Protein glycosylation as a diagnostic and prognostic marker of chronic inflammatory gastrointestinal and liver diseases

Glycans are sequences of carbohydrates that are added to proteins or lipids to modulate their structure and function. Glycans modify proteins required for regulation of immune cells, and alterations have been associated with inflammatory conditions. For example, specific glycans regulate T-cell activation, structures, and functions of immunoglobulins; interactions between microbes and immune and epithelial cells; and malignant transformation in the intestine and liver. We review the effects of protein glycosylation in regulation of gastrointestinal and liver functions, and how alterations in glycosylation serve as diagnostic or prognostic factors, or as targets for therapy

An International Urogynecological Association (IUGA)/International Continence Society (ICS) joint report on the terminology for the conservative and nonpharmacological management of female pelvic floor dysfunction

There has been an increasing need for the terminology on the conservative management of female pelvic floor dysfunction to be collated in a clinically based consensus report.This Report combines the input of members and elected nominees of the Standardization and Terminology Committees of two International Organizations, the International Urogynecological Association (IUGA) and the International Continence Society (ICS), assisted at intervals by many external referees. An extensive process of nine rounds of internal and external review was developed to exhaustively examine each definition, with decision-making by collective opinion (consensus). Before opening up for comments on the webpages of ICS and IUGA, five experts from physiotherapy, neurology, urology, urogynecology, and nursing were invited to comment on the paper.A Terminology Report on the conservative management of female pelvic floor dysfunction, encompassing over 200 separate definitions, has been developed. It is clinically based, with the most common symptoms, signs, assessments, diagnoses, and treatments defined. Clarity and ease of use have been key aims to make it interpretable by practitioners and trainees in all the different specialty groups involved in female pelvic floor dysfunction. Ongoing review is not only anticipated, but will be required to keep the document updated and as widely acceptable as possible.A consensus-based terminology report for the conservative management of female pelvic floor dysfunction has been produced, aimed at being a significant aid to clinical practice and a stimulus for research

Mitochondrial neurogastrointestinal encephalomyopathy: approaches to diagnosis and treatment

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an ultra-rare disease caused by mutations in TYMP, the gene encoding for the enzyme thymidine phosphorylase. The resulting enzyme deficiency leads to a systemic accumulation of thymidine and 2’-deoxyuridine and ultimately mitochondrial failure due to a progressive acquisition of secondary mitochondrial DNA (mtDNA) mutations and mtDNA depletion. MNGIE is characterised by gastrointestinal dysmotility, cachexia, peripheral neuropathy, ophthalmoplegia, ptosis and leukoencephalopathy. The disease is progressively degenerative and leads to death at an average age of 37.6 years. Patients invariably encounter misdiagnoses, diagnostic delays, and non-specific clinical management. Despite its rarity, MNGIE has invoked much interest in the development of therapeutic strategies, mainly because it is one of the few mitochondrial disorders where the molecular abnormality is metabolically and physically accessible to manipulation. This review provides a résumé of the current diagnosis and treatment approaches and aims to increase the clinical awareness of MNGIE and thereby facilitate early diagnosis and timely access to treatments, before the development of untreatable and irreversible organ damage

Utilizing Digital Health to Collect Electronic Patient-Reported Outcomes in Prostate Cancer: Single-Arm Pilot Trial

Background: Measuring patient-reported outcomes (PROs) requires an individual’s perspective on their symptoms, functional status, and quality of life. Digital health enables remote electronic PRO (ePRO) assessments as a clinical decision support tool to facilitate meaningful provider interactions and personalized treatment. Objective: This study explored the feasibility and acceptability of collecting ePROs using validated health-related quality of life (HRQoL) questionnaires for prostate cancer. Methods: Using Apple ResearchKit software, the Strength Through Insight app was created with content from validated HRQoL tools 26-item Expanded Prostate Cancer Index Composite (EPIC) or EPIC for Clinical Practice and 8-item Functional Assessment of Cancer Therapy Advanced Prostate Symptom Index. In a single-arm pilot study with patients receiving prostate cancer treatment at Thomas Jefferson University Hospital and affiliates, participants were recruited, and instructed to download Strength Through Insight and complete ePROs once a week over 12 weeks. A mixed methods approach, including qualitative pre- and poststudy interviews, was used to evaluate the feasibility and acceptability of Strength Through Insight for the collection and care management of cancer treatment. Results: Thirty patients consented to the study; 1 patient failed to complete any of the questionnaires and was left out of the analysis of the intervention. Moreover, 86% (25/29) reached satisfactory questionnaire completion (defined as completion of 60% of weekly questions over 12 weeks). The lower bound of the exact one-sided 95% CI was 71%, exceeding the 70% feasibility threshold. Most participants self-identified with having a high digital literacy level (defined as the ability to use, understand, evaluate, and analyze information from multiple formats from a variety of digital sources), and only a few participants identified with having a low digital literacy level (defined as only having the ability to gather information on the Web). Interviews were thematically analyzed to reveal the following: (1) value of emotional support and wellness in cancer treatment, (2) rise of social patient advocacy in online patient communities and networks, (3) patient concerns over privacy, and (4) desire for personalized engagement tools. Conclusions: Strength Through Insight was demonstrated as a feasible and acceptable method of data collection for ePROs. A high compliance rate confirmed the app as a reliable tool for patients with localized and advanced prostate cancer. Nearly all participants reported that using the smartphone app is easier than or equivalent to the traditional paper-and-pen approach, providing evidence of acceptability and support for the use of remote PRO monitoring. This study expands on current research involving the value of digital health, as a social and behavioral science, augmented with technology, can begin to contribute to population health management, as it shapes psychographic segmentation by demographic, socioeconomic, health condition, or behavioral factors to group patients by their distinct personalities and motivations, which influence their choices

Biomarkers for monitoring intestinal health in poultry : present status and future perspectives

Intestinal health is determined by host (immunity, mucosal barrier), nutritional, microbial and environmental factors. Deficiencies in intestinal health are associated with shifts in the composition of the intestinal microbiome (dysbiosis), leakage of the mucosal barrier and/or inflammation. Since the ban on growth promoting antimicrobials in animal feed, these dysbiosis-related problems have become a major issue, especially in intensive animal farming. The economical and animal welfare consequences are considerable. Consequently, there is a need for continuous monitoring of the intestinal health status, particularly in intensively reared animals, where the intestinal function is often pushed to the limit. In the current review, the recent advances in the field of intestinal health biomarkers, both in human and veterinary medicine are discussed, trying to identify present and future markers of intestinal health in poultry. The most promising new biomarkers will be stable molecules ending up in the feces and litter that can be quantified, preferably using rapid and simple pen-side tests. It is unlikely, however, that a single biomarker will be sufficient to follow up all aspects of intestinal health. Combinations of multiple biomarkers and/or metabarcoding, metagenomic, metatranscriptomic, metaproteomic and metabolomic approaches will be the way to go in the future. Candidate biomarkers currently are being investigated by many research groups, but the validation will be a major challenge, due to the complexity of intestinal health in the field

Population screening for colorectal cancer means getting FIT:the past, present, and future of colorectal cancer screening using the fecal immunochemical test for hemoglobin (FIT)

Fecal immunochemical tests for hemoglobin (FIT) are changing the manner in which colorectal cancer (CRC) is screened. Although these tests are being performed worldwide, why is this test different from its predecessors? What evidence supports its adoption? How can this evidence best be used? This review addresses these questions and provides an understanding of FIT theory and practices to expedite international efforts to implement the use of FIT in CRC screening

Exploring colorectal cancer patients' perceptions of the quality of their care

This report discusses the local situation in Halton with regard to colorectal cancer care by exploring how patients perceived the quality of their care.Widnes Primary Care Grou

A yeast fermentate improves gastrointestinal discomfort and constipation by modulation of the gut microbiome : results from a randomized double-blind placebo-controlled pilot trial

Background: Constipation and symptoms of gastrointestinal discomfort such as bloating are common among otherwise healthy individuals, but with significant impact on quality of life. Despite the recognized contribution of the gut microbiome to this pathology, little is known about which group(s) of microorganism(s) are playing a role. A previous study performed in vitro suggests that EpiCor (R) fermentate has prebiotic-like properties, being able to favorably modulate the composition of the gut microbiome. Therefore, the aim of this study was to investigate the effects of EpiCor fermentate in a population with symptoms of gastrointestinal discomfort and reduced bowel movements and to evaluate its effect at the level of the gut microbiome. Methods: This pilot study was performed according to a randomized, double-blind, placebo-controlled parallel design. Eighty subjects with symptoms of gastrointestinal discomfort and constipation were allocated to one of two trial arms (placebo or EpiCor fermentate). Randomization was done in a stratified manner according to symptom severity, resulting in two subgroups of patients: severe and moderate. Daily records of gastrointestinal symptoms were assessed on a 5-point scale, and also stool frequency and consistency were documented during a 2-week run-in and a 6-week intervention phases. Averages over two-week intervals were calculated. Constipation-associated quality of life and general perceived stress were assessed at baseline and after 3 and 6 weeks of intervention. Fecal samples were also collected at these same time points. Results: EpiCor fermentate led to a significant improvement of symptoms such as bloating/distension (p = 0.033 and p = 0.024 after 2 and 4 weeks of intervention, respectively), feeling of fullness (p = 0.004 and p = 0.023 after 2 and 4 weeks of intervention, respectively) and general daily scores (p = 0.046 after 2 weeks of intervention) in the moderate subgroup. A significant improvement in stool consistency was observed for the total population (p = 0.023 after 2 weeks of intervention) as well as for the severe subgroup (p = 0.046 after 2 weeks of intervention), and a nearly significant increase in stool frequency was detected for the total cohort (p = 0.083 and p = 0.090 after 2 and 4 weeks of intervention, respectively). These effects were accompanied by an improvement in constipation-associated quality of life and general perceived stress, particularly in the moderate subgroup. Members of the families Bacteroidaceae and Prevotellaceae, two groups of bacteria that have been previously reported to be deficient in constipated patients, were found to increase with EpiCor fermentate in the severe subgroup. In the moderate subgroup, a significant increase in Akkermansia muciniphila was observed. Conclusions: Despite the relatively low dose administered (500 mg/day), particularly when comparing to the high recommended doses for prebiotic fibers, EpiCor fermentate was able to modulate the composition of the gut microbiome, resulting in improvement of constipation-associated symptoms. Conversely, the reported increase in bowel movements may have altered the gut microbial community by increasing those groups of bacteria that are better adapted to a faster gastrointestinal transit time

Extracellular matrix remodeling and TGF-β1/Smad signaling in diabetic colon mucosa

Diabetes is associated with metabolic and functional alterations in the gut. Using an experimental model of streptozotocin (STZ)-induced diabetes in rodents, we analyzed the extracellular matrix (ECM) and TGF-β/Smad signaling in the colon mucosa. Male rats were divided into normal control, diabetic and insulin treated diabetic groups during 4 and 9 weeks. Sirius red staining showed marked increase in the extracellular matrix deposition in diabetic mucosa. High levels of fibrillar collagen (I and III) and fibronectin mRNAs were also detected with an imbalance between MMPs/TIMPs activities. Moreover, an increased mesenchymal cell proliferation together with an enhanced expression of myofibroblasts markers vimentin and α-SMA were observed. TGF-β/Smad signaling-related genes were determined using RT-PCR, Western blotting, and immunohistochemistry. Diabetic rats showed a significant up-regulation of TGF-β1, TGF-β receptors and the effectors p-Smad2/3 in the mucosa compared with control rats. Insulin treatment attenuated the stimulating effect of diabetes on colon ECM deposition and TGF-β/Smad signaling. In conclusion, the overall results showed a deregulation of the TGFβ1 pathway associated with the appearance of myofibroblasts and the accumulation of ECM in the mucosa of diabetic colon. These data provide the first in vivo evidence that TGF-β1/Smad is a key component of intestinal tissue remodeling in diabetes.Fil: D'arpino, María Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Fuchs, Alicia Graciela. Universidad Abierta Interamericana. Facultad de Medicina. Centro de Altos Estudios en Ciencias de la Salud; ArgentinaFil: Sanchez, Sara Serafina del V.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Honore, Stella Maris. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia; Argentin