Dangerous dietary supplements: Garcinia cambogia-associated hepatic failure requiring transplantation

Commercial dietary supplements are marketed as a panacea for the morbidly obese seeking sustainable weight-loss. Unfortunately, many claims cited by supplements are unsupported and inadequately regulated. Most concerning, how ever, are the associated harmful side effects, often unrecognized by consumers. Garcinia cambogia extract and Garcinia cambogia containing products are some of the most popular dietary supplements currently marketed for weight loss. Here, we report the first known case of fulminant hepatic failure associated with this dietary supplement. One active ingredient in this supplement is hydroxycitric acid, an active ingredient also found in weight-loss supplements banned by the Food and Drug Administration in 2009 for hepatotoxicity. Heightened awareness of the dangers of dietary supplements such as Garcinia cambogia is imperative to prevent hepatoxicity and potential fulminant hepatic failure in additional patients.

From bronchiolitis guideline to practice: A critical care perspective

Acute viral bronchiolitis is a leading cause of admission to pediatric intensive care units, but research on the care of these critically ill infants has been limited. Pathology of viral bronchiolitis revealed respiratory obstruction due to intraluminal debris and edema of the airways and vasculature. This and clinical evidence suggest that airway clearance interventions such as hypertonic saline nebulizers and pulmonary toilet devices may be of benefit, particularly in situations of atelectasis associated with bronchiolitis. Research to distinguish an underlying asthma predisposition in wheezing infants with viral bronchiolitis may one day lead to guidance on when to trial bronchodilator therapy. Considering the paucity of critical care research in pediatric viral bronchiolitis, intensive care practitioners must substantially rely on individualization of therapies based on bedside clinical assessments. However, with the introduction of new diagnostic and respiratory technologies, our ability to support critically ill infants with acute viral bronchiolitis will continue to advance.

Gut microbiome and pancreatic cancer cachexia:An evolving relationship

Nearly 80% of patients with pancreatic ductal adenocarcinoma(PDAC)develop cachexia along their disease course.Cachexia is characterized by progressive weight loss,muscle wasting,and systemic inflammation and has been linked to poorer outcomes and impairments in quality of life.Management of PDAC cachexia has historically involved a multidisciplinary effort comprised of nutritional support,pancreatic enzyme replacement therapy,and/or pharmacologic interventions.Despite current interventions to mitigate PDAC cachexia,a significant proportion of patients continue to die from complications associated with cachexia underscoring the need for novel insights and treatments for this syndrome.We highlight the feasibility and effectiveness of a recent enteral feeding prospective trial at our institution to improve cachexia outcomes in patients with advanced PDAC.Additionally,we were among the first to characterize the stool microbiome composition in patients with advanced PDAC receiving enteral feeding for the treatment of cachexia.Novel insights into the relationship between enteral nutritional support,cachexia,and the gut microbiome are presented.These promising results are discussed in the context of a potential ability to modulate the stool microbiome as a new interventional strategy to mitigate PDAC cachexia.

An Essay on the Prerequisites for the Probability Theory

The probability calculus and statistics as well permeate nearly every discipline and professional sector, while no theories underpinning this wide spreading field reached universal consensus so far. The probability interpretations present irreconcilable traits, so the concept of probability is still substantially unclear. Purpose of this work: The present paper intends to demonstrate how the different models of probability constitute the facial problem which conceals another hidden and more fundamental question. Method: We show how authors do not agree with the concept of probability P and moreover they have different ideas about the precise object qualified by P, which has priority from the point of logic. It is clear how the element X measured by P(X) influences its meaning. In consequence of the conflicting opinions, theorists tend toward a compromise. They use the outcome or result of an experiment as the argument X of P(X) and represent X as a subset of the event space. This paper suggests replacing the outcome-subset with the event-triad E, which provides a comprehensive mathematical support. Results: The last section shows how the triadic model is formally consistent with the conventional theories and can integrate the conflicting views on probability. This unifying result can help mathematicians to go beyond the present theoretical deadlock. In summary, this paper advocates a more explicit notation system for probability and points out how probability can be ambiguous without rigorous specification of the sample space and the experiment in general.

Tumor heterogeneity in VHL drives metastasis in clear cell renal cell carcinoma

Loss of function of the von Hippel-Lindau(VHL)tumor suppressor gene is a hallmark of clear cell renal cell carcinoma(ccRCC).The importance of heterogeneity in the loss of this tumor suppressor has been under reported.To study the impact of intratumoral VHL heterogeneity observed in human ccRCC,we engineered VHL gene deletion in four RCC models,including a new primary tumor cell line derived from an aggressive metastatic case.The VHL gene-deleted(VHL-KO)cells underwent epithelial-to-mesenchymal transition(EMT)and exhibited increased motility but diminished proliferation and tumorigenicity compared to the parental VHL-expressing(VHL+)cells.Renal tumors with either VHL+or VHL-KO cells alone exhibit minimal metastatic potential.Combined tumors displayed rampant lung metastases,highlighting a novel cooperative metastatic mechanism.The poorly proliferative VHL-KO cells stimulated the proliferation,EMT,and motility of neighboring VHL+cells.Periostin(POSTN),a soluble protein overexpressed and secreted by VHL non-expressing(VHL−)cells,promoted metastasis by enhancing the motility of VHL-WT cells and facilitating tumor cell vascular escape.Genetic deletion or antibody blockade of POSTN dramatically suppressed lung metastases in our preclinical models.This work supports a new strategy to halt the progression of ccRCC by disrupting the critical metastatic crosstalk between heterogeneous cell populations within a tumor.

辅助使用抗生素治疗可提高脓肿引流的临床治愈率

背景 皮肤脓肿的主要治疗方法是引流。在社区相关耐甲氧西林金黄色葡萄球菌（MRSA）感染出现前后，美国及其他一些国家曾对辅助用抗生素治疗进行过研究。但这些研究不仅规模小而且未清楚证明辅助用抗生素的疗效。2016年，Talan等,在美国进行了一项随机安慰剂对照试验（RCT），共有1265名受试者参加，其中大部分为成年人，一些有合并症的患者也包含在内。

Cellular and molecular mechanisms implicated in pathogenesis of selective neurodegeneration in Huntington＇s disease

Huntington＇s disease （HD） is one of the most common dominantly-inherited neurodegenerative disorders and is caused by a CAG repeat expansion in the huntingtin gene. HD is characterized by selective degeneration of subpopulations of neurons in the brain, however the precise underlying mechanisms how a ubiquitously expressed disease protein could target specific types of neurons for degeneration remains a critical, yet unanswered question for HD and other major neurodegenerative disorders. In this review, we describe the expanding view of selective neuronal vulnerability in HD, based on recent neuropathological and neuroimaging studies. We will also summarize the systematic effort to define the cell types in which mutant Huntingtin expression is critical for pathogenesis of vulnerable neurons in the striatum and cortex. Finally, we will describe selected, emerging molecular mechanisms that are implicated in selective disease processes in HD. Together, the field has begun to appreciate the distinct molecular pathogenic roles of mutant huntingtin in different cell types that may contribute to the selective neuronal vulnerability, with dissection of such mechanisms likely to yield novel molecular targets for HD therapy.

Comparative immunology

As a discipline,comparative immunology enhances zoology and has gained wide acceptance in the biological sciences.It is an offshoot of the parent field,immunology,and is an amalgam of immunology and zoology.All animals from protozoans to humans have solved the threat of extinction by having evolved an immune-defense strategy that ensures the capacity to react against foreign,non-self microorganisms and cancers that disturb the homeostatic self.Invertebrate-type innate immune responses evolved first and they characterize the metazoans.These rapid natural responses act immediately and are often essential for the occurrence of slower,more specific,adaptive vertebratetype immune responses.As components of the innate immune system,there is an emphasis on several major steps in the evolutionary process:(i)recognition;(ii)the phagocytic cell;and(iii)the natural killer cell.When vertebrates evolved,beginning with fish,thymus-controlled T cells first appeared,as did bone marrow-derived B cells(first found in amphibians with long bones).These were the precursors of the plasma cells that synthesize and secrete antibodies.Confirming the concept of self/non-self,invertebrates possess natural,non-adaptive,innate,non-clonal,non-anticipatory immune responses,whereas vertebrates possess adaptive,acquired,clonal,and anticipatory responses.This symposium concerns:(i)aspects of the immune spectrum in representative groups;(ii)specific findings(in particular models;e.g.earthworms);(iii)clues as to the possible biomedical application of relevant molecules derived from animals,notably invertebrates;and(iv)some views on the more practical applications of understanding immune systems of invertebrates and ectotherms,and their possible role in survival.