Focus on the gut-brain axis: multiple sclerosis,the intestinal barrier and the microbiome

The brain-gut axis serves as the bidirectional connection between the gut microbiome, the intestinal barrier and the immune system that might be relevant for the pathophysiology of inflammatory demyelinating diseases. People with multiple sclerosis have been shown to have an altered microbiome, increased intestinal permeability and changes in bile acid metabolism. Experimental evidence suggests that these changes can lead to profound alterations of peripheral and central nervous system immune regulation. Besides being of pathophysiological interest, the brain-gut axis could also open new avenues of therapeutic targets. Modification of the microbiome, the use of probiotics, fecal microbiota transplantation, supplementation with bile acids and intestinal barrier enhancers are all promising candidates. Hopefully, pre-clinical studies and clinical trials will soon yield significant results.     

COVID-19 as a trigger of irritable bowel syndrome: A review of potential mechanisms

In December 2019 a novel coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), started spreading from Wuhan city of Chinese Hubei province and rapidly became a global pandemic. Clinical symptoms of the disease range from paucisymptomatic disease to a much more severe disease. Typical symptoms of the initial phase include fever and cough, with possible progression to acute respiratory distress syndrome. Gastrointestinal manifestations such as diarrhoea, vomiting and abdominal pain are reported in a considerable number of affected individuals and may be due to the SARS-CoV-2 tropism for the peptidase angiotensin receptor 2. The intestinal homeostasis and microenvironment appear to play a major role in the pathogenesis of COVID-19 and in the enhancement of the systemic inflammatory responses. Long-term consequences of COVID-19 include respiratory disturbances and other disabling manifestations, such as fatigue and psychological impairment. To date, there is a paucity of data on the gastrointestinal sequelae of SARS-CoV-2 infection. Since COVID-19 can directly or indirectly affect the gut physiology in different ways, it is plausible that functional bowel diseases may occur after the recovery because of potential pathophysiological alterations (dysbiosis, disruption of the intestinal barrier, mucosal microinflammation, post-infectious states, immune dysregulation and psychological stress). In this review we speculate that COVID-19 can trigger irritable bowel syndrome and we discuss the potential mechanisms.     

“Role of exercise in preventing and restoring gut dysbiosis in patients with inflammatory bowel disease”: A letter to the editor

Exercise-induced changes of the microbiome in inflammatory bowel diseases (IBD) is a promising field of research with the potential for personalized exercise regimes as a promising therapeutic adjunct for restoring gut dysbiosis and additionally for regulating immunometabolic pathways in the management of IBD patients. Structured exercise programmes in IBD patients of at least of 12 wk duration are more likely to result in disease-altering changes in the gut microbiome and to harness potential anti-inflammatory effects through these changes along with immunometabolic pathways.     

Epidemiology of IBD during the twentieth century: an integrated view

Current incidence figures on ulcerative colitis and Crohn's disease--presented in a recent multicenter study in Europe--are given, and differences in the frequency and clinical appearances of the two conditions are discussed. Trends in the frequency and clinical appearance of inflammatory bowel disease during the twentieth century are summarized, as well as the differences over time and from place to place. Correlations between age, sex, localization of disease and clinical symptoms are given. Risk of progression to more extensive disease in patients with proctitis is shown. Incidences of inflammatory bowel disease in childhood and among migrated ethnic groups are discussed. Survival and cancer risk among patients with ulcerative colitis and Crohn's disease are shown from long-term clinical epidemiological studies of well-defined patient groups. Trends in these important prognostic parameters over time are shown, as well as factors influencing prognosis of the diseases.     

Intestinal permeability in the pathogenesis of liver damage: From non-alcoholic fatty liver disease to liver transplantation

The intimate connection and the strict mutual cooperation between the gut and the liver realizes a functional entity called gut-liver axis.The integrity of intestinal barrier is crucial for the maintenance of liver homeostasis.In this mutual relationship,the liver acts as a second firewall towards potentially harmful substances translocated from the gut,and is,in turn,is implicated in the regulation of the barrier.Increasing evidence has highlighted the relevance of increased intestinal permeability and consequent bacterial translocation in the development of liver damage.In particular,in patients with non-alcoholic fatty liver disease recent hypotheses are considering intestinal permeability impairment,diet and gut dysbiosis as the primary pathogenic trigger.In advanced liver disease,intestinal permeability is enhanced by portal hypertension.The clinical consequence is an increased bacterial translocation that further worsens liver damage.Furthermore,this pathogenic mechanism is implicated in most of liver cirrhosis complications,such as spontaneous bacterial peritonitis,hepatorenal syndrome,portal vein thrombosis,hepatic encephalopathy,and hepatocellular carcinoma.After liver transplantation,the decrease in portal pressure should determine beneficial effects on the gut-liver axis,although are incompletely understood data on the modifications of the intestinal permeability and gut microbiota composition are still lacking.How the modulation of the intestinal permeability could prevent the initiation and progression of liver disease is still an uncovered area,which deserves further attention.     

Characteristics of the Gut Microbiome of Healthy Young Male Soldiers in South Korea: The Effects of Smoking

Background/AimsSouth Korean soldiers are exposed to similar environmental factors. In this study, we sought to evaluate the gut microbiome of healthy young male soldiers (HYMS) and to identify the primary factors influencing the microbiome composition.MethodsWe prospectively collected stool from 100 HYMS and performed next-generation sequencing of the 16S rRNA genes of fecal bacteria. Clinical data, including data relating to the diet, smoking, drinking, and exercise, were collected.ResultsThe relative abundances of the bacterial phyla Firmicutes, Actinobacteria, Bacteroidetes, and Proteobacteria were 72.3%, 14.5%, 8.9%, and 4.0%, respectively. Fifteen species, most of which belonged to Firmicutes (87%), were detected in all examined subjects. Using cluster analysis, we found that the subjects could be divided into the two enterotypes based on the gut microbiome bacterial composition. Compared with enterotype 2 subjects, subjects classified as enterotype 1 tended to be characterized by higher frequencies of potentially harmful lifestyle habits (current smoker 55.6% vs 36.6%, p=0.222; heavy drinker 16.7% vs 3.7%, p=0.120; insufficient physical activity 27.8% vs 14.6%, p=0.318). We identified a significant difference in the microbiome compositions of current and noncurrent smokers (p=0.008); the former differed from the latter mainly in a relatively lower abundance of Bifidobacterium species and a higher abundance of Negativicutes.ConclusionsA high abundance of Actinobacteria and low abundance of Bacteroidetes were the main features distinguishing the gut microbiomes of HYMS, and current smokers could be differentiated from noncurrent smokers by their lower abundance of Bifidobacterium and higher abundance of Negativicutes.     

Biomarkers for schistosomiasis: Towards an integrative view of the search for an effective diagnosis

Human schistosomiasis, caused mainly by Schistosoma mansoni, S. japonicum, and S. hematobium, remains a prevalent and serious parasitic disease worldwide. Although it is a debilitating disease, a lack of sensitive methods for the precise diagnosis of active infection cases is important to prevent morbidity. The optimization of new diagnostic approaches may be accomplished by the selection of specific markers. In that manner, markers can be satisfactorily used for detection of different phases of infection, as acute and chronic phases, pre-patent and post-patent phases and after chemotherapy, improving the efficiency of methods. For that purpose, proteomics and glycomics analyses have been performed in schistosomes, in particular S. mansoni, using powerful high-throughput methodologies. These investigations have not only chartered protein, o-glycan and n-glycan profiles across developmental stages within mammalian host, but are also leading to the characterization of features of the surface tegument, the eggshell and excretory–secretory proteomes of schistosomes.     

The impact of a primary care physician cooperative on the caseload of an emergency department: The maastricht integrated out-of-hours service

OBJECTIVE: To determine the effect of an out-of-hours primary care physician (PCP) cooperative on the caseload at the emergency department (ED) and to study characteristics of patients utilizing out-of-hours care. DESIGN: A pre-post intervention design was used. During a 3-week period before and a 3-week period after establishing the PCP cooperative, all patient records with out-of-hours primary and emergency care were analyzed. SETTING: Primary care in Maastricht (the Netherlands) is delivered by 59 PCPs. Primary care physicians formerly organized out-of-hours care in small locum groups. In January 2000, out-of-hours primary care was reorganized, and a PCP cooperative was established. This cooperative is located at the ED of the University Hospital Maastricht, the city's only hospital, which has no emergency medicine specialists. MAIN OUTCOME MEASURES: The number of patients utilizing out-of-hours care, their age and sex, diagnoses, post-ED care, and serious adverse events. RESULTS: After establishing the PCP cooperative, the proportion of patients utilizing emergency care decreased by 53%, and the proportion of patients utilizing primary care increased by 25%. The shift was the largest for patients with musculoskeletal disorders or skin problems. There were fewer hospital admissions, and fewer subsequent referrals to the patient's own PCP and medical specialists. No substantial change in new outpatient visits at the hospital or in mortality occurred. CONCLUSIONS: In the city of Maastricht, the Netherlands, the PCP cooperative reduced the use of hospital emergency care during out-of-hours care.     

Traditional Bhutanese medicine (gSo-BA Rig-PA): an integrated part of the formal health care services

Traditional medicine in Bhutan is known as gSo-ba Rig-pa and is one of the oldest surviving medical traditions in the world. Other medical systems, such as Chinese medicine, Indian Ayurvedic medicine, Unani medicine, Greco-Roman medicine and the country's rich cultures and traditions have greatly influenced the way traditional Bhutanese medicine evolved. However, Buddhist philosophy remains the mainstream of this medical system. gSo-ba Rig-pa's principles are based on the perception the human body is composed of three main elements: rLung ('Air'), mKhris-pa ('Bile') and Bad-kan ('Phlegm'). When these three elements are balanced in the body a person is said to be healthy. The pathophysiology is also different from other medical systems, and the close link to Buddhism is reflected in the spiritual dimensions and the perception that all suffering is caused by ignorance. The treatment of diseases includes behavioral modification, physiotherapy, herbal medicines, minor surgery and spiritual healing. This makes the traditional Bhutanese medicine a unique and holistic health care system. The traditional medicine is an integrated and recognized part of the formal health care services in Bhutan under the auspices of the Ministry of Health. The article highlights three main points which can be learned from the Bhutanese experience: (1) the strong tradition of herbal medicines within gSo-ba Rig-pa forms a unique opportunity to prospect for new leads for development of pharmaceuticals, (2) the availability of the traditional medicine along with biomedicine broadens the health care choices for patients, and (3) the experiences of integrating two conceptually very different health care systems within one ministry contains important managerial lessons to be learned.     

Defining the domain of geriatric medicine in an urban public health system affiliated with an academic medical center

The American Geriatrics Society has recommended a reexamination of the roles and deployment of providers with expertise in geriatric medicine. Healthcare systems use a variety of strategies to maximize their geriatric expertise. In general, these health systems tend to focus geriatric medicine resources on a group of older adults that are locally defined as the most in need. This article describes a model of care within an academic urban public health system and describes how local characteristics interact to define the domain of geriatric medicine. This domain is defined using 4 years of data from an electronic medical record combined with data collected from clinical trials. From January 2002 to December 2005, 31,443 adults aged 65 and older were seen at any clinical site within this healthcare system. The mean age was 75 (range 65-105); 61% were women; 35% African American, and 2% Hispanic. The payer mix was 80% Medicare and 17% Medicaid. The local geriatric medicine program includes sites of care in inpatient, ambulatory, nursing home, and home-based settings. By design, this geriatric medicine clinical practice complements the care provided to older adults by the primary care practice. Primary care physicians tend to cede care to geriatric medicine for older adults with advanced disability or geriatric syndromes. This is most apparent for older adults in nursing facilities or those requiring home-based care. There is a dynamic interplay between design features, reputation, and capacity that modulates volume, location, and type of patients seen by geriatrics.     

Paradox, change and choice: an economist's view of some current health care resource issues

Health care delivery is a major industry in the United States, consuming large quantities of human and physical capital and generating impressive quantities of products, ideas, trained personnel and health services. The focus of current public policy attention upon the medical profession, which has only in this century become a highly respected scientific profession, is not on its substantial accomplishments, but on the health care delivery system as a consumer (generator?) of over 10% of our annual gross national product. The overwhelming focus of current public policy and public sentiment is on cost containment (i.e., developing strategies to limit the flow of resources into the existing health care delivery system). This shift in public sentiment and new focus of public policy is, in some sense, a paradox in view of the spectacular advances in medical science and access to health care that the medical profession has delivered in the last 2 decades. The source of this anxiety and the cause of current initiatives in public policy and private practices with respect to health care is costs. The health care sector has not only consumed more resources than anticipated, but has also been characterized by unusually rapidly escalating prices and skyrocketing government resource commitments. As a result, we are asking new questions and seeking new initiatives. We are asking whether the institutions and practices that characterize the existing health care delivery system are the most suitable arrangements for our future. This article raises some of the issues entailed by these questions and details some of the choices which lie ahead for the health care industry.     

Towards an integrative approach to understanding the role of chemerin in human health and disease

Chemerin is an adipocyte‐secreted protein with autocrine/paracrine roles on adipose development and function as well as endocrine roles in metabolism and immunity. Following prochemerin secretion, protease‐mediated generation of chemerin isoforms with a range of biological activities is a key regulatory mechanism controlling local, context‐specific chemerin bioactivity. Together, experimental and clinical data indicate that localized and/or circulating chemerin expression and activation are elevated in numerous metabolic and inflammatory diseases including psoriasis, obesity, type 2 diabetes, metabolic syndrome and cardiovascular disease. These elevations are positively correlated with deleterious changes in glucose, lipid, and cytokine homeostasis, and may serve as a link between obesity, inflammation and other metabolic disorders. This review highlights the current state of knowledge regarding chemerin expression, processing, biological function and relevance to human disease, particularly with respect to adipose tissue development, inflammation, glucose homeostasis and cardiovascular disease. Furthermore, it discusses study variability, deficiencies in current measurement, and questions concerning chemerin function in disease, with a special emphasis on techniques and tools used to properly assess chemerin biology. An integration of basic and clinical research is key to understanding how chemerin influences disease pathobiology, and whether modulation of chemerin levels and/or activity may serve as a potential method to prevent and treat metabolic diseases.     

To scan or not to scan: Use of transient elastography in an integrated health system

BACKGROUND Non-invasive tests,such as Fibrosis-4 index and transient elastography(commonly FibroScan),are utilized in clinical pathways to risk stratify and diagnose non-alcoholic fatty liver disease(NAFLD).In 2018,a clinical decision support tool(CDST) was implemented to guide primary care providers(PCPs) on use of FibroScan for NAFLD.AIM To analyze how this CDST impacted health care utilization and patient outcomes.METHODS We performed a retrospective review of adults who had FibroScan for NAF...