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Alev J Atalay,1 Kevin Ard,2 Emily Bethea,3 Kenneth B Christopher,4 Maria A Yialamas1 1Department of Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA; 2Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; 3Department of Gastroenterology, Massachusetts General Hospital, Boston, MA 02114, USA; 4Department of Medicine, Renal Division, Channing Division of Network Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USACorrespondence: Alev J Atalay; Maria A YialamasDepartment of Medicine, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115, USATel +1 617-732-6038; +1 857-307-4100Fax +1 857-307-1366Email aatalay@bwh.harvard.edu; myialamas@partners.orgBackground: Participation in scholarship is a requirement for Internal Medicine (IM) residencies, but programs struggle to successfully integrate research into busy clinical schedules. In 2013, the IM residency at Brigham and Women’s Hospital implemented the Housestaff Research Project (HRP)— a novel residency-wide research initiative designed to facilitate participation in scholarship. The HRP had two components—a formal research curriculum and an infrastructure that provided funding and mentorship for resident-led, housestaff wide projects.Methods: This is a mixed-methods study of 190 IM residents and two HRP-supported research projects. Seventy-seven residents responded to an electronic survey about their interests in research exposure in residency. Fifty-six residents responded to an electronic survey about their participation in the HRP. The success of HRP-supported projects was evaluated through resident comments, interviews with three residents leading the first two HRPs and a description of the success of the projects based on resident involvement and dissemination of the results.Results: Eighty-seven percent (n= 67/77) of residents were interested in additional research exposure during residency. Ninety-five percent (n = 53/56) of residents had heard of the HRP, and 77% had participate in at least one aspect of it. Approximately 20 residents were directly involved in the two resident-led projects. HRP-supported projects resulted in presentations at three local and three national conferences, one manuscript in press, and one manuscript in preparation. The resident project leaders felt that a strength and unique aspect of the HRP was the collaboration with co-residents.Conclusion: The HRP successfully created a culture of research and scholarship within the residency. The HRP leaders and residents that participated in HRP-supported projects expressed the most direct benefits from the program. All residents were exposed to research concepts and methods. Future directions for the HRP include selecting projects that maximize the number of resident participants and integrating a more robust research curriculum.Keywords: graduate medical education, internal medicine, postgraduate training, research training

Abstract Background During lactation, the CNS is less responsive to the anxiogenic neuropeptide, corticotropin-releasing factor (CRF). Further, central injections of CRF inhibit maternal aggression and some maternal behaviors, suggesting decreased CRF neurotransmission during lactation supports maternal behaviors. In this study, we examined the maternal profile of mice missing the CRF receptor 1 (CRFR1). Offspring of knockout (CRFR1-/-) mice were heterozygote to offset possible deleterious effects of low maternal glucocorticoids on pup survival and all mice contained a mixed 50:50 inbred/outbred background to improve overall maternal profiles and fecundity. Results Relative to littermate wild-type (WT) controls, CRFR1-/- mice exhibited significant deficits in total time nursing, including high arched-back, on each test day. Consistent with decreased nursing, pups of CRFR1-deficient dams weighed significantly less than WT offspring. Licking and grooming of pups was significantly higher in WT mice on postpartum Day 2 and when both test days were averaged, but not on Day 3. Time off nest was higher for CRFR1-/- mice on Day 2, but not on Day 3 or when test days were averaged. Licking and grooming of pups did not differ on Day 2 when this measure was examined as a proportion of time on nest. CRFR1-/- mice showed significantly higher nest building on Day 3 and when tests were averaged. Mean pup number was almost identical between groups and no pup mortality occurred. Maternal aggression was consistently lower in CRFR1-/- mice and in some measures these differences approached, but did not reach significance. Because of high variance, general aggression results are viewed as preliminary. In terms of sites of attacks on intruders, CRFR1-/- mice exhibited significantly fewer attacks to the belly of the intruder on Day 5 and when tests were averaged. Performance on the elevated plus maze was similar between genotypes. Egr-1 expression differences in medial preoptic nucleus and c-Fos expression differences in bed nucleus of stria terminalis between genotype suggest possible sites where loss of gene alters behavioral output. Conclusion Taken together, the results suggest that the presence of an intact CRFR1 receptor supports some aspects of nurturing behavior.

The financial impact of liver transplantation has been underexplored. We aimed to identify associations between high financial burden (≥10% annual income spent on out-of-pocket medical costs) and work productivity, financial distress (coping behaviors in response to the financial burden), and financial toxicity (health-related quality of life, HRQOL) among adult recipients of liver transplant. Between June 2021 and May 2022, we surveyed 207 adult recipients of liver transplant across 5 US transplant centers. Financial burden and distress were measured by 25 items adapted from national surveys of cancer survivors. Participants also completed the Work Productivity and Activity Impairment and EQ-5D-5L HRQOL questionnaires. In total, 23% of recipients reported high financial burden which was significantly associated with higher daily activity impairment (32.9% vs. 23.3%, p =0.048). In adjusted analyses, the high financial burden was significantly and independently associated with delayed or foregone medical care (adjusted odds ratio, 3.95; 95% CI, 1.85-8.42) and being unable to afford basic necessities (adjusted odds ratio, 5.12; 95% CI: 1.61-16.37). Recipients experiencing high financial burden had significantly lower self-reported HRQOL as measured by the EQ-5D-5L compared to recipients with low financial burden (67.8 vs. 76.1, p =0.008) and an age-matched and sex-matched US general population (67.8 vs. 79.1, p <0.001). In this multicenter cohort study, nearly 1 in 4 adult recipients of liver transplant experienced a high financial burden, which was significantly associated with delayed or foregone medical care and lower self-reported HRQOL. These findings underscore the need to evaluate and address the financial burden in this population before and after transplantation., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Background: Health care-related transportation insecurity (delayed or forgone medical care due to transportation barriers) is being increasingly recognized as a social risk factor affecting health outcomes. We estimated the national burden and adverse outcomes of health care-related transportation insecurity among US adults with chronic liver disease (CLD)., Methods: Using the U.S. National Health Interview Survey from 2014 to 2018, we identified adults with self-reported CLD. We used complex weighted survey analysis to obtain national estimates of health care-related transportation insecurity. We examined the associations between health care-related transportation insecurity and health care-related financial insecurity, food insecurity, self-reported health status, work productivity, health care use, and mortality., Results: Of the 3643 (representing 5.2 million) US adults with CLD, 267 [representing 307,628 (6%; 95% CI: 5%-7%)] reported health care-related transportation insecurity. Adults with CLD experiencing health care-related transportation insecurity had 3.5 times higher odds of cost-related medication nonadherence [aOR, 3.5; (2.4-5.0)], 3.5 times higher odds of food insecurity [aOR, 3.5; (2.4-5.3)], 2.5 times higher odds of worsening self-reported health status over the past year [aOR, 2.5; (1.7-3.7)], 3.1 times higher odds of being unable to work due to poor health over the past year [aOR, 3.1; (2.0-4.9)], and 1.7 times higher odds of being in a higher-risk category group for number of hospitalizations annually [aOR, 1.7; (1.2-2.5)]. Health care-related transportation insecurity was independently associated with mortality after controlling for age, income, insurance status, comorbidity burden, financial insecurity, and food insecurity [aHR, 1.7; (1.4-2.0)]., Conclusions: Health care-related transportation insecurity is a critical social risk factor that is associated with health care-related financial insecurity, food insecurity, poorer self-reported health status and work productivity, and increased health care use and mortality among US adults with CLD. Efforts to screen for and reduce health care-related transportation insecurity are warranted., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Background: Ascites is common in cirrhosis but uncommon after liver transplant. We aimed to characterize the incidence, natural history, and current management strategies of post-transplant ascites., Methods: We performed a retrospective cohort study of patients who underwent liver transplantation at 2 centers. We included patients who underwent deceased donor whole graft liver transplants between 2002 and 2019. Chart review identified patients with post-transplant ascites, requiring a paracentesis between 1 and 6-month post-transplants. Detailed chart review identified clinical and transplant characteristics, evaluation of ascites etiology, and treatments., Results: Of 1591 patients who successfully underwent a first-time orthotopic liver transplant for chronic liver disease, 101 (6.3%) developed post-transplant ascites. Only 62% of these patients required large volume paracentesis for ascites before transplant. 36% of patients with post-transplant ascites had early allograft dysfunction. Most patients with post-transplant ascites (73%) required a paracentesis within 2 months of transplant, but 27% had delayed ascites onset. From 2002 to 2019, ascites studies were obtained less often, and hepatic vein pressure measurement was performed more often. Diuretics were the mainstay of treatment (58%). The use of albumin infusion and splenic artery embolization to treat post-transplant ascites increased over time. Larger pre-transplant spleen size was associated with a greater number of post-transplant paracenteses (r=0.32 and p=0.003). For patients who underwent splenic intervention, paracentesis frequency was significantly reduced (1.6-0.4 paracenteses/month, p=0.0001). The majority (72%) of patients had clinical resolution of their ascites at 6-month post-transplant., Conclusions: Persistent or recurrent ascites continues to be a clinical issue in the modern era of liver transplantation. Most had clinical resolution within 6 months, some requiring intervention., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Background: Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are the leading causes of hepatocellular carcinoma (HCC) worldwide. Limited data exist on surgical outcomes for NAFLD/NASH-related HCC compared with other HCC etiologies. We evaluated differences in clinicopathological characteristics and outcomes of patients undergoing surgical resection for NAFLD/NASH-associated HCC compared with other HCC etiologies., Methods: Demographic, clinicopathological features, and survival outcomes of patients with surgically resected HCC were collected. NAFLD activity score (NAS) and fibrosis score were assessed by focused pathologic review in a subset of patients., Results: Among 492 patients screened, 260 met eligibility (NAFLD/NASH [n = 110], and other etiologies [n = 150]). Median age at diagnosis was higher in the NAFLD/NASH HCC cohort compared with the other etiologies cohort (66.7 vs. 63.4 years, respectively, P = .005), with an increased percentage of female patients (36% vs. 18%, P = .001). NAFLD/NASH-related tumors were more commonly >5 cm (66.0% vs. 45%, P = .001). There were no significant differences in rates of lymphovascular or perineural invasion, histologic grade, or serum AFP levels. The NAFLD/NASH cohort had lower rates of background liver fibrosis, lower AST and ALT levels, and higher platelet counts (P < .01 for all). Median overall survival (OS) was numerically shorter in NAFLD/NASH vs other etiology groups, however, not statistically significant., Conclusions: Patients with NAFLD/NASH-related HCC more commonly lacked liver fibrosis and presented with larger HCCs compared with patients with HCC from other etiologies. No differences were seen in rates of other high-risk features or survival. With the caveat of sample size and retrospective analysis, this supports a similar decision-making approach regarding surgical resection for NAFLD/NASH and other etiology-related HCCs., (© The Author(s) 2023. Published by Oxford University Press.)

The neutralizing monoclonal antibody combination of tixagevimab/cilgavimab has been shown to reduce the risk of SARS-CoV-2 infection in unvaccinated individuals during the Alpha (B.1.1.7) and Delta (B.1.617.2) waves. However, data on the efficacy and safety of tixagevimab/cilgavimab in vaccinated solid organ transplant recipients during the Omicron wave is limited. To address this, we conducted a retrospective cohort study comparing 222 solid organ transplant recipients (SOTRs) who received tixagevimab/cilgavimab for pre-exposure prophylaxis and 222 vaccine-matched solid organ transplant recipients who did not receive tixagevimab/cilgavimab. Breakthrough SARS-CoV-2 infections occurred in 11 (5%) of SOTRs who received tixagevimab/cilgavimab and in 32 (14%) of SOTRs in the control group (p < .001). In the tixagevimab/cilgavimab group, SOTRs who received the 150-150 mg dose had a higher incidence of breakthrough infections compared to those who received the 300-300 mg dose (p = .025). Adverse events were uncommon, occurring in 4% of our cohort and most were mild. There was no significant change in serum creatinine or liver chemistries in kidney and liver transplant recipients, respectively. In conclusion, we found that tixagevimab/cilgavimab use is safe and associated with a lower risk of breakthrough SARS-CoV-2 infection in vaccinated solid organ transplant recipients during the Omicron wave., (© 2022 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Intramuscular medroxyprogesterone acetate (MPA) products are commonly used to treat endometriosis and are the most widely used injectable contraceptives worldwide. Therefore, dependable quality screening of MPA injectables is a crucial measure necessary for ensuring that consumers are provided with safe and effective medications. Here, a thin-layer chromatography (TLC) method for MPA identification is combined with image analysis using a smartphone, 3D-printed light box, and open-source ImageJ software. The method's validation included two brands of MPA injectables, both at 150 mg mL -1 dosage. The TLC procedure used was based on the identity test found in The International Pharmacopoeia's Medroxyprogesterone injection monograph. Spots produced on the TLC plates were then photographed using a smartphone camera and quantified using ImageJ's image analysis software. The pixel data collected from each plate's standard spots were compared to the data generated from its sample spots. Data sets collected across multiple TLC plates and numerous days of method performance were evaluated to assess linearity, accuracy, precision, specificity, and robustness. Across the range of 75-125% of the target concentration, the method was found to have linearity of standard spots (with R 2 generally greater than 0.99), overall accuracy of 101.0% (4.1% RSD), repeatability pooled standard deviation of 2.44%, intermediate precision pooled standard deviation of 3.68%, and observed demonstration of specificity and robustness. In low and middle-income countries (LMICs), quality screening of pharmaceutical products like MPA injectables can be challenging when testing resources are expensive, difficult to procure, or complex to utilize. The results of the TLC/ImageJ method validation suggest that this simple procedure that requires minimal resources may serve as a viable option for reliable quality screening of MPA levels in injectable suspensions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Medroxyprogesterone acetate (MPA) injectable suspensions are used by millions of women for family planning and hormonal therapy. Falsified or substandard medications may result in a health risk for consumers. Near-infrared spectroscopy (NIR) has previously been applied as a means of non-destructive and rapid screening of product quality compliance. These methods offer advantages but can be logistically and cost prohibitive for field use in resource limited areas. Here, a handheld spectrometer (900-1700 nm) with open-sourced software is used to evaluate vials of MPA from three suppliers (N = 227 vials) and verified by a benchtop UV-VIS-NIR (350-2500 nm) with licensed software. Multivariate data analysis assesses the spectral signatures of samples and builds a discriminant classification method based on Mahalanobis distances calculated from a principal component analysis scores. The handheld device paired with open-source software resulted in a product discrimination accuracy of 100% (verified by benchtop UV-VIS-NIR and chemical testing data) as well indicating that the low-cost field portable device is suitable for rapidly assessing samples in resource limited areas for consistency of manufacturing and sourcing., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

The practice of transplanting hepatitis C (HCV)-infected livers into HCV-uninfected recipients has not previously been recommended in transplant guidelines, in part because of concerns over uncontrolled HCV infection of the allograft. Direct-acting antivirals (DAAs) provide an opportunity to treat donor-derived HCV-infection and should be administered early in the posttransplant period. However, evidence on the safety and efficacy of an immediate DAA treatment approach, including how to manage logistical barriers surrounding timely DAA procurement, are required prior to broader use of HCV-positive donor organs. We report the results of a trial in which 14 HCV-negative patients underwent successful liver transplantation from HCV-positive donors. Nine patients received viremic (nucleic acid testing [NAT]-positive) livers and started a 12-week course of oral glecaprevir-pibrentasvir within 5 days of transplant. Five patients received livers from HCV antibody-positive nonviremic donors and were followed using a reactive approach. Survival in NAT-positive recipients is 100% at a median follow-up of 46 weeks. An immediate treatment approach for HCV NAT-positive liver transplantation into uninfected recipients is safe and efficacious. Securing payer approval for DAAs early in the posttransplant course could enable need-based allocation of HCV-positive donor organs irrespective of candidate HCV status, while averting chronic HCV allograft infection., (© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Delisting for being "too sick" to be transplanted is subjective. Previous work has demonstrated that the mortality of patients delisted for "too sick" is unexpectedly low. Transplant centers use their best clinical judgment for determining "too sick," but it is unclear how social determinants influence decisions to delist for "too sick." We hypothesized that social determinants and Donor Service Area (DSA) characteristics may be associated with determination of "too sick" to transplant., Methods: Data were obtained from the Scientific Registry of Transplant Recipients for adults listed and removed from the liver transplant waitlist from 2002 to 2017. Patients were included if delisted for "too sick." Our primary outcome was Model for End-Stage Liver Disease (MELD) score at waitlist removal for "too sick." Regression assessed the association between social determinants and MELD at removal for "too sick.", Results: We included 5250 delisted for "too sick" at 127 centers, in 53 DSAs, over 16 years. The mean MELD at delisting for "too sick" was 25.8 (SD ± 11.2). On adjusted analysis, social determinants including age, race, sex, and education predicted the MELD at delisting for "too sick" (P < 0.05)., Conclusions: There is variation in delisting MELD for "too sick" score across DSA and time. While social determinants at the patient and system level are associated with delisting practices, the interplay of these variables warrants additional research. In addition, center outcome reports should include waitlist removal rate for "too sick" and waitlist death ratios, so waitlist management practice at individual centers can be monitored.

Objectives: Oral direct-acting antivirals (DAAs) for hepatitis C virus (HCV) have dramatically changed the treatment paradigm. Our aim was to project temporal trends in HCV diagnosis, treatment and disease burden in France, Germany, Italy, Spain and the UK., Design: A mathematical simulation model of natural history of HCV infection., Participants: HCV-infected patients defined based on country-specific age, fibrosis and genotype distributions., Interventions: HCV screening practice and availability of different waves of DAA treatment in each country., Outcome Measures: Temporal trends in the number of patients who achieve sustained virological response (SVR), fail treatment (by drug regimen) and develop advanced sequelae from 2014 to 2030 in each country., Results: We projected that 1 324 000 individuals would receive treatment from 2014 to 2030 in the five European countries and 12 000-37 000 of them would fail to achieve SVR. By 2021, the number of individuals cured of HCV would supersede the number of actively infected individuals in France, Germany, Spain and the UK. Under status quo, the diagnosis rate would reach between 65% and 75% and treatment coverage between 65% and 74% by 2030 in these countries. The number of patients who fail treatment would decrease over time, with the majority of those who fail treatment having been exposed to non-structural protein 5A inhibitors., Conclusions: In the era of DAAs, the number of people with HCV who achieved a cure will exceed the number of viraemic patients, but many patients will remain undiagnosed, untreated, fail multiple treatments and develop advanced sequelae. Scaling-up screening and treatment capacity, and timely and effective retreatment are needed to avail the full benefits of DAAs and to meet HCV elimination targets set by WHO., Competing Interests: Competing interests: JC received research grants and consulting fee from Gilead Science and Merck. TA received consulting fee from Gilead Sciences. SF has servered a speaker for Gilead Sciences, MSD, Abbvie, Bristol–Myers Squibb, Novartis, Bayer and Janssen. All other authors have nothing to report., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose of Review: Owing to long waitlist times and high waitlist morbidity and mortality, strategies to increase utilization of hepatitis C viremic-deceased donor organs are under investigation in kidney, liver, heart, and lung transplantation., Recent Findings: Direct-acting antiviral medications for hepatitis C virus infection have high cure rates and are well tolerated. Small, single-center trials in kidney and heart transplant recipients have demonstrated that with early posttransplant direct-acting antiviral therapy, 100% of uninfected recipients of hepatitis C viremic organs have been cured of infection after transplantation., Summary: In this manuscript, we review the risks and rewards of utilizing hepatitis C viremic organs for transplantation.

Background: The AIMS65 score and the Glasgow-Blatchford risk score (GBRS) are validated preendoscopic risk scores for upper gastrointestinal hemorrhage (UGIH)., Goals: To compare the 2 scores' performance in predicting important outcomes in UGIH., Study: A prospective cohort study in 2 tertiary referral centers and 1 community teaching hospital. Adults with UGIH were included. The AIMS65 score and GBRS were calculated for each patient. The primary outcome was inpatient mortality. Secondary outcomes were 30-day mortality, in-hospital rebleeding, 30-day rebleeding, length of stay, and a composite endpoint of in-hospital mortality, transfusions, or need for intervention (endoscopic, radiologic, or surgical treatment). The area under the receiver operating characteristic curve (AUROC) was calculated for each score and outcome., Results: A total of 298 patients were enrolled. The AIMS65 score was superior to the GBRS in predicting in-hospital mortality (AUROC, 0.85 vs. 0.66; P<0.01) and length of stay (Somer's D, 0.21 vs. 0.13; P=0.04). The scores were similar in predicting 30-day mortality (AUROC, 0.74 vs. 0.65; P=0.16), in-hospital rebleeding (AUROC, 0.69 vs. 0.62; P=0.19), 30-day rebleeding (AUROC, 0.63 vs. 0.63; P=0.90), and the composite outcome (AUROC, 0.57 vs. 0.59; P=0.49). The optimal cutoffs for predicting in-hospital mortality were an AIMS65 score of 3 and a GBRS score of 10. For predicting rebleeding, the optimal cutoffs were 2 and 10, respectively., Conclusions: The AIMS65 score is superior to the GBRS for predicting in-hospital mortality and hospital length of stay for patients with UGIH. The AIMS65 score and GBRS are similar in predicting 30-day mortality, rebleeding, and a composite endpoint.

ScOpi1p is a well-characterized transcriptional repressor and master regulator of inositol and phospholipid biosynthetic genes in the baker's yeast Saccharomyces cerevisiae. An ortholog has been shown to perform a similar function in the pathogenic fungus Candida glabrata, but with the distinction that CgOpi1p is essential for growth in this organism. However, in the more distantly related yeast Yarrowia lipolytica, the OPI1 homolog was not found to regulate inositol biosynthesis, but alkane oxidation. In Candida albicans, the most common cause of human candidiasis, its Opi1p homolog, CaOpi1p, has been shown to complement a S. cerevisiae opi1∆ mutant for inositol biosynthesis regulation when heterologously expressed, suggesting it might serve a similar role in this pathogen. This was tested in the pathogen directly in this report by disrupting the OPI1 homolog and examining its phenotypes. It was discovered that the OPI1 homolog does not regulate INO1 expression in C. albicans, but it does control SAP2 expression in response to bovine serum albumin containing media. Meanwhile, we found that CaOpi1 represses filamentous growth at lower temperatures (30 °C) on agar, but not in liquid media. Although, the mutant does not affect virulence in a mouse model of systemic infection, it does affect virulence in a rat model of vaginitis. This may be because Opi1p regulates expression of the SAP2 protease, which is required for rat vaginal infections.

Objective: The purpose of this study was to evaluate the reliability of polyp measurements at CT colonography and the factors that affect the measurements., Materials and Methods: Fifty colonoscopically proven cases of polyps 6 mm in diameter or larger were analyzed by two observers who measured each polyp in supine and prone views. Manual measurements of 2D volume by summation of areas, 2D maximum diameter, and 3D maximum diameter and automated measurements of 3D maximum diameter and volume were recorded for each observer and were repeated for one of the observers. Intraobserver and interobserver agreement was calculated. Analysis was performed to determine the measurement parameter that correlated most with summation-of-areas volume. Supine and prone measurements as a surrogate for tracking change in polyp size over time were analyzed to determine the measurement parameter with the least variation., Results: Maximum diameter measured manually on 3D images had the highest correlation with summation-of-areas volume. Manual summation-of-areas volume was found to have the least variation between supine and prone measurements., Conclusion: Linear polyp measurement in the 3D endoluminal view appears to be the most reliable parameter for use in the decision to excise a polyp according to current guidelines. In our study, manual calculation of volume with summation of areas was found to be the most reliable measurement parameter for observing polyp growth over serial examinations. High reliability of polyp measurements is essential for adequate assessment of change in polyp size over serial examinations because many patients with intermediate-size polyps are expected to choose surveillance.

This study demonstrated that chronic aspartame consumption in rats can lead to altered T-maze performance and increased muscarinic cholinergic receptor densities in certain brain regions. Control and treated rats were trained in a T-maze to a particular side and then periodically tested to see how well they retained the learned response. Rats that had received aspartame (250 mg/kg/day) in the drinking water for 3 or 4 months showed a significant increase in time to reach the reward in the T-maze, suggesting a possible effect on memory due to the artificial sweetener. Using [(3)H]quinuclidinyl benzilate (QNB) (1 nM) to label muscarinic cholinergic receptors and atropine (10(-6) M) to determine nonspecific binding in whole-brain preparations, aspartame-treated rats showed a 31% increase in receptor numbers when compared to controls. In aspartame-treated rats, there was a significant increase in muscarinic receptor densities in the frontal cortex, midcortex, posterior cortex, hippocampus, hypothalamus and cerebellum of 80%, 60%, 61%, 65%, 66% and 60%, respectively. The midbrain was the only area where preparations from aspartame-treated rats showed a significant increase in Na(+),K(+)-ATPase activity. It can be concluded from these data that long-term consumption of aspartame can affect T-maze performance in rats and alter receptor densities or enzymes in brain.