Objective: Increasing evidence indicates that intestinal microbiota play a role in diverse metabolic processes via intestinal butyrate production. Human bariatric surgery data suggest that the gut-brain axis is also involved in this process, but the underlying mechanisms remain unknown.
Methods: We compared the effect of fecal microbiota transfer (FMT) from post-Roux-en-Y gastric bypass (RYGB) donors vs oral butyrate supplementation on (I-FP-CIT-determined) brain dopamine transporter (DAT) and serotonin transporter (SERT) binding as well as stable isotope-determined insulin sensitivity at baseline and after 4 weeks in 24 male and female treatment-naïve metabolic syndrome subjects.
Objectives: To evaluate the effect of intrathecally (IT) delivered rituximab as a therapeutic intervention for progressive multiple sclerosis (PMS) during a 3-year follow-up period.
Methods: Participants of a 1-year open-label phase 1b study of IT delivered rituximab to patients with PMS were offered extended treatment with follow-up for an additional 2 years. During the extension phase, treatment with 25 mg rituximab was administered every 6 months via a subcutaneous Ommaya reservoir connected to the right frontal horn with a ventricular catheter.
Patients suffering from Barrett's Esophagus (BE) are at an increased risk of developing esophageal adenocarcinoma and early detection is crucial for a good prognosis. To aid the endoscopists with the early detection for this preliminary stage of esophageal cancer, this work concentrates on the development and extensive evaluation of a state-of-the-art computer-aided classification and localization algorithm for dysplastic lesions in BE. To this end, we have employed a large-scale endoscopic data set, consisting of 494,355 images, in combination with a novel semi-supervised learning algorithm to pretrain several instances of the proposed neural network architecture.
View Article and Find Full Text PDFAnhedonia, the loss of pleasure from previously rewarding activities, is implicated in several neuropsychiatric conditions, including major depressive disorder (MDD). In order to accelerate drug development for mood disorders, quantitative approaches are needed to objectively measure responsiveness to reward as a means to identify deficits. One such approach, the probabilistic reward task (PRT), uses visual discrimination methodology to quantify reward learning.
View Article and Find Full Text PDFSpinal cord injury (SCI) frequently engenders chronic pain which may be classified as occurring above, at, or below the level of injury. Since patients with SCI may have a complex combination of nociceptive and neuropathic pain, pharmacological interventions often fail. Peripheral subcutaneous field stimulation (PSFS) is a novel neuromodulation surgery for pain in which subcutaneous electrodes designed for spinal cord stimulation are placed subcutaneously in a region of pain.
View Article and Find Full Text PDFBackground And Aims: Volumetric laser endomicroscopy (VLE) is an advanced imaging modality used to detect Barrett's esophagus (BE) dysplasia. However, real-time interpretation of VLE scans is complex and time-consuming. Computer-aided detection (CAD) may help in the process of VLE image interpretation.
View Article and Find Full Text PDFBackground: The relationship between proteins in different CNS extracellular compartments is unknown. In this study the levels of selected proteins in three compartments in people with progressive multiple sclerosis (PMS) were compared.
Methods: During an open label, phase 1b study on intraventricular administration of rituximab for PMS, samples were collected from the interstitial space (ISS) of the brain through microdialysis.
Early Barrett's neoplasia are often missed due to subtle visual features and inexperience of the non-expert endoscopist with such lesions. While promising results have been reported on the automated detection of this type of early cancer in still endoscopic images, video-based detection using the temporal domain is still open. The temporally stable nature of video data in endoscopic examinations enables to develop a framework that can diagnose the imaged tissue class over time, thereby yielding a more robust and improved model for spatial predictions.
View Article and Find Full Text PDFPurpose: Accurate life expectancy estimates are required to inform prostate cancer treatment decisions. However, few models are specific to the population served or easily implemented in a clinical setting. We sought to create life expectancy estimates specific to Veterans diagnosed with prostate cancer.
View Article and Find Full Text PDFThe effect of berry polyphenols on glucose metabolism has been evaluated in several studies; however, the results are conflicting. A systematic review and meta-analysis was therefore conducted to evaluate the effect of berry polyphenol consumption on glucose metabolism in adults with impaired glucose tolerance or insulin resistance. PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, CINAHL (EBSCO), and Scopus were searched for randomized controlled trials published by June 2019.
View Article and Find Full Text PDFVolumetric laser endomicroscopy (VLE) has been shown to improve detection of early neoplasia in Barrett's esophagus (BE). However, diagnostic performance using histopathology-correlated VLE regions of interest (ROIs) has not been adequately studied. We evaluated the diagnostic accuracy of VLE assessors for identification of early BE neoplasia in histopathology-correlated VLE ROIs.
View Article and Find Full Text PDFBackground: Cannabis availability with high concentrations of Δ-9-tetrahydrocannabinol (THC) and a range of THC to cannabidiol (CBD) ratios has increased in parallel with a rise in daily cannabis consumption by adolescents. Unanswered questions in adolescents include: 1) whether THC blood concentrations and THC metabolites remain stable or change with prolonged daily dosing, 2) whether CBD modulates THC pharmacokinetic properties and alters THC accumulation in brain, 3) whether blood THC levels reflect brain concentrations.
Methods: In adolescent squirrel monkeys (Saimiri boliviensis), we determined whether a four-month regimen of daily THC (1 mg/kg) or CBD (3 mg/kg) + THC (1 mg/kg) administration (IM) affects THC, THC metabolites, and CBD concentrations in blood or brain.
Prostatic abscess is rare and mainly affects immunocompromised individuals, classically presenting with both systemic and lower urinary tract symptoms. Our case is unique as the patient presented with an exceptionally long duration of symptoms prior to seeing a health-care provider, had no systemic symptoms, and was managed via a multidisciplinary approach. We present a case of a 70-year-old man with type-two diabetes who endured two months of lower urinary tract symptoms and constipation without systemic symptoms prior to seeking medical attention.
View Article and Find Full Text PDFJ Pharmacol Exp Ther
September 2020
Attenuating emesis elicited by both disease and medical treatments of disease remains a critical public health challenge. Although cannabinergic medications have been used in certain treatment-resistant populations, Food and Drug Administration-approved cannabinoid antiemetics are associated with undesirable side effects, including cognitive disruption, that limit their prescription. Previous studies have shown that a metabolically stable analog of the endocannabinoid anandamide, methanandamide (mAEA), may produce lesser cognitive disruption than that associated with the primary psychoactive constituent in cannabis, Δ-tetrahydrocannabinol (Δ-THC), raising the possibility that endocannabinoids may offer a therapeutic advantage over currently used medications.
View Article and Find Full Text PDFBackground: In individuals below 65 years of age, primary prevention programs have not been successful in reducing the risk of cardiovascular disease (CVD) and death. However, no large study to our knowledge has previously evaluated the effects of prevention programs in individuals aged 65 years or older. The present cohort study evaluated the risk of CVD in a primary prevention program for community-dwelling 70-year-olds.
View Article and Find Full Text PDF(-)--Phenethyl analogs of optically pure -norhydromorphone were synthesized and pharmacologically evaluated in several in vitro assays (opioid receptor binding, stimulation of [S]GTPγS binding, forskolin-induced cAMP accumulation assay, and MOR-mediated β-arrestin recruitment assays). "Body" and "tail" interactions with opioid receptors (a subset of Portoghese's message-address theory) were used for molecular modeling and simulations, where the "address" can be considered the "body" of the hydromorphone molecule and the "message" delivered by the substituent (tail) on the aromatic ring of the -phenethyl moiety. One compound, N-p-chloro-phenethynorhydromorphone ((7aR,12bS)-3-(4-chlorophenethyl)-9-hydroxy-2,3,4,4a,5,6-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one, ), was found to have nanomolar binding affinity at MOR and DOR.
View Article and Find Full Text PDFHospital readmission is a common occurrence following kidney transplantation, but less is known about the predictors of early and recurrent hospitalization. We analyzed a cohort of adult kidney transplant recipients in Nova Scotia, Canada, from January 2010 to December 2015. Readmission rates for 30 days, 6 months, and 1 year were calculated as a proportion of total transplants.
View Article and Find Full Text PDFBackground: Volumetric laser endomicroscopy (VLE) allows for near-microscopic imaging of the superficial esophageal wall and may improve detection of early neoplasia in Barrett's esophagus (BE). Interpretation of a 6-cm long, circumferential VLE "full scan" may however be challenging for endoscopists. We aimed to evaluate the accuracy of VLE experts in correctly diagnosing VLE full scans of early neoplasia and non-dysplastic BE (NDBE).
View Article and Find Full Text PDFObjective: To assess urology residency program modifications in the context of COVID-19, and perceptions of the impact on urology trainees.
Methods: A cross-sectional survey of program leadership and residents at accredited US urology residencies was administered between April 28, 2020 to March 11, 2020. Total cohort responses are reported, and subanalyses were preformed comparing responses between those in in high vs low COVID-19 geographic regions, and between program leaders vs residents.
Background And Aims: The endoscopic evaluation of narrow-band imaging (NBI) zoom imagery in Barrett's esophagus (BE) is associated with suboptimal diagnostic accuracy and poor interobserver agreement. Computer-aided diagnosis (CAD) systems may assist endoscopists in the characterization of Barrett's mucosa. Our aim was to demonstrate the feasibility of a deep-learning CAD system for tissue characterization of NBI zoom imagery in BE.
View Article and Find Full Text PDFAims: The histopathological diagnosis of low-grade dysplasia (LGD) in Barrett's oesophagus (BO) is associated with poor interobserver agreement and guidelines dictate expert review. To facilitate nationwide expert review in the Netherlands, a web-based digital review panel has been set up, which currently consists of eight 'core' pathologists. The aim of this study was to evaluate if other pathologists from the Dutch BO expert centres qualify for the expert panel by assessing their performance in 80 consecutive LGD reviews submitted to the panel.
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