Hydrogen sulfide (H2S) has become recognized as an important signalling molecule throughout the body, contributing to many physiological and pathological processes. In recent years, improved methods ...for measuring H2S levels and the availability of a wider range of H2S donors and more selective inhibitors of H2S synthesis have helped to more accurately identify the many biological effects of this highly reactive gaseous mediator. Animal studies of several H2S-releasing drugs have demonstrated considerable promise for the safe treatment of a wide range of disorders. Several such drugs are now in clinical trials.
The COVID-19 pandemic is anticipated to continue spreading widely across the globe throughout 2020. To mitigate the devastating impact of COVID-19, social distancing and visitor restrictions in ...health care facilities have been widely implemented. Such policies and practices, along with the direct impact of the spread of COVID-19, complicate issues of grief that are relevant to medical providers. We describe the relationship of the COVID-19 pandemic to anticipatory grief, disenfranchised grief, and complicated grief for individuals, families, and their providers. Furthermore, we provide discussion regarding countering this grief through communication, advance care planning, and self-care practices. We provide resources for health care providers, in addition to calling on palliative care providers to consider their own role as a resource to other specialties during this public health emergency.
Inflammation Research Network, University of Calgary, Calgary, Alberta, Canada
Except in rare cases, the stomach can withstand exposure to highly concentrated hydrochloric acid, refluxed bile salts, ...alcohol, and foodstuffs with a wide range of temperatures and osmolarity. This is attributed to a number of physiological responses by the mucosal lining to potentially harmful luminal agents, and to an ability to rapidly repair damage when it does occur. Since the discovery in 1971 that prostaglandin synthesis could be blocked by aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs), there has been great interest in the contribution of prostaglandins to gastric mucosal defense. Prostaglandins modulate virtually every aspect of mucosal defense, and the importance of this contribution is evident by the increased susceptibility of the stomach to injury following ingestion of an NSAID. With chronic ingestion of these drugs, the development of ulcers in the stomach is a significant clinical concern. Research over the past two decades has helped to identify some of the key events triggered by NSAIDs that contribute to ulcer formation and/or impair ulcer healing. Recent research has also highlighted the fact that the protective functions of prostaglandins in the stomach can be carried out by other mediators, in particular the gaseous mediators nitric oxide and hydrogen sulfide. Better understanding of the mechanisms through which the stomach is able to resist injury in the presence of luminal irritants is helping to drive the development of safer anti-inflammatory drugs, and therapies to accelerate and improve the quality of ulcer healing.
Immunopathology of inflammatory bowel disease Wallace, Kori L; Zheng, Li-Bo; Kanazawa, Yoshitake ...
World journal of gastroenterology : WJG,
01/2014, Letnik:
20, Številka:
1
Journal Article
Odprti dostop
Inflammatory bowel disease(IBD)results from a complex series of interactions between susceptibility genes,the environment,and the immune system.The host microbiome,as well as viruses and fungi,play ...important roles in the development of IBD either by causing inflammation directly or indirectly through an altered immune system.New technologies have allowed researchers to be able to quantify the various components of the microbiome,which will allow for future developments in the etiology of IBD.Various components of the mucosal immune system are implicated in the pathogenesis of IBD and include intestinal epithelial cells,innate lymphoid cells,cells of the innate(macrophages/monocytes,neutrophils,and dendritic cells)and adaptive(T-cells and B-cells)immune system,and their secreted mediators(cytokines and chemokines).Either a mucosal susceptibility or defect in sampling of gut luminal antigen,possibly through the process of autophagy,leads to activation of innate immune response that may be mediated by enhanced toll-like receptor activity.The antigen presenting cells then mediate the differentiation of na?ve T-cells into effector T helper(Th)cells,including Th1,Th2,and Th17,which alter gut homeostasis and lead to IBD.In this review,the effects of these components in the immunopathogenesis of IBD will be discussed.
With the future of liberal internationalism in question, how will China's growing power and influence reshape world politics? We argue that views of the Liberal International Order (LIO) as ...integrative and resilient have been too optimistic for two reasons. First, China's ability to profit from within the system has shaken the domestic consensus in the United States on preserving the existing LIO. Second, features of Chinese Communist Party rule chafe against many of the fundamental principles of the LIO, but could coexist with a return to Westphalian principles and markets that are embedded in domestic systems of control. How, then, do authoritarian states like China pick and choose how to engage with key institutions and norms within the LIO? We propose a framework that highlights two domestic variables—centrality and heterogeneity—and their implications for China's international behavior. We illustrate the framework with examples from China's approach to climate change, trade and exchange rates, Internet governance, territorial sovereignty, arms control, and humanitarian intervention. Finally, we conclude by considering what alternative versions of international order might emerge as China's influence grows.
This article reviews the latest developments in understanding the pathogenesis, detection and treatment of small intestinal damage and bleeding caused by nonsteroidal anti-inflammatory drugs ...(NSAIDs). With improvements in the detection of NSAID-induced damage in the small intestine, it is now clear that this injury and the associated bleeding occurs more frequently than that occurring in the stomach and duodenum, and can also be regarded as more dangerous. However, there are no proven-effective therapies for NSAID-enteropathy, and detection remains a challenge, particularly because of the poor correlation between tissue injury and symptoms. Moreover, recent studies suggest that commonly used drugs for protecting the upper gastrointestinal tract (i.e., proton pump inhibitors) can significantly worsen NSAID-induced damage in the small intestine. The pathogenesis of NSAID-enteropathy is complex, but studies in animal models are shedding light on the key factors that contribute to ulceration and bleeding, and are providing clues to the development of effective therapies and prevention strategies. Novel NSAIDs that do not cause small intestinal damage in animal models offer hope for a solution to this serious adverse effect of one of the most widely used classes of drugs.
Global surface temperature is predicted to increase by 1.4–5.8°C by the end of this century. However, the impacts of this projected warming on soil C balance and the C budget of terrestrial ...ecosystems are not clear. One major source of uncertainty stems from warming effects on soil microbes, which exert a dominant influence on the net C balance of terrestrial ecosystems by controlling organic matter decomposition and plant nutrient availability. We, therefore, conducted an experiment in a tallgrass prairie ecosystem at the Great Plain Apiaries (near Norman, OK) to study soil microbial responses to temperature elevation of about 2°C through artificial heating in clipped and unclipped field plots. While warming did not induce significant changes in net N mineralization, soil microbial biomass and respiration rate, it tended to reduce extractable inorganic N during the second and third warming years, likely through increasing plant uptake. In addition, microbial substrate utilization patterns and the profiles of microbial phospholipid fatty acids (PLFAs) showed that warming caused a shift in the soil microbial community structure in unclipped subplots, leading to the relative dominance of fungi as evidenced by the increased ratio of fungal to bacterial PLFAs. However, no warming effect on soil microbial community structure was found in clipped subplots where a similar scale of temperature increase occurred. Clipping also significantly reduced soil microbial biomass and respiration rate in both warmed and unwarmed plots. These results indicated that warming‐led enhancement of plant growth rather than the temperature increase itself may primarily regulate soil microbial response. Our observations show that warming may increase the relative contribution of fungi to the soil microbial community, suggesting that shifts in the microbial community structure may constitute a major mechanism underlying warming acclimatization of soil respiration.
The mechanisms underlying the ability of nonsteroidal anti‐inflammatory drugs (NSAIDs) to cause ulceration in the stomach and proximal duodenum are well understood, and this injury can largely be ...prevented through suppression of gastric acid secretion (mainly with proton pump inhibitors). In contrast, the pathogenesis of small intestinal injury induced by NSAIDs is less well understood, involving more complex mechanisms than those in the stomach and proximal duodenum. There is clear evidence for important contributions to NSAID enteropathy of enteric bacteria, bile and enterohepatic recirculation of the NSAID. There is no evidence that suppression of gastric acid secretion will reduce the incidence or severity of NSAID enteropathy. Indeed, clinical data suggest little, if any, benefit. Animal studies suggest a significant exacerbation of NSAID enteropathy when proton pump inhibitors are co‐administered with the NSAID. This worsening of damage appears to be linked to changes in the number and types of bacteria in the small intestine during proton pump inhibitor therapy. The distinct mechanisms of NSAID‐induced injury in the stomach/proximal duodenum versus the more distal small intestine likely dictate distinct strategies for prevention.
From reviews of earlier editions: “Young people get into legal trouble for two reasons: they do not know what the law is, and they do not stop to think about the consequences of their actions. This ...book would make a good text for a preparation for life class. . . . The book is written in plain language, unencumbered by a lot of legal citations, and with no expectation that the reader will have any working knowledge of the law."—Texas Bar Journal“A book any parent should consider giving their child. . . . But before you do, take a look at it yourself. No matter the title, Wallace’s book . . . contains information everyone . . . should know."—Austin American-Statesman What Every Teen Should Know about Texas Law is the only single-source guide for accurate, easy-to-understand information about most areas of civil law in Texas. L. Jean Wallace drew on years of experience as a students’ attorney at Texas Tech University to inform young adults about the areas of law that affect them most: driving and car ownership, pranks and crimes (including alcohol and drug offenses), personal relationships, employment and consumer concerns, and living on their own. She illustrated her points with true, sometimes humorous, stories of young adults’ encounters with the law. For this new edition, municipal judge Christopher F. Cypert has completely updated the book to reflect the current state of the law. He covers specific topics that are now mandated to be taught in schools, including the proper way to interact with peace officers during traffic stops and other in-person encounters, as well as internet-era misbehaviors such as sexting and cyberbullying. Like Wallace, Cypert has helped many young people navigate the sometimes confusing processes of the legal world, often loaning earlier editions of this book to young offenders in his court. Both authors’ real-world experience and legal expertise ensure that What Every Teen Should Know about Texas Law is indeed a complete and practical guide for assuming the responsibilities of adulthood—as well as a good refresher course for all legal-age Texans.
Understanding of human structural brain development has rapidly advanced in recent years, but remains fundamentally “localizational” in nature. Here, we use 376 longitudinally acquired structural ...brain scans from 108 typically developing adolescents to conduct the first study of coordinated anatomical change within the developing cortex. Correlation in rates of anatomical change was regionally heterogeneous, with fronto-temporal association cortices showing the strongest and most widespread maturational coupling with other cortical areas, and lower-order sensory cortices showing the least. Canonical cortical systems with rich structural and functional interconnectivity showed significantly elevated maturational coupling. Evidence for sexually dimorphic maturational coupling was found within a frontopolar-centered prefrontal system involved in complex decision-making. By providing the first link between cortical connectivity and the coordination of cortical development, we reveal a hitherto unseen property of healthy brain maturation, which may represent a target for neurodevelopmental disease processes, and a substrate for sexually dimorphic behavior in adolescence.
► Rates of structural maturation are highly coordinated within the cortical sheet ► Maturational coupling with other cortices is maximal in association cortex ► Maturational coupling echoes known patterns of structural and functional connectivity ► Prefrontal maturational coupling in adolescence is sexually dimorphic
PDF
