Nonalcoholic fatty liver disease (NAFLD) and its inflammatory and often progressive subtype nonalcoholic steatohepatitis (NASH) are becoming the leading cause of liver-related morbidity and mortality ...worldwide, and a primary indication for liver transplantation. The pathophysiology of NASH is multifactorial and not yet completely understood; however, innate immunity is a major contributing factor in which liver-resident macrophages (Kupffer cells) and recruited macrophages play a central part in disease progression. In this Review, we assess the evidence for macrophage involvement in the development of steatosis, inflammation and fibrosis in NASH. In this process, not only the polarization of liver macrophages towards a pro-inflammatory phenotype is important, but adipose tissue macrophages, especially in the visceral compartment, also contribute to disease severity and insulin resistance. Macrophage activation is mediated by factors such as endotoxins and translocated bacteria owing to increased intestinal permeability, factors released from damaged or lipoapoptotic hepatocytes, as well as alterations in gut microbiota and defined nutritional components, including certain free fatty acids, cholesterol and their metabolites. Reflecting the important role of macrophages in NASH, we also review studies investigating drugs that target macrophage recruitment to the liver, macrophage polarization and their inflammatory effects as potential treatment options for patients with NASH.
New Zealand’s Pacific Reset, a significant shift in New Zealand’s foreign policy towards the Pacific Islands region, was launched in 2018 by the government of Prime Minister Jacinda Ardern. The ...Pacific Reset emphasises engagement, partnerships, and collaboration, and a greater focus on soft power, public diplomacy and people-to-people measures. It has resulted in an increase in New Zealand public diplomacy in the Pacific, including a new broadcasting initiative, and enhanced domestic public diplomacy. The language and objectives of the Pacific Reset replicate key characteristics of the New Public Diplomacy, which is frequently distinguished from the ‘old’ on the basis of two way engagement. This article argues that whilst the Pacific Reset seeks to reflect the ethos of the New Public Diplomacy, in practice, New Zealand’s Pacific public diplomacy is a mixed bag. In a contested and crowded strategic and public diplomacy environment, putting into practice a New Public Diplomacy demands a greater focus on listening.
Here we report a fully automated, flow-based approach to solid-phase polypeptide synthesis, with amide bond formation in 7 seconds and total synthesis times of 40 seconds per amino acid residue. ...Crude peptide purities and isolated yields were comparable to those for standard-batch solid-phase peptide synthesis. At full capacity, this approach can yield tens of thousands of individual 30-mer peptides per year.
Fecal microbiota transplantation (FMT) is recommended for treatment of recurrent Clostridium difficile infection (rCDI). We performed a single-center randomized trial to compare the effects of FMT ...with those of fidaxomicin and vancomycin.
We studied consecutive adults with rCDI seen at a gastroenterology clinic in Denmark from April 5, 2016 through June 10, 2018. Patients were randomly assigned to a group that received FMT, applied by colonoscopy or nasojejunal tube, after 4–10 days of vancomycin (125 mg 4 times daily; FMTv; n = 24), 10 days of fidaxomicin (200 mg twice daily; n = 24), or 10 days of vancomycin (125 mg 4 times daily; n = 16). Patients who had rCDI after this course of treatment and patients who could not be randomly assigned to groups were offered rescue FMTv. The primary outcome was combined clinical resolution and a negative result from a polymerase chain reaction test for Clostridium difficile (CD) toxin 8 weeks after the allocated treatment. Secondary end points included clinical resolution at week 8.
All 64 patients received their assigned treatment. The combination of clinical resolution and negative results from the test for CD were observed in 17 patients given FMTv (71%), 8 patients given fidaxomicin (33%), and 3 patients given vancomycin (19%; P = .009 for FMTv vs fidaxomicin; P = .001 for FMTv vs vancomycin; P = .31 for fidaxomicin vs vancomycin). Clinical resolution was observed in 22 patients given FMTv (92%), 10 patients given fidaxomicin (42%), and 3 patients given vancomycin (19%; P = .0002; P < .0001; P = .13). Results did not differ significantly between patients who received FMTv as their initial therapy and patients who received rescue FMTv. There was 1 serious adverse event that might have been related to FMTv.
In a randomized trial of patients with rCDI, we found the FMTv combination superior to fidaxomicin or vancomycin based on end points of clinical and microbiological resolution or clinical resolution alone. ClinicalTrials.gov, number NCT02743234; EudraCT, j.no 2015-003004-24.
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Assessing "dysbiosis" in intestinal microbial communities is increasingly considered a routine analysis in microbiota studies, and it has added relevant information to the prediction and ...characterization of diseases and other adverse conditions. However, dysbiosis is not a well-defined condition. A variety of different dysbiosis indexes have been suggested and applied, but their underlying methodologies, as well as the cohorts and conditions for which they have been developed, differ considerably. To date, no comprehensive overview and comparison of all the different methodologies and applications of such indexes is available. Here, we list all types of dysbiosis indexes identified in the literature, introduce their methodology, group them into categories, and discuss their potential descriptive and clinical applications as well as their limitations. Thus, our focus is not on the implications of dysbiosis for disease but on the methodological approaches available to determine and quantify this condition.
Abstract
IEC TS 60079-32-1 “ATEX - Electrostatic hazards, guidance” gives us the best practice to avoid ignition from electrostatic sources. In Solvay we follow this guideline but, when we find that ...our existing practice, at a particular site for a particular chemical process in a particular piece of equipment, does not comply with that guidance, we are faced with a difficult question: what priority should we give to putting it right? To answer that question we have to analyse the risk associated with electrostatic ignition sources for the particular process and that particular piece of equipment. It depends on many factors, including the frequency of the presence of an explosive atmosphere, the Minimum Ignition Energy of the flammable gas or combustible dust and the number of people who would be exposed to the blast wave or shrapnel from an explosion or the thermal radiation from a fire. Such considerations allow us to prioritize the risk in three levels, ranging from Risk 1 (Unacceptable), through Risk 2 (Intermediate) to Risk 3 = Acceptable. This paper shows how to estimate the risk level of scenarios involving electrostatic and indeed other ignition sources using the Solvay method.
Abstract
Background
Clostridioides (Clostridium) difficile infection (CDI) is a leading cause of antibiotics-associated diarrhoea. Faecal microbiota transplantation (FMT) is effective for recurrent ...CDI and may be provided as a home treatment to frail, older people.
Methods
We present four consecutive patients with recurrent CDI, treated at home using nasojejunal tube-delivered or encapsulated donor faeces. The primary outcome was combined clinical resolution and a negative CD toxin test 8 weeks post-treatment.
Results
All four patients had severe CDI and all improved clinically following one FMT. Sustained resolution following one FMT was observed in one patient. Two patients had recurrence and received a second FMT using capsules; both achieved resolution. One patient who had recurrence declined from further FMT due to fear of relapse and was established on long-term vancomycin. No adverse events related to FMT were observed.
Conclusion
Frail older people may benefit from FMT. Home treatment is a viable option and may be considered both for clinical cure and for palliation.
Summary
Background
Nutrition support teams (NST) may improve parenteral nutrition (PN) outcomes. No previous systematic review has provided conclusive data on catheter‐related infection (CRI) ...occurrence after NST introduction, nor have previous studies performed meta‐analysis or graded the evidence.
Aims
To systematically evaluate the effects of implementing an NST for hospitalised adults on PN and compare these with standard care.
Methods
This was a systematic review and meta‐analysis, pre‐registered in PROSPERO (CRD42020218094). On November 24, 2020, PubMed, Web of science, Scopus, Embase, Cochrane Library, and Clinical Key were searched. Clinical trials and observational studies with a standard care comparator were included. Primary outcome was relative reduction in CRI rate. A random‐effects meta‐analysis was used to estimate effects, and evidence was rated using Cochrane and GRADE methodologies.
Results
Twenty‐seven studies with 8166 patients were included. Across 10 studies, NST introduction reduced the CRI rate (IRR = 0.32, 95% CI: 0.19‐0.53) with −8 (95% CI: −12 to −5) episodes per 1000 catheter days compared with standard care. Hypophosphataemia occurred less frequently (IRD = −12%, 95% CI: −24% to −1%) and 30‐day mortality decreased (IRD = −6%, 95% CI: −11% to −1%). Inappropriate PN use decreased, both judged by indication (IRD = −18%, 95% CI: −28% to −9%) and duration (IRD = −21%, 95% CI: −33% to −9%). Evidence was rated very low to moderate.
Conclusions
This study documents the clinical impact of introducing an NST, with moderate‐grade evidence for the reduction of CRI occurrence compared with standard care. Further, NST introduction significantly reduced metabolic complications, mortality, and inappropriate PN use.
Summary of effects of implementing a nutrition support team for in‐hospital parenteral nutrition. Effects include significant improvements in key outcome and benchmarking variables of nutrition support team performance, including reduced occurrence of catheter‐related infections, mortality, metabolic complications, and inappropriate parenteral nutrition use.
As applied to the Russian case, identity politics means first and foremost a state strategy that regulates the public expressions of ethnicity-based solidarity in a way that prevents them from being ...motivated by a sense of injustice. With regard to Russia’s Central Asian residents, injustice lies in tacit racist treatment by officials, police officers, employers and landlords. The peculiarity of officially recognised Central Asian organisations operating on the basis of state nationalities policy institutions is that they contribute to maintaining the status quo. They do so through orchestrating cultural activities that reproduce stereotypical images of harmonious ethnic diversity in Russia, as well as by supervising labour migrants. However, there are members in these organisations who do manage to use the resources of Russia’s rather idiosyncratic nationalities policy to fulfil their own aspirations, i.e. to practice identity politics for which the policy is not intended.
OBJECTIVE
The study characterizes cannabis toxicity in relation to tetrahydrocannabinol (THC) dose in pediatric edible cannabis ingestions.
METHODS
This is a retrospective review of children aged <6 ...years presenting with edible cannabis ingestions of known THC dose within a pediatric hospital network (January 1, 2015–October 25, 2022). Cannabis toxicity was characterized as severe if patients exhibited severe cardiovascular (bradycardia, tachycardia/hypotension requiring vasopressors or intravenous fluids, other dysrhythmias), respiratory (respiratory failure, apnea, requiring oxygen supplementation), or neurologic (seizure, myoclonus, unresponsiveness, responsiveness to painful stimulation only, requiring intubation or sedation) effects. Cannabis toxicity was characterized as prolonged if patients required >6 hours to reach baseline. The relationship between THC dose and severe and prolonged toxicity was explored using multivariable logistic regression and receiver operator characteristic curve analyses.
RESULTS
Eighty patients met inclusion. The median age was 2.9 years. The median THC ingestion was 2.1 mg/kg. Severe and prolonged toxicity was present in 46% and 74%, respectively. THC dose was a significant predictor of severe (adjusted odds ratio 2.9, 95% confidence interval: 1.8–4.7) and prolonged toxicity (adjusted odds ratio 3.2, 95% confidence interval: 1.6–6.5), whereas age and sex were not. Area under the curve was 92.9% for severe and 87.3% for prolonged toxicity. THC ingestions of ≥1.7 mg/kg can predict severe (sensitivity 97.3%) and prolonged toxicity (sensitivity 75.4%).
CONCLUSIONS
The THC dose of edible cannabis correlates to the degree of toxicity in children <6 years old. The threshold of 1.7 mg/kg of THC may guide medical management and preventive regulations.
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