6 vs 3.0 days), adverse event rate (39.5% vs 13.3%), number of sessions (2.0 vs 1.0), number of repeat interventions (53.4% vs 13.3%), and postprocedure pain scores (3.8 vs 2.1) were significantly higher for PGBD than EGBD. LIMITATIONS: Retrospective analysis. CONCLUSION: Although EGBD has similar technical and clinical success compared with PGBD, it uses fewer hospital resources and results in fewer adverse events, improved pain scores, and decreased need for repeat gallbladder drainage. EGBD may provide a less-invasive, safer, cost-effective option for gallbladder drainage than PGBD with improved clinical outcomes.

Impact of Radiofrequency Ablation on Malignant Biliary Strictures: Results of a Collaborative Registry.

BACKGROUND: Radiofrequency ablation of malignant biliary strictures has been offered for the last 3 years, but only limited data have been published. AIM: To assess the safety, efficacy, and survival outcomes of patients receiving endoscopic radiofrequency ablation. METHODS: Between April 2010 and December 2013, 69 patients with unresectable neoplastic lesions and malignant biliary obstruction underwent 98 radiofrequency ablation sessions with stenting. RESULTS: A total of 69 patients (22 male, aged 66.1 ± 13.3) were included in the registry. The etiology of malignant biliary stricture included unresectable cholangiocarcinoma (n = 45), pancreatic cancer (n = 19), gallbladder cancer (n = 2), gastric cancer (n = 1), and liver metastasis from colon cancer (n = 3). Seventy-eight percentage of patients had prior chemotherapy. All strictures were stented post-radiofrequency ablation with either plastic stents or metal stents. The mean stricture length treated was 14.3 mm. There was a statistically significant improvement in stricture diameter post-ablation (p < 0.0001). The likelihood of stricture improvement was significantly greater in pancreatic cancer-associated strictures [RR 1.8 (95 % 1.03-5.38)]. Seven patients (10 %) had adverse events, not linked directly to radiofrequency ablation. Median survival was 11.46 months (6.2-25 months). CONCLUSION: Radiofrequency ablation is effective and safe in malignant biliary obstruction and seems to be associated with improved survival.

Pancreatic necrosectomy using covered esophageal stents: a novel approach.

BACKGROUND: Endoscopic necrosectomy for necrotizing pancreatitis has been increasingly used as an alternative to surgical or percutaneous interventions. The use of fully covered esophageal self-expandable metallic stents may provide a safer and more efficient route for internal drainage. The aim of this study was to evaluate the safety and efficacy of endoscopic treatment of pancreatic necrosis with these stents. METHODS: A retrospective study at 2 US academic hospitals included patients with infected pancreatic necrosis from July 2009 to November 2012. These patients underwent transgastric placement of fully covered esophageal metallic stents draining the necrosis. After necrosectomy, patients underwent regular sessions of endoscopic irrigation and debridement of cystic contents. The efficacy endpoint was successful resolution of infected pancreatic necrosis without the need for surgical or percutaneous interventions. RESULTS: Seventeen patients were included with the mean age of 41±12 years. A mean of 5.3±3.4 sessions were required for complete drainage and the follow-up period was 237.6±165 days. Etiology included gallstone pancreatitis (6), alcohol abuse (6), s/p distal pancreatectomy (2), postendoscopic retrograde cholangiopancreatography pancreatitis (1), medication-induced pancreatitis (1), and hyperlipidemia (1). Mean size of the necrosis was 14.8 cm (SD 5.6 cm), ranging from 8 to 19 cm. Two patients failed endoscopic intervention and required surgery. The only complication was a perforation during tract dilation, which was managed conservatively. Fifteen patients (88%) achieved complete resolution. CONCLUSIONS: Endoscopic necrosectomy with covered esophageal metal stents is a safe and successful treatment option for infected pancreatic necrosis.

Rationale and study protocol for the supporting children's outcomes using rewards, exercise and skills (SCORES) group randomized controlled trial: a physical activity and fundamental movement skills intervention for primary schools in low-income communities.

BACKGROUND: Many Australian children are insufficiently active to accrue health benefits and physical activity (PA) levels are consistently lower among youth of low socio-economic position. PA levels decline dramatically during adolescence and evidence suggests that competency in a range of fundamental movement skills (FMS) may serve as a protective factor against this trend. METHODS/DESIGN: The Supporting Children's Outcomes Using Rewards Exercise and Skills (SCORES) intervention is a multi-component PA and FMS intervention for primary schools in low-income communities, which will be evaluated using a group randomized controlled trial. The socio-ecological model provided a framework for the 12-month intervention, which includes the following components: teacher professional learning, student leadership workshops (including leadership accreditation and rewards, e.g., stickers, water bottles), PA policy review, PA equipment packs, parental engagement via newsletters, FMS homework and a parent evening, and community partnerships with local sporting organizations. Outcomes will be assessed at baseline, 6- and 12-months. The primary outcomes are PA (accelerometers), FMS (Test of Gross Motor Development II) and cardiorespiratory fitness (multi-stage fitness test). Secondary outcomes include body mass index [using weight (kg)/height (m2)], perceived competence, physical self-esteem, and resilience. Individual and environmental mediators of behavior change (e.g. social support and enjoyment) will also be assessed. The System for Observing Fitness Instruction Time will be used to assess the impact of the intervention on PA within physical education lessons. Statistical analyses will follow intention-to-treat principles and hypothesized mediators of PA behavior change will be explored. DISCUSSION: SCORES is an innovative primary school-based PA and FMS intervention designed to support students attending schools in low-income communities to be more skilled and active. The findings from the study may be used to guide teacher pre-service education, professional learning and school policy in primary schools. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry No: ACTRN12611001080910.

Neuronal-enriched extracellular vesicles in individuals with IBS: A pilot study of COMT and BDNF.

BACKGROUND: Irritable bowel syndrome (IBS) is characterized by abdominal pain, bowel habit alterations, and psychiatric comorbidities. Although pathophysiology remains incompletely understood, prior work demonstrates associations with brain-derived neurotrophic factor (BDNF) and catechol-O-methyltransferase (COMT). The purpose of this study was to quantify BDNF and COMT in plasma and in neuronal-enriched extracellular vesicles (nEVs), assess relationships with psychological symptoms, and gain insight on the brain-gut connection in IBS. METHODS: Clinical data and biorepository samples from a parent investigation were used, including scores on the Perceived Stress Scale (PSS) and Center for Epidemiological Studies Depression Scale (CES-D). Distinct subpopulations of nEVs were isolated using neural cell adhesion molecule L1CAM; levels of COMT, mature BDNF, and pro-BDNF were quantified in plasma and in nEVs using ELISA. KEY RESULTS: Data from 47 females (28.11 ± 6.85 years) included 18 IBS and 29 healthy control (HC) participants. IBS participants displayed reduced plasma levels of mature BDNF compared with HC (p = 0.024). Levels of COMT plasma and IBS grouping significantly predicted CES-D scores (p = 0.034). Exploratory analyses by IBS subtype and race revealed African American HC display lower levels of COMT EV than Caucasian HC (p = 0.022). CONCLUSIONS & INFERENCES: Lower levels of mature BDNF in IBS participants, preliminary patterns detected in cargo content of nEVs, and relevance of COMT and IBS status to CES-D scores, offer insight on depressive symptomatology and brain-gut dysregulation in IBS. Lower COMT levels in nEVs of African Americans highlight the relevance of race when conducting such analyses across diverse populations.

Pain Expectancy and Positive Affect Mediate the day-to-day Association Between Objectively Measured Sleep and Pain Severity Among Women With Temporomandibular Disorder.

The majority of individuals with temporomandibular disorders (TMD) experience sleep disturbance, which can maintain and exacerbate chronic pain. However, the factors underlying the sleep-pain link have not been fully elucidated, especially beyond the laboratory. Sleep deprivation can induce threat interpretation bias, as well as impairment in positive affective functioning. Using both actigraphy and daily diaries, we examined whether morning pain expectancy and positive affect mediate the association between previous night's sleep disturbance and next-day overall pain severity. Total sleep time (TST) was selected as the primary measure of sleep. The sample included 144 women (mean age = 36 [SD = 11.1]) with TMD who displayed at least subclinical insomnia. Sleep was assessed for 14 days using actigraphy which was validated by concurrent sleep diaries. Daily diary assessments of pain-related experiences and affective states were conducted twice per day (ie, once upon participants' waking and the other prior to going to sleep) for the same 14-day period. Multilevel structural equation modeling revealed that both morning pain expectancy (95% CI: -.0004, -.00003) and positive affect (95% CI: -.0005, -.000001) mediated the association between previous night's TST and next-day's overall pain severity, such that shorter previous night TST was associated with higher next-morning pain expectancy and lower positive affect, which in turn were associated with a greater level of next-day's overall pain severity while controlling for morning pain severity. Reducing exaggerated daily pain expectancy and up-regulating positive affect may be important intervention targets for disengaging the sleep-pain link among individuals with co-occurring TMD and sleep disturbance. PERSPECTIVE: The daily link between previous night sleep duration and next day pain severity is mediated by morning pain expectancy and positive affect among women with temporomandibular disorder and sleep disturbance. Reducing pain expectancy and increasing positive affect may serve an important role in improving self-management of chronic pain.

Sex Hormones, BDNF, Leptin, and TGF-ß1 in Females With IBS: A Pilot Investigation.

BACKGROUND: Irritable bowel syndrome (IBS) is a chronic gastrointestinal condition predominantly affecting the female sex, and is characterized by brain-gut axis dysregulation. Relevance of hormones along the hypothalamic-pituitary gonadal axis and hypothalamic-pituitary adrenal axis to IBS symptomatology remain unclear, as does the significance of other modulators including brain derived neurotrophic factor (BDNF), leptin, and transforming growth factor ßeta 1 (TGF-ß1). METHODS: Females with IBS were compared with female healthy controls (HC) on age, race, hormonal contraceptive use, body mass index, adrenocorticotropic hormone, cortisol, estradiol, follicular stimulating hormone, luteinizing hormone, progesterone, total cholesterol, Center for Epidemiological Studies Depression Scale (CES-D) and Perceived Stress Scale (PSS). BDNF, leptin, and TGF-ß1 were quantified using enzyme-linked immunosorbent assay. Descriptive statistics, non-parametric techniques, and regression analyses were performed. RESULTS: Participants with IBS (n = 12) displayed higher estradiol (p = .027) than did HC (n = 21). Direction of associations among study variables often differed between groups: BDNF and progesterone in HC (rs = .623) and in IBS (rs = -.723). The relationship between log (CES-D) and log (estradiol) varied by IBS status (interaction term p = 0.019). DISCUSSION: Elevated estradiol in participants with IBS, and differential patterns of biological and psychological indices between groups, encourages further inquiry on the relevance of sex hormones, BDNF, leptin, and TGF-ß1 to symptoms of IBS. Future research endeavors should conduct longitudinal quantification of sex hormones with subjective symptom assessment to facilitate insight on the pathophysiology and female sex bias in IBS.

Quantitative Sensory Testing Across Chronic Pain Conditions and Use in Special Populations.

Chronic pain imposes a significant burden to the healthcare system and adversely affects patients' quality of life. Traditional subjective assessments, however, do not adequately capture the complex phenomenon of pain, which is influenced by a multitude of factors including environmental, developmental, genetic, and psychological. Quantitative sensory testing (QST), established as a protocol to examine thermal and mechanical sensory function, offers insight on potential mechanisms contributing to an individual's experience of pain, by assessing their perceived response to standardized delivery of stimuli. Although the use of QST as a research methodology has been described in the literature in reference to specific pain populations, this manuscript details application of QST across a variety of chronic pain conditions. Specific conditions include lower extremity chronic pain, knee osteoarthritis, chronic low back pain, temporomandibular joint disorder, and irritable bowel syndrome. Furthermore, we describe the use of QST in placebo/nocebo research, and discuss the use of QST in vulnerable populations such as those with dementia. We illustrate how the evaluation of peripheral sensory nerve function holds clinical promise in targeting interventions, and how using QST can enhance patient education regarding prognostic outcomes with particular treatments. Incorporation of QST methodology in research investigations may facilitate the identification of common mechanisms underlying chronic pain conditions, guide the development of non-pharmacological behavioral interventions to reduce pain and pain-related morbidity, and enhance our efforts toward reducing the burden of chronic pain.

Relevance of Sex and Subtype in Patients With IBS: An Exploratory Study of Gene Expression.

BACKGROUND: Psychological state, stress level, and gastrointestinal function are intricately related and relevant to symptom exacerbation in patients with irritable bowel syndrome (IBS), but genetic contributors to this brain-gut connection are not fully understood. The purpose of this exploratory study was to compare gene expression in participants with IBS to that of healthy controls (HC) and to examine patterns of expression in participants with IBS by sex and IBS subtype. METHOD: Participants were recruited to an ongoing protocol at the National Institutes of Health. Differences in demographic and clinical characteristics were assessed using descriptive statistics and Mann-Whitney U tests. Expression levels of 84 genes were evaluated in peripheral whole blood using Custom RT2 Profiler polymerase chain reaction (PCR) Arrays, and data analysis was performed through GeneGlobe Data Analysis Center. RESULTS: Participants with IBS (n = 27) reported greater levels of perceived stress (p = .037) and differed in expression values of ±2 for the genes ADIPOR1, ADIPOR2, CNR2, COMT, OXTR, and PPARA compared to HC (n = 43). Further analyses by sex and IBS subtype revealed differential patterns of gene expression related to the endocannabinoid system, cytokines, stress, and sex steroid hormones. CONCLUSIONS: Diverse yet interconnected processes such as metabolism, inflammation, immunity, social behavior, and pain are associated with differences in gene expression between participants with IBS and HC. These findings lend support for genomic associations with the brain-gut connection in patients with IBS and highlight the relevance of sex and IBS subtype in performing such analyses.

GLOBE Observer Data: 2016-2019.

This technical report summarizes the GLOBE Observer data set from 1 April 2016 to 1 December 2019. GLOBE Observer is an ongoing NASA-sponsored international citizen science project that is part of the larger Global Learning and Observations to Benefit the Environment (GLOBE) Program, which has been in operation since 1995. GLOBE Observer has the greatest number of participants and geographic coverage of the citizen science projects in the Earth Science Division at NASA. Participants use the GLOBE Observer mobile app (launched in 2016) to collect atmospheric, hydrologic, and terrestrial observations. The app connects participants to satellite observations from Aqua, Terra, CALIPSO, GOES, Himawari, and Meteosat. Thirty-eight thousand participants have contributed 320,000 observations worldwide, including 1,000,000 georeferenced photographs. It would take an individual more than 13 years to replicate this effort. The GLOBE Observer app has substantially increased the spatial extent and sampling density of GLOBE measurements and more than doubled the number of measurements collected through the GLOBE Program. GLOBE Observer data are publicly available (at observer.globe.gov).

Fully covered self-expanding metal stents for refractory pancreatic duct strictures in symptomatic chronic pancreatitis, US experience.

Background and study aims Fully covered self-expanding metal stents (FCSEMS) have been used to treat refractory pancreatic duct strictures. We aimed to evaluate the feasibility, safety, and efficacy of FCSEMS in chronic pancreatitis with refractory pancreatic duct strictures. Patients and methods This was a retrospective multicenter cases series of patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) with FCSEMS placement in the main pancreatic duct (MPD) at five tertiary care centers between February 2010 and June 2016. Primary endpoints were technical success, clinical success, and procedure-related morbidity. Secondary endpoints were pain relief at the end of follow-up and resolution of the pancreatic stricture on ERCP. Results Thirty-three patients with previously drained stents, 76 % of whom were male, underwent ERCP with FCSEMS placement. Mean duration of follow-up was 14 months. All of the patients had prior therapy. The technical success rate for FCSEMS placement was 100 % (n = 33) and the clinical success rate was 93 % (was n = 31). Stents were removed after a median duration of 14.4 weeks. After stent removal, the diameter of the narrowest MPD stricture had increased significantly from 1 mm to 4.5 mm ( P  < 0.001). There was a statistically significant improvement on the Visual Analogue Scale (VAS) from a median of 8.5 to 2.5. At the end of the study, (n = 27) 87.1 % of patients reported significant pain reduction with reduced narcotic use. Conclusion FCSEMS appeared to be a feasible, safe, and potentially effective Intervention in patients who had not responded to endoscopic therapy with plastic stents.

Effects of a comprehensive self-management intervention on extraintestinal symptoms among patients with IBS.

OBJECTIVE: Adults with irritable bowel syndrome (IBS) often report extraintestinal pain, fatigue, and sleep disturbances in addition to abdominal pain. Few interventions have sought to reduce these extraintestinal symptoms within the IBS population. To address this, we compared the effects of a comprehensive self-management (CSM) intervention to a control intervention (usual care) on extraintestinal pain, fatigue, and sleep disturbances among patients with IBS. METHOD: Data were obtained from 243 IBS patients participating in two CSM intervention trials. Daily symptom diaries were collected at baseline, 3 and 6 months post-randomization. Daily symptoms of headache, backache, muscle pain, joint pain, fatigue, sleepiness during the day, sleep quality, and refreshed by sleep were analyzed. Analysis of covariance was used to determine the effects of the intervention on each symptom at 3 and 6 months controlling for 'study' and baseline symptom levels. RESULTS: Patients in the CSM intervention group reported decreased symptoms of fatigue, sleep disturbances, backache and headache compared to usual care at 3 and 6 months. The CSM group also reported significantly decreased joint pain at 3 months compared to usual care, but not 6 months. No significant difference was found for muscle pain. CONCLUSIONS: An existing CSM intervention is effective in reducing fatigue and sleep disturbances. However, mixed results for extraintestinal pain indicates a need to better differentiate between underlying mechanisms. Addressing such symptoms is important to decrease the overall burden of IBS, reduce health care expenditures, and improve patients' quality of life. TRIAL REGISTRATION: NCT00907790; NCT00167635.

Perceived Stress, Its Physiological Correlates, and Quality of Life in Patients With Irritable Bowel Syndrome.

Irritable bowel syndrome (IBS) is a chronic, common disorder of the gastrointestinal tract associated with high psychological comorbidity and diminished quality of life. Patients with IBS display a heightened sensitivity to stress, although the literature is inconsistent as to whether they have a dysregulated stress response. The purpose of the present investigation, a substudy of a larger research effort, was to examine physiological correlates of perceived stress in patients with IBS (cortisol and adrenocorticotropic hormone) and to explore associations between perceived stress and quality of life. A total of 101 participants (35 with IBS [predominant subtypes IBS-constipation and IBS-diarrhea] and 66 healthy controls [HCs]) completed self-report inventories regarding perceived stress and quality of life, and fasting peripheral blood was drawn. Participants with IBS did not differ from the HC in demographic or physiological measures but did differ in psychological measures, reporting significantly higher levels of perceived stress and lower levels of quality of life. Perceived stress and quality of life were not significantly associated in IBS participants. However, differential findings of the stress response were found within IBS participants by sex, race, and subtype. These findings illustrate the heterogeneity of the IBS patient population, underscore the necessity of evaluating larger sample sizes and increasing the diversity of such samples to include males and ethnic minorities, and demonstrate the importance of taking an individualized approach to evaluation and treatment in the IBS patient population.

Colon Epithelial MicroRNA Network in Fatty Liver.

Background & Aims: Intestinal barrier alterations are associated with fatty liver (FL) and metabolic syndrome (MetS), but microRNA (miR) signaling pathways in MetS-FL pathogenesis remain unclear. This study investigates an epithelial-focused miR network in colorectal cell models based on the previously reported MetS-FL miR trio of hsa-miR-142-3p, hsa-miR-18b, and hsa-miR-890. Methods: Each miR mimic construct of MetS-FL miR trio was transfected into human colorectal cells, CRL-1790 or Caco-2. Global miRNome changes posttransfection were profiled (nCounter® Human v3 miRNA, NanoString Technologies). Changes in barrier (transepithelial electrical resistance, TEER) and epithelial cell junction structure (Occludin and Zona Occludens-1/ZO-1 immunofluorescence staining-confocal microscopy) were examined pre- and posttransfection in Caco-2 cell monolayers. A signaling network was constructed from the MetS-FL miR trio, MetS-FL miR-induced colorectal miRNome changes, ZO-1, and Occludin. Results: Transfection of CRL-1790 cells with each MetS-FL miR mimic led to global changes in the cellular miRNome profile, with 288 miRs being altered in expression by more than twofold. Eleven miRs with known cytoskeletal and metabolic roles were commonly altered in expression by all three miR mimics. Transfection of Caco-2 cell monolayers with each MetS-FL miR mimic induced barrier-associated TEER variations and led to structural modifications of ZO-1 and Occludin within epithelial cell junctions. Pathway analysis incorporating the MetS-FL miR trio, eleven common target miRs, ZO-1, and Occludin revealed a signaling network centered on TNF and AKT2, which highlights injury, inflammation, and hyperplasia. Conclusions: Colon-specific changes in epithelial barriers, cell junction structure, and a miRNome signaling network are described from functional studies of a MetS-FL miR trio signature.

Irritable Bowel Syndrome.

: Irritable bowel syndrome (IBS) is a common, chronic gastrointestinal (GI) condition characterized by disturbances in bowel habits and abdominal pain in the absence of known organic pathology. IBS reduces quality of life and is costly to treat. It is diagnosed using the symptom-based Rome criteria for functional GI disorders, which was recently updated and released as Rome IV. Both physiologic and psychological variables play a role in the etiology of IBS and perpetuate symptoms. Although research has shed light on IBS pathophysiology, therapeutic interventions remain symptom driven, employing both pharmacologic and nonpharmacologic approaches. Here, the authors review the epidemiology and pathophysiology of IBS, summarize diagnostic and treatment strategies, and discuss implications for nursing practice.

Endoscopic Ultrasound (EUS)-Directed Transgastric Endoscopic Retrograde Cholangiopancreatography or EUS: Mid-Term Analysis of an Emerging Procedure.

BACKGROUND/AIMS: Performing endoscopic retrograde cholangiopancreatography (ERCP) in patients who have undergone Rouxen-Y gastric bypass (RYGB) is challenging. Standard ERCP and enteroscopy-assisted ERCP are associated with limited success rates. Laparoscopy- or laparotomy-assisted ERCP yields improved efficacy rates, but with higher complication rates and costs. We present the first multicenter experience regarding the efficacy and safety of endoscopic ultrasound (EUS)-directed transgastric ERCP (EDGE) or EUS. METHODS: All patients who underwent EDGE at two academic centers were included. Clinical success was defined as successful ERCP and/or EUS through the use of lumen-apposing metal stents (LAMS). Adverse events related to EDGE were separated from ERCP- or EUS-related complications and were defined as bleeding, stent migration, perforation, and infection. RESULTS: Sixteen patients were included in the study. Technical success was 100%. Clinical success was 90% (n=10); five patients were awaiting maturation of the fistula tract prior to ERCP or EUS, and one patient had an aborted ERCP due to perforation. One perforation occurred, which was managed endoscopically. Three patients experienced stent dislodgement; all stents were successfully repositioned or bridged with a second stent. Ten patients (62.5%) had their LAMS removed. The average weight change from LAMS insertion to removal was negative 2.85 kg. CONCLUSIONS: EDGE is an effective, minimally invasive, single-team solution to the difficulties associated with ERCP in patients with RYGB.

Data supporting the effects of lysozyme on mRNA and protein expression in a colonic epithelial scratch wound model.

Colonic epithelial health is implicated in a host of gastrointestinal (GI) diseases and disorders. Lysozyme is suspected to play a role in the ability of the epithelium to recover from injury (Abey et al., in press; Gallo, 2012; Rubio, 2014) [1], [2], [3]. Disrupted repair mechanisms may lead to delayed or ineffective recovery and disruptions to epithelial biology resulting in GI symptoms and altered barrier function (Peterson and Artis, 2014) [4]. The effect of lysozyme on the transcriptomic and proteomic profile of healthy colonic epithelial cells was investigated. Epithelial cells in culture were scratch wounded and treated with lysozyme. mRNA and protein profiles were simultaneously quantified in the same sample using a digital counting technology. Gene and protein expressions altered by the presence or absence of lysozyme are described in this article. Extensive statistical and bioinformatic analysis, and interpretation of the results can be found in "Lysozyme association with circulating RNA, extracellular vesicles, and chronic stress" (Abey et al., in press) [1].