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The human population is dependent on agriculture for its food requirements and survival. Several insecticides and pesticides have found their use for improvements in agricultural yields. Organophosphates (OP) are one of the many compounds used as insecticides and pesticides. OPs have also been used to develop G and V-series chemicals which act as highly toxic nerve agents that can severely influence the normal function of the nervous system in all living beings. Thus, OP compounds utilized as insecticides/pesticides and nerve agents are hazardous to the environment, lethal for humans and other non-target animals. To avoid their toxicity, approaches to detect and neutralize them have become essential. A variety of analytical procedures such as electrochemical processes and chromatography methods, namely liquid and gas chromatography, have been employed to detect OPs. Though these techniques are sensitive and highly accurate they suffer from drawbacks, for instance: their bulky nature and expensive instrumentation, the difficulty of operation, long detection times, and they can yield unpredictable results with variable sample complexities. With the advent of several types of biosensors, the assay of OP compounds has become simpler, faster, cost-effective with improved sensitivity, and provides the capability for onsite detection. OP biosensor assays typically utilize several enzymes with the capability to hydrolyze/degrade OP compounds, such as organophosphate hydrolase (OPH) and organophosphate acid hydrolase (OPAA). This review focuses on discussing various aspects of OPAA as biological recognition unit in terms of its: structure, properties, activity enhancement methods, and utilization for developing OPAA-based biosensing technologies for insecticides, pesticides, and nerve agents.

Nowadays, awareness and concern regarding food safety are growing publicly in developing countries across the world. Various factors like sickness, misery, and even death are caused by contaminated food consumption. The increasing population across the globe increases food consumption. To overcome the gaps between the demand and supply of food products, people practice adulterating the food products (urea in milk). This work reports the synthesis of a solution-phase system containing fluorophores (FITC: act as indicator and Rubpy, serves as a reference) and enzymes (urease) for the real-time monitoring of samples. A color sensor-based device (CSD) has been developed and used to analyze the pH (4-9 pH) and urea (0-70 mM) in milk. The results obtained on CSD were cross-referenced on FOS simultaneously and found to be suitable for detecting degradation and urea adulteration in milk.

Exhaust system typically experiences vibration during engine operating conditions due to periodic disturbing forces (firing force and inertia force) which are generated from the engine. Natural frequency of the exhaust system gets excited due to the periodic forces causing resonance which often leads to high cycle fatigue (HCF) failure. Turbocharger is a part of exhaust system and it is mounted on the exhaust manifold. The periodic forces are transferred from engine base (Cylinder head and Block) and these forces gets amplified to overhanging components like exhaust system turbocharger. It is an industrywide practice to perform modal analysis to determine the natural frequencies of the system. However, modal analysis cannot predict the intensity with which the system would vibrate. Thus, we need to make some assumptions about the system vibration ‘g’ levels. Based on accuracy of this assumption, we may end up under-designing or over-designing the system. Harmonic analysis enables us to accurately predict the ‘g’ level at turbocharger using experimental cylinder head base excitations. After recording the correlation with experimental data in many cases it was found that this approach further aided in establishing damping constant factor of the exhaust manifold at elevated temperature. This analysis process has been validated with multiple cases as it has turned out to be a potential approach while doing design risk assessments and optimizing the engine vibration validation efforts. The benefit of prediction of exhaust system vibration level allows us to avoid iterative design process in the early stage of product development thus optimizing the design by taking advantage of shifting the natural frequency of exhaust system to lower source excitation (cylinder head). This saves vast amount of simulation lead time. Another benefit of this process is that the prediction of resonance condition of exhaust system through simulation helps us to estimate the fatigue life against the predicted ‘g’ level.

Patients with acute-on-chronic liver failure (ACLF) have coagulation failure in the setting of systemic inflammatory syndrome (SIRS), sepsis and extra-hepatic organ failures.Consecutive ACLF patients without sepsis at baseline were assessed at days 0, 3 and 7 with thromboelastography (TEG) and specific assays (Factor VIII, von Willebrand factor [vWF], protein C and antithrombin III [ATIII]) and followed for development of sepsis, bleeding and outcome.Of 243 patients, 114 (63% ethanol related; mean age 44.3 ± 11.7 years; 90% male) were recruited. SIRS was noted in 39 (34.2%), 45 (39.5%) and 46 (40%) patients at days 0, 3 and 7 and sepsis in 28 (24%) and 52 (56.1%) patients at days 3 and 7 respectively. The 28- and 90-day survivals were 62% and 51% respectively. A hypocoagulable TEG at baseline was a predictor of bleeding (hazard ratio [HR] 2.1; CI 1.6-4.9; P = 0.050) and mortality (HR 1.9; CI 1.3-7.9; P = 0.043). ACLF patients had increased Factor VIII, vWF, tissue factor levels and tissue plasminogen activator (tPA) activity with reduced protein C and ATIII. Coagulation parameters like Coagulation Index (HR 2.1; CI 1.1-4.5; P = 0.044),clot lysis (HR 3.2; CI 1.9-3.4; P = 0.033), low protein C 30% (HR 2.1; CI 1.5-2.8; P = 0.017), ATIII (HR 1.4; CI 1.7-3.1; P = 0.052) and tPA (HR 1.5; CI 1.1-2.4; P = 0.052) were predictors of mortality at day 28. Protein C activity30% (HR 1.3; CI 1.0-2.9; P = 0.042) and tPA20 ng/mL (HR 1.2; CI 1.1-2.1; P = 0.040) predicted mortality when adjusted for age, gender and baseline MELD.Dynamic coagulation derangements, measured by TEG, determine the likelihood of bleeding and mortality in ACLF.

Hibernomas are uncommon benign soft-tissue tumors which are composed of brown fat. They are usually seen in adults in the fourth and fifth decades and the common locations are thigh, shoulder, and back. Only few cases in the posterior neck region have been reported in literature. Hibernoma is very uncommon in the pediatric age group and those in the neck region are extremely rare. We present a hibernoma presenting as a swelling on the posterior aspect of base of the neck in a 5-month-old male infant. Considering the rare occurrence in the pediatric age group and difficulty in diagnosis, the clinical features, radiological features, pathological characteristics, differential diagnosis, and management of this rare tumor of childhood are discussed herewith.

The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set up in 2004 on acute-on-chronic liver failure (ACLF) was published in 2009. With international groups volunteering to join, the “APASL ACLF Research Consortium (AARC)” was formed in 2012, which continued to collect prospective ACLF patient data. Based on the prospective data analysis of nearly 1400 patients, the AARC consensus was published in 2014. In the past nearly four-and-a-half years, the AARC database has been enriched to about 5200 cases by major hepatology centers across Asia. The data published during the interim period were carefully analyzed and areas of contention and new developments in the field of ACLF were prioritized in a systematic manner. The AARC database was also approached for answering some of the issues where published data were limited, such as liver failure grading, its impact on the ‘Golden Therapeutic Window’, extrahepatic organ dysfunction and failure, development of sepsis, distinctive features of acute decompensation from ACLF and pediatric ACLF and the issues were analyzed. These initiatives concluded in a two-day meeting in October 2018 at New Delhi with finalization of the new AARC consensus. Only those statements, which were based on evidence using the Grade System and were unanimously recommended, were accepted. Finalized statements were again circulated to all the experts and subsequently presented at the AARC investigators meeting at the AASLD in November 2018. The suggestions from the experts were used to revise and finalize the consensus. After detailed deliberations and data analysis, the original definition of ACLF was found to withstand the test of time and be able to identify a homogenous group of patients presenting with liver failure. New management options including the algorithms for the management of coagulation disorders, renal replacement therapy, sepsis, variceal bleed, antivirals and criteria for liver transplantation for ACLF patients were proposed. The final consensus statements along with the relevant background information and areas requiring future studies are presented here., Article Highlights Updated on the basis of AARC data of >3300 cases enrolled into AARC registry prospectivelyACLF is distinct form Acute Decompensation of cirrhosisNewer sections on DILI-ACLF, AIH-ACLF, PVT/HVOTO–ACLFReversibility of Chronic Liver Disease in ACLFPortal and systemic hemodynamics and their relevance in ACLFAcute Portal Hypertension and Variceal progression in ACLFAARC score as a guide for treatment strategies in ACLFACLF in Children-first consensus on pediatric ACLF

BACKGROUND Left ventricular diastolic dysfunction (LVDD) refers to impaired cardiac diastolic relaxation and may be improved by targeted heart rate reduction (THR). The authors evaluated whether a combination of carvedilol and ivabradine, an If channel blocker that reduces heart rate without affecting blood pressure, could improve LVDD and outcomes in cirrhosis. PATIENTS AND METHODS THR was defined as heart rate reduction to 55 to 65 beats per minute. Of 260 patients with cirrhosis, 189 (72%) with LVDD were randomized to THR [group (Gr.)A; n=94; carvedilol±ivabradine)] or standard care (Gr.B; n=95; no β-blockers) and followed for 12 months. RESULTS In Gr.A, THR was achieved at 4 weeks in 88 (93%) patients (responders, R): 48 (61.5%) with carvedilol alone and 40 (86.9%) of 46 patients with additional ivabradine. In Gr.A, LVDD reversed in 16 (20.5%) and improved from grade 2 to 1 in 34 (35.4%)], whereas in Gr.B, it progressed from grade 1 to 2 in 10 (10.5%) patients. At 12 months, 21 (11.1%) patients died, 6 (14%) in Gr.A and 15 (18%) in Gr.B (P=0.240), but no mortality was seen in those who had persistent THR at 1 year (n=78; P=0.000). In multivariate analysis, model for end-stage liver disease [hazard ratio (HR), 1.52; 95% confidence interval (CI), 1.22-2.75; P=0.034] and E-wave transmitral/early diastolic mitral annular velocity (HR, 1.28; 95% CI, 1.23-2.42; P=0.048) predicted 1-year mortality. Nonresponders had an increased mortality risk (HR, 1.3; 95% CI, 1.2-1.8; P=0.046) independent of age, gender, and baseline model for end-stage liver disease. Levels of norepinephrine, N terminal brain natriuretic peptide, plasma renin activity, and aldosterone were reduced (P

Recurrent pyogenic cholangitis (RPC) is a disease characterized by multiple strictures of the biliary tree, impaired biliary drainage, formation of intrahepatic biliary pigment stones and recurrent bouts of cholangitis. We report the case of a 39-year-old businessman with diagnosed chronic calcific pancreatitis, who presented to us with recurrent episodes of cholangitis, leading to portal pyaemia, and progressive liver failure, which could not be controlled despite adequate biliary drainage. The patient rapidly developed progressive liver failure and sepsis-related coagulation failure. He was also found to have idiopathic CD4+ T cell lymphocytopenia (ICL), which resulted in refractory sepsis and formation of metastatic abscesses in the lung and spleen. ICL is now recognised in patients with recurrent and difficult to treat opportunistic infections. The combination of RPC, sepsis and liver failure in the setting of an acquired immunosuppressed state makes this a unique management scenario.

Endogenous heparinoids or heparin-like effects (HLEs) can cause coagulation failure in patients with cirrhosis and sepsis. We performed a prospective study of the association between HLE and bleeding events, sepsis, and outcomes of patients with severe alcohol-associated hepatitis.Our final analysis comprised 78 patients with severe alcohol-associated hepatitis (44.3 ± 11.7 years; all male; discriminant function32) who presented without sepsis at a single center in India from August 2015 through August 2016. Blood samples were collected at days 0, 3, and 7 after presentation and assessed by a global coagulation assay; by SONOCLOT (global and heparinase treated); and in assays for factor VIII, von Willebrand factor, protein C, and antithrombin. Patients were followed for sepsis, bleeding and outcome. The primary outcome was association of HLE with survival 28 days after presentation.HLEs were observed in 32 patients (41%) at day 0, 27 patients (34.6%) at day 3, and 28 patients (35.9%) patients at day 7. Factors associated with mortality at day 0 were factor VIII activity160% (hazard ratio [HR], 3.1; 95% CI, 1.4-9.5; P = .026), level of protein C34% (HR, 0.7; 95% CI, 0.5-0.8; P = .037), antithrombin activity28% (HR, 0.7; 95% CI, 0.3-1.1; P = .008) and international normalized ratio2.6 (HR, 2.3; 95% CI, 1.8-9.7; P = .010). In multivariate analyses, only factor VIII activity (HR, 2.3; 95% CI, 1.6-7.8; P = .046), international normalized ratio (1.9; 95% CI, 1.2-4.3; P = .039), level of protein C (HR, 0.9; 95% CI, 0.7-1.1; P = .052) and model for end-stage liver disease score (HR, 3.2; 95% CI, 1.9-10.2; P = .042) were associated with mortality. Episodes of epistaxis, hemorrhoid bleeding, hemoperitoneum, and pulmonary hemorrhage occurred in 10.2%, 12.3%, 3.4%, and 4.5% of patients respectively. The presence of HLE at day 0 increased the risk of sepsis (HR, 2.5; 95% CI, 2.2-4.3; P = .002), bleeding (HR, 1.4; 95% CI, 1.2-5.3; P = .004) and death (HR, 1.2; 95% CI, 1.4-1.7; P = .044).In a prospective study of patients with severe alcohol-associated hepatitis, we associated HLE with coagulation abnormalities, risk of sepsis, and mortality. Clinicaltrials.govNCT02307409.

Background The presence of left ventricular diastolic dysfunction (LVDD) in patients with cirrhosis leads to a restriction of activities and a poor health related quality of life (HRQoL), which should be taken into consideration when treating them for liver and cardiac complications. Aims The prevalence, complications, predictors of HRQoL and survival in cirrhotic patients with LVDD were studied. Methods We report a prospective cohort study of 145 consecutive cirrhotic patients with LVDD who were evaluated for cardiac functional status at enrollment and followed up for hepatic complications, cardiac events, outcome and HRQoL using the Minnesota Living With Heart Failure Questionnaire (MLHFQ) over a period of 2 years. Results In total, 145 (mean age 61 years, 59% male) patients were included. Seventeen patients died with 10.5%, 22.5% and 40% mortality rates in patients with Grades 1, 2 and 3 LVDD respectively over 24 months. The parameters that were significant for predicting mortality on bivariate analysis were MELD, MELDNa, hepatic venous pressure gradient, MLHFQ, and left ventricular (LV) diastolic function (e′ and E/e′ ratio), but only MELD, MELDNa and E/e′ remained significant on multivariate analysis. The E/e′ ratio (8.7 ± 3.3 in survivors vs. 9.1 ± 2.3 in non-survivors) predicted outcome. On univariate analysis, the predictors of poor HRQoL were the Child-Pugh score ≥9.8 (OR 2.6; 95% confidence intervals (CI) 2.3–9.1, P = 0.041), MELD score ≥ 15.7 (OR 2.48; 95% CI 1.4–3.9, P = 0.029), refractory ascites (OR 1.9; 95% CI 1.1–6.1, P = 0.050), and E/e′ ratio ≥7.6 (OR 1.9; 95% CI 1.8–7.1, P = 0.036) The presence of Class II/III (P = 0.046) symptoms of heart failure and MLHFQ≥ 45 (P = 0.042) were predictors of mortality at 24 months. Conclusion The grade of LVDD correlates with liver function, clinical events, risk of renal dysfunction and HRQoL. Evaluation of novel therapies which target symptomatic improvement in LVDD, should be done with suitable outcome measures, including HRQoL assessment.

Sister Mary Joseph nodules represent metastatic cancer of the umbilicus. More than half of these cases are attributable to gastrointestinal malignancies including gastric, colonic, and pancreatic cancer. In addition, gynecologic (ovarian, uterine cancer), unknown primary tumors, and, rarely, bladder or respiratory malignancies may cause umbilical metastasis. We report the case of a Sister Mary Joseph nodule originating from a hilar cholangiocarcinoma. Umbilical nodules should prompt clinical evaluation, as these tumors are usually associated with poor prognosis.

Systemic amyloidosis of amyloid light chain associated protein (AL), also called primary amyloidosis, frequently involves the liver, but rarely causes clinically apparent liver disease. The more common presentation is with acute renal failure. Hepatomegaly and mild elevation of alkaline phosphatase are the most common clinical and biochemical findings, respectively. We report a case of systemic amyloidosis of AL that clinically presented as acute-on-chronic liver failure and resulted in a fatal clinical course in a 56-year-old man.

CML originates due to reciprocal translocation in Philadelphia chromosome leading to the formation of fusion product BCR-ABL which constitutively activates tyrosine kinase signaling pathways eventually leading to abnormal proliferation of granulocytic cells. As a therapeutic strategy, BCR-ABL inhibitors have been clinically approved which terminates its phosphorylation activity and retards cancer progression. However, a number of patients develop resistance to inhibitors which demand for the discovery of new inhibitors. Given the drawbacks of present inhibitors, by high throughput virtual screening approaches, present study pursues to identify high affinity compounds targeting BCR-ABL1 anticipated to have safer pharmacological profiles. Five established BCR-ABL inhibitors formed the query compounds for identification of structurally similar compounds by Tanimoto coefficient based linear fingerprint search with a threshold of 95% against PubChemdatabase. Assisted by MolDock algorithm all compounds were docked against BCR-ABL protein in order to retrieve high affinity compounds. The parents and similars were further tested for their ADMET propertiesand bioactivity. Rebastinib formed higher affinity inhibitor than rest of the four established compound investigated in the study. Interestingly, Rebastinib similar compound with Pubchem ID: 67254402 was also shown to have highest affinity than other similars including the similars of respective five parents. In terms of ADMET properties Pubchem ID: 67254402 had appreciable ADMET profile and bioactivity. However, Rebastinib still stood as the best inhibitor in terms of binding affinity and ADMET properties than Pubchem ID: 67254402. Nevertheless, owing to the similar pharmacological properties with Rebastinib, Pubchem ID: 67254402 can be expected to form potential BCR-ABL inhibitor.