Rivaroxaban-loaded SLNs with treatment potential of deep vein thrombosis: in-vitro, in-vivo, and toxicity evaluation.

OBJECTIVES: Rivaroxaban (RXB), a novel Xa inhibitor having groundbreaking therapeutic potential. However, this drug is associated with few limitations, including its pharmacokinetics related toxicities. Here, we developed RXB-loaded SLNs (RXB-SLNs) to improve its biopharmaceutical profile. Methods: High pressure homogenizer was used to prepare RXB-SLNs, followed by their particle characterization, Transmission electron microscopy (TEM), Dynamic light scattering (DSC), and Powder X-ray diffraction (PXRD) analysis. Beside this, in-vitro, ex-vivo, and in-vivo evaluation, prothrombin time assessment and toxicity was investigated. RESULTS: RXB-SLNs had their particle size in nano range (99.1 ± 5.50 nm) with excellent morphology and low polydispersity index (0.402 ± 0.02) and suitable zeta potential (-25.9 ± 1.4 mV). The incorporation efficiency was observed around 95.9 ± 3.9%. In-vitro release profiles of the RXB-SLNs exhibited enhanced dissolution (89 ± 9.91%) as compared to pure drug (11 ± 1.43%) after 24 h of the study. PK study demonstrated a seven times enhanced bioavailability of RXB-SLNs when compared with pure drug. Furthermore, RXB-SLNs exhibited an expressive anti-coagulant behavior in human and rat blood plasma. Also, the final formulation exhibited no toxicity after oral administration of the SLNs. CONCLUSIONS: All together, these studies revealed the capability of the SLNs for carrying the RXB with enhanced therapeutic efficacy and no toxicity, most importantly for the treatment of deep vein thrombosis.

Variations in the Behaviour, Survival, Haematology, and Biochemistry of Ctenopharyngodon idella (Grass Carp) After Exposure to Commercial Grade Atrazine.

The current study assessed the harmful effects of Atrazine (ATZ) herbicide on haematology and biochemistry of the freshwater fish Ctenopharyngodon idella, a commercially significant fish in Pakistan. C. idella (13 ± 8.4 cm; 132 ± 5.6 g) was exposed to graded levels of ATZ, and its 96-hour LC50 value at 25°C was calculated to be 150.5 µl/L. After exposure to ATZ, fish displayed rapid movements, a loss of balance in position and equilibrium, anxious swimming patterns, colour changes, and increased mucous production. The MCHC, MCH, RBCs, and Hb in C. idella decreased significantly (P < 0.05), whereas the MCV, Ht, and WBCs were significantly increased (P < 0.05). At different time intervals (24, 48, 72, and 96 h) following ATZ administration (50, 100, 150, and 200 µl/L), biochemical analysis significantly decreased (P < 0.05) triglyceride, total protein, cholesterol, and albumin levels, whereas glucose levels significantly increased (P < 0.05). We concluded that ATZ is toxic to C. idella, altering their haematology and blood biochemistry even after only a brief exposure.

Comparative analysis of gut microbiota in healthy and diarrheic yaks.

BACKGROUND: Yak (Bos grunniens) mainly inhabiting Tibet Plateau, displayed a high incidence of diarrhea due to harsh living environment and nutritional deficit. Gut microbial community has been reported to be closely related to many diseases including diabetes, obesity and inflammatory bowel disease, but information regarding diarrheic influence on gut microbiota in yaks remains scarce. Here, this study was performed to investigate the gut bacterial and fungal alternations of diarrheic yaks. RESULTS: Results revealed that the gut bacterial and fungal communities of diarrheic yaks showed a distinct decline in alpha diversity, accompanied by significant shifts in taxonomic compositions. Specifically, diarrhea caused a distinct increase in the relative abundance of 1 phylum and 8 genera as well as a distinct decrease in 3 phyla and 30 genera. Fungal taxonomic analysis indicated that the relative richness of 1 phylum and 2 genera dramatically increased, whereas the relative richness of 2 phylum and 43 genera significantly decreased during diarrhea. Surprisingly, 2 bacterial genera and 5 fungal genera even cannot be detected in the gut microbiota of diarrheic yaks. CONCLUSIONS: In summary, this study indicated that the gut bacterial and fungal compositions and diversities of yaks altered significantly during diarrhea. Moreover, these findings also contribute to understanding the gut microbial composition and diversity of yaks and developing strategies to alleviate and prevent diarrhea from gut microbial perspective.

Long-term hexavalent chromium exposure disturbs the gut microbial homeostasis of chickens.

Industrial production, ore smelting and sewage disposal plant can discharge large amounts of heavy metals every year, which may contaminate soil, water and air, posing a great threat to ecological environment and animal production. Hexavalent chromium [Cr (VI)], a recognized metallic contaminant, has been shown to impair kidney, liver and gastrointestinal tract of many species, but little is known about the gut microbial characteristics of chickens exposed to Cr (VI). Herein, this study characterized the gut microbial alternations of chickens exposed to Cr (VI). Results indicated that the gut microbial alpha-diversity in chickens exposed to Cr (VI) decreased significantly, accompanied by a distinct shifts in taxonomic composition. Microbial taxonomic analysis demonstrated that the preponderant phyla (Firmicutes, Bacteroidetes, Proteobacteria and Epsilonbacteraeota) were the same in both groups, but different in types and relative abundances of dominant genera. Moreover, some bacterial taxa including 2 phyla and 47 genera significantly decreased, whereas 3 phyla and 17 genera significantly increased during Cr (VI) exposure. Among decreased taxa, 9 genera (Coprobacter, Ruminococcus_1, Faecalicoccus, Eubacterium_nodatum_group, Parasutterella, Slackia, Barnesiella, Family_XIII_UCG-001 and Collinsella) even cannot be detected. In conclusion, this study revealed that Cr (VI) exposure dramatically decrased the gut microbial diversity and altered microbial composition of chickens. Additionally, this study also provided a theoretical basis for relieving Cr (VI) poisoning from the perspective of gut microbiota.

Anti-Inflammatory, analgesic and anti-pyretic activity of Fagonia bruguieri DC in rats.

Traditional medicine has employed the plant Fagonia bruguieri DC. to alleviate inflammation, fever and pain. The goal of this study was to test the anti-inflammatory, analgesic and antipyretic properties of the methanol extract of whole plant of Fagonia bruguieri (F. bruguieri). The writhing test and Eddy's hot plate test were used to assess the analgesic potential of F. bruguieri at three different doses. Carrageenan-induced rat paw edema was applied to investigate anti-inflammatory activity, whereas antipyretic activity was estimated in Brewer's yeast induced pyrexia model. Flavonoids, alkaloids, saponins, tannins and glycosides were found in F. bruguieri's phytochemical analysis. F. bruguieri at 750 mg/kg reduced writhing count by 62.23 percent, while F. bruguieri enhanced latency in Eddy's hot plate test. In carrageenan-induced edema, F. bruguieri at 750 mg/kg exhibited considerable anti-inflammatory effect (41.11 percent) after 2 nd, 3 rd and 4 th hours of therapy. F. bruguieri was also found to show antipyretic properties. The anti-inflammatory, analgesic and antipyretic properties of F. bruguieri were confirmed in this study, which might be attributable to the presence of several phyto-constituents.

A computational subtractive genome analysis for the characterization of novel drug targets in Klebsiella pneumonia strain PittNDM01.

The emergence of carbapenem-resistant Klebsiella Pneumoniae had been reported previously, which needs rapid attention. Currently, Pittsburgh University Hospital reported a new strain of carbapenem-resistant Klebsiella pneumoniae that was co-producing OXA-232 and NDM-1 named as PittNDM01. This strain is resistant to almost all beta-lactam antibiotics such as Carbapenem as well as to fluoroquinolones and aminoglycosides. Globally, failure to the wide-spread pathogenic strains had been observed due to the increased and antibiotic resistance, which leads to less antimicrobial drug efficacy. Since last decades, computational genomic approaches have been introduced to fight against resistant pathogens, which is an advanced approach for novel drug targets investigation. The current study emphasizes the utilization of the available genomic and proteomic data of Klebsiella pneumoniae PittNDM01 for the identification of novel drug targets for future drug developments. Comparative genomic analysis and molecular biological tools were applied, results in observing 582 non-human homologous-essential proteins of Klebsiella pneumoniae. Among the total 582 proteins, 66 were closely related to the pathogen-specific pathway. Out of all 66-targeted proteins, ten non-homologous essential proteins were found to have druggability potential. The subcellular localization of these proteins revealed; 6 proteins in the cytoplasm, 2 in the inner membrane, and one each in periplasmic space and outer membrane. All the above 10 proteins were compared to the proteins sequences of gut flora to eliminate the homologous proteins. In total, 6-novel non-human and non-gut flora essential drug targets of Klebsiella pneumoniae PittNDM01 strain were identified. Further, the 3D structures of the identified drug target proteins were developed, and protein-protein interaction network analysis was performed to know the functional annotation of the desire proteins. Therefore, these non-homologous essential targets ensure the survival of the pathogen and hence can be targeted for drug discovery.

Role of halotolerant and chitinolytic bacteria in phytoremediation of saline soil using spinach plant.

Novel technologies are required for rapid reclamation of saline soils. The halotrophic and chitinolytic bacterial strains were used for phytoremediation of saline soils using spinach plants (Spinacia oleracea L.). The previously isolated chitinolytic bacteria showed high antifungal potential against Fusarium oxysporum, and Alternaria spp. The halotolerant bacterial strains were previously isolated showing a salt tolerance of up to 20% in culture media. Specially designed microcosms were used here to investigate the reclamation of saline soil by bacteria. The soil salinity was reduced by both types of bacteria (from 6.5 to 2 dS/m). A decline in Na contents from 22-24 to 9-12 meq/L and in sodium adsorption ratio from 10-11 to 7-8 was also observed in saline soils. The Ca/Mg contents increased from 24 to 30-33 meq/L. The bioassays were performed to evaluate the effect of the bacteria on the phytoremediation. The shoot, root weights (both fresh (1.927 g, 0.244 g) and dry (0.387 g, 0.104 g)) increased by bacterial inoculation as compared to control in saline soils. The Na/K ratio decreased in plant tissues. Here we report the increased efficacy of phytoremediation by combined inoculation of chitinolytic and halotolerant bacterial strains in soil which has never been reported before.

Closed-Loop Elastic Demand Control under Dynamic Pricing Program in Smart Microgrid Using Super Twisting Sliding Mode Controller.

Electricity demand is rising due to industrialisation, population growth and economic development. To meet this rising electricity demand, towns are renovated by smart cities, where the internet of things enabled devices, communication technologies, dynamic pricing servers and renewable energy sources are integrated. Internet of things (IoT) refers to scenarios where network connectivity and computing capability is extended to objects, sensors and other items not normally considered computers. IoT allows these devices to generate, exchange and consume data without or with minimum human intervention. This integrated environment of smart cities maintains a balance between demand and supply. In this work, we proposed a closed-loop super twisting sliding mode controller (STSMC) to handle the uncertain and fluctuating load to maintain the balance between demand and supply persistently. Demand-side load management (DSLM) consists of agents-based demand response (DR) programs that are designed to control, change and shift the load usage pattern according to the price of the energy of a smart grid community. In smart grids, evolved DR programs are implemented which facilitate controlling of consumer demand by effective regulation services. The DSLM under price-based DR programs perform load shifting, peak clipping and valley filling to maintain the balance between demand and supply. We demonstrate a theoretical control approach for persistent demand control by dynamic price-based closed-loop STSMC. A renewable energy integrated microgrid scenario is discussed numerically to show that the demand of consumers can be controlled through STSMC, which regulates the electricity price to the DSLM agents of the smart grid community. The overall demand elasticity of the current study is represented by a first-order dynamic price generation model having a piece-wise linear price-based DR program. The simulation environment for this whole scenario is developed in MATLAB/Simulink. The simulations validate that the closed-loop price-based elastic demand control technique can trace down the generation of a renewable energy integrated microgrid.

Antibiotic prescribing trends in patients with upper respiratory tract infections reporting to tertiary care hospitals of Lahore.

To estimate the antibiotic utilization and treatment compliance in URTIs reported to tertiary care hospitals of Lahore. A cross-sectional study was conducted by including 423 prescription files from public and private hospitals of Lahore. Descriptive statistics were used to estimate percentage frequencies. The reporting frequency of URTIs, tonsillitis, pharyngitis and otitis media, was higher in public hospitals (JH; 27.4%, LGH; 25.8%) compared to private (NHMC;16.3%, DHMC;15.1%) hospitals in patients aged 21-40 years. Patients aged 18-40 years (59%) received most antibiotics. Broad spectrum antibiotics (95%) were prescribed in both public (JH; 27.4%, LGH;25.9%) and private hospitals (NHMC;16.3%, DHMC;14.8%) - co-amoxiclave (30%) in penicillin class, ceftriaxone (15.4%) and cefixime (11.6%) in cephalosporin class, levofloxacin (11.3%) in quinolone class and clarithromycin (10.4%) in macrolide class, in tonsillitis, pharyngitis and otitis media. The diagnosis that received most antibiotics included tonsillitis (30%), pharyngitis (29.1%) and otitis media (11.1%). Superior treatment compliance was observed in public hospitals compared to private hospitals. The highest treatment non-compliance was observed in laryngitis (36.4%), otitis media (34%) and pharyngitis (26%). 1st line and over all treatment compliance was superior in public hospitals - sore throat, tonsillitis, sinusitis, otitis media and pharyngitis received the most appropriate choices.

Patterns of physicians' knowledge, attitude and prescribing trends against upper respiratory tract infections in Lahore, Pakistan.

Although viruses cause most of upper respiratory tract infections but still antibiotics are irrationally prescribed in mild infections, especially in upper respiratory tract infections. To identify gaps among prescribers, due to lack of standard guidelines and antimicrobial stewardship programs, it is needed to check knowledge, attitude, perception and current prescribing pattern of antibiotics. Based on the data recommendations can be specified to overcome the prescribing deficiencies and increasing rates of antimicrobial resistance. It is inevitable to educate patients about ineffectiveness of antibiotics in viral infections, and to develop guidelines for prescribing antibiotics, running continuing medical education and establishing antibiotic stewardship programs. We conducted a cross-sectional survey-based study by engaging physicians of public and private sector hospitals in Lahore, Pakistan. About 66% agreed for semi-structured interview and met the inclusion criteria. Fifty percent of physicians have an understanding that antibiotics should be prescribed in URTIs, otherwise symptoms may get worsen. The only encouraging thing is that 78.8% believe that antibiotics are being misused and are major cause of increasing rate of resistance. Most of prescribers have an understanding that antibiotics should be prescribed in upper respiratory tract infections. They are prescribing antibiotics ignoring Center for Disease Control guidelines for the treatment or prophylaxis of upper respiratory infections.

Effect of varying quantities of polymer on preparation and stability evaluation of carbamazepine cocrystals with dicarboxylic acid coformers.

The current study is an attempt to explore the effect of varying quantities of hydroxypropyl cellulose (HPC) polymer on carbamazepine (CBZ) cocrystal formation with dicarboxylic acid coformers i.e., malonic acid (MA), succinic acid (SA), glutaric acid (GA), and adipic acid (AA). The cocrystals were first prepared without polymer by slurry crystallization method and then tried with different quantities of the polymer. The prepared samples were characterized by Powder X-ray Diffraction (XRPD). The characterization results indicate that in methanol pure carbamazepine-malonic (CBZ-MA) and carbamazepine-adipic acid (CBZ-AA) cocrystal can be prepared, while in ethanol and acetone pure carbamazepine-succinic (CBZ-SA) and carbamazepine-glutaric acid (CBZ-GA) cocrystals can be obtained respectively. The same cocrystals were tried using HPC polymer in three different quantities. The characterization results showed that a higher quantity of HPC polymer transforms CBZ-MA cocrystal polymorph-I to polymorph-II. The CBZ-SA and CBZ-GA cocrystal formation somehow inhibited as the concentration of HPC polymer increases. But on the other side, the formation of CBZ-AA cocrystal utterly not inhibited in the presence of varying quantities of HPC polymer. Furthermore, 11 different quantities of HPC were tried to know about the inhibitory concentration of HPC on CBZ-AA cocrystal formation. The CBZ-AA cocrystal preparation was not inhibited even at higher quantities of HPC compared to the coformer. Additionally, the effect of three different quantities of HPC on the thermal stability of the CBZ-AA cocrystal was investigated. Moreover, the stability of pure CBZ at 92% relative humidity (RH) condition was compared to CBZ-AA cocrystal with and without HPC polymer. The CBZ-AA cocrystal with and without HPC polymer was more stable than pure CBZ.

Synthesis, characterization and docking studies of amide ligands as anti-leishmanial agents.

Aim of this study was to synthesize new inhibitors on the basis of active site of aspartic protease enzyme and to evaluate their intended biological activity. A3D model of an enzyme was generated via homology modeling and series of novel amide ligands were synthesized by using a short high yield process, subsequently, analyzed in-silico and in-vitro anti-leishmanial activities. Characterization and identification was accomplished via NMR (H1& C13), infrared and mass spectroscopic techniques. Among all compound (4) was found to show significant activity (IC50 58±0.01) against Leishmania major (L. major) species. Furthermore, docking studies confirmed the inhibition of a targeted enzyme that supported the interaction of potent compound (4) with key residues (aspartic protease) via hydrogen bonds. Present study conferred about novel compound (4) as a promising compound to antagonize L. major activities in future.

Rubella seroprevalence and demographic feature analysis in pregnant women from Southern Pakistan.

The present study was conducted to estimate the prevalence of rubella infection in pregnant women of district Lakki Marwat leading to foetal death, abortion, premature birth or congenital rubella syndrome. A total of 200 blood samples were collected from pregnant women visiting different maternal health care centers of the study area. Sera samples were tested for rubella-specific IgG and IgM antibodies through ELISA. The overall sero-positivity rate for IgG was 16% and for IgM was 2.5% in the pregnant women respectively. A higher sero-positivity rate was observed in the age group of 26-33 years. Women of rural areas showed higher sero-positivity rate than urban areas. The high sero-prevalence of rubella in the pregnant women of the study area poses a serious threat to the developing foetus.

Effects of structurally different noncoplanar and coplanar PCBs on HELF cell proliferation, cell cycle, and potential molecular mechanisms.

Polychlorinated biphenyls (PCBs) are a group of chemicals that persist in the environment, indoors, and humans. Lung exposure to airborne and food contaminants, such as PCBs, may cause possible lung disorders, such as cancer. In the present study, we investigated the effects of structurally different lower chlorinated (≤4Cl), noncoplanar PCB40, and coplanar PCB77 on human lung fibroblast cell line (HELF) cell proliferation, cell cycle progression, and possible molecular mechanisms. Noncoplanar PCB40 and coplanar PCB77 exhibited concentration- and time-dependent biphasic dose-response effects on HELF cell proliferation. Noncoplanar PCB40 and coplanar PCB77 induced 23 and 45% cytotoxicity at higher concentrations than the control. The flow cytometry analysis showed that exposure to PCB40 caused a significant increase in time spent in the G1 phase but decreased length of the S phase in a concentration- and time-dependent manner, whereas PCB77 exposure decreased time spent in the G1 and S phases but increased time spent in the G2 phase. Western blot analysis indicated that PCB77 increased the expression of cyclin E, CDK2, p21, and caspase-9, while PCB40 decreased the expression of these proteins (except CDK2 and p21). An increase in CDK expression after exposure to PCB77 suggests that it may cause carcinogenic effects on HELF cells at higher doses. Our results also demonstrate that the different cytotoxic effects induced by coplanar and nonplanar PCBs were correlated with their structural characteristics; the coplanar congener was more cytotoxic than the nonplanar congener. The study elaborates threshold levels for these chemicals and suggests that the cytotoxicity mechanisms by which PCB congeners act on HELF cells depend on their planarity and chemical structures. Furthermore, the study will be important for developing antidotes to the adverse effects and risk assessment practices for PCBs. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1183-1190, 2017.

Effects of altered expression and activity levels of CK1δ and ɛ on tumor growth and survival of colorectal cancer patients.

Colorectal cancer (CRC) is the fourth leading cause of cancer related death worldwide due to high apoptotic resistance and metastatic potential. Because mutations as well as deregulation of CK1 isoforms contribute to tumor development and tumor progression, CK1 has become an interesting drug target. In this study we show that CK1 isoforms are differently expressed in colon tumor cell lines and that growth of these cell lines can be inhibited by CK1-specific inhibitors. Furthermore, expression of CK1δ and ɛ is changed in colorectal tumors compared to normal bowel epithelium, and high CK1ɛ expression levels significantly correlate with prolonged patients' survival. In addition to changes in CK1δ and ɛ expression, mutations within exon 3 of CK1δ were detected in colorectal tumors. These mutations influence ATP binding resulting in changes in kinetic parameters of CK1δ. Overexpression of these mutants in HT29 cells alters their ability to grow anchorage independently. Consistent with these results, these CK1δ mutants lead to differences in proliferation rate and tumor size in xenografts due to changes in gene expression, especially in genes involved in regulation of cell proliferation, cell cycle, and apoptosis. In summary, our results provide evidence that changes in the expression levels of CK1 isoforms in colorectal tumors correlate with patients' survival. Furthermore, CK1 mutants affect growth and proliferation of tumor cells and induce tumor growth in xenografts, leading to the assumption that CK1 isoforms provide interesting targets for the development of novel effective therapeutic concepts to treat colorectal cancer.

Enhancing heart disease prediction using a self-attention-based transformer model.

Cardiovascular diseases (CVDs) continue to be the leading cause of more than 17 million mortalities worldwide. The early detection of heart failure with high accuracy is crucial for clinical trials and therapy. Patients will be categorized into various types of heart disease based on characteristics like blood pressure, cholesterol levels, heart rate, and other characteristics. With the use of an automatic system, we can provide early diagnoses for those who are prone to heart failure by analyzing their characteristics. In this work, we deploy a novel self-attention-based transformer model, that combines self-attention mechanisms and transformer networks to predict CVD risk. The self-attention layers capture contextual information and generate representations that effectively model complex patterns in the data. Self-attention mechanisms provide interpretability by giving each component of the input sequence a certain amount of attention weight. This includes adjusting the input and output layers, incorporating more layers, and modifying the attention processes to collect relevant information. This also makes it possible for physicians to comprehend which features of the data contributed to the model's predictions. The proposed model is tested on the Cleveland dataset, a benchmark dataset of the University of California Irvine (UCI) machine learning (ML) repository. Comparing the proposed model to several baseline approaches, we achieved the highest accuracy of 96.51%. Furthermore, the outcomes of our experiments demonstrate that the prediction rate of our model is higher than that of other cutting-edge approaches used for heart disease prediction.

The Pathogenesis of Foot-and-Mouth Disease Virus Infection: How the Virus Escapes from Immune Recognition and Elimination.

Foot-and-mouth disease virus (FMDV) is a highly contagious and economically devastating pathogen that affects cloven-hoofed animals worldwide. FMDV infection causes vesicular lesions in the mouth, feet, and mammary glands, as well as severe systemic symptoms such as fever, salivation, and lameness. The pathogenesis of FMDV infection involves complex interactions between the virus and the host immune system, which determine the outcome of the disease. FMDV has evolved several strategies to evade immune recognition and elimination, such as antigenic variation, receptor switching, immune suppression, and subversion of innate and adaptive responses. This review paper summarizes the current knowledge on the pathogenesis of FMDV infection and the mechanisms of immune evasion employed by the virus. It also discusses the challenges and opportunities for developing effective vaccines and therapeutics against this important animal disease.

The potential toxicity of chemically fabricated silver nanomaterials based on accumulation and histological changes in fish (Cyprinus carpio).

The bio-reductive fabrication of nanomaterials is a developing arena of study that seeks to fabricate nanoparticles (NPs) using microorganisms, plants, and animal blood. However, the chemical approach of AgNPs fulfills the need of abundant need of NPs. In contrast, chemically fabricated AgNPs are more toxic than biological AgNPs. Therefore, the current study aimed to assess and evaluate the chemically fabricated silver nanoparticles (AgNPs) for their possible toxicity in Common carp fish (Cyprinus carpio). The chemically synthesized silver nanoparticles were purchased from the market and applied for their possible toxicity. The chemically fabricated AgNPs were used against the Cyprinus carpio for bioaccumulation in different organs and histological alterations in the intestine and muscles. The results revealed that the AgNPs were mostly accumulated in the intestines followed by the gills, liver, and muscles (p < .05). The accumulated AgNPs caused histological alterations in gills and intestines at the highest concentration (0.08 mg/L). However, no alterations were observed by the middle and lowest concentration of AgNPs, particularly, in the intestine. In conclusion, more extensive research is required to establish the hazards related to the use of nanoparticles to disclose their negative effects on fish and the aquatic environment. REASEARCH HIGHLIGHTS: The chemical method fabricates a large amount of AgNPs Additionally, considered more toxic than the bio-reductive method AgNPs have excellent and diverse applications AgNPs deposited in various organs and cause histological changes.

Aiding the well celebrated Kuk's randomized response technique through auxiliary and prior information.

Asking direct questions in face to face surveys about sensitive traits is an intricate issue. One of the solutions to this issue is the randomized response technique (RRT). Being the most widely used indirect questioning technique to obtain truthful data on sensitive traits in survey sampling RRT has been applied in a variety of fields including behavioral science, socio-economic, psychological, epidemiology, biomedical, criminology, data masking, public health engineering, conservation studies, ecological studies and many others. This paper aims at exploring the methods to subsidize the randomized response technique through additional information relevant to the parameter of interest. Specifically, we plan to contribute by proposing more efficient hybrid estimators compared to existing estimator based on (Kuk, 1990) [31] family of randomized response models. The proposed estimators are based on the methodology of incorporating the pertinent information, available on the basis of either historical records or expert opinion. Specifically, in case of availability of auxiliary information, the regression-cum-ratio estimator is found to be the best to further enhance the estimation through (Kuk, 1990) [31] model while the (Thompson, 1968) [49] shrinkage estimation is observed to be yielding more precise and accurate estimator of sensitive proportion. The findings in this study signify the importance of the proposed methodology. Additionally, to support the mathematical findings, a detailed numerical investigation to evaluate the comparative performances is also conducted. Based on performance analysis, overwhelming evidences are witnessed in the favor of proposed strategies.

Trends in Monkeypox transmission: Investigation into 30 most affected countries.

This research is based on the analysis of Monkeypox transmission, from may 7, 2022 to October 11, 2022, in 30 most affected countries around the globe. The most affected countries are selected through the cut point of at least 100 reported confirmed cases of infected persons over the aforementioned time span. We novely argue the exhibition of distributional similarities between the viral flow and well known power law in context of this neglected zoonotic disease. Moreover, model-based evidence suggesting the capability of pathogen to spread far and wide around its nucleus, are collected and presented. It is estimated that 70 % of the reported confirmed cases belonged to 20 % of the top most affected countries. Also, 70 % of the reported transmission was inflicted in 34 % of the days of reporting at least one case, on average.