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•Serum FGF19 and bile acids are significantly increased in patients with alcoholic hepatitis.•Total and conjugated bile acids correlated positively with FGF19 and with disease ...severity (MELD score).•Modulation of bile acid metabolism or signaling could represent a promising target for treatment of alcoholic hepatitis.
The degree of cholestasis is an important disease driver in alcoholic hepatitis, a severe clinical condition that needs new biomarkers and targeted therapies. We aimed to identify the largely unknown mechanisms and biomarkers linked to cholestasis in alcoholic hepatitis.
Herein, we analyzed a well characterized cohort of patients with alcoholic hepatitis and correlated clinical and histological parameters and outcomes with serum bile acids and fibroblast growth factor 19 (FGF19), a major regulator of bile acid synthesis.
We found that total and conjugated bile acids were significantly increased in patients with alcoholic hepatitis compared with controls. Serum FGF19 levels were strongly increased and gene expression of FGF19 was induced in biliary epithelial cells and ductular cells of patients with alcoholic hepatitis. De novo bile acid synthesis (CYP7A1 gene expression and C4 serum levels) was significantly decreased in patients with alcoholic hepatitis. Importantly, total and conjugated bile acids correlated positively with FGF19 and with disease severity (model for end-stage liver disease score). FGF19 correlated best with conjugated cholic acid, and model for end-stage liver disease score best with taurine-conjugated chenodeoxycholic acid. Univariate analysis demonstrated significant associations between FGF19 and bilirubin as well as gamma glutamyl transferase, and negative correlations between FGF19 and fibrosis stage as well as polymorphonuclear leukocyte infiltration, in all patients with alcoholic hepatitis.
Serum FGF19 and bile acids are significantly increased in patients with alcoholic hepatitis, while de novo bile acid synthesis is suppressed. Modulation of bile acid metabolism or signaling could represent a promising target for treatment of alcoholic hepatitis in humans.
Understanding the underlying mechanisms that drive alcoholic hepatitis is important for the development of new biomarkers and targeted therapies. Herein, we describe a molecule that is increased in patients with alcoholic hepatitis. Modulating the molecular pathway of this molecule might lead to promising targets for the treatment of alcoholic hepatitis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
We report an economically- and environmentally-promising microalgae biorefinery pathway, which uses catalytic pyrolysis with HZSM-5 catalyst to convert whole microalgae into aromatic hydrocarbons. ...This process produces valuable petrochemicals and ammonia, the latter of which can be recycled as a fertilizer for microalgae cultivation. We tested samples of lipid-lean green microalgae,
Chlorella vulgaris
, at various reaction temperatures and catalyst loads. We also tested samples of lignocellulosic biomass, red oak, for comparison. Our results demonstrated that catalytic pyrolysis of microalgae produces better aromatic yields and better aromatic distributions than catalytic pyrolysis of red oak. The maximum carbon yield of aromatics from microalgae was 24%, while that from red oak was 16.7%. Moreover, catalytic pyrolysis of microalgae produced more monocyclic aromatics than were produced by catalytic pyrolysis of lignocellulosic biomass. Microalgae present many advantages as a feedstock for biofuel. With the promise catalytic pyrolysis offers for solving some of microalgae's disadvantages, microalgae biorefineries move one step closer to economic and environmental feasibility.
Catalytic pyrolysis of microalgae converts protein-rich microalgae into green aromatics, while nitrogen in protein is released in ammonia and recycled for algae growth.
Two patients with amyotrophic lateral sclerosis caused by
SOD1
mutations received an intrathecal infusion of adeno-associated virus containing microRNA targeting
SOD1
. SOD1 protein levels did not ...change in the patients’ cerebrospinal fluid, but one patient had reduced spinal cord SOD1 expression.
The current pandemic due to the severe acute respiratory syndrome coronavirus 2 has caused an extreme burden for health care systems globally, and the number of cases is expected to continue to ...increase, at least in the immediate future. The virus is estimated to have infected more than 1.5 million individuals. The available reports suggest that gastrointestinal (GI) involvement in coronavirus disease 2019 (COVID-19) is common and in some cases the GI symptoms may precede the respiratory symptoms. In addition to direct effects of severe acute respiratory syndrome coronavirus 2, the infected patients remain at risk for the complications commonly managed by gastroenterology and hepatology consultants. The most commonly reported GI manifestation of COVID-19 is diarrhea, which is reported in a third to up to more than half of the patients. Mild to moderate elevation of the liver enzymes are also common, although no case of acute liver failure has been reported so far. Many of the medications used for treatment of COVID-19 can also be associated with GI symptoms or liver injury and can be included in the differential diagnosis in these patients. Although the diagnosis of the infection is currently based on RNA analysis in respiratory samples, the available literature on fecal shedding of this virus suggests that fecal RNA testing might prove to be a useful diagnostic test. It is reasonable to delay all non-urgent endoscopic procedures during the peak of the pandemic and use additional protective equipment such as N95 respirators during endoscopy while most patients can be considered high risk for having been exposed to the virus.
Solid organ transplant recipients may be at a high risk for SARS‐CoV‐2 infection and poor associated outcomes. We herein report our initial experience with solid organ transplant recipients with ...SARS‐CoV‐2 infection at two centers during the first 3 weeks of the outbreak in New York City. Baseline characteristics, clinical presentation, antiviral and immunosuppressive management were compared between patients with mild/moderate and severe disease (defined as ICU admission, intubation or death). Ninety patients were analyzed with a median age of 57 years. Forty‐six were kidney recipients, 17 lung, 13 liver, 9 heart, and 5 dual‐organ transplants. The most common presenting symptoms were fever (70%), cough (59%), and dyspnea (43%). Twenty‐two (24%) had mild, 41 (46%) moderate, and 27 (30%) severe disease. Among the 68 hospitalized patients, 12% required non‐rebreather and 35% required intubation. 91% received hydroxychloroquine, 66% azithromycin, 3% remdesivir, 21% tocilizumab, and 24% bolus steroids. Sixteen patients died (18% overall, 24% of hospitalized, 52% of ICU) and 37 (54%) were discharged. In this initial cohort, transplant recipients with COVID‐19 appear to have more severe outcomes, although testing limitations likely led to undercounting of mild/asymptomatic cases. As this outbreak unfolds, COVID‐19 has the potential to severely impact solid organ transplant recipients.
In this multicenter study of 90 solid organ transplant recipients diagnosed with COVID‐19 during the first three weeks of the outbreak in New York City, the authors report on the clinical presentation, laboratory abnormalities, risk factors, disease severity, and outcomes.
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BFBNIB, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•A mixture of red oak and HDPE is fast pyrolyzed in a fluidized bed.•Optimum pyrolysis temperature was 625°C.•A significant synergistic effect between red oak and HDPE was found.•Co-pyrolysis reduces ...char formation from red oak.•Pyrolysis char had a lower BET surface area than red oak biochar.
Co-pyrolysis of red oak and high density polyethylene (HDPE) was conducted in a laboratory-scale, continuous fluidized bed reactor in a temperature range from 525 to 675°C. Pyrolysis products, including two fractions of pyrolysis-oil, non-condensable gases and char were analyzed to assess the influence of pyrolysis temperature and co-feeding of biomass with HDPE. It was found that increasing pyrolysis temperature up to 625°C promoted the production of pyrolysis-oil and its yield reached 57.6wt%. Further increase in pyrolysis temperature caused the cracking of pyrolysis-oil to form light gases rich in hydrocarbons. Organic phase of pyrolysis-oil produced from plastic-biomass mixture (PBM) had a higher heating value (HHV) up to 36.6MJ/kg contributed by the additive effect of HDPE-derived aliphatic hydrocarbons. A significant synergetic effect was also observed during co-pyrolysis. Co-pyrolysis with HDPE increased the production of furan, acids and water from red oak. Co-presence of HDPE also inhibited char formation from red oak and improved the HHV of the resulting char. The char produced from co-pyrolysis had a significantly lower BET surface area than red oak biochar. Not only did HDPE-derived particulate matter blocks the pores, the synergetic interaction also resulted in the formation of large and shallow micro-pores on the char surface.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Overt hepatic encephalopathy is a generally reversible neurologic complication of cirrhosis. Overt hepatic encephalopathy has been associated with poor hospitalization- and mortality-related ...outcomes, which is important given increasing hepatic encephalopathy-related hospitalizations over time. The aim of this narrative review is to provide an overview of hospital- and mortality-related outcomes in patients with overt hepatic encephalopathy and the pharmacologic therapies that may improve these outcomes. Guideline-recommended prophylaxis with lactulose (first-line therapy) or secondary prophylaxis with rifaximin plus lactulose decreases hospital admissions and mortality rates. Rifaximin or lactulose treatment was beneficial for reducing the hospitalization rate in patients with hepatic encephalopathy compared with no treatment. Further, retrospective studies have shown that rifaximin with or without lactulose was effective for decreasing the number of hepatic encephalopathy episodes, hepatic encephalopathy-related hospitalizations, and duration of hospitalization. Ornithine phenylacetate, an ammonia-reducing agent currently in development, is also being investigated in hospitalized patients with hepatic encephalopathy. Overall, data support that prophylaxis for the prevention of hepatic encephalopathy recurrence improves outcomes in patients with cirrhosis and a history of hepatic encephalopathy.
We report on the catalytic pyrolysis of switchgrass and its three main components (cellulose, hemicellulose and lignin) over H-ZSM5 catalyst. The yields of aromatic hydrocarbons for the three ...components decreased in the following order: cellulose > hemicellulose >> lignin. Moderately higher temperature favored formation of aromatics. The results indicate that H-ZSM5 catalyst did not remove oxygen in an optimal pathway for catalytic pyrolysis of biomass. Dehydration was the dominant oxygen removal mechanism for catalytic pyrolysis, while decarbonylation to CO was favored over decarboxylation to CO sub(2). This suggests that higher yields of aromatics might be achieved by catalyst improvements or reactor design that optimizes deoxygenation pathway. For cellulose and hemicellulose, coke produced catalytically contributed a larger fraction of solid carbonaceous residue than char from purely thermal processes. In the case of lignin, thermal rather than catalytic processes primarily contribute to the production of solid carbonaceous residue. Product distribution from catalytic pyrolysis of switchgrass appeared to be the additive contribution of the three individual components, which indicates that there was no significant interaction among the biomass-derived products.
Expansions of a G
C
repeat in the C9ORF72 gene are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), two devastating adult-onset ...neurodegenerative disorders. Using C9-ALS/FTD patient-derived cells and C9ORF72 BAC transgenic mice, we generated and optimized antisense oligonucleotides (ASOs) that selectively blunt expression of G
C
repeat-containing transcripts and effectively suppress tissue levels of poly(GP) dipeptides. ASOs with reduced phosphorothioate content showed improved tolerability without sacrificing efficacy. In a single patient harboring mutant C9ORF72 with the G
C
repeat expansion, repeated dosing by intrathecal delivery of the optimal ASO was well tolerated, leading to significant reductions in levels of cerebrospinal fluid poly(GP). This report provides insight into the effect of nucleic acid chemistry on toxicity and, to our knowledge, for the first time demonstrates the feasibility of clinical suppression of the C9ORF72 gene. Additional clinical trials will be required to demonstrate safety and efficacy of this therapy in patients with C9ORF72 gene mutations.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Nirmatrelvir/ritonavir (NR) use has not yet been described in solid organ transplant recipients (SOTRs) with mild COVID‐19. The objective was to evaluate outcomes among SOTR and describe the ...drug–drug interaction of NR. This is an IRB‐approved, retrospective study of all adult SOTR on a calcineurin inhibitor (CNI) or mammalian target of rapamycin inhibitor who were prescribed NR between December 28, 2021 and January 6, 2022. A total of 25 adult SOTR were included (n = 21 tacrolimus, n = 4 cyclosporine, n = 3 everolimus, n = 1 sirolimus). All patients were instructed to follow the following standardized protocol during treatment with 5 days of NR: hold tacrolimus or mTOR inhibitor or reduce cyclosporine dose to 20% of baseline daily dose. Four patients (16%) were hospitalized by day 30; one for infectious diarrhea and three for symptoms related to COVID‐19. No patients died within 30 days of receipt of NR. Median tacrolimus level pre‐ and post‐NR were 7.4 ng/ml (IQR, 6.6–8.6) and 5.2 (IQR, 3.6–8.7), respectively. Four patients experienced a supratherapeutic tacrolimus concentration after restarting tacrolimus post‐NR. Our results show the clinically significant interaction between NR and immunosuppressive agents can be reasonably managed with a standardized dosing protocol. Prescribers should carefully re‐introduce CNI after the NR course is complete.
Clinically significant drug‐drug interaction between nirmatrelvir/ritonavir and immunosuppressive agents can be managed in solid organ transplant recipients using a standardized dosing protocol.
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BFBNIB, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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