Plasma-Activated Water for Food Safety and Quality: A Review of Recent Developments.

Plasma-activated water (PAW) has received a lot of attention lately because of its antibacterial efficacy and eco-friendly nature. Compared to traditional disinfectants, this novel and intriguing option has a high disinfectant capacity while causing little to no modifications to the foodstuffs. Until now, PAW has successfully demonstrated its effectiveness against a broad range of microorganisms on a wide variety of food items. Though the efficacy of PAW in microbial reduction has been extensively reviewed, a relatively significant issue of food quality has been largely overlooked. This review aims to summarize the current studies on the physicochemical characteristics and antimicrobial potential of PAW, with an in-depth focus on food quality and safety. According to recent studies, PAW can be a potential microbial disinfectant that extends the shelf life of various food products, such as meat and fish products, fruits and vegetables, cereal products, etc. However, the efficacy varies with treatment conditions and the food ingredients applied. There is a mixed opinion about the effect of PAW on food quality. Based on the available literature, it can be concluded that there has been no substantial change in the biochemical properties of most of the tested food products. However, some fruits and vegetables had a higher value for the enzyme superoxide dismutase (SOD) after PAW treatment, while only a few demonstrated a decrease in the Thiobarbituric acid reactive substances (TBARS) value. Sensory properties also showed no significant difference, with some exceptions in meat and fish products.

The severity prediction of the binary and multi-class cardiovascular disease - A machine learning-based fusion approach.

In today's world, a massive amount of data is available in almost every sector. This data has become an asset as we can use this enormous amount of data to find information. Mainly health care industry contains many data consisting of patient and disease-related information. By using the machine learning technique, we can look for hidden data patterns to predict various diseases. Recently CVDs, or cardiovascular disease, have become a leading cause of death around the world. The number of death due to CVDs is frightening. That is why many researchers are trying their best to design a predictive model that can save many lives using the data mining model. In this research, some fusion models have been constructed to diagnose CVDs along with its severity. Machine learning(ML) algorithms like artificial neural network, SVM, logistic regression, decision tree, random forest, and AdaBoost have been applied to the heart disease dataset to predict disease. Randomoversampler only for multi-class classification to make the imbalanced dataset balanced. To improve the performance of classification, a weighted score fusion approach was taken. At first, the models were trained. After training, two algorithms' decision was combined using a weighted sum rule. A total of three fusion models have been developed from the six ML algorithms. The results were promising in the performance parameter. The proposed approach has been experimented with different test training ratios for binary and multiclass classification problems, and for both of them, the fusion models performed well. The highest accuracy for multiclass classification was found as 75%, and it was 95% for binary.

Interaction between Naegleria fowleri and pathogenic Escherichia coli by mannose and changes in N. fowleri protease.

Naegleria fowleri can cause acute primary amoebic encephalitis. It is known that contact-dependent pathogenicity in free-living amoeba may be mediated through a carbohydrate-dependent pathway. In this study, the effect of mannose on the interaction between N. fowleri and pathogenic Escherichia coli O157:H7 and non-pathogenic E. coli DH5α was analyzed. In particular, the changes in proteases expressed by N. fowleri in response to mannose were analyzed. Unlike the conventional method, mannose was treated with N. fowleri for 1 h. The association between N. fowleri and E. coli O157:H7 treated with 50-mM and 100-mM mannose was significantly reduced by approximately 70.9% and 128.5%, respectively. E. coli O157:H7 invasion was reduced by about 10.8% by 100-mM mannose. Moreover, as a result of culturing N. fowleri invaded by E. coli O157:H7 for 24 h, E. coli O157:H7 also grew about 1.2 times in the group not treated with mannose. E. coli DH5α association was reduced by 25.7% by 100-mM mannose. On the other hand, there was almost no inhibitory effect by 100-mM glucose. In the analysis in which mannose bound to either N. fowleri or bacteria and affected the interaction, there was little effect on the interaction between N. fowleri and bacteria. In zymographic analysis, about 135-kDa and 75-kDa bands were observed by 50-mM and 100-mM mannose, and two bands were significantly increased by 100-mM mannose. This study suggests that mannose can be mediated in the contact-dependent pathway of N. fowleri and will serve as a basis for inducing changes in the protease of N. fowleri by other monosaccharides.

A Comprehensive Review on Bio-Preservation of Bread: An Approach to Adopt Wholesome Strategies.

Bread is a food that is commonly recognized as a very convenient type of food, but it is also easily prone to microbial attack. As a result of bread spoilage, a significant economic loss occurs to both consumers and producers. For years, the bakery industry has sought to identify treatments that make bread safe and with an extended shelf-life to address this economic and safety concern, including replacing harmful chemical preservatives. New frontiers, on the other hand, have recently been explored. Alternative methods of bread preservation, such as microbial fermentation, utilization of plant and animal derivatives, nanofibers, and other innovative technologies, have yielded promising results. This review summarizes numerous research findings regarding the bio-preservation of bread and suggests potential applications of these techniques. Among these techniques, microbial fermentation using lactic acid bacteria strains and yeast has drawn significant interest nowadays because of their outstanding antifungal activity and shelf-life extending capacity. For example, bread slices with Lactobacillus plantarum LB1 and Lactobacillus rossiae LB5 inhibited fungal development for up to 21 days with the lowest contamination score. Moreover, various essential oils and plant extracts, such as lemongrass oil and garlic extracts, demonstrated promising results in reducing fungal growth on bread and other bakery products. In addition, different emerging bio-preservation strategies such as the utilization of whey, nanofibers, active packaging, and modified atmospheric packaging have gained considerable interest in recent days.

Forecasting the spread of the third wave of COVID-19 pandemic using time series analysis in Bangladesh.

During the third wave of the coronavirus epidemic in Bangladesh, the death and infection rate due to this devastating virus has increased dramatically. The rapid spread of the virus is one of the reasons for this terrible condition. So, identifying the subsequent cases of coronavirus can be a great tool to reduce the mortality and infection rate. In this article, we used the autoregressive integrated moving average-ARIMA(8,1,7) model to estimate the expected daily number of COVID-19 cases in Bangladesh based on the data from April 20, 2021, to July 4, 2021. The ARIMA model showed the best results among the five executed models over Autoregressive Model (AR), Moving Average (MA), Autoregressive Moving Average (ARMA), and Rolling Forest Origin. The findings of this article were used to anticipate a rise in daily cases for the next month in Bangladesh, which can help governments plan policies to prevent the spread of the virus. The forecasting outcome indicated that this new trend(named delta variant) in Bangladesh would continue increasing and might reach 18327 daily new cases within four weeks if strict rules and regulations are not applied to control the spread of COVID-19.

Production of a monoclonal antibody against a galactose-binding protein of Acanthamoeba castellanii and its cytotoxicity.

In this study, it was confirmed whether the galactose-binding protein (GBP) was present in Acanthamoeba castellanii, and its function on a target cell was confirmed by production of an antibody against the GBP. Since the genes for GBP have not yet been identified at all, the purification of GBP was done using galactose-beads from amoebial lysates, and monoclonal antibodies were produced using cell fusion. GBP was confirmed to have a size of about 35 kDa. After the third immunization with purified GBP in BALB/c mice, monoclonal antibody production was analyzed. The clone cultured before limiting dilution was named 2AB2 and showed the highest antibody titer in the culture supernatant of a 24-well plate. AF6 clone cultured after limiting dilution showed an antibody titer of 0.259 in a 75-T flask. Antibodies generated by collecting ascites by injecting monoclonal colonies into the abdominal cavity of mice were confirmed through gel analysis and were observed to belong to the isotype of the IgM having kappa chains. Since the cytotoxicity of A. castellanii was inhibited by about 26% by the monoclonal antibody against GBP, it was confirmed that the antibody against GBP had an inhibitory effect on cytotoxicity. This study was the first report on GBP isolated and purified from A. castellanii, and similarly to a mannose-binding protein (MBP), its involvement in contact-dependent cytotoxicity was demonstrated with monoclonal antibody production.

Type 1 Fimbriae and Motility Play a Pivotal Role During Interactions of Salmonella typhimurium with Acanthamoeba castellanii (T4 Genotype).

Amoebic bacterial interactions are the most ancient form of host pathogen interactions. Here, we investigate the fate of Salmonella typhimurium and Acanthamoeba castellanii T4 genotype upon mutual interactions in a nutrition free environment. The role of type 1 fimbriae and motility of S. typhimurium during interactions with A. castellanii has also been investigated. Deletion of genes encoding the type 1 fimbriae subunit FimA, type 1 fimbriae tip protein FimH, chemotaxis regulatory proteins CheA and CheY and major flagella subunits FliC and FljB was performed through homologous recombination. In vitro association, invasion and survival assays of S. typhimurium wild-type and mutant strains were performed upon co-incubation of bacteria with A. castellanii trophozoites in a nutrition free environment. The deletion gene encoding type 1 fimbriae subunit FimA reduced, whereas the deletion of genes encoding flagella subunits FliC and FljB of flagella enhanced the association capability of S. typhimurium with A. castellanii. Invasion of A. castellanii by Salmonella was significantly reduced upon the loss of type 1 fimbriae subunit FimA and type 1 fimbriae tip protein FimH. Co-incubation of S. typhimurium with A. castellanii in phosphate buffered saline medium stimulated the growth of S. typhimurium wild-type and mutant strains. Viable A. castellanii trophozoites count became significantly reduced upon co-incubation with S. typhimurium within 48 h. Type 1 fimbriae play a pivotal role in the adherence of S. typhimurium to the A. castellanii cell surface. Subsequently, this interaction provides S. typhimurium an advantage in growth.

Rural community perceptions of antibiotic access and understanding of antimicrobial resistance: qualitative evidence from the Health and Demographic Surveillance System site in Matlab, Bangladesh.

BACKGROUND: The use of large quantities of antimicrobial drugs for human health and agriculture is advancing the predominance of drug resistant pathogens in the environment. Antimicrobial resistance is now a major public health threat posing significant challenges for achieving the Sustainable Development Goals. In Bangladesh, where over one third of the population is below the poverty line, the achievement of safe and effective antibiotic medication use for human health is challenging. OBJECTIVE: To explore factors and practices around access and use of antibiotics and understanding of antimicrobial resistance in rural communities in Bangladesh from a socio-cultural perspective. METHODS: This qualitative study comprises the second phase of the multi-country ABACUS (Antibiotic Access and Use) project in Matlab, Bangladesh. Information was collected through six focus group discussions and 16 in-depth interviews. Informants were selected from ten villages in four geographic locations using the Health and Demographic Surveillance System database. The Access to Healthcare Framework guided the interpretation and framing of the findings in terms of individuals' abilities to: perceive, seek, reach, pay and engage with healthcare. RESULTS: Village pharmacies were the preferred and trusted source of antibiotics for self-treatment. Cultural and religious beliefs informed the use of herbal and other complementary medicines. Advice on antibiotic use was also sourced from trusted friends and family members. Access to government-run facilities required travel on poorly maintained roads. Reports of structural corruption, stock-outs and patient safety risks eroded trust in the public sector. Some expressed a willingness to learn about antibiotic resistance. CONCLUSION: Antimicrobial resistance is both a health and development issue. Social and economic contexts shape medicine seeking, use and behaviours. Multi-sectoral action is needed to confront the underlying social, economic, cultural and political drivers that impact on the access and use of antibiotic medicines in Bangladesh.

Report: Effect of macrophage alone or primed with cytokines on Balamuthia mandrillaris interactions with human brain microvascular endothelial cells in vitro.

Balamuthia mandrillaris is well known to cause fatal Balamuthia amoebic encephalitis (BAE). Amoebic transmission into the central nervous system (CNS), haematogenous spread is thought to be the prime step, followed by blood-brain barrier (BBB) dissemination. Macrophages are considered to be the foremost line of defense and present in excessive numbers during amoebic infections. The aim of the present investigation was to evaluate the effects of macrophages alone or primed with cytokines on the biological characteristics of Balamuthia in vitro. Using human brain microvascular endothelial cells (HBMEC), which constitutes the BBB, we have shown that Balamuthia demonstrated <90% binding and <70% cytotoxicity to host cells. However, macrophages further increased amoebic binding and Balamuthia-mediated cell cytotoxicity. Furthermore macrophages exhibited no amoebicidal effect against Balamuthia. Zymography assay demonstrated that macrophages exhibited no inhibitory effect on proteolytic activity of Balamuthia. Overall we have shown for the first time macrophages has no inhibitory effects on the biological properties of Balamuthia in vitro. This also strengthened the concept that how and why Balamuthia can cause infections in both immuno-competent and immuno-compromised individuals.

The cellulose synthase BcsA plays a role in interactions of Salmonella typhimurium with Acanthamoeba castellanii genotype T4.

Pathogenic bacteria share their natural habitat with many other organisms such as animals, plants, insects, parasites and amoeba. Interactions between these organisms influence not only the life style of the host organisms, but also modulate bacterial physiology. Adaptation can include biofilm formation, capsule formation, and production of virulence factors. Although biofilm formation is a dominant mode of bacterial life in environmental settings, its role in host-pathogen interactions is not extensively studied. In this work, we investigated the role of molecular pathways involved in rdar biofilm formation in the interaction of Salmonella typhimurium with the Acanthamoeba castellanii genotype T4. Genes coding for the rdar biofilm activator CsgD, the cellulose synthase BcsA, and curli fimbriae subunits CsgBA were deleted from the genome of S. typhimurium. Assessment of interactions of wild-type and mutant strains of S. typhimurium with A. castellanii revealed that deletion of the cellulose synthase BcsA promoted association and uptake by A. castellanii, whereas the interactions with csgD and csgBA mutants were not changed. Our findings suggest that cellulose synthase BcsA inhibits the capabilities of S. typhimurium to associate with and invade into A. castellanii.

Assessment of heavy metal pollution, distribution and source apportionment in the sediment from Feni River estuary, Bangladesh.

Heavy metal pollution in sediment resources may pose serious threat to ecosystem and human health through food web. In this study, surface sediment samples of 10 stations along the Feni River estuary were analyzed to profile the accumulation, sources and pollution levels of heavy metals. The results revealed that the average contents (µg g-1) of eight selected heavy metals followed the order of Mn (37.85) > Cr (35.28) > Ni (33.27) > Co (31.02) > Pb (6.47) > Ag (1.09) > As (0.85) > Hg (0.71), and the concentrations varied spatially and seasonally with relatively higher levels at upward stations and during the rainy season. According to sediment quality guidelines (SQGs), the sediment samples were heavily contaminated with Ag and Hg, and moderately with Co. Threshold effect concentration (TEC) and probable effect concentration (PEC) values indicated that the concentration of only Ni and Cr were likely to occasionally exhibit adverse effects on the ecosystem. Enrichment factor (EF), geo-accumulation index (Igeo) and contamination factor (CF) analyses revealed that Ag, Co and Hg were at moderate to high pollution levels and the rests (As, Cr, Ni, Pb and Mn) were at no to low pollution levels. Potential ecological risk index (PERI) also showed that Ag, Co and Hg were the most potential ecological risk factor being determined in this studied area. Correlation matrix combined with multivariate principal component analysis and cluster analysis suggest that Ag, Co, Ni and Hg originated from anthropogenic sources (agrochemicals, silver nanoparticles anti-microbial agent, silver plating), whereas As, Cr, Pb and Mn primarily originated from natural geological background.

Handgrip Strength as an Important Bed Side Tool to Assess Malnutrition in Patient with Liver Disease.

BACKGROUND: Malnutrition is frequently present in patients with cirrhosis. Anthropometric measures such as body mass index (BMI), mid arm muscle circumference (MAMC), triceps skin fold thickness (TST) and subjective global assessment (SGA) have some limitations in assessment of malnutrition. This study aims to determine the prevalence of malnutrition in non-hospitalized cirrhotic and chronic hepatitis patients and to assess handgrip (HG) strength as a tool for identifying malnutrition. METHODS: Consecutive patients of cirrhosis (n = 352), chronic hepatitis (n = 189) and healthy controls (n = 159) were enrolled. All patients underwent MAMC, TST, HG and SGA assessment. Malnutrition was diagnosed on basis of SGA score. Values of MAMC, TST and HG below the 5th percentile or less than 60% of healthy controls were considered as abnormal. RESULTS: According to SGA (taken as standard) 24% patients with chronic hepatitis and 56% of patients with cirrhosis had malnutrition (P = 0.001). In patients with chronic hepatitis prevalence of malnutrition according to MAMC (12%), TST (31%) and HG (18%). In patients with cirrhosis prevalence of malnutrition according to MAMC (27%), TST (60%) and HG (42%). HG exercise strength had the highest area under curve 0.82 (95% confidence interval (CI) 0.78-0.86, P = 0.001) compared to MAMC 0.60 (95% CI 0.55-0.64, P = 0.001) and TST 0.65 (95% CI 0.61-0.69, P = 0.001) for assessing malnutrition. On comparison of HG, TST and MAMC, the sensitivity was 67%, 60% and 31%, respectively, Specificity was 95%, 71% and 89%, respectively, and diagnostic accuracy was 87%, 67% and 71%, respectively. CONCLUSION: HG strength is an excellent tool to assess at bed side the nutrition status in patients with cirrhosis and has the highest diagnostic accuracy compared to other anthropometric tests such as MAMC and TST.

Bacterial and viral pathogen spectra of acute respiratory infections in under-5 children in hospital settings in Dhaka city.

The study aimed to examine for the first time the spectra of viral and bacterial pathogens along with the antibiotic susceptibility of the isolated bacteria in under-5 children with acute respiratory infections (ARIs) in hospital settings of Dhaka, Bangladesh. Nasal swabs were collected from 200 under-five children hospitalized with clinical signs of ARIs. Nasal swabs from 30 asymptomatic children were also collected. Screening of viral pathogens targeted ten respiratory viruses using RT-qPCR. Bacterial pathogens were identified by bacteriological culture methods and antimicrobial susceptibility of the isolates was determined following CLSI guidelines. About 82.5% (n = 165) of specimens were positive for pathogens. Of 165 infected cases, 3% (n = 6) had only single bacterial pathogens, whereas 43.5% (n = 87) cases had only single viral pathogens. The remaining 36% (n = 72) cases had coinfections. In symptomatic cases, human rhinovirus was detected as the predominant virus (31.5%), followed by RSV (31%), HMPV (13%), HBoV (11%), HPIV-3 (10.5%), and adenovirus (7%). Streptococcus pneumoniae was the most frequently isolated bacterial pathogen (9%), whereas Klebsiella pneumaniae, Streptococcus spp., Enterobacter agglomerans, and Haemophilus influenzae were 5.5%, 5%, 2%, and 1.5%, respectively. Of 15 multidrug-resistant bacteria, a Klebsiella pneumoniae isolate and an Enterobacter agglomerans isolate exhibited resistance against more than 10 different antibiotics. Both ARI incidence and predominant pathogen detection rates were higher during post-monsoon and winter, peaking in September. Pathogen detection rates and coinfection incidence in less than 1-year group were significantly higher (P = 0.0034 and 0.049, respectively) than in 1-5 years age group. Pathogen detection rate (43%) in asymptomatic cases was significantly lower compared to symptomatic group (P<0.0001). Human rhinovirus, HPIV-3, adenovirus, Streptococcus pneumonia, and Klebsiella pneumaniae had significant involvement in coinfections with P values of 0.0001, 0.009 and 0.0001, 0.0001 and 0.001 respectively. Further investigations are required to better understand the clinical roles of the isolated pathogens and their seasonality.

Synthesis, characterization and amoebicidal potential of locally synthesized TiO2 nanoparticles against pathogenic Acanthamoeba trophozoites in vitro.

Acanthamoeba is an opportunistic protozoan pathogen that plays a pivotal role in the ecosystem. It may cause blinding keratitis and fatal encephalitis involving the central nervous system. Here we synthesized pure and Zn doped TiO2 nanoparticles (~10-30nm) via sol-gel and sol-hydrothermal methods and demonstrated its impact on the biological characteristics of pathogenic Acanthamoeba castellanii. Our results revealed that pure and Zn doped TiO2 nanoparticles synthesized by sol-hydrothermal methods (ranging 5, 10, 25 and 50µg/ml) exhibited amoebicidal effects i.e., >60% of trophozoites executed under normal light at maximum dose (50µg/ml) within 1h incubation. In contrast pure/doped TiO2 obtained via sol gel method showed ~40% amoeba damage. Furthermore, amoebae growth assay demonstrated that Zn doped TiO2 also inhibited Acanthamoeba numbers up to 7days in dose dependent manner. It was interesting to note that all the tested TiO2 nanoparticles have shown maximum amoebicidal effects at pH7 which is quite relevant to amoebic growth favorable conditions. Our results confirmed that TiO2 has inhibitory effects on Acanthamoeba growth and viability. Overall, we reported the amoebicidal and amoebic growth inhibition potential of pure and Zn doped TiO2 nanoparticles against Acanthamoeba due to attached OH(-) groups, reduced size and decreased band gap of sol hydrothermally synthesized TiO2 nanoparticles.

Methanolic extract of Peganum harmala exhibit potent activity against Acanthamoeba castellanii cysts and its encystment in vitro.

Acanthamoeba castellanii is member of free living amoeba that may cause painful sight-threatening keratitis and life threatening encephalitis which involves central nervous system. Treatments for both infections are problematic because of the amoebic cysts resistance to therapeutic agents. Here we evaluated in vitro strength of methanolic seed extract of Peganum harmala on Acanthamoeba cysts and its encystment mechanism. Our results revealed seed extracts (1 to 30mg/ml) exhibited amoebicidal effects against Acanthamoeba cysts. Furthermore Acanthamoeba encystment was also inhibited in concentration dependent manner with maximum inhibition at 2µg/ml after 48h incubation. In conclusion, we demonstrated for the first time that methanolic extracts exhibit remarkable inhibition of Acanthamoeba cysts and encystment in vitro which could serve a potential new natural agent against Acanthamoeba.

Synthesis, characterization and in vitro evaluation of methotrexate conjugated fluorescent carbon nanoparticles as drug delivery system for human lung cancer targeting.

Nanotechnology based cancer therapeutics have rapidly advanced towards the solution of many limitations associated with other drug delivery agents such as nonspecific distribution within the body, low water solubility and non-biocompatibility. Carbon nanoparticles have demonstrated unique properties that are useful to combat with these issues, including their properties dependent on size, high stability in different solvents, compatible size for drug delivery and ease of surface modifications. Fluorescent carbon nanoparticles with good water solubility were obtained from a carbohydrate source by acid assisted ultrasonic treatment at 35kHz for 4h. This simple and economical method can be used for large scale production. Electron microscopic, spectroscopic and thermo gravimetric analysis techniques were used to characterize these carbon nanoparticles. Functionalized CNPs were further conjugated with anticancer drug-methotrexate and used as fluorescent nano-carriers. In this research work, we determined the in vitro bioactivity of CNPs-methotrexate conjugates by lactate dehydrogenase assay, cell adhesion assay and sulforhodamine B assay in human lung carcinoma cell line (H157). The CNPs showed promising biocompatibility and CNPs-MTX conjugates demonstrated potent cytotoxic effects and high anticancer activities in human lung cancer cell line.

Quick survey for detection, identification and characterization of Acanthamoeba genotypes from some selected soil and water samples across Pakistan.

Acanthamoeba is an opportunistic protozoan pathogen which is widely distributed in nature and plays a pivotal role in ecosystem. Acanthamoeba species may cause blinding keratitis and fatal granulomatous encephalitis involving central nervous system. In this study, we investigated the presence of Acanthamoeba in soil and water resources of Pakistan. Here, Acanthamoeba were recovered on non-nutrient agar plate lawn with E. coli and identified by morphological characteristics of the cyst. Furthermore PCR was performed with genus-specific primers followed by direct sequencing of the PCR product for molecular identification. Overall our PCR and sequencing results confirmed pathogenic genotypes including T4 and T15 from both soil and water samples. This is our first report of Acanthamoeba isolation from both soil and water resources of Pakistan which may serve as a potential treat to human health across the country.

Role of Transient Elastography (Fibroscan) in Differentiating Severe Acute Hepatitis and Acute on Chronic Liver Failure.

INTRODUCTION: It is difficult to differentiate acute severe hepatitis (AH) with acute on chronic liver failure (ACLF). Aim was to study the role of transient elastography (Fibroscan) in identifying the patients with AH and ACLF. MATERIALS AND METHODS: Consecutive patients of severe AH or ACLF presented within two weeks of jaundice were enrolled. LSM and liver function tests were done at admission, week 1, 4 and at 6 months. Diagnosis of ACLF was based on documenting cirrhotic morphology on imaging and/or liver biopsy and follow-up of these patients for six months. Similarly, AH patients were diagnosed based on serology, no features of cirrhosis on imaging and follow-up of these patients for 6 months documenting reversal of liver stiffness measurement (LSM) to normal. RESULTS: 104 patients were included in the final analysis (AH, n = 59, ACLF, n = 45). Out of 59 patients in severe AH group, etiology of acute hepatitis included hepatitis A (HAV, n = 22), hepatitis E (HEV, n = 21), hepatitis B (HBV, n = 4), indeterminate (n = 8) and drug induced liver injury (n = 4). Similarly for ACLF, the causes of chronic liver disease were alcohol (n = 26), hepatitis B (n = 7), hepatitis C (n = 2) and cryptogenic (n = 10). Patients with ACLF were significantly older, had low hemoglobin, low albumin, high bilirubin and lower transaminases level compared to severe AH at admission. LSM was higher in patients with ACLF compared to severe AH (61 ± 18 kPa vs 15 ± 6.4 kPa, P = 0.001) at admission. On multivariate analysis of noninvasive tests only LSM was found to differentiate AH with ACLF significantly. When we took a cutoff of 26 kPa the sensitivity and specificity of diagnosis of ACLF were 96% and 93%, respectively, with area under the curve was 0.98 (0.95-1.005), P = 0.001. CONCLUSION: LSM could differentiate patients with severe AH and ACLF at admission.

Usefulness of transient elastography by FibroScan for the evaluation of liver fibrosis.

INTRODUCTION: Liver stiffness measurement (LSM) is used for the assessment of liver fibrosis. However, there is limited data in Indian patients. AIMS AND OBJECTIVE: The aim of this study was to find the correlation of LSM, aspartate transaminase to platelet ratio index (APRI) with fibrosis as assessed by liver biopsy (LB), and predictors of discordance between LB and LSM. METHODS: One hundred and eighty-five consecutive patients who underwent liver biopsy and transient elastography (TE) were enrolled. Fibrosis was graded by two independent pathologists using the METAVIR classification. Area under receiver operating curves (AUROC) was used to evaluate the accuracy of transient elastography and APRI in diagnosing significant fibrosis (F>2) and cirrhosis (F4). RESULTS: Predominant etiologies were hepatitis B (46 %) and hepatitis C (26 %). LSM was unsuccessful in ten patients (5 %) because of small intercostal space (n = 3) and obesity (n = 7). Fibrosis is significantly correlated with LSM (r = 0.901, p = 0.001) and APRI (r = 0.736, p = 0.001). There was a significant difference in median LSM value in patients with no fibrosis (F0) in comparison to patients having mild fibrosis [mild portal fibrosis (F1) + fibrosis with few septa (F2)] (4.5 vs. 7.5 kPa, p = 0.001) and advanced fibrosis [bridging fibrosis that is spreading and connecting to other areas that contain fibrosis (F3) + cirrhosis or advanced scarring of the liver (F4)] (4.5 vs. 19.4 kPa, p = 0.001). Similarly, there was a significant difference in mean APRI value in patients with F0 in comparison to patients having mild fibrosis (F1 + F2) (0.55 ± 0.31 vs. 1.09 ± 0.81, p = 0.001) and advanced fibrosis (F3 + F4) (2.3 ± 1.3, p = 0.001). AUROC for diagnosis of significant fibrosis was 0.98 (95 % confidence interval (CI) 0.963-0.999) for TE and 0.865 (95 % CI 0.810-0.920) for APRI. Optimal TE value was 10.0 kPa for diagnosis of significant fibrosis and 14.7 kPa for cirrhosis with specificity and sensitivity of 89 %, 98 % and 96 %, and 97 %, respectively. On multivariate analysis, total bilirubin and histological activity index (HAI) were identified as an independent predictor of TE inaccuracy. CONCLUSION: LSM is a reliable predictor of hepatic fibrosis in Indian patients. LSM is superior to APRI for noninvasive diagnosis of hepatic fibrosis and cirrhosis, and high bilirubin (10.5 mg/dL) and Ishak HAI grade (>11) were independent predictors of discordance between LB and LSM.

Synthesis, cytotoxicity and molecular modelling studies of new phenylcinnamide derivatives as potent inhibitors of cholinesterases.

The present study reports the synthesis of cinnamide derivatives and their biological activity as inhibitors of both cholinesterases and anticancer agents. Controlled inhibition of brain acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) may slow neurodegeneration in Alzheimer's diseases (AD). The anticholinesterase activity of phenylcinnamide derivatives was determined against Electric Eel acetylcholinesterase (EeAChE) and horse serum butyrylcholinesterase (hBChE) and some of the compounds appeared as moderately potent inhibitors of EeAChE and hBChE. The compound 3-(2-(Benzyloxy)phenyl)-N-(3,4,5-trimethoxyphenyl)acrylamide (3i) showed maximum activity against EeAChE with an IC50 0.29 ± 0.21 µM whereas 3-(2-chloro-6-nitrophenyl)-N-(3,4,5-trimethoxyphenyl)acrylamide (3k) was proved to be the most potent inhibitor of hBChE having IC50 1.18 ± 1.31 µM. To better understand the enzyme-inhibitor interaction of the most active compounds toward cholinesterases, molecular modelling studies were carried out on high-resolution crystallographic structures. The anticancer effects of synthesized compounds were also evaluated against cancer cell line (lung carcinoma). The compounds may be useful leads for the design of a new class of anticancer drugs for the treatment of cancer and cholinesterase inhibitors for Alzheimer's disease (AD).