The etiopathogenesis of the irritable bowel syndrome (IBS), one of the most prevalent gastrointestinal disorders, is not well known. The most accepted hypothesis is that IBS is the result of the disturbance of the 'brain-gut axis.' Although the pathophysiological mechanisms of intestinal dysfunction are complex and not completely understood, stress, infections, gut flora, and altered immune response are thought to play a role in IBS development. The intestinal barrier, composed of a single-cell layer, forms a physical barrier that separates the intestinal lumen from the internal milieu. The loss of integrity of this barrier is related with mucosal immune activation and intestinal dysfunction in IBS. The number of mast cells and T lymphocytes is increased in the intestinal mucosa of certain IBS patients, and the mediators released by these cells could compromise the epithelial barrier function and alter nerve signaling within the enteric nervous system. The association of clinical symptoms to structural and functional abnormalities of the mucosal barrier in IBS patients highlights the importance of understanding the physiological role of the gut barrier in the pathogenesis of this disorder. This review summarizes the clinical and experimental evidences indicating the cellular and molecular mechanisms of IBS symptomatology, and its relevance for future translational research.
Enteric Nervous System ; Humans ; Intestinal Mucosa ; Irritable Bowel Syndrome ; Mast Cells ; T-Lymphocytes ; Tight Junctions ; Translational Medical Research

Background/Aims: Chronic psychological stress affects gastrointestinal physiology which may underpin alterations in the immune response and epithelial transport, both functions are partly regulated by enteric nervous system. However, its effects on enteric neuroplasticity are still unclear.This study aims to investigate the effects of chronic unpredictable psychological stress on intestinal motility and prominent markers of enteric function. Methods: Adult male C57BL/6J mice were exposed to 19 day of unpredictable stress protocol schedule of social defeat and overcrowding. We investigated the effects on plasma corticosterone, food intake, and body weight. In vivo gastrointestinal motility was assessed by fecal pellet output and by whole-gastrointestinal transit (using the carmine red method). Tissue monoamine level, neural and glial markers, neurotrophic factors, monoamine signaling, and Toll-like receptor expression in the proximal and distal colon, and terminal ileum were also assessed. Results: Following chronic unpredictable psychological stress, stressed mice showed increased food intake and body weight gain (P < 0.001), and reduced corticosterone levels (P < 0.05) compared to control mice. Stressed mice had reduced stool output without differences in water content, and showed a delayed gastrointestinal transit compared to control mice (P < 0.05). Stressed mice exhibited decreased mRNA expression of tyrosine hydroxylase (Th), brain-derived neurotrophic factor (Bdnf) and glial cell-derived neurotrophic factor (Gdnf), as well as Toll-like receptor 2 (Tlr2) compared to control (P < 0.05), only proximal colon. These molecular changes in proximal colon were associated with higher levels of monoamines in tissue. Conclusion Unpredictable psychological chronic stress induces region-specific impairment in monoamine levels and neuroplasticity markers that may relate to delayed intestinal transit.

After the declaration of the coronavirus disease 2019 (COVID-19) pandemic, gynecological surgery joins the readjustment process that this great global health crisis implies. In the light of current literature, the five steps towards its resilience are described as below; (1) Dynamic prioritization of surgical indications and reintroduction of elective surgeries: Diverse surgical prioritization lists are published including the most common gynecological pathologies. (2) Minimally invasive surgery through laparoscopy and robotic assistance: Some authors suggest a theoretical but unproven risk of viral transmission during these approaches because of the aerosol generation. These theories are opposed to the well-proven advantages of these approaches compared to open surgery. (3) Optimization of surgical procedures, according to the recommendations of different societies aimed at reducing the dispersion of aerosols and surgical smoke. (4) Clinical, epidemiological and microbiological screening of all patients awaiting prompt surgery: This screening should be adapted to the local alert state. (5) Protection through the reduction of number of persons present in the operating room, and the use of adapted personal protective equipment according to physical proximity to the patient.

The interface between the intestinal lumen and the mucosa is the location where the majority of ingested immunogenic particles face the scrutiny of the vast gastrointestinal immune system. Upon regular physiological conditions, the intestinal micro-flora and the epithelial barrier are well prepared to process daily a huge amount of food-derived antigens and non-immunogenic particles. Similarly, they are ready to prevent environmental toxins and microbial antigens to penetrate further and interact with the mucosal-associated immune system. These functions promote the development of proper immune responses and oral tolerance and prevent disease and inflammation. Brain-gut axis structures participate in the processing and execution of response signals to external and internal stimuli. The brain-gut axis integrates local and distant regulatory networks and super-systems that serve key housekeeping physiological functions including the balanced functioning of the intestinal barrier. Disturbance of the brain-gut axis may induce intestinal barrier dysfunction, increasing the risk of uncontrolled immunological reactions, which may indeed trigger transient mucosal inflammation and gut disease. There is a large body of evidence indicating that stress, through the brain-gut axis, may cause intestinal barrier dysfunction, mainly via the systemic and peripheral release of corticotropin-releasing factor. In this review, we describe the role of stress and corticotropin-releasing factor in the regulation of gastrointestinal permeability, and discuss the link to both health and pathological conditions.
Axis, Cervical Vertebra ; Corticotropin-Releasing Hormone* ; Housekeeping ; Immune System ; Inflammation ; Mucous Membrane ; Permeability*

Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been associated with multiple entities and several types of cancers. They can be assumed as markers of inflammatory imbalance. The objective of this study is to evaluate the NLR and PLR in Peyronie's disease (PD) and to establish a comparison of its values in the acute and chronic stages. We recruited patients with PD from March 2018 to March 2019. The patients enrolled underwent medical and sexual history as well as a physical examination. The values of blood count of each patient were collected both in the acute and chronic stages. Wilcoxon test was used to compare the acute and chronic stage ratios. Kruskal-Wallis test was carried out to evaluate the impact of treatments on the ratios. To identify cutoff values, we used sensibility and specificity tables and receiver operating characteristic (ROC) curves. A total of 120 patients were enrolled. Their mean age was 55.85 (range: 18-77) years and the mean penile curvature was 48.43° (range: 10°-100°). In the acute stage, the mean NLR was 2.35 and the mean PLR was 111.22. These ratios, in the chronic stage, were 1.57 and 100.00, respectively. Statistically significant differences between acute and stable stages for both indices were found (NLR: P< 0.0001; PLR: P= 0.0202). The optimal cutoff for classification in acute or stable stage was 2 for NLR and 102 for PLR. According to our results, with an ordinary blood count, we could have important indications regarding the disease stage of the patient, and consequently on the most appropriate type of therapy to choose.

Background: and Purpose Visual hallucinations (VH) and subjective cognitive complaints (SCC) are associated with cognitive impairment (CI) in Parkinson’s disease. Our aims were to determine the association between VH and SCC and the risk of CI development in a cohort of patients with Parkinson’s disease and normal cognition (PD-NC). Methods: Patients with PD-NC (total score of >80 on the Parkinson’s Disease Cognitive Rating Scale [PD-CRS]) recruited from the Spanish COPPADIS cohort from January 2016 to November 2017 were followed up after 2 years. Subjects with a score of ≥1 on domain 5 and item 13 of the Non-Motor Symptoms Scale at baseline (V0) were considered as “with SCC” and “with VH,” respectively. CI at the 2-year follow-up (plus or minus 1 month) (V2) was defined as a PD-CRS total score of <81. Results: At V0 (n=376, 58.2% males, age 61.14±8.73 years [mean±SD]), the frequencies of VH and SCC were 13.6% and 62.2%, respectively. VH were more frequent in patients with SCC than in those without: 18.8% (44/234) vs 4.9% (7/142), p<0.0001. At V2, 15.2% (57/376) of the patients had developed CI. VH presenting at V0 was associated with a higher risk of CI at V2 (odds ratio [OR]=2.68, 95% confidence interval=1.05–6.83, p=0.039) after controlling for the effects of age, disease duration, education, medication, motor and nonmotor status, mood, and PD-CRS total score at V0. Although SCC were not associated with CI at V2, presenting both VH and SCC at V0 increased the probability of having CI at V2 (OR=3.71, 95% confidence interval=1.36–10.17, p=0.011). Conclusions VH were associated with the development of SCC and CI at the 2-year follow-up in patients with PD-NC.