Publications by authors named "Samuel Ho"

217 Publications

Fear and anxiety about COVID-19 among local and overseas Chinese university students.

Health Soc Care Community 2021 Apr 6. Epub 2021 Apr 6.

Psychology Laboratory, Department of Social and Behavioural Sciences, City University of Hong Kong, Hong Kong.

This study aimed to establish a new COVID-19 Fear (Higher Education) scale to investigate the relationship between fear and generalised anxiety symptoms among Chinese students in mainland China, Hong Kong, and other countries. 219 Chinese university students studying in universities in mainland China (n = 76, 34.7%), Hong Kong (n = 66, 30.1%), and overseas (i.e., outside of China as international students, n = 77, 35.2%) participated in an online study from March 31, 2020 to April 4. Participants completed a newly developed COVID-19 Fear (Higher Education) scale to measure three domains of fear including fear of infection, fear of instability and fear of insecurity related to the COVID-19 pandemic. They also completed the Generalized Anxiety Disorder 7-item scale (GAD-7) on the severity of anxiety symptoms. About 9.6% of the participants could be classified as exhibiting high anxiety level according to the GAD-7. More students studying overseas (about 15%) were classified into the high GAD group when compared to students studying in both mainland China (6.6%) and Hong Kong (6.1%). MANOVA results showed that students studying in Hong Kong and overseas had more concerns related to preventive measures related to COVID-19 than their mainland counterparts did. We concluded that international students studying away from their home country would have higher risk to develop anxiety problems during a collective trauma such as the COVID-19 pandemic. Education institutions should provide support services including online support groups, social media groups for mutual support to alleviate the fear and anxiety of international students.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/hsc.13347DOI Listing
April 2021

Response to "RE: COVID-19 and healthcare workers: A systematic review and meta-analysis."

Int J Infect Dis 2021 Mar 16;106:140-141. Epub 2021 Mar 16.

College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai Healthcare City, Dubai, United Arab Emirates. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijid.2021.03.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962501PMC
March 2021

Aluminum-Hydride-Catalyzed Hydroboration of Carbon Dioxide.

Inorg Chem 2021 Apr 18;60(7):4569-4577. Epub 2021 Mar 18.

Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371.

This study describes the first use of a bis(phosphoranyl)methanido aluminum hydride, [ClC(PPhNMes)AlH] (, Mes = MeCH), for the catalytic hydroboration of CO. Complex was synthesized by the reaction of a lithium carbenoid [Li(Cl)C(PPhNMes)] with 2 equiv of AlH·NEtMe in toluene at -78 °C. (10 mol %) was able to catalyze the reduction of CO with HBpin in CD at 110 °C for 2 days to afford a mixture of methoxyborane [MeOBpin] (; yield: 78%, TOF: 0.16 h) and bis(boryl)oxide [pinBOBpin] (). When more potent [BH·SMe] was used instead of HBpin, the catalytic reaction was extremely pure, resulting in the formation of trimethyl borate [B(OMe)] () [catalytic loading: 1 mol % (10 mol %); reaction time: 60 min (5 min); yield: 97.6% (>99%); TOF: 292.8 h (356.4 h)] and BO (). Mechanistic studies show that the Al-H bond in complex activated CO to form [ClC(PPhNMes)Al(H){OC(O)H}] (), which was subsequently reacted with BH·SMe to form and , along with the regeneration of complex . Complex also shows good catalytic activity toward the hydroboration of carbonyl, nitrile, and alkyne derivatives.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.inorgchem.0c03507DOI Listing
April 2021

COVID-19 under 19: A meta-analysis.

Pediatr Pulmonol 2021 Feb 25. Epub 2021 Feb 25.

College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates.

Background: The coronavirus disease 2019 (COVID-19) pandemic continues to cause global havoc posing uncertainty to educational institutions worldwide. Understanding the clinical characteristics of COVID-19 in children is important because of the potential impact on clinical management and public health decisions.

Methods: A meta-analysis was conducted for pediatric COVID-19 studies using PubMed and Scopus. It reviewed demographics, co-morbidities, clinical manifestations, laboratory investigations, radiological investigations, treatment, and outcomes. The 95% confidence interval (CI) was utilized.

Results: Out of 3927 articles, 31 articles comprising of 1816 patients were selected from December 2019 to early October 2020 and were defined by 77 variables. Of these studies 58% originated from China and the remainder from North America, Europe and the Middle East. This meta-analysis revealed that 19.2% (CI 13.6%-26.4%) of patients were asymptomatic. Fever (57%, CI 49.7%-64%) and cough (44.1%, CI 38.3%-50.2%) were the most common symptoms. The most frequently encountered white blood count abnormalities were lymphopenia 13.5% (CI 8.2%-21.4%) and leukopenia 12.6% (CI 8.5%-18.3%). Ground glass opacities were the most common radiological finding of children with COVID-19 (35.5%, CI 28.9%-42.7%). Hospitalization rate was 96.3% (CI 92.4%-98.2%) of which 10.8% (CI 4.2%-25.3%) were ICU admissions, and 2.4% (CI 1.7%-3.4%) died.

Conclusion: The majority of pediatric patients with COVID-19 were asymptomatic or had mild manifestations. Among hospitalized patients there remains a significant number that require intensive care unit care. Overall across the literature, a considerable level of understanding of COVID-19 in children was reached, yet emerging data related to multisystemic inflammatory syndrome in children should be explored.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ppul.25312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013606PMC
February 2021

COVID-19 and healthcare workers: A systematic review and meta-analysis.

Int J Infect Dis 2021 Mar 11;104:335-346. Epub 2021 Jan 11.

College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai Healthcare City, Dubai, United Arab Emirates; Department of Medicine, Mediclinic City Hospital, Dubai Healthcare City, Dubai, United Arab Emirates. Electronic address:

Background: The COVID-19 pandemic has focused attention on the challenges and risks faced by frontline healthcare workers (HCW). This study aimed to describe the clinical outcomes and risk factors for SARS-CoV-2 infection in HCW.

Methods: Three databases were surveyed and 328 articles were identified. Of these, 225 articles did not meet inclusion criteria; therefore, 97 full-text article were reviewed. Finally, after further revision, 30 articles were included in the systematic review and 28 were used for meta-analysis.

Results: Twenty-eight studies were identified involving 119,883 patients. The mean age of the patients was 38.37 years (95% CI 36.72-40.03) and males comprised 21.4% (95% CI 12.4-34.2) of the population of HCW. The percentage of HCW who tested positive for COVID-19 was 51.7% (95% CI 34.7-68.2). The total prevalence of comorbidities in seven studies was 18.4% (95% CI 15.5-21.7). The most prevalent symptoms were fever 27.5% (95% CI 17.6-40.3) and cough 26.1% (95% CI 18.1-36). The prevalence of hospitalisation was 15.1% (95% CI 5.6-35) in 13 studies and of death was 1.5% (95% CI 0.5-3.9) in 12 studies. Comparisons of HCW with and without infection showed an increased relative risk for COVID-19 related to personal protective equipment, workplace setting, profession, exposure, contacts, and testing.

Conclusion: A significant number of HCW were reported to be infected with COVID-19 during the first 6 months of the COVID-19 pandemic, with a prevalence of hospitalisation of 15.1% and mortality of 1.5%. Further data are needed to track the continued risks in HCW as the pandemic evolves and health systems adapt.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijid.2021.01.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798435PMC
March 2021

Coping profiles predict long-term anxiety trajectory in breast cancer survivors.

Support Care Cancer 2021 Jan 6. Epub 2021 Jan 6.

Department of Psychiatry, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan.

This study examined the long-term trajectory patterns of anxiety in breast cancer survivors and identified its predicting variables, especially the type of coping profile. Eighty-one patients who completed all four questionnaires from the 10-year study were included in the analysis. Anxiety scores from the Hospital Anxiety and Depression Scale were used in latent class growth analysis to chart the anxiety trajectory of cancer survivors. Demographic variables, clinical variables, depression level, and coping profiles (adaptive versus maladaptive) were used as predictors. Our study identified a two-class model of long-term anxiety trajectory among breast cancer survivors, with a resistant group (85.2%) and a distress group (14.8%). Demographic and clinical variables were not associated with anxiety trajectory paths. On the other hand, maladaptive coping characterized by higher scores in helplessness/hopelessness, cognitive avoidance, and anxious preoccupation, and lower scores in fighting spirit and fatalism in the Mini-MAC was a significant predictor of distressed anxiety. Coping profiles identified using the Mini-MAC were predictive of long-term anxiety trajectory among breast cancer survivors in our survey. Early interventions on coping with cancer could reduce long-term anxiety problems.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00520-020-05936-6DOI Listing
January 2021

Mucin secretion in cystic fibrosis - a systematic review.

Dig Dis 2020 Oct 13. Epub 2020 Oct 13.

Background Mucus protects the epithelium against invaders and toxic materials. Sticky and thick mucus is characteristic of CF. Objective The aim of this systematic review is to characterize the specific mucins secreted in the lung and intestinal tract of CF patients. Methods A systematic literature search was conducted up to 31.12.2019. The following terms were used: "cystic fibrosis" AND "mucin". Case control studies comparing mucin expression in CF patients to healthy controls were included. Results We found 741 eligible studies, 694 studies rejected because they were performed in animals and not in full text, and 32 studies were excluded being editorials, duplications, review articles, meta-analysis, or not in English. Fifteen studies were eligible for our study, including 150 CF patients compared to 82 healthy controls all fulfilled the inclusion criteria. The main mucin types expressed in the sinus sub-mucosal glands, sputum, trachea-bronchial surface epithelium and lung sub -mucosal glands were MUC5AC and MUC5B. Increase in the number of sinusoidal sub-mucosal glands and expression of MUC5B was found in CF patients, but no such difference from healthy controls was found for the number of goblet cells in the surface epithelium nor in the expression of MUC5AC. The opposite was found in the trachea-bronchial surface epithelium and in the lungs. Conclusions Increased expression of MUC5AC in the surface epithelium and of MUC5B in the sub-epithelial glands may be the result of higher secretion rate of mucin into the lumen of the respiratory tract, causing mucus plaque, infection and inflammation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000512268DOI Listing
October 2020

Identification of TNO155, an Allosteric SHP2 Inhibitor for the Treatment of Cancer.

J Med Chem 2020 11 24;63(22):13578-13594. Epub 2020 Sep 24.

SHP2 is a nonreceptor protein tyrosine phosphatase encoded by the gene and is involved in cell growth and differentiation via the MAPK signaling pathway. SHP2 also plays an important role in the programed cell death pathway (PD-1/PD-L1). As an oncoprotein as well as a potential immunomodulator, controlling SHP2 activity is of high therapeutic interest. As part of our comprehensive program targeting SHP2, we identified multiple allosteric binding modes of inhibition and optimized numerous chemical scaffolds in parallel. In this drug annotation report, we detail the identification and optimization of the pyrazine class of allosteric SHP2 inhibitors. Structure and property based drug design enabled the identification of protein-ligand interactions, potent cellular inhibition, control of physicochemical, pharmaceutical and selectivity properties, and potent antitumor activity. These studies culminated in the discovery of TNO155, (3,4)-8-(6-amino-5-((2-amino-3-chloropyridin-4-yl)thio)pyrazin-2-yl)-3-methyl-2-oxa-8-azaspiro[4.5]decan-4-amine (), a highly potent, selective, orally efficacious, and first-in-class SHP2 inhibitor currently in clinical trials for cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jmedchem.0c01170DOI Listing
November 2020

Intestinal Virome in Patients With Alcoholic Hepatitis.

Hepatology 2020 12 10;72(6):2182-2196. Epub 2020 Oct 10.

Department of Medicine, University of California San Diego, La Jolla, CA.

Background And Aims: Alcoholic hepatitis (AH) is a severe manifestation of alcohol-associated liver disease (ALD) with high mortality. Although gut bacteria and fungi modulate disease severity, little is known about the effects of the viral microbiome (virome) in patients with ALD.

Approach And Results: We extracted virus-like particles from 89 patients with AH who were enrolled in a multicenter observational study, 36 with alcohol use disorder (AUD), and 17 persons without AUD (controls). Virus-like particles from fecal samples were fractionated using differential filtration techniques, and metagenomic sequencing was performed to characterize intestinal viromes. We observed an increased viral diversity in fecal samples from patients with ALD, with the most significant changes in samples from patients with AH. Escherichia-, Enterobacteria-, and Enterococcus phages were over-represented in fecal samples from patients with AH, along with significant increases in mammalian viruses such as Parvoviridae and Herpesviridae. Antibiotic treatment was associated with higher viral diversity. Specific viral taxa, such as Staphylococcus phages and Herpesviridae, were associated with increased disease severity, indicated by a higher median Model for End-Stage Liver Disease score, and associated with increased 90-day mortality.

Conclusions: In conclusion, intestinal viral taxa are altered in fecal samples from patients with AH and associated with disease severity and mortality. Our study describes an intestinal virome signature associated with AH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hep.31459DOI Listing
December 2020

Motivational interviewing to prevent early childhood caries: A randomized controlled trial.

J Dent 2020 06 21;97:103349. Epub 2020 Apr 21.

Faculty of Dentistry & Saw Swee Hock School of Public Health, National University of Singapore, Singapore. Electronic address:

Objectives: Prevailing health education (PE) often fails to achieve sustained behavioral changes. This randomized controlled trial integrated motivational interviewing (MI) and a patient communication tool featuring interactive caries risk assessment (RA) into PE and investigated the effectiveness of PE, PE + MI, and PE + MI + RA in preventing early childhood caries.

Methods: This study targeted children aged 3-4 years with unfavorable oral health behaviors. 692 parent-child dyads were recruited, randomly assigned into three groups (PE, PE + MI, and PE + MI + RA), and received respective interventions. A questionnaire was completed at baseline and after 6 and 12 months to collect information on socio-demographic background, parental efficacy and children's oral health behaviors. Children's oral hygiene status and dental caries were recorded at baseline and after 12 months.

Results: 655 (94.7%) parent-child dyads remained in the study after 12 months. Caries increment was significantly lower in PE + MI group (β=-0.717, 95% CI: -1.035, -0.398) and PE + MI + RA group [β=-0.600, 95% CI: -0.793, -0.407] than in PE group. There was significantly greater reduction in plaque score in PE + MI group (β=-0.077, 95% CI: -0.106, -0.048) and PE + MI + RA group (β=-0.075, 95% CI: -0.113, -0.036), as compared with PE group. Significantly greater improvements were found in parental efficacy and children's oral health behaviors in PE + MI and PE + MI + RA groups than in PE group (all p < 0.05). There was no significant difference between PE + MI group and PE + MI + RA group across all outcome measures (all p > 0.05).

Conclusions: Intergration of motivational interviewing improves the effectiveness of prevailing health education in preventing early childhood caries, enhancing parental efficacy, and improving children's oral health behaviors. Incorporation of the communication tool for caries risk assessment does not further improve the effectiveness of motivational interviewing in protecting children's oral health.

Clinical Significance: The findings of this study provide much needed evidence for dentists, dental auxiliary staff and public health workers to select effective intervention to empower parents for improving children's oral health behaviors and preventing early childhood caries.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jdent.2020.103349DOI Listing
June 2020

Editorial: Positive Education: Theory, Practice, and Evidence.

Front Psychol 2020 9;11:427. Epub 2020 Mar 9.

Department of Social and Behavioral Sciences, City University of Hong Kong, Hong Kong, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpsyg.2020.00427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7075418PMC
March 2020

Inverted Yield Curve: The Alarming Rising Incidence of CRC in Young People.

Dig Dis Sci 2020 06;65(6):1590-1592

College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, UAE.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10620-020-06083-yDOI Listing
June 2020

Enzymatic Labeling of Bacterial Proteins for Super-resolution Imaging in Live Cells.

ACS Cent Sci 2019 Dec 21;5(12):1911-1919. Epub 2019 Nov 21.

Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, California 91125, United States.

Methods that enable the super-resolution imaging of intracellular proteins in live bacterial cells provide powerful tools for the study of prokaryotic cell biology. Photoswitchable organic dyes exhibit many of the photophysical properties needed for super-resolution imaging, including high brightness, photostability, and photon output, but most such dyes require organisms to be fixed and permeabilized if intracellular targets are to be labeled. We recently reported a general strategy for the chemoenzymatic labeling of bacterial proteins with azide-bearing fatty acids in live cells using the eukaryotic enzyme -myristoyltransferase. Here we demonstrate the labeling of proteins in live using cell-permeant bicyclononyne-functionalized photoswitchable rhodamine spirolactams. Single-molecule fluorescence measurements on model rhodamine spirolactam salts show that these dyes emit hundreds of photons per switching event. Super-resolution imaging was performed on bacterial chemotaxis proteins Tar and CheA and cell division proteins FtsZ and FtsA. High-resolution imaging of Tar revealed a helical pattern; imaging of FtsZ yielded banded patterns dispersed throughout the cell. The precision of radial and axial localization in reconstructed images approaches 15 and 30 nm, respectively. The simplicity of the method, which does not require redox imaging buffers, should make this approach broadly useful for imaging intracellular bacterial proteins in live cells with nanometer resolution.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acscentsci.9b00617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6935894PMC
December 2019

Development of a national Department of Veterans Affairs mortality risk prediction model among patients with cirrhosis.

BMJ Open Gastroenterol 2019 26;6(1):e000342. Epub 2019 Nov 26.

Veteran's Health Administration, VA Tennessee Valley Healthcare System, Nashville, Tennessee, USA.

Objective: Cirrhotic patients are at high hospitalisation risk with subsequent high mortality. Current risk prediction models have varied performances with methodological room for improvement. We used current analytical techniques using automatically extractable variables from the electronic health record (EHR) to develop and validate a posthospitalisation mortality risk score for cirrhotic patients and compared performance with the model for end-stage liver disease (MELD), model for end-stage liver disease with sodium (MELD-Na), and the CLIF Consortium Acute Decompensation (CLIF-C AD) models.

Design: We analysed a retrospective cohort of 73 976 patients comprising 247 650 hospitalisations between 2006 and 2013 at any of 123 Department of Veterans Affairs hospitals. Using 45 predictor variables, we built a time-dependent Cox proportional hazards model with all-cause mortality as the outcome. We compared performance to the three extant models and reported discrimination and calibration using bootstrapping. Furthermore, we analysed differential utility using the net reclassification index (NRI).

Results: The C-statistic for the final model was 0.863, representing a significant improvement over the MELD, MELD-Na, and the CLIF-C AD, which had C-statistics of 0.655, 0.675, and 0.679, respectively. Multiple risk factors were significant in our model, including variables reflecting disease severity and haemodynamic compromise. The NRI showed a 24% improvement in predicting survival of low-risk patients and a 30% improvement in predicting death of high-risk patients.

Conclusion: We developed a more accurate mortality risk prediction score using variables automatically extractable from an EHR that may be used to risk stratify patients with cirrhosis for targeted postdischarge management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjgast-2019-000342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6904155PMC
November 2019

The relationship between types of posttraumatic growth and prospective psychological adjustment in women with breast cancer: A follow-up study.

Psychooncology 2020 03 12;29(3):586-588. Epub 2020 Jan 12.

Department of Social and Behavioural Sciences, City University of Hong Kong, Hong Kong.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pon.5312DOI Listing
March 2020

Bacteriophage targeting of gut bacterium attenuates alcoholic liver disease.

Nature 2019 11 13;575(7783):505-511. Epub 2019 Nov 13.

Department of Medicine, University of California San Diego, La Jolla, CA, USA.

Chronic liver disease due to alcohol-use disorder contributes markedly to the global burden of disease and mortality. Alcoholic hepatitis is a severe and life-threatening form of alcohol-associated liver disease. The gut microbiota promotes ethanol-induced liver disease in mice, but little is known about the microbial factors that are responsible for this process. Here we identify cytolysin-a two-subunit exotoxin that is secreted by Enterococcus faecalis-as a cause of hepatocyte death and liver injury. Compared with non-alcoholic individuals or patients with alcohol-use disorder, patients with alcoholic hepatitis have increased faecal numbers of E. faecalis. The presence of cytolysin-positive (cytolytic) E. faecalis correlated with the severity of liver disease and with mortality in patients with alcoholic hepatitis. Using humanized mice that were colonized with bacteria from the faeces of patients with alcoholic hepatitis, we investigated the therapeutic effects of bacteriophages that target cytolytic E. faecalis. We found that these bacteriophages decrease cytolysin in the liver and abolish ethanol-induced liver disease in humanized mice. Our findings link cytolytic E. faecalis with more severe clinical outcomes and increased mortality in patients with alcoholic hepatitis. We show that bacteriophages can specifically target cytolytic E. faecalis, which provides a method for precisely editing the intestinal microbiota. A clinical trial with a larger cohort is required to validate the relevance of our findings in humans, and to test whether this therapeutic approach is effective for patients with alcoholic hepatitis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41586-019-1742-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6872939PMC
November 2019

RIPK1 Mediates TNF-Induced Intestinal Crypt Apoptosis During Chronic NF-κB Activation.

Cell Mol Gastroenterol Hepatol 2020 10;9(2):295-312. Epub 2019 Oct 10.

Department Rheumatology, San Diego, California; Department of Medicine, Autonomous University of Barcelona, Plaça Cívica, Bellaterra, Barcelona, Spain. Electronic address:

Background And Aims: Tumor necrosis factor (TNF) is a major pathogenic effector and a therapeutic target in inflammatory bowel disease (IBD), yet the basis for TNF-induced intestinal epithelial cell (IEC) death is unknown, because TNF does not kill normal IECs. Here, we investigated how chronic nuclear factor (NF)- κB activation, which occurs in human IBD, promotes TNF-dependent IEC death in mice.

Methods: Human IBD specimens were stained for p65 and cleaved caspase-3. C57BL/6 mice with constitutively active IKKβ in IEC (Ikkβ(EE)), Ripk1 knockin mice, and Ripk3 mice were injected with TNF or lipopolysaccharide. Enteroids were also isolated from these mice and challenged with TNF with or without RIPK1 and RIPK3 inhibitors or butylated hydroxyanisole. Ripoptosome-mediated caspase-8 activation was assessed by immunoprecipitation.

Results: NF-κB activation in human IBD correlated with appearance of cleaved caspase-3. Congruently, unlike normal mouse IECs that are TNF-resistant, IECs in Ikkβ(EE) mice and enteroids were susceptible to TNF-dependent apoptosis, which depended on the protein kinase function of RIPK1. Constitutively active IKKβ facilitated ripoptosome formation, a RIPK1 signaling complex that mediates caspase-8 activation by TNF. Butylated hydroxyanisole treatment and RIPK1 inhibitors attenuated TNF-induced and ripoptosome-mediated caspase-8 activation and IEC death in vitro and in vivo.

Conclusions: Contrary to common expectations, chronic NF-κB activation induced intestinal crypt apoptosis after TNF stimulation, resulting in severe mucosal erosion. RIPK1 kinase inhibitors selectively inhibited TNF destructive properties while preserving its survival and proliferative properties, which do not require RIPK1 kinase activity. RIPK1 kinase inhibition could be a potential treatment for IBD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcmgh.2019.10.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957844PMC
October 2019

A clinical risk prediction model to identify patients with hepatorenal syndrome at hospital admission.

Int J Clin Pract 2019 Nov 7;73(11):e13393. Epub 2019 Aug 7.

Tennessee Valley Healthcare System (TVHS) Veterans Administration Medical Center, Veteran's Health Administration, Nashville, Tennessee.

Background: Hepatorenal syndrome (HRS) is a life-threatening complication of cirrhosis and early detection of evolving HRS may provide opportunities for early intervention. We developed a HRS risk model to assist early recognition of inpatient HRS.

Methods: We analysed a retrospective cohort of patients hospitalised from among 122 medical centres in the US Department of Veterans Affairs between 1 January 2005 and 31 December 2013. We included cirrhotic patients who had Kidney Disease Improving Global Outcomes criteria based acute kidney injury on admission. We developed a logistic regression risk prediction model to detect HRS on admission using 10 variables. We calculated 95% confidence intervals on the model building dataset and, subsequently, calculated performance on a 1000 sample holdout test set. We report model performance with area under the curve (AUC) for discrimination and several calibration measures.

Results: The cohort included 19 368 patients comprising 32 047 inpatient admissions. The event rate for hospitalised HRS was 2810/31 047 (9.1%) and 79/1000 (7.9%) in the model building and validation datasets, respectively. The variable selection procedure designed a parsimonious model involving ten predictor variables. Final model performance in the validation dataset had an AUC of 0.87, Brier score of 0.05, slope of 1.10 and intercept of 0.04.

Conclusions: We developed a probabilistic risk model to diagnose HRS within 24 hours of hospital admission using routine clinical variables in the largest ever published HRS cohort. The performance was excellent and this model may help identify high-risk patients for HRS and promote early intervention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ijcp.13393DOI Listing
November 2019

Descriptive Usability Study of CirrODS: Clinical Decision and Workflow Support Tool for Management of Patients With Cirrhosis.

JMIR Med Inform 2019 Jul 3;7(3):e13627. Epub 2019 Jul 3.

Department of Veterans Affairs San Diego Healthcare System, San Diego, CA, United States.

Background: There are gaps in delivering evidence-based care for patients with chronic liver disease and cirrhosis.

Objective: Our objective was to use interactive user-centered design methods to develop the Cirrhosis Order Set and Clinical Decision Support (CirrODS) tool in order to improve clinical decision-making and workflow.

Methods: Two work groups were convened with clinicians, user experience designers, human factors and health services researchers, and information technologists to create user interface designs. CirrODS prototypes underwent several rounds of formative design. Physicians (n=20) at three hospitals were provided with clinical scenarios of patients with cirrhosis, and the admission orders made with and without the CirrODS tool were compared. The physicians rated their experience using CirrODS and provided comments, which we coded into categories and themes. We assessed the safety, usability, and quality of CirrODS using qualitative and quantitative methods.

Results: We created an interactive CirrODS prototype that displays an alert when existing electronic data indicate a patient is at risk for cirrhosis. The tool consists of two primary frames, presenting relevant patient data and allowing recommended evidence-based tests and treatments to be ordered and categorized. Physicians viewed the tool positively and suggested that it would be most useful at the time of admission. When using the tool, the clinicians placed fewer orders than they placed when not using the tool, but more of the orders placed were considered to be high priority when the tool was used than when it was not used. The physicians' ratings of CirrODS indicated above average usability.

Conclusions: We developed a novel Web-based combined clinical decision-making and workflow support tool to alert and assist clinicians caring for patients with cirrhosis. Further studies are underway to assess the impact on quality of care for patients with cirrhosis in actual practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2196/13627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6636234PMC
July 2019

Intestinal Fungal Dysbiosis and Systemic Immune Response to Fungi in Patients With Alcoholic Hepatitis.

Hepatology 2020 02 20;71(2):522-538. Epub 2019 Aug 20.

Department of Medicine, University of California San Diego, La Jolla, CA.

Chronic alcohol consumption causes increased intestinal permeability and changes in the intestinal microbiota composition, which contribute to the development and progression of alcohol-related liver disease. In this setting, little is known about commensal fungi in the gut. We studied the intestinal mycobiota in a cohort of patients with alcoholic hepatitis, patients with alcohol use disorder, and nonalcoholic controls using fungal-specific internal transcribed spacer amplicon sequencing of fecal samples. We further measured serum anti-Saccharomyces cerevisiae antibodies (ASCA) as a systemic immune response to fungal products or fungi. Candida was the most abundant genus in the fecal mycobiota of the two alcohol groups, whereas genus Penicillium dominated the mycobiome of nonalcoholic controls. We observed a lower diversity in the alcohol groups compared with controls. Antibiotic or steroid treatment was not associated with a lower diversity. Patients with alcoholic hepatitis had significantly higher ASCA levels compared to patients with alcohol use disorder and to nonalcoholic controls. Within the alcoholic hepatitis cohort, patients with levels of at least 34 IU/mL had a significantly lower 90-day survival (59%) compared with those with ASCA levels less than 34 IU/mL (80%) with an adjusted hazard ratio of 3.13 (95% CI, 1.11-8.82; P = 0.031). Conclusion: Patients with alcohol-associated liver disease have a lower fungal diversity with an overgrowth of Candida compared with controls. Higher serum ASCA was associated with increased mortality in patients with alcoholic hepatitis. Intestinal fungi may serve as a therapeutic target to improve survival, and ASCA may be useful to predict the outcome in patients with alcoholic hepatitis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hep.30832DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6925657PMC
February 2020

N-Myristoyl Transferase (NMT)-Catalyzed Labeling of Bacterial Proteins for Imaging in Fixed and Live Cells.

Methods Mol Biol 2019 ;2012:315-326

Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA, USA.

Methods for selective protein imaging are critical for elucidating how cells orchestrate fundamental biological processes. We recently developed a chemoenzymatic method to modify bacterial proteins in situ for fluorescence imaging using N-myristoyl transferase (NMT). Target proteins outfitted with an N-terminal NMT recognition sequence are covalently modified with an azido fatty acid. Subsequent strain-promoted azide-alkyne cycloaddition allows for conjugation to cell-permeant fluorophores and imaging by fluorescence microscopy. Here we describe sample preparation and labeling protocols for imaging bacterial proteins in fixed and live cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/978-1-4939-9546-2_16DOI Listing
March 2020

Serum and Fecal Oxylipins in Patients with Alcohol-Related Liver Disease.

Dig Dis Sci 2019 07 10;64(7):1878-1892. Epub 2019 May 10.

Department of Medicine, University of California San Diego, La Jolla, CA, USA.

Background: Alcohol-related liver disease is one of the most prevalent chronic liver diseases worldwide. Mechanisms involved in the pathogenesis of alcohol-related liver disease are not well understood. Oxylipins play a crucial role in numerous biological processes and pathological conditions. Nevertheless, oxylipins are not well studied in alcohol-related liver disease.

Aims: (1) To characterize the patterns of bioactive ω-3 and ω-6 polyunsaturated fatty acid metabolites in alcohol use disorder and alcoholic hepatitis patients and (2) to identify associations of serum oxylipins with clinical parameters in patients with alcohol-related liver disease.

Methods: We performed a comprehensive liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis of serum and fecal oxylipins derived from ω-6 arachidonic acid, ω-3 eicosapentaenoic acid, and docosahexaenoic acid in a patient cohort with alcohol-related liver disease.

Results: Our results show profound alterations in the serum oxylipin profile of patients with alcohol use disorder and alcoholic hepatitis compared to nonalcoholic controls. Spearman correlation of the oxylipins with clinical parameters shows a link between different serum oxylipins and intestinal permeability, aspartate aminotransferase, bilirubin, albumin, international normalized ratio, platelet count, steatosis, fibrosis and model for end-stage liver disease score. Especially, higher level of serum 20-HETE was significantly associated with decreased albumin, increased hepatic steatosis, polymorphonuclear infiltration, and 90-day mortality.

Conclusions: Patients with alcohol-related liver disease have different oxylipin profiles. Future studies are required to confirm oxylipins as disease biomarker or to connect oxylipins to disease pathogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10620-019-05638-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6588282PMC
July 2019

Effect of Obesogenic Medications on Weight-Loss Outcomes in a Behavioral Weight-Management Program.

Obesity (Silver Spring) 2019 05;27(5):716-723

Veterans Affairs San Diego Healthcare System, San Diego, California, USA.

Objective: This study aimed to evaluate a possible association between the use of obesogenic medications and inadequate weight loss in a behavioral weight-management program.

Methods: This is a case-control, single-center study of 666 adult patients within a Veterans Health Administration health system who participated in the MOVE! behavioral weight-loss program. The cohort was divided into responders (n = 150), patients who achieved ≥ 5% total weight loss by the end of the MOVE! program, and nonresponders (n = 516), those who achieved < 5% total weight loss. We reviewed each patient's medical records for exposure to obesogenic medication during the time of treatment.

Results: Approximately 62% (n = 411) of patients entering MOVE! had a prescription for obesogenic medications. Obesogenic medication use was associated with worse weight-loss outcomes, and participants were 37% less likely to achieve a clinically meaningful (≥ 5% total weight loss) outcome at the end of the MOVE! program (odds ratio, 0.633; 95% CI: 0.427-0.937; adjusted P = 0.022). Patients who received three or more medications (n = 72) had the greatest difficulty achieving 5% weight loss compared with the control group (odds ratio, 0.265; 95% CI: 0.108-0.646; adjusted P = 0.003).

Conclusions: The use of provider-prescribed obesogenic medications was associated with worse weight-loss outcomes in a behavioral weight-loss program. Closer scrutiny of patient medications is necessary to help improve outcomes of weight-loss treatments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/oby.22444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6544176PMC
May 2019

Reply.

Gastroenterology 2019 03 19;156(4):1218-1220. Epub 2019 Feb 19.

Division of Gastroenterology and Research and Development, Veterans Affairs Puget Sound Healthcare System and University of Washington, Seattle, Washington.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.gastro.2019.02.024DOI Listing
March 2019

Identification of Phytoconstituents in (Burm. F.) Merr. Leaves by High Performance Liquid Chromatography Micro Time-of-Flight Mass Spectrometry.

Molecules 2019 Feb 16;24(4). Epub 2019 Feb 16.

Department of Pharmacy, Faculty of Science, National University of Singapore, 18 Science Drive 4, Singapore 117543, Singapore.

(Vitaceae) is a Southeast Asian medicinal plant. In this study, an ethyl acetate fraction of leaves was studied for its phytoconstituents using high-performance liquid chromatography-electrospray ionization-mass spectrometry (HPLC-ESI-microTOF-Q-MS/MS) analysis. A total of 31 compounds of different classes, including benzoic acid derivatives, phenolics, flavonoids, catechins, dihydrochalcones, coumarins, megastigmanes, and oxylipins were identified using LC-MS/MS. Among them, six compounds including gallic acid, methyl gallate, (-)-epigallocatechin-3--gallate, myricetin-3--rhamnoside, quercetin-3--rhamnoside, and 4',6'-dihydroxy-4-methoxydihydrochalcone 2'--β-d-glucopyranoside were isolated and identified by NMR analysis. The LC-MS/MS analysis led to the tentative identification of three novel dihydrochalcones namely 4',6'-dihydroxy-4-methoxydihydrochalcone 2'--rutinoside, 4',6'-dihydroxy-4-methoxydihydrochalcone 2'--glucosylpentoside and 4',6'-dihydroxy-4-methoxydihydrochalcone 2'--(3″--galloyl)-β-d-glucopyranoside. The structural identification of novel dihydrochalcones was based on the basic skeleton of the isolated dihydrochalcone, 4',6'-dihydroxy-4-methoxydihydrochalcone 2'--β-d-glucopyranoside and characteristic LC-MS/MS fragmentation patterns. This is the first comprehensive analysis for the identification of compounds from using LC-MS. A total 24 compounds including three new dihydrochalcones were identified for the first time from the genus .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/molecules24040714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412998PMC
February 2019

Discovery of a ZIP7 inhibitor from a Notch pathway screen.

Nat Chem Biol 2019 02 14;15(2):179-188. Epub 2019 Jan 14.

Novartis Institutes for Biomedical Research, Cambridge, MA, USA.

The identification of activating mutations in NOTCH1 in 50% of T cell acute lymphoblastic leukemia has generated interest in elucidating how these mutations contribute to oncogenic transformation and in targeting the pathway. A phenotypic screen identified compounds that interfere with trafficking of Notch and induce apoptosis via an endoplasmic reticulum (ER) stress mechanism. Target identification approaches revealed a role for SLC39A7 (ZIP7), a zinc transport family member, in governing Notch trafficking and signaling. Generation and sequencing of a compound-resistant cell line identified a V430E mutation in ZIP7 that confers transferable resistance to the compound NVS-ZP7-4. NVS-ZP7-4 altered zinc in the ER, and an analog of the compound photoaffinity labeled ZIP7 in cells, suggesting a direct interaction between the compound and ZIP7. NVS-ZP7-4 is the first reported chemical tool to probe the impact of modulating ER zinc levels and investigate ZIP7 as a novel druggable node in the Notch pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41589-018-0200-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7251565PMC
February 2019

Opioid Use is Associated with Higher Severity-Adjusted Episode Costs in Patients with Conservatively Managed Degenerative Joint Disease of the Back and Neck.

Pharmacoeconomics 2019 03;37(3):419-433

Clinical Data Services and Analytics, UnitedHealthcare, 9700 Health Care Lane, Minnetonka, MN, 55343, USA.

Background: Opioid use and misuse are urgent health issues. Previous studies suggest that opioid use increases healthcare resource use but severity adjustment is lacking.

Objective: The objective of this study was to evaluate the severity-adjusted cost difference between opioid users and non-users among patients with conservatively managed degenerative joint disease of the spine within a large commercial health plan population in the United States.

Methods: A retrospective observational study was performed using a national commercial database covering 531,819 patients aged 18-64 years with non-surgically managed cervical or lumbar degenerative spine disease during 2015-6. Patients were grouped based on whether there was evidence for an opioid prescription. Costs for the opioids themselves were excluded. Severity adjustment, on an ascending integer scale from 1 to 4, was performed based on member demographics, clinical comorbidities, disease progression indicators, and complications.

Results: Median episode costs for patients given opioids were approximately twice that for patients not given opioids after severity adjustment. For patients with episodes in both years and stable severity, patients with new prescriptions for opioids in 2016 doubled their median 2015 costs, and patients who had opioids discontinued in 2016 had a 60% cost reduction. Episode costs showed a nearly linear increase based on the length of time taking opioids, as well as with a higher average daily dose. Cost increases with opioids were broad across service categories even when comparing within the same severity-adjusted episodes of care.

Conclusions: The data suggest a clinically and statistically significant increase in episode costs associated with opioid use for degenerative joint disease of the spine, both within and between patients, and higher costs with a longer duration of opioid use as well as with higher daily dosages. Given the health consequences surrounding the overuse of opioids, concerted efforts to move towards a non-opioid pain control strategy are needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40273-018-0753-zDOI Listing
March 2019

Cognitive factors associated with depression and anxiety in adolescents: A two-year longitudinal study.

Int J Clin Health Psychol 2018 Sep-Dec;18(3):227-234. Epub 2018 May 7.

Psychology Laboratory, Department of Applied Social Sciences, City University of Hong Kong.

: To examine the roles of anxiety sensitivity and attentional bias in the development of anxiety and depression symptoms among adolescents. : 214 grade 7 to grade 10 Hong Kong Chinese students completed a package of psychometric inventories to measure levels of anxiety sensitivity, selective attentional processing, and anxiety and depressive symptoms in 2016 and then again in 2017. Girls, when compared with boys, exhibited more anxiety symptoms and anxiety sensitivity in 2016. They also reported a significant increase in mean depression level from 2016 to 2017. Regression analyses revealed that the physical-concerns dimension of anxiety sensitivity, positive attentional bias, and to a lesser extent negative attentional bias were related to the development of both anxiety and depression symptoms one year later. Fear of mental incapacity could predict depression one year later but not anxiety symptoms. : Intervention through anxiety sensitivity training to reduce somatic concerns and attentional bias modification to increase habitual attention to positive stimuli and to disengage from negative stimuli can reduce anxiety and depression symptoms among high school students.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijchp.2018.04.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6224862PMC
May 2018

Bacteria engineered to produce IL-22 in intestine induce expression of REG3G to reduce ethanol-induced liver disease in mice.

Gut 2019 08 17;68(8):1504-1515. Epub 2018 Nov 17.

Department of Medicine, University of California San Diego, La Jolla, California, USA.

Objective: Antimicrobial C-type lectin regenerating islet-derived 3 gamma (REG3G) is suppressed in the small intestine during chronic ethanol feeding. Our aim was to determine the mechanism that underlies REG3G suppression during experimental alcoholic liver disease.

Design: Interleukin 22 (IL-22) regulates expression of REG3G. Therefore, we investigated the role of IL-22 in mice subjected to chronic-binge ethanol feeding (NIAAA model).

Results: In a mouse model of alcoholic liver disease, we found that type 3 innate lymphoid cells produce lower levels of IL-22. Reduced IL-22 production was the result of ethanol-induced dysbiosis and lower intestinal levels of indole-3-acetic acid (IAA), a microbiota-derived ligand of the aryl hydrocarbon receptor (AHR), which regulates expression of IL-22. Importantly, faecal levels of IAA were also found to be lower in patients with alcoholic hepatitis compared with healthy controls. Supplementation to restore intestinal levels of IAA protected mice from ethanol-induced steatohepatitis by inducing intestinal expression of IL-22 and REG3G, which prevented translocation of bacteria to liver. We engineered to produce IL-22 (/IL-22) and fed them to mice along with the ethanol diet; these mice had reduced liver damage, inflammation and bacterial translocation to the liver compared with mice fed an isogenic control strain and upregulated expression of REG3G in intestine. However, /IL-22 did not reduce ethanol-induced liver disease in mice.

Conclusion: Ethanol-associated dysbiosis reduces levels of IAA and activation of the AHR to decrease expression of IL-22 in the intestine, leading to reduced expression of REG3G; this results in bacterial translocation to the liver and steatohepatitis. Bacteria engineered to produce IL-22 induce expression of REG3G to reduce ethanol-induced steatohepatitis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/gutjnl-2018-317232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387784PMC
August 2019

The effects of provider-prescribed obesogenic drugs on post-laparoscopic sleeve gastrectomy outcomes: a retrospective cohort study.

Int J Obes (Lond) 2019 06 21;43(6):1154-1163. Epub 2018 Sep 21.

School of Medicine, University of California, San Diego, CA, USA.

Background: Laparoscopic sleeve gastrectomy (LSG) is one of the most commonly performed bariatric procedures and has proven effective in providing weight loss. However, considerable variance has been noted in the degree of weight loss. Physician prescription practices may be negatively affecting weight loss post-LSG and, thus, contributing to the broad range of weight loss outcomes. The aim of our study was to determine whether commonly prescribed obesogenic medications negatively affect weight loss outcomes post-LSG.

Subjects/methods: This single center retrospective cohort study performed at a University hospital included 323 patients (≥18 years) within the University California, San Diego Healthcare System who underwent LSG between 2007 and 2016. We identified a list of 32 commonly prescribed medications that have weight gain as a side effect. We compared the percent excess weight loss (%EWL) of patients divided into two groups based on post-LSG exposure to obesogenic medications. A linear regression model was used to analyze %EWL at 12 months post-LSG while controlling for age, initial body mass index (BMI), and use of leptogenic medications.

Results: A total of 150 patients (Meds group) were prescribed obesogenic medications within the one-year post-LSG follow up period, whereas 173 patients (Control group) were not prescribed obesogenic medications. The Meds group lost significantly less weight compared to the Control group (%EWL ± SEM at 12 months 53.8 ± 2.4 n = 78, 65.0 ± 2.6, n = 84 respectively, P = 0.002). This difference could not be attributed to differences in age, gender, initial BMI, co-morbidities, or prescription of leptogenic medications between the two groups.

Conclusions: The use of provider-prescribed obesogenic medications was associated with worse weight loss outcomes post-LSG. Closer scrutiny of patient medications may be necessary to help improve outcomes of weight loss treatments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41366-018-0207-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6428627PMC
June 2019