Randomized controlled pilot study assessing fructose tolerance during fructose reintroduction in non-constipated irritable bowel syndrome patients successfully treated with a low FODMAP diet.

BACKGROUND: Limited data exist to guide FODMAP (fermentable oligo-, di-, monosaccharides, and polyols) reintroduction to assess tolerance following a low FODMAP diet (LFD). Fructose reintroduction is often stepwise up to 7.5 g fructose (e.g., three tsp of honey). We aimed to determine the fructose tolerance threshold in non-constipated, LFD-responsive patients with irritable bowel syndrome (IBS) and assess whether stool microbiome predicted LFD response or fructose tolerance. METHODS: Thirty-nine non-constipated IBS patients (51% women, mean age 33.7 years) completed a 4-week LFD. LFD responders were defined as those who reported adequate relief of IBS symptoms following the LFD. Responders were randomized to one of the three solution groups (100% fructose, 56% fructose/44% glucose, or 100% glucose) and received four doses (2.5, 5, 10, 15 g) for 3 days each. Patients reached their tolerance dose if their mean daily IBS symptom severity (visual analog scale [VAS], 0-100 mm) was >20 mm higher than post-LFD VAS. Stool samples before and after LFD were analyzed using shotgun metagenomics. RESULTS: Seventy-nine percent of patients were LFD responders. Most responders tolerated the 15 g sugar dose. There was no significant difference in mean dose tolerated between solution groups (p = 0.56). Compared to baseline, microbiome composition (beta diversity) significantly shifted and six bacterial genes in fructose and mannose metabolism pathways decreased after LFD, irrespective of LFD response or the solution group. CONCLUSIONS: Non-constipated, LFD-responsive IBS patients should be reintroduced to fructose in higher doses than 15 g to assess tolerance. LFD is associated with significant changes in microbial composition and bacterial genes involved in FODMAP metabolism.

Barriers to Follow-up Colonoscopies for Patients With Positive Results From Fecal Immunochemical Tests During Colorectal Cancer Screening.

BACKGROUND & AIMS: Colorectal cancer is common yet largely preventable. The fecal immunochemical test (FIT) is a highly recommended screening method, but patients with positive results must receive a follow-up colonoscopy to determine if they have precancerous or cancerous lesions. We characterized colonoscopic follow-up evaluations and reasons for lack of follow-up in a Veterans Affairs (VA) cohort. METHODS: We conducted a retrospective cross-sectional analysis of patients 50 to 75 years old with a positive FIT result from January 1, 2014, through May 31, 2016, in a network of 12 VAs sites in southern California. We determined the proportion of patients who received a follow-up colonoscopy, median time to colonoscopy, and colonoscopy findings. For patients who did not undergo colonoscopy, we determined the documented reason for lack of colonoscopy and factors associated with declining the colonoscopy examination. RESULTS: Of the 10,635 FITs performed, 916 (8.6%) produced positive results; 569 of these (62.1%) were followed by colonoscopy. The median time to colonoscopy after a positive FIT result was 83 days (interquartile range, 54-145 d), which did not vary between veterans who received a colonoscopy at a VA facility (81 d; interquartile range, 52-143 d) vs a non-VA site (87 d; interquartile range, 60-154 d) (P = .2). For the 347 veterans (37.9%) who did not undergo follow-up colonoscopy, the reasons were patient-related (49.3%), provider-related (16.4%), system-related (12.1%), or multifactorial (22.2%). Overall, patient decline of colonoscopy (35.2%) was the most common reason. CONCLUSIONS: In a cohort of veterans with positive results from FITs during CRC screening, reasons for lack of follow-up colonoscopy varied and included patient, provider, and system factors. These findings can be used to reduce barriers to follow-up colonoscopy and to address system-level challenges in scheduling and attrition for colonoscopy.

Impact of student-run clinics on preclinical sociocultural and interprofessional attitudes: a prospective cohort analysis.

INTRODUCTION: Descriptive studies suggest student-run clinics (SRCs) positively affect preclinical students' sociocultural and interprofessional attitudes, but few studies use validated measures. METHODS: In a pre-post design, first-year medical, nursing, and pharmacy students who did and did not participate in SRCs completed demographic and open-ended questions, as well as two validated surveys, the Sociocultural Attitudes in Medicine Inventory (SAMI) and Readiness for Interprofessional Learning Scale (RIPLS), at the beginning and end of the year. RESULTS: With 68% (n=182/267) matched surveys we found no significant differences between groups over time (SAMI p=.53, RIPLS p≥.28 for each subcategory). However, of SRC participants, 99% reported commitment to the underserved and 57% reported improved interprofessional attitudes. DISCUSSION: Students participating in SRCs perceive positive benefits, but do not score differently from those who do not. The SRC experiences may not be frequent enough to affect these measures, particularly since our students were high-scoring upon entry.

Identification of a Golgi complex-targeting signal in the cytoplasmic tail of the severe acute respiratory syndrome coronavirus envelope protein.

The 2003 global outbreak of progressive respiratory failure was caused by a newly emerged virus, severe acute respiratory syndrome coronavirus (SARS-CoV). In contrast to many well-studied enveloped viruses that assemble and bud at the plasma membrane, coronaviruses assemble by budding into the lumen of the endoplasmic reticulum-Golgi intermediate compartment and are released from the cell by exocytosis. For this to occur, the viral envelope proteins must be efficiently targeted to the Golgi region of the secretory pathway. Although the envelope protein (E) makes up only a small percentage of the viral envelope, it plays an important, as-yet-undefined role in virus production. To dissect the targeting of the SARS-CoV E protein to the Golgi region, we exogenously expressed the protein and various mutants from cDNA and determined their localization using immunofluorescence microscopy and biochemical assays. We show that the cytoplasmic tail of the SARS-CoV E protein is sufficient to redirect a plasma membrane protein to the Golgi region. Through site-directed mutagenesis, we demonstrate that a predicted beta-hairpin structural motif in the tail is sufficient for Golgi complex localization of a reporter protein. This motif is conserved in E proteins of beta and gamma coronaviruses (formerly referred to as group 2 and 3 coronaviruses), where it also functions as a Golgi complex-targeting signal. Dissecting the mechanism of targeting of the SARS-CoV E protein will lead to a better understanding of its role in the assembly and release of virions.

Learning through service: student perceptions on volunteering at interprofessional hepatitis B student-run clinics.

Student-run clinics (SRCs) are widespread, but studies on their educational impact are limited. We surveyed preclinical medical, nursing, and pharmacy students about their experiences in a hepatitis B elective which provided opportunities to they could volunteer at hepatitis B screening and vaccination SRCs. Student responses revealed positive perceptions of the volunteer experience. Benefits included interacting with patients, developing clinical skills, providing service to disadvantaged populations, and collaborating with health professional peers. Students who participated in clinic reported enhanced skills compared to those who did not attend. SRCs play a valuable role in instilling positive attitudes and improving skills.