Immunogenicity of Covishield vaccine in patients with autoimmune rheumatic diseases.

Introduction: The Coronavirus disease 2019 (COVID-19) pandemic has been the biggest threat to humankind during the last 3 years. It has caused the loss of more than 6.9 million precious lives across the world. The only method by which the massacre could be stopped was by mass vaccination or mass immunization. The patients suffering from autoimmune rheumatic disorders (AIRDs) and treated with immunosuppressants were the high-priority candidates for vaccination. However, the data regarding the efficacy of COVID-19 vaccines in this group of patients are very less. Hence, this study was planned to study the immunogenicity of Covishield in patients with AIRDs attending the rheumatology OPD at DMCH, Ludhiana. Materials and Methods: It was a prospective cohort study and was planned by the Department of Biochemistry and Department of Clinical Immunology and Rheumatology at Dayanand Medical College and Hospital, Ludhiana. Fifty patients with AIRDs attending the DMCH rheumatology OPD and 52 age and sex-matched healthy controls who had received two doses of Covishield vaccine were included in this study. Patients having any other immunosuppressive conditions like uncontrolled diabetes, hepatitis, malignancy or HIV were excluded. Patients who had suffered from previous laboratory-confirmed COVID-19 infection (by RT-PCR) were also excluded. Blood samples were collected following all aseptic precautions from patients and controls on the 28th day after administration of a second dose of Covishield vaccine and total antibodies to the severe acute respiratory syndrome coronavirus 2 spike (S) protein receptor binding domain was measured using Elecsys Anti-SARS-CoV-2 S kit from Roche. Results: It was observed that no significant difference was there in antibody titre between cases and controls (6213 ± 4418 vs. 8331 ± 7979, P = 0.1022). It was also observed that no statistically significant difference in antibody titre in cases without prednisolone and those taking treatment with prednisolone was found (P = 0.7058). A similar observation was found in terms of methotrexate also (P = 0.457). No significant difference in antibody titres was there when compared with controls (for prednisolone, P = 0.169, for methotrexate, P = 0.078). We found that only the patients receiving mycophenolate mofetil showed a statistically significant decrease in antibody titre in comparison to healthy controls (P = 0.03). Our study showed no statistically significant difference in antibody titres between patients suffering from different AIRDs. Conclusion: Our study supplements the fact that patients with AIRDs in India can receive Covishield as the primary vaccine against COVID-19 without concerns regarding decreased immunogenicity or increased adverse effects.

Breakthrough COVID-19 Infection Among the General Community, Frontline Workers, and Healthcare Workers During the Second and Third Wave in North India: A Longitudinal Study.

BACKGROUND: Vaccination is among the most important public health tools for preventing the harm caused by communicable diseases. This was particularly true in the case of COVID-19 vaccination during the COVID-19 pandemic. However, no vaccine is 100% effective, and all carry the risk of breakthrough infection in vaccinated individuals. METHODOLOGY: This longitudinal observational study was done on COVID-19-vaccinated individuals at a vaccination site in a tertiary care hospital. The study participants were categorized into the general community, frontline workers, and healthcare workers and were followed up during the study period from June 2021 to May 2022 post-vaccination. They were interviewed by telephone regarding adverse effects and breakthrough infections post-vaccination during the second and third wave of the COVID-19 pandemic in India. Incidence of breakthrough infection was calculated in all three categories after they received their first, second, and booster doses of vaccination. RESULTS: Fever was the most common adverse effect among all the categories of participants after the first and second doses. Incidence of breakthrough infection after the second dose of vaccination among frontline workers (RR: 5.7, 95% CI: 0.7-44.2) and healthcare workers (RR: 18.9, 95% CI: 2.6-138.6) was observed to be higher compared to the general community, but no such difference was observed among the three categories after the first dose of vaccination. CONCLUSIONS: The incidence of breakthrough infection was found to be the highest in healthcare workers, followed by frontline workers compared to the general community, justifying their work profile and the risk associated with it.

Heated and humidified high flow therapy (HHHFT) in extreme and very preterm neonates with respiratory distress syndrome (RDS): a retrospective cohort from a tertiary care setting in Pakistan.

OBJECTIVE: To determine the role of heated humidified high flow therapy (HHHFT) as primary respiratory support in spontaneously breathing moderate-late, very and extreme preterm neonates with respiratory distress syndrome (RDS) at a tertiary care hospital from a developing country. DESIGN: Retrospective cohort study. SETTING: Neonatal intensive care unit of Indus Hospital and Health Network, Karachi, Pakistan. PATIENTS: All preterm neonates with RDS and who received HHHFT as primary respiratory support were included retrospectively, while neonates with orofacial anomalies, congenital heart and lung diseases other than RDS, abdominal wall defects, encephalopathy, congenital pneumonia and received continuous positive airway pressure or invasive ventilation were excluded. INTERVENTIONS: HHHFT as primary respiratory support for RDS. MAIN OUTCOME MEASURES: Effectiveness, duration, failure rate and complications of HHHFT as a primary respiratory support in moderate-late, very and extremely preterm neonates were evaluated. RESULTS: The cohort included 138 neonates during a period of 12 months. The median gestational age was 32 weeks, and the median birth weight was 1607 g. Grade 1-2 RDS was seen in 97%, surfactant instillation was done in 10.8% and HHHFT was provided in all the neonates as primary respiratory support. The total duration of HHHFT support was <1 week in 94% of neonates. Bronchopulmonary dysplasia and pneumothorax until discharge or death were observed in one neonate, haemodynamically significant Patent Ductus Artriosus (HsPDA) in two neonates and intraventricular haemorrhage Grade ≥2 in five neonates, while only one neonate died. CONCLUSION: This study appears to show that HHHFT is a simple, safe, efficient and cheap mode of primary respiratory support that can be given to spontaneously breathing moderate-late, very and extremely preterm neonates with RDS, especially in low- or middle-income countries.

Hybridizing slime mould algorithm with simulated annealing algorithm: a hybridized statistical approach for numerical and engineering design problems.

The existing slime mould algorithm clones the uniqueness of the phase of oscillation of slime mould conduct and exhibits slow convergence in local search space due to poor exploitation phase. This research work exhibits to discover the best solution for objective function by commingling slime mould algorithm and simulated annealing algorithm for better variation of parameters and named as hybridized slime mould algorithm-simulated annealing algorithm. The simulated annealing algorithm improves and accelerates the effectiveness of slime mould technique as well as assists to take off from the local optimum. To corroborate the worth and usefulness of the introduced strategy, nonconvex, nonlinear, and typical engineering design difficulties were analyzed for standard benchmarks and interdisciplinary engineering design concerns. The proposed technique version is used to evaluate six, five, five unimodal, multimodal and fixed-dimension benchmark functions, respectively, also including 11 kinds of interdisciplinary engineering design difficulties. The technique's outcomes were compared to the results of other on-hand optimization methods, and the experimental results show that the suggested approach outperforms the other optimization techniques.

Epidemiological correlates of hepatitis C infection- A case control analysis from a tertiary care hospital.

Background: Hepatitis C virus (HCV) infection is considered one of the growing public health problems. Identification of HCV-associated risk factors is pivotal for developing appropriate prevention strategies. Objectives: To determine the epidemiological variables of HCV infection in a tertiary care hospital. Methods: This hospital-based case-control study was conducted in a tertiary care hospital in Punjab on 320 subjects, including 160 cases and controls each. Cases and controls were matched by age (±5 years), gender, and residence. A patient ≥18 years of age fulfilling the biomarker criteria with or without clinical criteria diagnosed in the last 1 month was considered as a case. The information on socio-demographic characteristics and previous exposures to selected risk factors was collected through detailed interviews of the subjects. Analysis was performed using SPSS 20 statistical software. Odds ratio (OR) with 95% confidence interval (CI) was calculated to measure the strength of association between cases and controls for each risk factor. Results: Odds of having HCV infection was significantly higher among those with a history of blood transfusion (OR: 2.30, 95%CI: 1.14-4.63), dental procedure (OR: 4.82, 95%CI: 2.38-9.77) and intravenous injection/infusion from quacks (OR: 3.26, 95%CI: 1.47-7.19), injectable drug use (OR: 26.69, 95%CI: 3.55-200.24), non-injectable drug use (OR: 2.37, 95%CI: 1.44-3.90), tattooing (OR: 7.91, 95%CI: 2.31-27.08), and piercing from street hawkers (OR: 2.25, 95%CI: 1.18-4.29). Multivariate analysis identified history of blood transfusion, dental procedure, intravenous injection/infusion from quacks, injecting drug use, and piercing as independent risk factors for HCV infection. Conclusion: The study identified multiple risk factors for acquiring HCV infection and suggest appropriate interventions targeting high-risk populations.

Sustainable control of malaria employing Gambusia fishes as biological control in Jalore and Barmer districts of Western Rajasthan.

Sardar Sarovar Irrigation Canal system was constructed by Narmada Valley Development Authority (NVDA) to cater to drinking water as well as for irrigation purposes in Jalore and Barmer districts of Western Rajasthan. To cater to the needs of water for the villagers in the command areas, 'Diggies' (surface water tanks) with 'Sumpwells' (water supply surface tanks) were installed. In a health impact assessment study of the irrigation canals from December 2010 to February 2016, the breeding of two major malaria vectors. An. culicifacies and An. stephensi were observed in diggies and sumpwells. As a biological control, Gambusia affanis fishes were employed for larval control in such stagnated water sites during the intervention phase viz. February 2012 in 251 diggies and 251 sumpwells. A significant reduction of breeding in diggies (99.54%) and sumpwells (97.81%) was observed. The positivity and larval density (dip index) were monitored in the control from up to February 2016 for their sustainability.

Fabrication and characterization of noble crystalline silver nanoparticles from Pimenta dioica leave extract and analysis of chemical constituents for larvicidal applications.

The current works report the bio-efficacy of Pimenta dioica leaf derived silver nanoparticles (Pd@AgNPs) and leaf extract obtained trough different solvents against the larvae of malaria, filarial and dengue vectors. Synthesis of silver nanoparticles (AgNPs) was done by adding 10 ml of P. dioica leaf extract into 90 ml of 1 mM silver nitrate solution, a slow colour change was observed depicting the formation of AgNPs. Further, Pd@AgNPs was confirmed through Ultraviolet-visible spectroscopy which exhibited characteristic absorption peak at 422 nm wavelength. X-ray diffraction and selected area electron diffraction analysis confirmed monodispersed and crystalline nature of Pd@AgNPs with 32 nm an average size. Scanning electron microscopy and transmission electron microscopy showed the most of Pd@AgNPs were spherical and triangular in shape and energy-dispersive X-ray spectroscopy revealed silver elemental nature of nanoparticles. Zeta potential of Pd@AgNPs is highly negative which confirmed its stable nature. Pd@AgNPs showed prominent absorption peaks at 1015, 1047, 1243, 1634, 2347, 2373, 2697 and 3840 cm-1 which are corresponding to following compounds polysaccharides, carboxylic acids, water, alcohols, esters, ethers, amines, amides and phenol, respectively as reported by Fourier-transform infrared spectroscopy analysis. Gas chromatography-mass spectrometry and Liquid chromatography-mass spectrometry analysis revealed 39 and 70 compounds, respectively, which might be contributed for bio-reduction, capping, stabilization and larvicidal behavior of AgNPs. A comparable lethality (LC50 and LC90) was observed in case of Pd@AgNPs over leaf extract alone. The potential larvicidal activity of Pd@AgNPs was observed against the larvae of Aedes aegypti,(LC50, 2.605; LC90, 5.084 ppm) Anopheles stephensi (LC50, 3.269; LC90, 7.790 ppm) and Culex quinquefasciatus (LC50, 5.373; LC90, 14.738 ppm without affecting non-targeted organism, Mesocyclops thermocyclopoides after 72 hr of exposure. This study entails green chemistry behind synthesis of AgNPs which offers effective technique for mosquito control and other therapeutic applications.

A boosted chimp optimizer for numerical and engineering design optimization challenges.

Chimp optimization algorithm (ChoA) has a wholesome attitude roused by chimp's amazing thinking and hunting ability with a sensual movement for finding the optimal solution in the global search space. Classical Chimps optimizer algorithm has poor convergence and has problem to stuck into local minima for high-dimensional problems. This research focuses on the improved variants of the chimp optimizer algorithm and named as Boosted chimp optimizer algorithms. In one of the proposed variants, the existing chimp optimizer algorithm has been combined with SHO algorithm to improve the exploration phase of the existing chimp optimizer and named as IChoA-SHO and other variant is proposed to improve the exploitation search capability of the existing ChoA. The testing and validation of the proposed optimizer has been done for various standard benchmarks and Non-convex, Non-linear, and typical engineering design problems. The proposed variants have been evaluated for seven standard uni-modal benchmark functions, six standard multi-modal benchmark functions, ten standard fixed-dimension benchmark functions, and 11 types of multidisciplinary engineering design problems. The outcomes of this method have been compared with other existing optimization methods considering convergence speed as well as for searching local and global optimal solutions. The testing results show the better performance of the proposed methods excel than the other existing optimization methods.

From rapid antigen testing for COVID-19 to final outcome: An experience from industrial city of Ludhiana.

Context: The ongoing corona pandemic has created medical crises all over the world. An increased surge in the number of COVID-19 cases was observed in the month of August, September and October 2020. Punjab has around 10 Lakh migrant workers. Intensive rapid antigen testing was done during this surge among factory workers. With this background, the study aims to find out the positivity rate of rapid antigen testing and to find out the final outcome of the COVID positive cases in terms of morbidity. Materials and methods: Screening of factory workers working in various factories was done for COVID-19 by rapid antigen testing from 26th august to 31st October 2020. Those who tested positive were clinically examined, counseled, and followed up telephonically to get information regarding their course of illness. The collected information was entered in Microsoft excel sheet and analyzed using SPSS. Results: A total of 11045 factory workers were screened using the rapid antigen test. The mean age of subjects was 33.37 ± 10.97 years. The majority of them were males (88.3%) and migrants (who did not belong to Punjab) (97.3%). The majority of the subjects (97.3%) had no symptoms at the time of screening. COVID-19 positivity rate increased with age, was found to be higher in males (2.3%) as compared to females. Conclusion: The positivity rate was higher in asymptomatic males and local resident workers. Rapid antigen testing is an important public health measure to prevent the further spread of the disease during a pandemic due to its quick results and detection of asymptomatic patients.

SARS-CoV-2 Seroprevalence Among Whole Blood Donors During First Wave of Covid-19 Pandemic in India.

The current study aimed to estimate the seroprevalence of SARS-CoV-2 IgG (S-protein) antibodies along with neutralizing assay (RBD-domain) among the whole blood donors without any prior Covid-19 history or symptoms visiting Blood Centre at a Tertiary care institution, South India amidst the ongoing pandemic. During September 2020 to March 2021, 1034 whole blood donors were enrolled into the study and were screened for anti-SARS-CoV-2 IgG antibodies using Chemiluminescence assay followed by neutralizing antibodies using surrogate neutralization ELISA. The study reported seroprevalence of 49.4%, (95% CI 46.3-52.5) among whole blood donors, with test sensitivity and specificity adjusted prevalence of 54.9% (95% CI 51.5-58.3). Seroprevalence was similar across age groups, gender, voluntary/replacement donations, area of residence, ABO and Rh groups without any statistical significance. However higher IgG antibody responses were found to be elicited in the 30-45 years age group when compared with 18-29 years age group (p value 0.046). This study also analysed the mean neutralizing capacity of SARS-CoV-2 antibodies among 97 blood donors which was 71.9 (SD: + 21.03, range 15.5 to 97.3). Donor samples with SARS-CoV-2 IgG S/Co > 9.5 had significantly higher neutralising capacity (> 68%) when compared with donor samples of S/Co < 9.5 (p value 0.000). Real-time seroprevalence studies will help to know the herd immunityamong the blood donors which will assist in knowing the Covid-19 transmission dynamics, distribution of immunity levels at a particular point in time, immunity gaps, development of novel therapeutics and prioritize the vaccination programmes to high risk individuals.

An effective solution to numerical and multi-disciplinary design optimization problems using chaotic slime mold algorithm.

Slime mold algorithm (SMA) is a recently developed meta-heuristic algorithm that mimics the ability of a single-cell organism (slime mold) for finding the shortest paths between food centers to search or explore a better solution. It is noticed that entrapment in local minima is the most common problem of these meta-heuristic algorithms. Thus, to further enhance the exploitation phase of SMA, this paper introduces a novel chaotic algorithm in which sinusoidal chaotic function has been combined with the basic SMA. The resultant chaotic slime mold algorithm (CSMA) is applied to 23 extensively used standard test functions and 10 multidisciplinary design problems. To check the validity of the proposed algorithm, results of CSMA has been compared with other recently developed and well-known classical optimizers such as PSO, DE, SSA, MVO, GWO, DE, MFO, SCA, CS, TSA, PSO-DE, GA, HS, Ray and Sain, MBA, ACO, and MMA. Statistical results suggest that chaotic strategy facilitates SMA to provide better performance in terms of solution accuracy. The simulation result shows that the developed chaotic algorithm outperforms on almost all benchmark functions and multidisciplinary engineering design problems with superior convergence.

The impact of mosquito proof lids of underground tanks "tanka" on the breeding of Anopheles stephensi in a village in western Rajasthan, India.

BACKGROUND: Western Rajasthan in India has a typical desert climate. Until the introduction of the canal water irrigation system, malaria was an unstable and seasonal occurrence. Due to the scarcity of water, the community practised having one large underground tank (locally known as the tanka) in their house to collect rainwater for long-term household use. Anopheles stephensi, one of the major malaria vectors, breeds in improperly covered "tankas" if not properly covered and harbours a vector population throughout the year. METHODS: Two villages, Ajasar (intervention) and Tota (control), with similar ecological features, were selected for the study. A pre-intervention survey was carried out in both villages to assess the presence and quality of lids of tankas, and mosquito breeding and adult mosquito density. Awareness of the community about malaria and mosquitoes was also assessed during the pre-intervention period. In the intervention village, damaged or improper lids were replaced with improved mosquito proof polyvinyl chloride plastic (PVC) lids and lasted longer than the conventional lids. The fitness of the lids was assessed one year after the pre-intervention survey. The entomological assessment was carried out in both intervention and non-intervention villages. The level of community awareness about malaria, mosquitoes, their breeding places, and the role of tankas in malaria transmission was assessed both during pre- and post-intervention. RESULTS: During the pre-intervention survey, Anopheles breeding was found in 22.1% (58/262) of tankas in the intervention village and 27.1% (19/70) in tankas in the control village. Mosquito breeding was observed in the tankas with iron lids in the intervention village (48.3%) and the control village (42.1%). In the intervention village, out of 262 tankas in the village, 200 lids were replaced, resulting in the complete absence of mosquito breeding. In the pre-intervention survey conducted in May 2018, Anopheles stephensi consisted of 46% of adult mosquitoes in the intervention village and 55% in the control village. Its density was significantly reduced to 0.55 per man-hour (94.95%) and 0.22 per man-hour (97.8%) in the post-intervention survey in June 2018 and a follow-up survey in May 2019, respectively, in the intervention village. DISCUSSION: The density of Anopheles stephensi adults was reduced significantly (97.8%) in the intervention village due to complete prevention of breeding in the underground tankas in the intervention village as compared to the control with no density reduction. The awareness level of the community was also improved due to their involvement in the study. CONCLUSION: Provision of proper metal lids or replacement of damaged lids on underground water storage tanks as an environmental management approach prevented the breeding of  the malaria vector, Anopheles stephensi, in a desert village in western Rajasthan.

Evaluation of heavy metal leaching under simulated disposal conditions and formulation of strategies for handling solar panel waste.

With the steady growth in the worldwide solar installed capacity, there is an immediate concern about the fate of the solar panels at the end of their life. Solar panel waste is often disposed of indiscriminately, exposing the environment to chemical hazards. The major objective of the current study was to evaluate the leaching potential of the polycrystalline solar panel waste under different simulated disposal conditions through toxicity characteristic leaching procedure (TCLP), synthetic precipitation leaching procedure (SPLP) and pH static leaching procedure tests. Moreover, the study evaluates the effects of ageing and the breakage of the Glass Laminate Encapsulation (GLE) of solar panels on their leaching potential. Among the metals studied (silver (Ag), aluminium (Al), cadmium (Cd), chromium (Cr), copper (Cu), manganese (Mn), lead (Pb), and zinc (Zn)), the concentrations of Pb were as high as 9.3 mg/L, 1.4 mg/L, 6.7 mg/L in the TCLP, SPLP, and pH static test respectively. This indicated the hazardous nature of the waste with leaching potential of Pb above the permissible limits stipulated by various regulatory bodies. The presence of GLE reduced the mobility of Pb by a factor of 4.1-8.8 in the TCLP test, thereby rendering the waste as non-hazardous for its disposal in a landfill. However, the indiscriminate disposal of solar panel waste in the natural environment as simulated by the SPLP test indicated its harmful nature irrespective of the physical condition. Ageing of the solar panels before disposal and acidic pH conditions also positively influenced the leaching potential of the selected metals subjected to their reactivity and the accessibility of internal layers of waste to the leaching solution. Strategies such as extended producer responsibilty, advance-recycling fee, and incentivizing the recycling industry will lead to both economic benefit creation and effective waste management of this waste stream.

Mobile app based pictorial identification key for Indian anophelines.

BACKGROUND & OBJECTIVES: Malaria control strategies for a particular area largely depends on the correct identification of the mosquito species prevalent in that area. This study aimed to develop an android mobile app named 'Pictorial Indian anophelines key', which can be used to identify the 58 species of Indian female adult anophelines based on morphological characteristics. METHODS: The pre-requisite to use this app requires a minimum basic knowledge of mosquito morphological characteristics and features. The user needs to view the collected mosquito under a dissecting binocular microscope and has to select the observations on the app presented in the form of labelled picture format. The app uses a divide and conquer algorithm which narrows the selection from genus level to final identification of species. RESULTS: The app is user-friendly, quick and it accurately identifies the mosquito species in a maximum of six consecutive clicks. The result displays a complete image of identified mosquito along with its quick identification features. It can be used for both subgenus Cellia and Anopheles. INTERPRETATION & CONCLUSION: This pictorial key-based mobile app could be helpful for entomologists, malariologists, researchers, public health workers as well as students in the quick and correct identification of anopheline mosquitoes prevalent in India which in turn could be helpful in devising appropriate approaches towards malaria control and prevention. The app can be modified as per future requirements.

Co-distribution of dengue and Chikungunya viruses in Aedes mosquitoes of Delhi, India.

BACKGROUND & OBJECTIVES: In India, vector-borne diseases, dengue and chikungunya are major public health concerns. In recent decades, dengue outbreaks have been reported in almost every part of India. In 2016, India recorded 101388 dengue cases and 210 deaths, including 4337 cases and six deaths in Delhi, whereas Chikungunya outbreaks were reported from several states in 2006, with 1.3 million cases. The Dengue virus (DENV) and Chikungunya virus (CHIKV) are both transmitted by the same Aedes mosquito species. DENV and CHIKV co-infections have been reported in 13 of 98 countries, with both viruses being transmitted locally. The reasons for the sudden upsurge in cases of these diseases are undetermined. METHODS: From March to December 2016, a study was carried out in 66 localities of Delhi in collaboration with the Municipal Corporation of Delhi. Localities were selected on the basis of confirmed dengue cases reported during the last five years and the study area was visited once a month. A door-to-door entomological survey was conducted to identify Aedes breeding in all water-filled containers in and around houses. Both immature and mature stages of Aedes mosquitoes were collected. Mosquitoes were pooled (n≤10 each for male and female) breeding site-wise and stored in Trizol at -80°C. The Chikungunya and dengue viruses were detected using a multiplex RT-PCR. RESULTS: A total of 981 Aedes mosquitos were distributed among 146 Pools, and DENV and CHIKV were detected using Multiplex Reverse Transcriptase-PCR. Chikungunya virus was identified in 19 pools of females captured adults, whereas dengue virus was found in 8 pools of females captured adults. There was no evidence of coinfection in any of the pools. INTERPRETATION & CONCLUSION: In endemic areas, continuous surveillance for both dengue and Chikungunya viruses is required to identify and characterize these viral pathogens. This information will also help implement effective strategies to combat outbreaks produced by these emerging viral pathogens.

Early Detection of Covid-19 in Canadian Provinces and its Anticipatory Measures for a Medical Emergency.

The spread of COVID-19 is incearsing day by day and it has put the entire world and the whole humankind at the stack. The assets of probably the biggest economies are worried because of the enormous infectivity, and transmissibility of this ailment. Because of the developing extent of the number of cases and its ensuing weight on the organization and wellbeing experts, some expectation strategies would be required to anticipate the quantity of evidence in the future. In this paper, we have utilized time series forecasting approach entitled autoregressive integrated moving average, and bend fitting for the forecast of the quantity of COVID-19 cases in Canadian Province for 30 days ahead. The estimates of different parameters (number of positive cases, number of recouped cases, and decrease cases) got by the proposed strategy is exact inside a specific range, and will be a beneficial apparatus for overseers, and wellbeing officials to organize the clinical office in the distinctive Canadian Province.

Scrub typhus and leptospirosis in rural and urban settings of central India: a preliminary evaluation.

Scrub typhus and leptospirosis are bacterial zoonotic diseases reported from different parts of India, whose prevalence in Chhattisgarh is unknown. Our study was carried out to delineate the prevalence of these illnesses there and to assess the clinical profiles of rural and urban patients. A total of 169 patients with acute febrile illnesses (AFI) was enrolled in our study from May to December 2018, of whom 35 (20.7%) tested positive for scrub typhus and only one tested positive for leptospirosis by respective IgM ELISA. Scrub typhus seropositivity was higher in rural patients (25.0%) than in urban (18.1%). Patients in the age group 16-30 years were the most commonly affected. The commonest presenting symptoms were fever with headache (68.57%), extreme weakness (57.14%), myalgia/arthralgia (54.29%) and abdominal pain (51.43%). The preliminary evidence for the presence of scrub typhus in Chhattisgarh necessitates its inclusion in the panel of tests for AFI.

YAP promotes multi-drug resistance and inhibits autophagy-related cell death in hepatocellular carcinoma via the RAC1-ROS-mTOR pathway.

BACKGROUND: Multi-drug resistance is the major cause of chemotherapy failure in hepatocellular carcinoma (HCC). YAP, a critical effector of the Hippo pathway, has been shown to contribute to the progression, metastasis and invasion of cancers. However, the potential role of YAP in mediating drug resistance remains obscure. METHODS: RT-qPCR and western blot were used to assess YAP expression in HCC cell lines. CCK-8 assays, flow cytometry, a xenograft tumour model, immunochemistry and GFP-mRFP-LC3 fusion proteins were utilized to evaluate the effect of YAP on multi-drug resistance, intracellular ROS production and the autophagy of HCC cells in vitro and in vivo. Autophagy inhibitor and rescue experiments were carried out to elucidate the mechanism by which YAP promotes chemoresistance in HCC cells. RESULTS: We found that BEL/FU, a typical HCC cell line with chemoresistance, exhibited overexpression of YAP. Moreover, the inhibition of YAP by shRNA or verteporfin conferred the sensitivity of BEL/FU cells to chemotherapeutic agents through autophagy-related cell death in vitro and in vivo. Mechanistically, YAP silencing significantly enhanced autophagic flux by increasing RAC1-driven ROS, which contributed to the inactivation of mTOR in HCC cells. In addition, the antagonist of autophagy reversed the enhanced effect of YAP silencing on cell death under treatment with chemotherapeutic agents. CONCLUSION: Our findings suggested that YAP upregulation endowed HCC cells with multi-drug resistance via the RAC1-ROS-mTOR pathway, resulting in the repression of autophagy-related cell death. The blockade of YAP may serve as a promising novel therapeutic strategy for overcoming chemoresistance in HCC.

ABO-Incompatible Adult Living Donor Liver Transplantation in the Era of Rituximab: A Systematic Review and Meta-Analysis.

AIM: The primary aim of this study is to compare the short- and long-term outcomes between ABO-incompatible (ABOi) adult living donor liver transplantation (ALDLT) with rituximab prophylaxis and ABO-compatible (ABOc) ALDLT. BACKGROUND: The strategy of ABOi liver transplantation (LT) was originated initially to increase the donor pool and to enable liver transplantation in emergency conditions. However, ABOi ALDLT remains a controversial approach in comparison to ABOc ALDLT. METHODS: PubMed, Embase, and the Cochrane Library study search were accomplished to recognize studies comparing ABOi and ABOc ALDLT. Meta-analyses were conducted based on the evaluation of heterogeneity using a fixed-effect model and a random-effect model to assess the short- and long-term outcomes following ABOi ALDLT with rituximab prophylaxis. RESULTS: Nine studies comprising a total of 3,922 patients (ABOi = 671 and ABOc = 3,251) were identified. There was no significant difference between ABOi and ABOc groups for 1-year, 3-year, and 5-year OS and graft survival, respectively. Moreover, 1-year and 3-year OS and DFS were similar between both groups for HCC patients. However, ABOi ALDLT had higher incidences of CMV infection, AMR, overall biliary complications, and biliary stricture than ABOc ALDLT and had other comparable postoperative complications. CONCLUSION: Our meta-analysis included studies comparing ABOi and ABOc ALDLT after the introduction of rituximab in a desensitization protocol for ABOi ALDLT. The results of ABOi ALDLT were comparable with those of ABOc ALDLT. However, biliary complications, CMV infection, and AMR remain a concern in the era of rituximab.