Bacillus Calmette-Guérin vaccination and clinical characteristics and outcomes of COVID-19 in Rhode Island, United States: a cohort study.

Coronavirus disease 2019 (COVID-19) has resulted in a global pandemic, and there is limited data on effective therapies. Bacillus Calmette-Guérin (BCG) vaccine, a live-attenuated strain derived from an isolate of Mycobacterium bovis and originally designed to prevent tuberculosis, has shown some efficacy against infection with unrelated pathogens. In this study, we reviewed 120 consecutive adult patients (≥18 years old) with COVID-19 at a major federally qualified health centre in Rhode Island, United States from 19 March to 29 April 2020. Median age was 39.5 years (interquartile range, 27.0-50.0), 30% were male and 87.5% were Latino/Hispanics. Eighty-two (68.3%) patients had BCG vaccination. Individuals with BCG vaccination were less likely to require hospital admission during the disease course (3.7% vs. 15.8%, P = 0.019). This association remained unchanged after adjusting for demographics and comorbidities (P = 0.017) using multivariate regression analysis. The finding from our study suggests the potential of BCG in preventing more severe COVID-19.

Cyclophilin A and nuclear factor of activated T cells are essential in cyclosporine-mediated suppression of polyomavirus BK replication.

Immunosuppressants have impacts on the development of polyomavirus-associated nephropathy. We previously demonstrated that cyclosporin A (CsA) suppressed polyomavirus BK (BKV) replication. The role of cyclophilin A (CypA) and nuclear factor of activated T cells (NFAT) in CsA-imposed suppression of BKV replication was determined in this study. Results demonstrated that knockdown of CypA but not CypB significantly reduced BKV large T antigen (TAg) expression and BKV titer. Overexpression of CypA reversed CypA siRNA-induced inhibition in BKV TAg expression. In addition, CypA overexpression attenuated the suppressive effect of CsA on TAg expression, suggesting CypA implicated in CsA-mediated anti-BKV effect. Knockdown of NFATc3 abrogated TAg expression, while overexpression of NFATc3 promoted TAg expression and augmented BKV promoter activity. NFATc3 binding to the BKV promoter was verified by chromatin immunoprecipitation assay and electrophoretic mobility shift assay. Renal histology also displayed an increase in NFATc3 expression in tubulointerstitium of BKV-associated nephropathy. Furthermore, overexpression of NFATc3 rescued CsA-mediated inhibition of BKV load and TAg expression. A CsA analog, NIM811, which cannot block NFAT functionality, failed to suppress TAg expression. In conclusion, CypA and NFAT are indispensable in BKV replication. CsA inhibits BKV replication through CypA and NFAT, which may be potential targets of anti-BKV treatment.

An artificial intelligence algorithm for analyzing acetaminophen-associated toxic hepatitis.

INTRODUCTION: Very little artificial intelligence (AI) work has been performed to investigate acetaminophen-associated hepatotoxicity. The objective of this study was to develop an AI algorithm for analyzing weighted features for toxic hepatitis after acetaminophen poisoning. METHODS: The medical records of 187 patients with acetaminophen poisoning treated at Chang Gung Memorial Hospital were reviewed. Patients were sorted into two groups according to their status of toxic hepatitis. A total of 40 clinical and laboratory features recorded on the first day of admission were selected for algorithm development. The random forest classifier (RFC) and logistic regression (LR) were used for artificial intelligence algorithm development. RESULTS: The RFC-based AI model achieved the following results: accuracy = 92.5 ± 2.6%; sensitivity = 100%; specificity = 60%; precision = 92.3 ± 3.4%; and F1 = 96.0 ± 1.8%. The area under the receiver operating characteristic curve (AUROC) was approximately 0.98. The LR-based AI model achieved the following results: accuracy = 92.00 ± 2.9%; sensitivity = 100%; specificity = 20%; precision = 92.8 ± 3.4%; recall = 98.8 ± 3.4%; and F1 = 95.6 ± 1.5%. The AUROC was approximately 0.68. The weighted features were calculated, and the 10 most important weighted features for toxic hepatitis were aspartate aminotransferase (ALT), prothrombin time, alanine aminotransferase (AST), time to hospital, platelet count, lymphocyte count, albumin, total bilirubin, body temperature and acetaminophen level. CONCLUSION: The top five weighted features for acetaminophen-associated toxic hepatitis were ALT, prothrombin time, AST, time to hospital and platelet count.

Outcome of patients with chlorpyrifos intoxication.

INTRODUCTION: There is a paucity of literature analyzing outcome of chlorpyrifos intoxication. METHODS: A total of 40 patients with chlorpyrifos intoxication were seen at Chang Gung Memorial Hospital between 2008 and 2017. Patients were stratified into two subgroups according to their prognosis, as good (n = 12) or poor (n = 28). Good prognosis group were defined as patients who survived without serious complications, and poor prognosis group included patients who died and survived after development of severe complications. Demographic, clinical, laboratory, and mortality data were obtained for analysis. RESULTS: Patients aged 53.8 ± 16.3 years and most were male (80.0%). All patients (100.0%) developed acute cholinergic crisis such as emesis (45.0%), respiratory failure (42.5%), tachycardia (30.0%), kidney injury (22.5%), and seizure (7.5%). Intermediate syndrome developed in 12.5% of patients, but none had delayed neuropathy (0%). The poor prognosis group suffered higher incidences of respiratory failure (p = 0.011), kidney injury (p = 0.026), and prolonged corrected QT interval (p = 0.000), and they had higher blood urea nitrogen level (p = 0.041), lower Glasgow coma scale score (p = 0.011), and lower monocyte count (p = 0.023) than good prognosis group. All patients were treated with atropine and pralidoxime therapy, but six patients (15.0%) still died of intoxication. In a multivariate logistic regression model, blood urea nitrogen was a significant risk factor for poor prognosis (odds ratio: 1.375, 95% confidence interval: 1.001-1.889, p = 0.049). Nevertheless, no mortality risk factor could be identified. CONCLUSION: The mortality rate of patients with chlorpyrifos intoxication was 15.0%. Furthermore, acute cholinergic crisis, intermediate syndrome, and delayed neuropathy developed in 100.0%, 12.5%, and 0% of patients, respectively.

Serum aluminum level correlates with arterial stiffness in haemodialysis patients.

BACKGROUND: In addition to pulse wave velocity (PWV), serum aluminum level is predictive of mortality in haemodialysis (HD) patients. This cross-sectional study evaluated the correlations between serum aluminum and brachial-ankle PWV (baPWV). METHODS: One hundred twenty-seven HD patients (average age 58.46 +/- 9.95 years) were enrolled. Medical data were obtained via chart reviews and hospital database. Associations between biomarker levels and baPWV were analysed by multiple linear regression. RESULTS: Serum aluminum, high sensitivity C-reactive protein (hsCRP), age, pulse pressure (PP), mean arterial pressure (MAP) and diabetes mellitus (DM) are important correlates of baPWV. CONCLUSION: Further, hsCRP, PP, age and DM are positively related to arterial stiffness in HD patients.

Nano-adsorbents for the removal of metallic pollutants from water and wastewater.

Of the variety of adsorbents available for the removal of heavy and toxic metals, activated carbon has been the most popular. A number of minerals, clays and waste materials have been regularly used for the removal of metallic pollutants from water and industrial effluents. Recently there has been emphasis on the application of nanoparticles and nanostructured materials as efficient and viable alternatives to activated carbon. Carbon nanotubes also have been proved effective alternatives for the removal of metallic pollutants from aqueous solutions. Because of their importance from an environmental viewpoint, special emphasis has been given to the removal of the metals Cr, Cd, Hg, Zn, As, and Cu. Separation of the used nanoparticles from aqueous solutions and the health aspects of the separated nanoparticles have also been discussed. A significant number of the latest articles have been critically scanned for the present review to give a vivid picture of these exotic materials for water remediation.

Preventing arteriovenous shunt failure in hemodialysis patients: a population-based cohort study.

Essentials Uncertainty remains about antiplatelets for vascular access patency in hemodialysis patients. 95 971 people under hemodialysis were followed in a claims database in Taiwan. Aspirin reduced vascular access failure rate and did not increase major bleeding rate. Clopidogrel, Aggrenox, and warfarin might increase major bleeding rate. SUMMARY: Background Dialysis adequacy is a major determinant of survival for patients with end-stage renal disease. Good vascular access is essential to achieve adequate dialysis. Objectives This study evaluated the impacts of different drugs on the vascular access failure rate of an arteriovenous fistula or an arteriovenous graft and the rate of major bleeding in hemodialysis patients. Patients and methods We studied patients with end-stage renal disease registered in the Taiwan National Health Insurance program from 1 January 1997 to 31 December 2012. A total of 95 971 patients were enrolled in our study. Vascular access dysfunction was defined as the need for thrombectomy or percutaneous angioplasty. Major bleeding was defined as emergency department visits or hospitalization with a primary diagnosis of gastrointestinal bleeding or intracerebral hemorrhage. The adjusted odds ratios between person-quarters with or without antiplatelet or oral anticoagulant use were calculated using a generalized estimating equation. Results The odds ratio of vascular access failure was 0.21 (0.11-0.39) for aspirin, 0.76 (0.74-0.79) for clopidogrel, 0.67 (0.59-0.77) for dipyridamole, 0.67 (0.53-0.86) for Aggrenox and 0.96 (0.90-1.03) for warfarin. The highest odds ratio for intracerebral hemorrhage was 5.33 (1.25-22.72) in younger patients using Aggrenox. The highest odds ratio for gastrointestinal bleeding was 1.34 (1.10-1.64) for clopidogrel. Conclusion Antiplatelet agents, but not warfarin, might reduce the vascular access thrombosis rate. The gastrointestinal bleeding rate was increased in the group using clopidogrel. Aggrenox should be used with caution in young individuals because it might increase the rate of intracerebral hemorrhage.

Removal of chromium by riverbed sand from water and wastewater: effect of important parameters.

Application of riverbed sand, a non-toxic substance for the removal of Cr(VI) for aqueous solutions has been investigated. Removal of Cr(VI) was dependent on initial concentration and removal increased from 43.2% to 74.3% by decreasing initial concentration from 7.5x10(-5) M to 1.0x10(-5) M at 25 degrees C, 1.0x10(-2) M NaClO4 ionic strength and 100 rpm. Higher removal was obtained at particles of smaller sizes of the adsorbent. Removal decreased from 74.3% to 40.7% by increasing temperature from 25 degrees C to 35 degrees C exhibiting exothermic nature of the process of removal. Thermodynamic parameters, namely change in free energy (DeltaG degrees), enthalpy (DeltaH degrees) and entropy (DeltaS degrees), were calculated and were found to be -0.81 kcal mol(-1), -17.21 kcal mol(-1) and 56.94 cal mol(-1), respectively at 25 degrees C. pH of the solution has pronounced effect on the removal and higher removal was obtained in acidic pH ranges, maximum (74.3%) being at 2.5 pH.

Adsorptive separation of cadmium from aqueous solutions and wastewaters by riverbed sand.

Application of riverbed sand for the adsorptive separation of cadmium(II) from aqueous solutions has been investigated. Removal increased from 26.8 to 56.4% by decreasing the initial concentration of cadmium from 7.5 x 10(-5) to 1.0 x 10(-5)M at pH 6.5, 25 degrees C temperature, agitation speed of 100 rpm, 100 microm particle size and 1.0 x 10(-2) NaClO4 ionic strength. Process of separation is governed by first order rate kinetics. The value of rate constant of adsorption, k(ad), was found to be 2.30 x 10(-2)per min at 25 degrees C. Values of coefficient of mass transfer, beta L, were calculated and its value at 25 degrees C was found to be 1.92 x 10(-2)cm/s. Values of Langmuir constant were calculated. Values of thermodynamic parameters delta G0, delta H0 and delta S0 were also calculated and were recorded as -0.81 kcal/mol, -9.31 kcal/mol and -28.10 cal/mol at 25 degrees C. pH has been found to affect the removal of cadmium significantly and maximum removal, 58.4%, has been found at pH 8.5. Process can be used for treatment of cadmium(II) rich wastewaters.

Removal of chromium(VI) from water and wastewater by using riverbed sand: kinetic and equilibrium studies.

Cr(VI) is a priority pollutant and has been documented to be harmful to fauna, flora and human beings and chromium containing water and wastewater are hazardous. Removal of Cr(VI) by adsorption on a non-toxic natural substance, riverbed sand has been investigated. A maximum removal of 74.3% was noted at 0.50 x 10(-4)M concentration of Cr(VI) in solution. Kinetic and equilibrium studies of Cr(VI) removal have been carried out. Chemical analysis of the adsorbent revealed SiO2 to be its major component. Kinetic data of adsorption was fitted by Lagergreen's model and k(ad), the rate constant of adsorption, was found be maximum 2.69 x 10(-2)min(-1) at 25 degrees C with minimum at 35 degrees C. Values of coefficients of intra-particle diffusion and mass transfer have been determined at different values of temperature. Langmuir's model has been used for equilibrium studies and the constants have been calculated. The studies conducted show the process of Cr(VI) removal to be exothermic in nature.

Characteristics of new coccine dye adsorption onto digested sludge particulates.

The adsorption characteristics of an anionic azo dye (new coccine) onto digested sludge have been studied. Results show that the dye can effectively be removed by sludge. It was found that the adsorption rate is very rapid and the equilibrium can be reached in 10 min. The adsorption kinetics can be expressed by the modified Freundlich equation. Also, the solution pH, ionic strength, and temperature are the key factors affecting the adsorption. The effect of electrical double layer thickness on the adsorption was also discussed. The adsorption standard free energy, enthalpy, and entropy were determined. The adsorption follows a nonlinear multilayer adsorption isotherm. The specific surface area of sludge was determined as 82 to approximately 150m2/g on the basis of its monolayer dye adsorption capacity.

Proliferation of myofibroblasts in the stroma of renal oncocytoma.

OBJECTIVES: Myofibroblasts are a vital component of stroma of many malignant neoplasms, but it is not yet established whether stromal myofibroblasts also exist in benign tumours such as oncocytoma of the kidney. MATERIALS AND METHODS: Histomorphological and immunohistochemical analysis of 16 renal oncocytomas diagnosed at Chang Gung Memorial Hospital, Taiwan, has been performed. RESULTS: Renal oncocytomas were composed of oncocytes, large cells with granular eosinophilic cytoplasm, arranged mostly in sheets, in tubulocystic or combined pattern. Few oncocytes appeared to be undergoing proliferation or apoptosis. MIB-1 and active caspase 3 indices were low, but higher in tumour than in surrounding non-tumour parenchyma (MIB-1: 0.93 +/- 0.09 versus 0.46 +/- 0.07, P < 0.001 and active caspase 3: 0.76 +/- 0.08 versus 0.41 +/- 0.09, P < 0.001). Wnt/beta-catenin signalling was not implicated in this neoplasm, as there was no loss of E-cadherin membranous localization or expression of intranuclear beta-catenin in the cells. Clumps of oncocytes were stained with periodic acid Schiff and had collagen I-, collagen III- and fibronectin-positive, but desmin- and human caldesmon-negative stromas. Importantly, alpha-smooth muscle actin (SMA)-immunostaining established the myofibroblastic nature of many of the stromal cells. Some of the myofibroblasts were also positive for MIB-1, indicating a proliferative role for them in the stroma. CONCLUSIONS: Renal oncocytomas were composed of two independent compartments: benign oncocytes and pronounced fibrotic stroma, which consisted of proliferating myofibroblasts (SMA- and MIB-1-positive) which were associated with excessive deposition of extracellular matrix (periodic acid Schiff-component, collagen I-, collagen III- and fibronectin-positive, and desmin- and human caldesmon-negative).

Selective subcellular redistributions of protein kinase C isoforms by chemical hypoxia.

The mechanisms of neuronal degeneration following hypoxia/ischemia remain undefined, but the processes include increases in neurotransmitter release, elevation of cytosolic-free calcium concentration, and changes in signal transduction pathways. Activation of the multigene family of protein kinase C (PKC) has been associated with the release of neurotransmitter and the survival of neurons. Therefore, to understand which PKC isozymes are involved in hypoxia/ischemia-induced neuronal degeneration, we examined PKC isozymes after chemical hypoxia (i.e., KCN exposure) in PC12 cells. Cell toxicity, as measured by lactate dehydrogenase (LDH) release, was increased significantly by KCN in glucose-free DMEM and was exaggerated by acute 12-O-tetradecanoyl phorbol-13-acetate (TPA) pretreatment. Under parallel conditions, KCN elevated cytosolic-free calcium ([Ca2+]i) in glucose-free but not in glucose containing DMEM, and TPA pretreatment did not exaggerate KCN's effect on [Ca2+]i. Thus, increases in [Ca2+]i are not sufficient for the synergistic toxic effect of KCN and TPA. In the glucose-free DMEM, selective PKC isozyme inhibitor Go 6976 at 10 nM completely inhibited KCN-induced LDH release and at higher concentrations (1 microM) inhibited the basal levels of LDH release. The protein levels of PKCs in the nuclear, membrane, and cytosolic fractions were measured by Western blot analysis using antibodies against specific isoforms. Two Ca2+-dependent (-alpha, -gamma) and four Ca2+-independent (-delta, -epsilon, -zeta, and -lambda) isozymes were identified and two isozymes (-beta and -theta) were not detected in the subcellular fractions of PC12 cells. Treatment of the cells with TPA significantly activated translocation of conventional PKC-gamma from the cytosol to the membrane and nuclear fractions and other PKC isozymes (-alpha, -delta, and -epsilon) from the cytosol to the membrane, but not atypical PKC-zeta and -lambda. Although only the levels in the nuclear PKC-gamma but not other PKC isozymes were increased significantly following KCN, the levels of cPKC-alpha and -gamma in the membrane mainly- and those and PKC-epsilon in the nucleus-were increased when KCN was combined with TPA. In addition, this condition (TPA + KCN) did not affect the TPA insensitive atypical isozymes, PKC-zeta or -lambda. Taking the results together, differential activation/translocation of PKC isozymes by KCN and TPA is important in the regulation of chemical hypoxia-induced cell injury in PC12 cells.