This study compares three deep learning algorithms for cardiovascular disease risk prediction. While RBFN boasts the highest accuracy (84.07%), wekaDeeplearning4j excels in identifying high-risk individuals via better AUC and PRC area, valuable for prioritizing early intervention despite slightly lower overall accuracy (81.85%). Conversely, MLP's low mean absolute error indicates high precision in individual case prediction, ideal for personalized treatments. However, tradeoffs exist: wekaDeeplearning4j requires longer training times, and MLP's precision may sacrifice sensitivity. Choosing the optimal algorithm depends on context and priorities. High accuracy and speed favor RBFN, while superior high-risk identification or precise individual predictions favor wekaDeeplearning4j or MLP, respectively. Understanding these trade-offs is crucial for maximizing deep learning's effectiveness in cardiovascular disease risk prediction.

Introduction: Carbon tetrachloride (CCl4 ) is a chemical that can induce injury in the liver. The aim was to evaluate any potential hepatoprotective potential of a seed extract from Cassia absus against CCl4 -induced liver toxicity in Wister rats. Methods: To this end, an aqueous-methanolic extract of C. absus seeds was prepared by maceration. In vitro testing of the extract included phytochemical screening and high-performance liquid chromatography (HPLC) analysis to evaluate the phenolic compound constituents. An in vivo study involved a single exposure to CCl4 either alone or in combination with the hepatoprotective agent, silymarin, or C. absus seed extract administered orally over 28 days. Serum biochemical markers of liver cell injury were measured and post-mortem liver tissues were examined histopathologically using eosin-hematoxylin staining and microscopy. Results: The HPLC analysis specifically identified the presence of gallic acid, vanillic acid, catechin, and p-coumaric acid. In addition, no changes were observed in animal body and liver weights during the treatment protocol. However, both the plant seed extract and silymarin reversed the CCl4 induced elevated serum concentrations of aspartate aminotransferase (AST), total bilirubin, alkaline phosphatase (ALP), and alanine transaminase (P<0.05) in addition to the histopathological injury. The plant extract also had a dose-related hepatotoxic mitigating effect, and the findings were analogous to those with the hepatoprotective standard comparator, silymarin. Conclusion: These study outcomes substantiate a protective effect of C. absus seed extract against CCl4 -induced hepatotoxicity in the animal model.

This paper addresses the evolving landscape of global infectious diseases, emphasizing the pivotal role of vector-borne diseases in public health. Focusing on eleven formidable diseases, including Chikungunya, Dengue, Zika, Yellow Fever, West Nile Fever, Malaria, Rift Valley Fever, Tungiasis, Japanese Encephalitis, Plague, and Lyme Disease, the study utilizes machine learning algorithms for prediction, risk factor identification, and correlation analysis. Data, collected from diverse sources, undergoes thorough preprocessing, ensuring quality and consistency. Four machine learning models are employed-Multilayer Perceptron, Sequential Minimal Optimization, J48 Decision Tree, and Naive Bayes-revealing the Naive Bayes model as particularly promising with a 94% correlation coefficient and high precision. Association rules shed light on complex attribute relationships, guiding future research, and interventions. The ranked attributes, led by itchiness, provide valuable insights for understanding and mitigating vector-borne diseases. This research contributes to a deeper comprehension of these diseases, facilitating informed decision-making and effective public health strategies amid evolving global health challenges.

Major obstacles faced by the use of nonsteroidal anti-inflammatory drugs (NSAID) are their gastrointestinal toxicity induced by non-selective inhibition of both cyclooxygenases (COX) 1 and 2 and their cardiotoxicity associated with a certain class of COX-2 selective inhibitors. Recent studies have demonstrated that selective COX-1 and COX-2 inhibition generates compounds with no gastric damage. The aim of the current study is to develop novel anti-inflammatory agents with a better gastric profile. In our previous paper, we investigated the anti-inflammatory activity of 4-methylthiazole-based thiazolidinones. Thus, based on these observations, herein we report the evaluation of anti-inflammatory activity, drug action, ulcerogenicity and cytotoxicity of a series of 5-adamantylthiadiazole-based thiazolidinone derivatives. The in vivo anti-inflammatory activity revealed that the compounds possessed moderate to excellent anti-inflammatory activity. Four compounds 3, 4, 10 and 11 showed highest potency (62.0, 66.7, 55.8 and 60.0%, respectively), which was higher than the control drug indomethacin (47.0%). To determine their possible mode of action, the enzymatic assay was conducted against COX-1, COX-2 and LOX. The biological results demonstrated that these compounds are effective COX-1 inhibitors. Thus, the IC50 values of the three most active compounds 3, 4 and 14 as COX-1 inhibitors were 1.08, 1.12 and 9.62 μΜ, respectively, compared to ibuprofen (12.7 μΜ) and naproxen (40.10 μΜ) used as control drugs. Moreover, the ulcerogenic effect of the best compounds 3, 4 and 14 were evaluated and revealed that no gastric damage was observed. Furthermore, compounds were found to be nontoxic. A molecular modeling study provided molecular insight to rationalize the COX selectivity. In summary, we discovered a novel class of selective COX-1 inhibitors that could be effectively used as potential anti-inflammatory agents.

The application of “Internet of Things” is a new phenomenon which has supported organisation, individuals and others to transform the manner in which the business operations and other aspects are being connected. The IoT based future technology in an effective manner. The implementation of Blockchain tend to contain more strong protections against any form of data leakage, tampering of the information Hence, it has been stated by many researchers that the application of Blockchain based security support in enhancing the future technology through IoT. This research focuses in understanding the opportunities and address key aspects related to security aspects through IoT in creating better future technology. The researchers tend to use both primary data and secondary data for performing the study, the researchers collate the data from the respondents through survey method, the analysis are then made using AMOS statistical software and meaningful interpretation were presented based on the analysis.

The development of an environmentally friendly analytical technique for simultaneous measurement of medicines with large concentration differences is difficult yet critical for environmental protection. Hence, in this work, new manipulated UV-spectroscopic methods with high scaling factors were established for concurrent quantification of telmisartan (TEL) and benidipine (BEN) in fixed-dose combinations. Two different methods were developed and established by calculation of peak height at zero crossing point of second derivative and the ratio of first derivative spectra with a scaling factor of 200 and 100, respectively. The absorption difference between the peaks and troughs of the ratio spectra, as well as continuous subtraction from ratio spectra, were established as additional methods. In addition, new procedures were validated using ICH recommendations. The proposed methods’ linearity curves were constructed in the range of 0.5–10 µg mL−1 and 1–30 µg mL−1 for BEN and TEL, respectively, under optimized conditions. Furthermore, both the detection (0.088–0.139 µg mL−1 for BEN and 0.256–0.288 µg mL−1 for TEL) and quantification limits (0.293–0.465 µg mL−1 for BEN and 0.801–0.962 µg mL−1 for TEL) were adequate for quantifying both analytes in the formulation ratios. The accuracy and precision were confirmed by the good recovery percent (98.37%–100.6%), with low percent relative error (0.67%–1.70%) and less than 2 percent relative standard deviation, respectively. The specificity of the methods was proven by accurate and precise outcomes from the standard addition method and analysis of laboratory mixed solutions with large differences in concentrations of both analytes. Finally, the BEN and TEL content of the formulations was determined simultaneously without prior separation using these first ever reported spectroscopic methods. Furthermore, developed UV derivative spectroscopic methods demonstrated high greenness and whiteness when compared to the reported HPLC methods. These findings show that the projected methods were effective, practical, and environmentally acceptable for quality control of BEN and TEL in multicomponent formulations.

A rapid and reproducible hydrophilic liquid chromatography (HILIC) process was established for concomitant determination of remogliflozin etabonate (RE), vildagliptin (VD), and metformin (MF) in a formulation. A face-centered central composite experimental design was employed to optimize and predict the chromatographic condition by statistically studying the surface response model and design space with desirability close to one. A HILIC column with a simple mobile phase of acetonitrile (65% v/v) and 20 mM phosphate buffer (35% v/v, pH 6, controlled with orthophosphoric acid) was used to separate RE, VD, and MF. RE, VD, and MF were separated in 3.6 min using an isocratic mode mobile phase flow at a flow rate of 1.4 mL at room temperature, and the analytes were examined by recording the absorption at 210 nm. The developed HILIC method was thoroughly validated for all parameters recommended by ICH, and linearity was observed in the ranges 20–150 µg/mL, 10–75 µg/mL, and 50–750 µg/mL for RE, VD, and MF, respectively, along with excellent regression coefficients (r2 > 0.999). The calculated percentage relative deviation and relative error ascertained the precision and accuracy of the method. The selectivity and accuracy were further confirmed by the high percentage recovery of added standard drugs to the formulation using the standard addition technique. The robustness of the HILIC processes was confirmed by developing a half-normal probability plot and Pareto chart, as the slight variation of a single factor had no significant influence on the assay outcomes. Utilization of the optimized HILIC procedure for concurrent quantification of RE, VD, and MF in solid dosage forms showed accurate and reproducible results. Hence, the fast HILIC method can be regularly employed for the quality assurance of pharmaceutical preparations comprising RE, VD, and MF.

A combination of antibiotics and antiprotozoal and antisecretory medicines has been prescribed for the treatment of diarrhea. A rapid, reproducible liquid chromatographic procedure was established for the concurrent analysis of metronidazole (MET), ofloxacin (OFL), and racecadotril (RAC) in suspension. The Box–Behnken design, a full factorial multivariate optimization technique, was utilized to optimize chromatographic parameters with fewer runs. The separation of MET, OFL, and RAC was accomplished within 3.2 min, using a Zorbax C18 high-performance liquid chromatography column with a simple mobile phase comprising acetonitrile (55 vol.%): methanol (10 vol.%):20 mM phosphate buffer (35 vol.%, pH 6, regulated with ortho-phosphoric acid). The mobile phase was pumped in the isocratic mode at a rate of 1.4 mL/min at ambient temperature. Analytes were monitored by adjusting the wavelength at 295 nm for MET and OFL and 231 nm for RAC. Validation of the proposed HPLC method exhibited linearity in the concentration of 20–250 µg/mL, 10–150 µg/mL, and 5–80 µg/mL for MET, OFL, and RAC respectively, along with an excellent regression coefficient (r2 > 0.999). The accuracy and precision of the chromatographic procedure were also evidenced by the low percent relative error and relative standard deviation. A Pareto chart developed by the two-factor interaction (2FI) study confirmed that the method was robust, as the slight variation in a single factor had no significant influence on the assay outcomes. Lastly, the developed HPLC process was utilized for the concurrent quantification of MET, OFL, and RAC in liquid oral preparation. Furthermore, when the assay results were compared to the described techniques, it was discovered that there was no significant difference in the accuracy and precision of the results. Hence, the developed rapid HPLC method could be employed for the quality control study of a preparation comprising of MET, OFL, and RAC in industries and regulatory authority laboratories.

A simple, eco-friendly four analytical methods were established by improving the selectivity through the application of mathematical processing of UV absorption spectra for concurrent quantification of chlorthalidone (CTL) and azelnidipine (AZE). The UV absorption spectra were recorded using environment-friendly ethanol (10% v/v) and were mathematically processed using simple software provided with a UV spectrophotometer. The analytes’ peak amplitude was determined using zero-crossing point first derivative spectra and ratio first derivative spectra of CTL and AZE, which were measured at 238.5 nm and 239.5 nm for CTL and 272.1 nm and 342.1 nm for AZE, respectively. The peak amplitude difference was determined from the ratio spectra of CTL and AZE by measuring the peak amplitudes at 211.8 and 267.2 nm for CTL and 328.4 and 286.1 nm for AZE. Further, ratio spectra of CTL and AZE were converted into zero-order spectra by subtracting the constant followed by multiplication with divisor spectra, and the peak amplitudes were measured at 226.9 nm and 257.3 nm for CTL and AZE zero-order spectra, respectively. Further, validation results of all the four methods confirmed the accuracy and precision of the methods by displaying good recovery (98.37–100.34%) and percentage relative standard deviation (0.397–1.758%), respectively. Good linearity was observed in the range of 1–15 μg/mL for both analytes with less than a 1 μg/mL limit of quantification. Further, the greenness and whiteness of the methods were evaluated by recently proposed AGREEness, complexGAPI, and white analytical chemistry techniques. The proposed UV spectroscopic methods were environmentally friendly, safe, economic, and effective, hence, could be used for regular quality control study of a formulation containing CTL and AZE.

Although methotrexate (MTX) is an effective immunosuppressive and anti-cancer agent, it is associated with side effects, including nephrotoxicity. Capsaicin, a component of hot chilli peppers, induces rapid desensitization of TRPV1 pain receptors and therefore has uses in pain treatment. Capsaicin also has anti-cancer activity, including anti-inflammatory properties. Thus, capsaicin may have potential in preventing MTX-induced nephrotoxicity. The purpose of this research work was to observe protective effects of capsaicin towards renal toxicity caused by methotrexate and mechanisms responsible for these effects. As expected, capsaicin had nephroprotective effects in MTX-intoxicated rats. Serum creatinine urea, nitric oxide (NO) and renal malondialdehyde (MDA) levels decreased significantly, with a concurrent increase in superoxide dismutase (SOD) and renal glutathione peroxidase (GPx) activities as compared to rats that had been untreated with nephrotoxic. Biochemical analyses confirmed the protective effects of capsaicin. We conclude that capsaicin provides protection against MTX-nephrotoxicity in rats via anti-inflammatory and antioxidant activities.

A rapid, synchronized liquid chromatographic method was established for the estimation of hydrochlorothiazide (HCZ), amlodipine (AMD), olmesartan (OLM), telmisartan (TEL), and irbesartan (IRB) in binary and ternary coformulations using the same chromatographic conditions. Five analytes were separated on a Zorbax C18 column using isocratic elution with a mobile phase consisting of acetonitrile, methanol, and 20 mM phosphate buffer (pH 3.5) in a ratio of 45:20:35% v/v. The analytes were detected at a wavelength of 230 nm at ambient temperature. Furthermore, the proposed liquid chromatographic procedure was validated for linearity, precision, accuracy, stability, and robustness using an experimental design. Analytes were separated with good resolution within 3.5 min. Analytes showed good linearity in a concentration satisfactory to analyze the different ratios of these analytes in the formulations. Pareto charts showed that the flow rate and mobile phase composition have a significant effect on the peak area of analytes and hence need to be carefully controlled, however, the method is robust. Finally, the different formulations consisting of HCZ, AMD, OLM, TEL, and IRB in different ratios were analyzed with high accuracy using an optimized HPLC method and compared with reported methods. Furthermore, the reported HPLC procedure is simple, rapid, and accurate and therefore can used for regular quality control of binary and ternary formulations using the same stationary and mobile phase.

Vancomycin, an antibiotic used occasionally as a last line of treatment for methicillin-resistant Staphylococcus aureus, is reportedly associated with nephrotoxicity. This study aimed at evaluating the protective effects of lutein against vancomycin-induced acute renal injury. Peroxisome proliferator-activated receptor gamma (PPARγ) and its associated role in renoprotection by lutein was also examined. Male BALB/c mice were divided into six treatment groups: control with normal saline, lutein (200 mg/kg), vancomycin (250 mg/kg), vancomycin (500 mg/kg), vancomycin (250 mg/kg) with lutein, and vancomycin (500 mg/kg) with lutein groups; they were euthanized after 7 days of treatment. Thereafter, samples of blood, urine, and kidney tissue of the mice were analyzed, followed by the determination of levels of N-acetyl-β-D-glucosaminidase (NAG) in the urine, renal creatine kinase; protein carbonyl, malondialdehyde, and caspase-3 in the kidney; and the expression of PPARγ, nuclear factor erythroid 2-related factor 2 (Nrf2), and nuclear factor-kappaB (NF-κB) in renal tissue. Results showed that the levels of protein carbonyl and malondialdehyde, and the activity of NAG, creatine kinase and caspase-3, were significantly increased in the vancomycin-treatment groups. Moreover, the levels of Nrf2 significantly decreased, while NF-κB expression increased. Lutein ameliorated these effects, and significantly increased PPARγ expression. Furthermore, it attenuated vancomycin-induced histological alterations such as, tissue necrosis and hypertrophy. Therefore, we conclude that lutein protects against vancomycin-induced renal injury by potentially upregulating PPARγ/Nrf2 expression in the renal tissues, and consequently downregulating the pathways: inflammation by NF-κB and apoptosis by caspase-3.

Background: Diclofenac Sodium (DCL) and Moxifloxacin HCl (MOX) were simultaneously used after cataract surgery to reduce the post-operative inflammation and to control infection respectively. Objectives: Three simple, accurate, eco-friendly and reproducible UV spectroscopic methods were established for concurrent determination of diclofenac sodium and moxifloxacin in ophthalmic preparation without prior separation. Methods: The first technique was established on the measurement of a peak amplitude of the first derivative spectra at the zero-crossing wavelength of one analyte. The second method was the determination of peak amplitude difference between peak and trough of ratio spectra. The third method involves the measurement of the peak amplitude of the first derivative of ratio spectra. Water has been used as a solvent. Results: The analytes exhibited good linearity in the range of 1 -15 mu g/mL for DCL and 1-18 mu g/mL for MOX with excellent correlation coefficient (r(2)> 0.999). Low percent relative standard deviation confirmed the precision of the methods. Excellent recovery with low percent relative error proved the accuracy of the methods. The specificity of the methods was evaluated by analyzing the laboratory prepared solutions of DCL and MOX. Conclusion: Proposed three techniques were effectively utilized for the simultaneous determination of DCL and MOX from ophthalmic preparation. The outcomes of the proposed procedures were compared with the earlier described methods and no statistical difference was found between the methods in terms of accuracy and precision.

Background: The limiting factor in the use of cyclophosphamide (CYP) in cancer chemotherapy is its induced oxidative cardiotoxicity. Objectives: This study aims to investigate the possible protective effect of caffeic acid phenethyl ester (CAPE) in the co-administration of CYP and naproxen (NAP) with acute and subchronic treatments in mice. Materials and Methods: Male BALB/c mice were divided into two phases of acute (24 h) and subchronic (30 days) treatments, of which seven groups each were used. Two groups from both acute and subchronic treatments represented untreated controls and CAPE groups, while others were CYP, NAP, CYP+NAP, CYP+CAPE and CYP+NAP+CAPE groups for both treatments. The activity of the cardiac antioxidative enzyme catalase was measured. The levels of cardiac reduced glutathione (GSH), protein carbonyl and malondialdehyde (MDA) were also assayed. In addition, histopathology of the heart tissues and immunohistochemistry of endothelial nitric oxide synthase (eNOS) expression were evaluated. Results: Our results showed that catalase and GSH were significantly decreased in all subchronic treatments. Furthermore, protein carbonyl and MDA were increased in both acute and subchronic treatments. Histopathological examination showed hypertrophic cells induced by CYP, NAP, and in combination. Moreover, CYP, NAP and in combination, significantly reduced eNOS levels. However, CAPE significantly prevented changes induced by CYP and NAP in both treatment groups. Conclusion: These observations highlight the protective potentials of CAPE in CYP-NAP-induced cardiotoxicity.

The Middle East Respiratory Syndrome (MERS) is an emerging disease caused by a recently identified human coronavirus (CoV). Over 2494 laboratory-confirmed cases and 858 MERS-related deaths have been reported from 27 countries. MERS-CoV has been associated with a high case fatality rate, especially in patients with pre-existing conditions. Despite the fatal nature of MERS-CoV infection, a comprehensive study to explore its evolution and adaptation in different hosts is lacking. We performed codon usage analyses on 4751 MERS-CoV genes and determined underlying forces that affect the codon usage bias in the MERS-CoV genome. The current analyses revealed a low but highly conserved, gene-specific codon usage bias in the MERS-CoV genome. The codon usage bias is mainly shaped by natural selection, while mutational pressure emerged as a minor factor affecting codon usage in some genes. Other contributory factors included CpG dinucleotide bias, physical and chemical properties of encoded proteins and gene length. Results reported in this study provide considerable insights into the molecular evaluation of MERS-CoV and could serve as a theoretical basis for optimizing MERS-CoV gene expression to study the functional relevance of various MERS-CoV proteins. Alternatively, an attenuated vaccine strain containing hundreds of silent mutations could be engineered. Codon de-optimization will not affect the amino acid sequence or antigenicity of a vaccine strain, but the sheer number of mutations would make viral reversion to a virulent phenotype extremely unlikely.

Three simple UV spectrophotometric methods were established and validated for the concurrent estimation of a ternary mixture of an antihypertensive formulation consisting of amlodipine (AMD), hydrochlorothiazide (HCZ) and telmisartan (TEL) using 50% v/v ethanol-water as solvent. The first method was based on the determination of AMD using zero-order spectra (371.0 nm), whereas, HCZ and TEL were quantified by measuring the peak height at zero crossing wavelength of the second derivative of ratio spectra (279.4 nm and 314.7 nm). The second procedure was accomplished by determining the absorption difference between peak and trough at two different wavelengths of double devisor ratio spectra (369.4 nm-297.5 nm for AMD; 272.1 nm-241.5 nm for HCZ; 297.2 nm-272.7 nm for TEL) The third method involved the measurement of the peak amplitude of maxima or minima of first derivative spectra of double devisor ratio spectra. (390.4 nm for AMD, 278.9 nm for HCZ 288.1 nm for TEL) All the drugs showed good linearity with an acceptable correlation coefficient in all the three proposed methods. Further accuracy, precision, sensitivity, robustness, recovery studies and selectivity were determined according to the ICH strategies and the results were in agreement with the acceptable range. In addition, the proposed techniques were applied effectively for quantification of AMD, HCZ and TEL from the solid dosage form. The comparison of assay outcomes, using the student's t-test and F test, revealed that there is no significant change among the proposed UV and the reported HPLC procedures. The manipulation of UV spectra is simple, fast, and the proposed methods were environment friendly and economical when compared to very expensive chromatographic methods. Hence, these procedures can be employed for the routine quality control examination in industries and laboratories. (C) 2020 Elsevier B.V. All rights reserved.

Simple, fast, and precise reversed-phase (RP)-high-performance liquid chromatography (HPLC) and two ecofriendly spectrophotometric methods were established and validated for the simultaneous determination of moxifloxacin HCl (MOX) and flavoxate HCl (FLX) in formulations. Chromatographic methods involve the separation of two analytes using an Agilent Zorbax SB C18 HPLC column (150 mm × 4.6 mm; 5 µm) and a mobile phase consisting of phosphate buffer (50 mM; pH 5): methanol: acetonitrile in a proportion of 50:20:30 v/v, respectively. Valsartan was used as an internal standard. Analytes were monitored by measuring the absorbance of elute at 299 nm for MOX and 250 nm for FLX and valsartan. Two environmentally friendly spectrophotometric (first derivative and ratio first derivative) methods were also developed using water as a solvent. For the derivative spectrophotometric determination of MOX and FLX, a zero-crossing technique was adopted. The wavelengths selected for MOX and FLX were −304.0 nm and −331.8 nm for the first derivative spectrophotometric method and 358.4 nm and −334.1 nm for the ratio first-derivative spectrophotometric method, respectively. All methods were successfully validated, as per the International Conference on Harmonization(ICH) guidelines, and all parameters were well within acceptable ranges. The proposed analytical methods were successfully utilized for the simultaneous estimation of MOX and FLX in formulations.

Purpose: To evaluate the effectiveness of vitamin C on paraquat-induced hepatic and renal toxicity in Swiss albino mice. Methods: Three groups of Swiss albino mice (n = 10), i.e., control, paraquat (15 mg/kg) and paraquat (15 mg/kg) + vitamin C (20 mg/kg) were used in the study. The drugs were administered intraperitoneally for four days. Blood samples were collected on day 5 for determination of serum levels of liver and renal biomarkers. Thereafter, the animals were sacrificed; liver and kidney were excised and preserved in neutral formalin for histopathological analysis. Results: The paraquat-treated animals showed higher levels of aspartate transaminase (AST), alanine transaminase (ALT), serum urea and creatinine, relative to values for control. Histopathological examination of the paraquat-treated animals showed cytoplasmic vacuolar degeneration and congestion of central vein in the liver, and glomerular necrosis in the kidneys. Control and vitamin C-treated mice showed normal architecture of liver and kidney. Conclusion : These results indicate that vitamin C modulated the paraquat-induced liver and renal abnormalities in the experimental animals. Thus vitamin C exerts hepatoprotective and renoprotective effects against paraquat poisoning. Keywords : Paraquat poisoning, Liver, Kidney, Vitamin C, Toxicity, Histopathology

This article describes a case of unusual origin of left vertebral artery from the arch of aorta as a case report. This variation was found in one of the cadavers at the department of Anatomy, Rashid Latif Medical College, Lahore. Pakistan. During routine dissection of anadult male cadaver, in the region of superior mediastinum and neck, we observed an atypical origin of left vertebral artery from the arch of aorta.