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The pathophysiology of irritable bowel syndrome (IBS) is incompletely understood, but in at least some patients, alterations in the gut microbiome are likely to be etiologically relevant. The purpose of this review is to evaluate the available evidence to date for the use of prebiotics and probiotics in the treatment of IBS, with particular attention to broad themes in therapeutic rationale as well as critical gaps in the literature. A number of individual studies and meta-analyses have demonstrated efficacy in the use of prebiotics and probiotics for IBS. Even so, variability in study design, risk of bias, and short follow-up intervals limit the ability to draw robust conclusions in aggregate. More research is needed to understand the intricacy of the gut microbiome and how it relates to IBS symptomatology, but the effectiveness of prebiotic and probiotic agents demonstrated so far implies a worthy therapeutic signal within the noise.

Several surgical options exist for refractory gastroparesis (Gp) including gastric electric stimulation (GES) and pyloric surgery (PS) such as pyloromyotomy or pyloroplasty. Few studies exist comparing the outcomes of these surgeries. Compare the clinical outcomes of GES, PS, and simultaneous GES+PS for refractory Gp. Patients undergoing surgical intervention at our medical center from January 2016 to April 2019 were given pre- and post-surgery questionnaires to assess their response to intervention: Patient Assessment of Upper Gastrointestinal Symptoms (PAGI-SYM) grading symptoms and Clinical Patient Grading Assessment Scale (CPGAS) grading response to treatment. Results are expressed as mean ± SE. One hundred thirty-two patients underwent surgical intervention; 12 were excluded. Mean CPGAS improvement overall was 2.8 ± 0.2 (p 0.05). Mean improvement in Gastroparesis Cardinal Symptom Index (GCSI) total score was 1.0 ± 0.1 (p 0.05). GES and GES + PS, but not PS only, significantly improved symptoms of nausea and vomiting (p

Background Gastroparesis can be associated with severe symptoms. Health care utilization for gastroparesis has increased in part due to an increase in hospital admissions. Goals To characterize patients admitted for gastroparesis-related symptoms and determine risk factors associated with 30-day readmissions. Study The Nationwide Readmission Database (NRD) for the year 2014 was used to identify patients admitted to hospitals using the International Classification of Diseases (ICD)-9 code for gastroparesis as primary diagnosis or as the secondary diagnosis with first diagnosis code of a gastroparesisrelated symptom. Logistic regression was used to determine risk factors associated with 30-day readmission. Results There were 5268 gastroparesis patients admitted with the average length of stay (LOS) of 5.4±6.6 days. Age averaged 48.9±18.1 years, 73.8% were female individuals, and 31% had diabetes. Inpatient mortality was 0.4%. The overall 30-day readmission rate was 6.2%. Longer LOS [odds ratio (OR)=1.4; 95% confidence interval (CI), 1.0-1.9], younger age, drug abuse (OR=1.6; 95% CI, 1.2-2.2), and marijuana use (OR=1.7; 95% CI, 1.0-2.7) were associated with increased risk of 30-day readmission. Female gender (P=0.083), opioid use (P=0.057), and admission to larger hospital (P=0.070) showed a trend toward higher readmission rates. Older patients, and patients with hypertension and diabetes showed lower rates of readmission. Conclusions Use of the Nationwide Readmission Database (NRD) allows better understanding of gastroparesis admissions and readmissions. Average hospital stay was 5.4 days with 0.4% mortality rate. Overall 30-day readmission rate was 6.2%. Higher LOS, drug abuse, and marijuana use increased the 30-day readmission rate. Diabetes, hypertension, and older age were associated with lower readmissions.

Background Symptoms of gastroparesis (Gp) can fluctuate at different times of the day. Our aims are (1) To characterize Gp symptom variability throughout the day and in relation to meals and (2) to compare the daily symptom variability in subtypes of Gp-diabetic gastroparesis (DGp) and idiopathic gastroparesis (IGp). Methods Patients with Gp filled Patient Assessment of Gastrointestinal Symptoms (PAGI-SYM) and completed a modified GCSI-DD seven times a day (GCSI-Throughout the Day [GCSI-TTD]; before and after meals, and before going to bed) over a 2-week period. KEY RESULTS: A total of 44 patients participated (86% females), including 29 (66%) with IGp, 13 (30%) with DGp, and 2 (4%) with postsurgical Gp. Using the GCSI-TTD, patients with Gp reported significant postprandial worsening of overall symptom severity, as well as severities of nausea, early satiety, stomach fullness, and abdominal pain. Patients also had progressive worsening of the overall symptom severity, early satiety, stomach fullness, and abdominal pain during the day; however, nausea severity did not differ during the day. Number of vomiting and retching episodes did not show significant variations postprandially or during the day. Patients with IGp had greater symptom severity throughout the day and greater postprandial increase in symptoms compared to patients with DGp. CONCLUSIONS AND INFERENCES: Patients with Gp experience postprandial worsening of overall symptom severity, as well as severities of nausea, early satiety, stomach fullness, and abdominal pain. These symptoms also progressively worsen during the day, except for the severity of nausea which persists throughout the day. Understanding the symptom variability in patients with Gp throughout the day and postprandially may be useful in treatment of patients with Gp.

Filamentous tau aggregates, the hallmark lesions of Alzheimer disease (AD), play key roles in neurodegeneration. Activation of protein degradation systems has been proposed to be a potential strategy for removing pathological tau, but it remains unclear how effectively tau aggregates can be degraded by these systems. By applying our previously established cellular model system of AD-like tau aggregate induction using preformed tau fibrils, we demonstrate that tau aggregates induced in cells with regulated expression of full-length mutant tau can be gradually cleared when soluble tau expression is suppressed. This clearance is at least partially mediated by the autophagy-lysosome pathway, although both the ubiquitin-proteasome system and the autophagy-lysosome pathway are deficient in handling large tau aggregates. Importantly, residual tau aggregates left after the clearance phase leads to a rapid reinstatement of robust tau pathology once soluble tau expression is turned on again. Moreover, we succeeded in generating monoclonal cells persistently carrying tau aggregates without obvious cytotoxicity. Live imaging of GFP-tagged tau aggregates showed that tau inclusions are dynamic structures constantly undergoing "fission" and "fusion," which facilitate stable propagation of tau pathology in dividing cells. These findings provide a greater understanding of cell-to-cell transmission of tau aggregates in dividing cells and possibly neurons.

BACKGROUND Gastroparesis (GP) is characterized by delayed gastric emptying with symptoms of nausea, vomiting, early satiety, postprandial fullness, and abdominal pain. Various surgical options exist to treat GP not responding to medical treatments (refractory GP), including gastric electric stimulation (GES), gastrectomy (GTx), and pyloric interventions (PI), whereas the outcomes of these procedures have been published; few comparison studies exist. METHODS PubMed literature review for articles from September 1988 to October 2017 was performed for prospective and retrospective analyses reporting >5 patients. Unweighted (per study) and weighted (per patient) overall improvement and improvement in symptoms of nausea, vomiting, and abdominal pain were calculated and compared for the different procedures. RESULTS Of 325 studies satisfying search criteria, 38 met the study criteria and were included for analysis. Total response to intervention, both weighted and unweighted, was greater with PIs compared to GES (P