The devastating effects of the recent global pandemic (termed COVID-19 for “coronavirus disease 2019”) caused by the severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) are paramount with ...new cases and deaths growing at an exponential rate. In order to provide a better understanding of SARS CoV-2, this article will review the proteins found in the SARS CoV-2 that caused this global pandemic.
Recent advances in small-bowel endoscopy such as capsule endoscopy have shown that non-steroidal anti-inflammatory drugs (NSAIDs) frequently damage the small intestine, with the prevalence rate of ...mucosal breaks of around 50% in chronic users. A significant proportion of patients with NSAIDs-induced enteropathy are asymptomatic, but some patients develop symptomatic or complicated ulcers that need therapeutic intervention. Both inhibition of prostaglandins due to the inhibition of cyclooxygenases and mitochondrial dysfunction secondary to the topical effect of NSAIDs play a crucial role in the early process of injury. As a result, the intestinal barrier function is impaired, which allows enterobacteria to invade the mucosa. Gram-negative bacteria and endogenous molecules coordinate to trigger inflammatory cascades via Toll-like receptor 4 to induce excessive expression of cytokines such as tumor necrosis factor-α and to activate NLRP3 inflammasome, a multiprotein complex that processes pro-interleukin-1β into its mature form. Finally, neutrophils accumulate in the mucosa, resulting in intestinal ulceration. Currently, misoprostol is the only drug that has a proven beneficial effect on bleeding small intestinal ulcers induced by NSAIDs or low-dose aspirin, but its protection is insufficient. Therefore, the efficacy of the combination of misoprostol with other drugs, especially those targeting the innate immune system, should be assessed in the next step.
Peptic ulcer disease Lanas, Angel, Prof; Chan, Francis K L, MD
The Lancet (British edition),
08/2017, Letnik:
390, Številka:
10094
Journal Article
Recenzirano
Summary The rapidly declining prevalence of Helicobacter pylori infection and widespread use of potent anti-secretory drugs means peptic ulcer disease has become substantially less prevalent than it ...was two decades ago. Management has, however, become more challenging than ever because of the threat of increasing antimicrobial resistance worldwide and widespread use of complex anti-thrombotic therapy in the ageing population. Peptic ulcers not associated with H pylori infection or the use of non-steroidal anti-inflammatory drugs are now also imposing substantial diagnostic and therapeutic challenges. This Seminar aims to provide a balanced overview of the latest advances in the pathogenetic mechanisms of peptic ulcers, guidelines on therapies targeting H pylori infection, approaches to treatment of peptic ulcer complications associated with anti-inflammatory analgesics and anti-thrombotic agents, and the unmet needs in terms of our knowledge and management of this increasingly challenging condition.
The arcsine square root transformation has long been standard procedure when analyzing proportional data in ecology, with applications in data sets containing binomial and non-binomial response ...variables. Here, we argue that the arcsine transform should not be used in either circumstance. For binomial data, logistic regression has greater interpretability and higher power than analyses of transformed data. However, it is important to check the data for additional unexplained variation, i.e., overdispersion, and to account for it via the inclusion of random effects in the model if found. For non-binomial data, the arcsine transform is undesirable on the grounds of interpretability, and because it can produce nonsensical predictions. The logit transformation is proposed as an alternative approach to address these issues. Examples are presented in both cases to illustrate these advantages, comparing various methods of analyzing proportions including untransformed, arcsine- and logit-transformed linear models and logistic regression (with or without random effects). Simulations demonstrate that logistic regression usually provides a gain in power over other methods.
Th17 cells have critical roles in mucosal defense and are major contributors to inflammatory disease. Their differentiation requires the nuclear hormone receptor RORγt working with multiple other ...essential transcription factors (TFs). We have used an iterative systems approach, combining genome-wide TF occupancy, expression profiling of TF mutants, and expression time series to delineate the Th17 global transcriptional regulatory network. We find that cooperatively bound BATF and IRF4 contribute to initial chromatin accessibility and, with STAT3, initiate a transcriptional program that is then globally tuned by the lineage-specifying TF RORγt, which plays a focal deterministic role at key loci. Integration of multiple data sets allowed inference of an accurate predictive model that we computationally and experimentally validated, identifying multiple new Th17 regulators, including Fosl2, a key determinant of cellular plasticity. This interconnected network can be used to investigate new therapeutic approaches to manipulate Th17 functions in the setting of inflammatory disease.
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► Integrated function of multiple transcription factors in Th17 cell differentiation ► Binding of BATF-IRF4 complexes to DNA mediates chromatin accessibility ► Network-predicted AP-1 factor Fosl2 restricts plasticity of Th17 cells ► Integration of multiple data sets in network most accurately predicts Th17 regulators
Integrating genome-wide regulatory information for key transcription factors involved in the development of proinflammatory Th17 cells produces a highly accurate and predictive network model for lineage specification and function.
Alterations of gut microbiota are associated with colorectal cancer (CRC) in different populations and several bacterial species were found to contribute to the tumorigenesis. The potential use of ...gut microbes as markers for early diagnosis has also been reported. However, cohort specific noises may distort the structure of microbial dysbiosis in CRC and lead to inconsistent results among studies. In this regard, our study targeted at exploring changes in gut microbiota that are universal across populations at species level.
Based on the combined analysis of 526 metagenomic samples from Chinese, Austrian, American, and German and French cohorts, seven CRC-enriched bacteria (Bacteroides fragilis, Fusobacterium nucleatum, Porphyromonas asaccharolytica, Parvimonas micra, Prevotella intermedia, Alistipes finegoldii, and Thermanaerovibrio acidaminovorans) have been identified across populations. The seven enriched bacterial markers classified cases from controls with an area under the receiver-operating characteristics curve (AUC) of 0.80 across the different populations. Abundance correlation analysis demonstrated that CRC-enriched and CRC-depleted bacteria respectively formed their own mutualistic networks, in which the latter was disjointed in CRC. The CRC-enriched bacteria have been found to be correlated with lipopolysaccharide and energy biosynthetic pathways.
Our study identified potential diagnostic bacterial markers that are robust across populations, indicating their potential universal use for non-invasive CRC diagnosis. We also elucidated the ecological networks and functional capacities of CRC-associated microbiota.
Many oxidation–reduction (redox) enzymes, particularly oxygenases, have roles in reactions that make and break C–C bonds. The list includes cytochrome P450 and other heme-based monooxygenases, ...heme-based dioxygenases, nonheme iron mono- and dioxygenases, flavoproteins, radical S-adenosylmethionine enzymes, copper enzymes, and peroxidases. Reactions involve steroids, intermediary metabolism, secondary natural products, drugs, and industrial and agricultural chemicals. Many C–C bonds are formed via either (i) coupling of diradicals or (ii) generation of unstable products that rearrange. C–C cleavage reactions involve several themes: (i) rearrangement of unstable oxidized products produced by the enzymes, (ii) oxidation and collapse of radicals or cations via rearrangement, (iii) oxygenation to yield products that are readily hydrolyzed by other enzymes, and (iv) activation of O2 in systems in which the binding of a substrate facilitates O2 activation. Many of the enzymes involve metals, but of these, iron is clearly predominant.
Peptic ulcer disease Malfertheiner, Peter, Prof; Chan, Francis KL, MD; McColl, Kenneth EL, MD
The Lancet (British edition),
10/2009, Letnik:
374, Številka:
9699
Journal Article
Recenzirano
Summary Peptic ulcer disease had a tremendous effect on morbidity and mortality until the last decades of the 20th century, when epidemiological trends started to point to an impressive fall in its ...incidence. Two important developments are associated with the decrease in rates of peptic ulcer disease: the discovery of effective and potent acid suppressants, and of Helicobacter pylori . With the discovery of H pylori infection, the causes, pathogenesis, and treatment of peptic ulcer disease have been rewritten. We focus on this revolution of understanding and management of peptic ulcer disease over the past 25 years. Despite substantial advances, this disease remains an important clinical problem, largely because of the increasingly widespread use of non-steroidal anti-inflammatory drugs (NSAIDs) and low-dose aspirin. We discuss the role of these agents in the causes of ulcer disease and therapeutic and preventive strategies for drug-induced ulcers. The rare but increasingly problematic H pylori -negative NSAID-negative ulcer is also examined.
Inappropriate use of antibiotics is a global public health challenge and has been associated with antibiotic resistance. WHO reports show that efforts to promote rational antibiotic use in developing ...countries are poor. With the growing number of infections with antibiotic resistant bacteria, rational drug use becomes imperative and studies that promote rational drug use are highly necessary. Considering this, we investigated prescribing patterns and predictors of antibiotic prescription in primary health care facilities in Kumbo East (KE) and Kumbo West (KW) health districts in North West Cameroon, to contribute data which could influence policy on antibiotic use.
A cross sectional retrospective study was conducted from April 2014 to April 2015 in 26 randomly selected primary care facilities. Questionnaires were administered to 59 antibiotic prescribers to determine factors that predict antibiotic prescribing. Data on antibiotic prescription were collected by review of consultation registers. Prescription rates and demographics, prescriber and institution factors were analyzed using ANOVA. The best predictor of prescription was determined using multiple linear regression analysis.
A total of 30,096 prescriptions were reviewed. Overall antibiotic prescription rate was 36.71%, with a mean of 1.14 antibiotics prescribed per patient. Amoxicillin was the most prescribed (29.9%). The most prevalent indications for prescribing were respiratory tract infections (21.27%). All antibiotics prescribed were broad-spectrum. Antibiotics were prescribed for patients with malaria and also in situations where diagnosis was uncertain. Prescribing by generic name was 98.36% while 99.87% was from Essential Drug List. Use of laboratory results, patient turnout and Performance Based Financing (PBF) were significantly associated with antibiotic prescribing rates (p < 0.05). PBF moderated prescribing.
There was misuse of antibiotics in primary care facilities in study area. We recommend all primary care health facilities in study area to be included in the PBF scheme and that prescribing should only be done by physicians as the have adequate training.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The gastrointestinal tract is involved in coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The gut microbiota has important roles in viral ...entry receptor angiotensin-converting enzyme 2 (ACE2) expression, immune homeostasis, and crosstalk between the gut and lungs, the 'gut-lung axis'. Emerging preclinical and clinical studies indicate that the gut microbiota might contribute to COVID-19 pathogenesis and disease outcomes; SARS-CoV-2 infection was associated with altered intestinal microbiota and correlated with inflammatory and immune responses. Here, we discuss the cutting-edge evidence on the interactions between SARS-CoV-2 infection and the gut microbiota, key microbial changes in relation to COVID-19 severity and host immune dysregulations with the possible underlying mechanisms, and the conceivable consequences of the pandemic on the human microbiome and post-pandemic health. Finally, potential modulatory strategies of the gut microbiota are discussed. These insights could shed light on the development of microbiota-based interventions for COVID-19.
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