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Background: Team-based care (TBC), a team of ≥2 healthcare professionals working collaboratively toward a shared clinical goal, is a recommended strategy to manage blood pressure (BP). However, the most effective and cost-effective TBC strategy is unknown. Methods: A meta-analysis of clinical trials in US adults (aged ≥20 years) with uncontrolled hypertension (≥140/90 mm Hg) was performed to estimate the systolic BP reduction for TBC strategies versus usual care at 12 months. TBC strategies were stratified by the inclusion of a nonphysician team member who could titrate antihypertensive medications. The validated BP Control Model-Cardiovascular Disease Policy Model was used to project the expected BP reductions out to 10 years and simulate cardiovascular disease events, direct healthcare costs, quality-adjusted life years, and cost-effectiveness of TBC with physician and nonphysician titration. Results: Among 19 studies comprising 5993 participants, the 12-month systolic BP change versus usual care was −5.0 (95% CI, −7.9 to −2.2) mm Hg for TBC with physician titration and −10.5 (−16.2 to −4.8) mm Hg for TBC with nonphysician titration. Relative to usual care at 10 years, TBC with nonphysician titration was estimated to cost $95 (95% uncertainty interval, −$563 to $664) more per patient and gain 0.022 (0.003–0.042) quality-adjusted life years, costing $4400/quality-adjusted life year gained. TBC with physician titration was estimated to cost more and gain fewer quality-adjusted life years than TBC with nonphysician titration. Conclusions: TBC with nonphysician titration yields superior hypertension outcomes compared with other strategies and is a cost-effective way to reduce hypertension-related morbidity and mortality in the United States.

Terms of Service (ToS) are fundamental factors in the creation of physical as well as online legally relevant relationships. Very often, they disregard the consumer protection law. In this perspective, a relevant issue is that public agencies in charge of control concretely lack the resources needed to effectively fight against such unlawful practices. We propose a definition of ToS unfairness and a novel machine learning-based approach to classify clauses in ToS, represented by using sentence embedding, into both categories and fairness classes. We use Naïve Bayes Classifier to achieve the desired categorization and result. Terms of Service (ToS) are fundamental factors in the creation of physical as well as online legally relevant relationships. They not only define mutual rights and obligations but also inform users about contract key issues that, in online settings, span from liability limitations to data management and processing conditions. Despite their crucial role, however, ToS are often neglected by users that frequently accept without even reading what they agree upon, representing a critical issue when there exist potentially unfair clauses. To enhance users’ awareness and uphold legal safeguards, we first propose a definition of ToS unfairness based on a novel unfairness measure computed counting the unfair clauses contained in a ToS, and therefore, weighted according to their direct impact on the customers concrete interests.

Devanagari script is widely used across India. It forms many languages like Hindi, Marathi, Nepali and Sanskrit languages. As the Devanagari characters are similar to the hindi character the national language of India. It is important to recognize the characters to understand the message that particular tries to tell. The automatic character recognition system is thus developing for the Devanagari script. The character recognition process converts an image of a character into machine-readable format also its English corresponds. In this paper, we are using Convolutional Neural Network for developing the character recognition system. Convolutional neural network learns directly from data. It is a type of Deep learning neural network architecture. CNN is useful as it does not require any human intervention and performs the identification of important features on its own. The proposed paper uses a CNN algorithm applied to a dataset of 49 characters of Devanagari script. The dataset contains of total 4018 Images. The algorithm of the Convolutional Neural Network is applied to train the dataset. The input image to be predicted is first preprocessed and then the model predicts the output result. The system is designed in Jupyter Lab using Python. The Convolutional Neural Network model's overall accuracy is 98%.

Quality of life in chronic kidney disease (CKD) is impaired by a large burden of symptoms including some that overlap with the symptoms of heart failure (HF). We studied a group of individual with CKD to understand the patterns and trajectories of HF-type symptoms in this setting.Prospective cohort study.3,044 participants in the Chronic Renal Insufficiency Cohort (CRIC) without prior diagnosis of HF.Sociodemographics, medical history, medications, vital signs, laboratory values, echocardiographic and EKG parameters.Trajectory over 5.5 years of a HF-type symptom score (modified Kansas City Cardiomyopathy Questionnaire [KCCQ] Overall Summary Score with a range of 0-100 where75 reflects clinically significant symptoms).Latent class mixed models were used to model trajectories. Multinomial logistic regression was used to model relationships of predictors with trajectory group membership.Five trajectories of KCCQ score were identified in the cohort of 3,044 adults, 45% of whom were female, and whose median age was 61 years. Group 1 (41.7%) had a stable high score (minimal symptoms, average score of 96); Groups 2 (35.6%) and 3 (15.6%) had stable but lower scores (mild symptoms, average 81, and clinically significant symptoms, average 52, respectively). Group 4 (4.9%) had a substantial worsening in symptoms over time (mean 31-point decline) and Group 5 (2.2%) had a substantial improvement (mean 33-point increase) in KCCQ score. A majority of Group 1 was male, non-diabetic, non-obese, and had higher baseline kidney function. A majority of Groups 2 and 3 had diabetes and obesity. A majority of Group 4 was male and had substantial proteinuria. Group 5 had the highest proportion of baseline cardiovascular disease (CVD).No validation cohort available, CKD management changes in recent years may alter trajectories, and latent class models depend on the missing at random assumption.Distinct HF-type symptom burden trajectories were identified in the setting of CKD, corresponding to different baseline characteristics. These results highlight the diversity of HF-type symptom experiences in individuals with CKD.

Rythu Bharosa Kendram is One Stop Shop for supplying Government Certified Agri Inputs (Seeds, Fertilizers & Pesticides), Animal Husbandry & Fisheries Inputs to the farmers and has an attached workshop / Knowledge Center for giving scientific Agri Advisories to the farmers. It is integrated with a Call. The study investigated the effectiveness of services of RBK perceived by farmers in the East Godavari district of Andhra Pradesh during 2021-2022. A total sample of 120 farmers was randomly selected from twelve villages viz. Kadiyam, Vemagiri, Muramanda, Kalavacherla, Rajanagram, Velugubanda, Geddanapalli, Bhupalapatnam, S. thimmapuram, Bhatnavalli, Rollapalem and Nadipudi of East Godavari district of Andhra Pradesh. The data were collected with structured interview schedule. The perceived effectiveness of the services of RBKs was studied. It was observed that half (50.83%) of the farmers perceived that services rendered by RBKs were moderately effective followed by highly effective (34.17%) and less effective (15.00%) categories. It can be recommended to the government and policy makers for improvement, restructuring, reforming and modifying the services from RBKs to enhance its effectiveness further.

An image processing technique called edge detection is used to find and identify the edges, curves, and objects in digital images. Edge detection includes various mathematical calculations that focus on locating the edges and curves where a digital image's brightness abruptly shifts or has discontinuities. In the fields of feature detection and feature extraction in image processing and computer vision, edge detection is a fundamental tool. The application of an edge detector results in the development of a set of connected curves that represent surface marks, character boundaries, and discontinuities in surface orientation. Character boundaries are described via edges. The majority of a feature is described by its edges. A group of pixels called an edge is used to describe an area where abrupt variations in intensity occur. Because it removes items of interest for actions like description, segmentation is a vital stage in an image recognition system. This paper focuses on edge detection techniques that can be implemented on characters for effective character recognition. Devanagari text includes curvy edges which need to be detected for proper recognition hence different edge detector operators are implemented to find the most effective amongst them to acquire clear edges of the text. There are several methods for segmenting images, including segmentation based on artificial neural networks, clustering, edges, regions, and thresholds. In this paper, edge-based segmentation is used. The Canny, Laplacian, Sobel, Prewitt, and Robert operators are used to detect edges, and the generated image is compared to the original binary image. The pre-processing phase includes the binarization step.

Background We carried out a study of the aptamer proteomic assay, SomaScan V4, to evaluate the analytical and biological variability of the assay in plasma samples of patients with moderate to severe chronic kidney disease (CKD). Methods Plasma samples were selected from 2 sources: (a) 24 participants from the Chronic Renal Insufficiency Cohort (CRIC) and (b) 49 patients from the Brigham and Women’s Hospital–Kidney/Renal Clinic. We calculated intra-assay variability from both sources and examined short-term biological variability in samples from the Brigham clinic. We also measured correlations of aptamer measurements with traditional biomarker assays. Results A total of 4656 unique proteins (4849 total aptamer measures) were analyzed in all samples. Median (interquartile range [IQR] intra-assay CV) was 3.7% (2.8–5.3) in CRIC and 5.0% (3.8–7.0) in Brigham samples. Median (IQR) biological CV among Brigham samples drawn from one individual on 2 occasions separated by median (IQR) 7 (4–14) days was 8.7% (6.2–14). CVs were independent of CKD stage, diabetes, or albuminuria but were higher in patients with systemic lupus erythematosus. Rho correlations between aptamer and traditional assays for biomarkers of interest were cystatin C = 0.942, kidney injury model-1 = 0.905, fibroblast growth factor-23 = 0.541, tumor necrosis factor receptors 1 = 0.781 and 2 = 0.843, P < 10−100 for all. Conclusions Intra-assay and within-subject variability for SomaScan in the CKD setting was low and similar to assay variability reported from individuals without CKD. Intra-assay precision was excellent whether samples were collected in an optimal research protocol, as were CRIC samples, or in the clinical setting, as were the Brigham samples.

The eyelid has four layers: skin and the subcutis, orbicularis oculi muscle, tarsal plates (one in each eyelid) and the conjunctiva. Tumors can arise from any of these and can range from non-neoplastic masses to neoplasms that include benign tumors, premalignant conditions and malignancies. The malignant tumors are of different histologic types depending upon the region and tissue of origin. Malignant tumors, especially basal cell and squamous cell carcinomas, are common in the skin around the eyes. Early detection and treatment are crucial due to the location of the tumors and is cosmetically and functionally important. Eyelid tumors are rare and most ophthalmologists/ pathologists will see only a handful in the course of their career. In this case series, we describe seven cases with different types of eyelid malignancies, the clinical and pathologic features of these patients who presented with various tumors of the eyelid to our tertiary care teaching hospital in coastal India.

Synaptic functions are mimicked in a supramolecular nanofibre device with UV stimulus exhibiting potentiation and plasticity behaviors closely following the Ebbinghaus forgetting and Hebbian rules. A device array serves as a potential visual system.

This study aims to show that four maps in a b-metric space that satisfy pairwise weak compatibility have common fixed points under certain conditions. In the main results of this paper, (CLR) property is employed, and common fixed points for four weakly compatible mappings are established. All our findings are backed up by befitting examples. Our results generalize and extend certain previous findings in the literature.

A novel white light emitting dysprosium doped Na3Ba2LaNb10O30 phosphor, having a good internal quantum yield were synthesized.

Gamma irradiation of Gelatin brings important changes in its chemical structure, making it suitable for different applications. The irradiated Gelatin may be subjected to different thermal treatments during these applications. Therefore, temperature-dependent changes in irradiated gelatins are a point of interest. Electron spin resonance (ESR) is vital for detecting free radical processes in irradiated polymers. As such, ESR spectra of temperature-dependent porcine Gelatin with low bloom are recorded, and they are analyzed by computer simulation techniques. Component spectra under different conditions are evaluated by the magnetic parameters employed to simulate the ESR spectra. The results indicate that the spectral shape at 300 K (RT) is stable up to 350 K, and signal intensity begins to decay beyond 350 K. The signal vanished around 355 K, designated as radical decay temperature. Bloch analysis is applied to evaluate activation energy associated with free radical decay, calculated around 35 KJ/mole.

The Karnataka Multisectoral Nutrition Pilot Project (2015–2018) was implemented in Devadurga Block, Raichur District and Chincholi Block, Gulbarga District—two most backward Blocks in Karnataka. Special interventions for behaviour change and appropriate dietary supplementation for adolescent girls (11–18 years) were implemented through an inter-sectoral, intergenerational strategy. This article analyses real time data regarding thinness/severe thinness among 8,847 adolescent girls in the cross-sectional group and 1,545 adolescent girls in the cohort group. Both BMI-cut-offs method and BMI-for-age Z-score methods provide strong evidence of significant increase in percentage of ‘normal’ adolescent girls from baseline to endline; significant decrease in severe thinness; non-significant decrease/increase in moderate thinness. Data also indicates that while 68.2% of baseline moderately thin girls transitioned to normal category, 71.8% new moderately thin girls (44.3% from improved severely thin girls and 27.5% from normal girls), transitioned into the moderately thin category. Data provides strong evidence that thinness/severe thinness among adolescent girls reduced significantly through project interventions, which are simple to replicate. Tallest girls at baseline, and those gaining fastest height, transitioned to becoming/remaining moderately/severely thin, an area for further research. Further research is required regarding the ideal duration of interventions to improve moderate underweight/thinness to normal status.

Retroperitoneal teratoma is a rare occurrence in neonates. They are usually asymptomatic and the only finding may be abdominal distension. We report an unusual case of a large retroperitoneal teratoma in a neonate who presented with abdominal distension. Imaging done showed a cystic lesion with calcifications, internal septations and fat dense areas. It was successfully managed by surgical excision, findings of which were consistent with that of a mature cystic teratoma. Despite being rare, we must consider retroperitoneal teratomas as a differential diagnosis of an abdominal mass in a newborn. Early detection and complete surgical excision may be life-saving.

Introduction: Early recognition of neonatal hyperbilirubinemia is essential to prevent bilirubin encephalopathy. Transcutaneous bilirubin (TCB) measurement is a simple and easy method to predict neonatal hyperbilirubinemia. We aimed to study the efficacy of TCB as a predictor of subsequent significant neonatal hyperbilirubinemia in low birth neonates and compared the forehead and sternal sites for TCB measurement. Methods: A prospective study was conducted from August to October 2018 at a teaching hospital in South India including term and late preterm neonates weighing < 2.5 kg. The TCB values were obtained from the forehead (TCB-FH) and sternum (TCB-S) by a non-Invasive Bilirubin Analyser. The average of TCB (TCB- AV) was determined for each baby with TCB-FH and TCB –S values. Neonates were followed up subsequently till discharge for the development of significant hyperbilirubinemia. Receiver operating characteristic (ROC) curve was generated and the best cut-off value for 24-hour TCB as a predictor of significant hyperbilirubinemia was established. Results: The study included 88 neonates, of which 39 (44.3%) were late preterm and 49 (55.7%) term small for gestation age. Mean values of TCB –AV 6.25 ± 1.58, TCB – FH 6.24 ± 1.57391, and TCB – S 6.27 ± 1.56 were noted. The cut off value for TCB – AV was found to be 6.85 as a predictor for subsequent neonatal hyperbilirubinemia. TCB – AV was a better predictor than TCB - FH or TCB – S. Conclusions: TCB measurement is an easy and reliable predictor for subsequent significant hyperbilirubinemia in low birth weight neonates. The average of TCB forehead and sternum was a better predictor of significant hyperbilirubinemia.

Background: COVID -19 has wide range of presentation, from asymptomatic infection to severe viral pneumonia and death. D-dimer >1μg/ml is one of the risk factors for mortality. CT chest plays an important role in early detection and monitoring of disease. Objectives: 1. To compare D-dimer value and CT chest findings in Covid-19 patients. 2. To study platelet count, PT, aPTT and CRP in Covid-19 patients. Methodology: RT-PCR confirmed Covid- 19 patients admitted in hospital investigated with D-dimer and CT chest were included in the study. Case details retrieved from medical records. Venous blood collected and plasma processed in coagulation analyser for PT, aPTT, INR and D-dimer. Platelet count was performed using auto analyser. CT findings were retrieved from radiology software (PACS). Statistical tests used were mean, percentage and Fisher’s exact test (SPSS Version 20). Results: During study period of January-June 2021, 38 patients were included. Mean age was 51.1±15.6 years and M:F ratio 2.8:1. 65.8% patients had comorbidities (25/38). D-dimer elevated in 60.5% (23/38) patients. CT showed 10.53%, 28.94%, 60.53% of patients had affected lungs of

Each year, over 300,000 people older than 65 years are hospitalized for hip fractures. Given the notable morbidity and mortality faced by elderly patients in the postinjury period, recommendations have been put forth for integrating palliative and, when needed, hospice care to improve patients' quality of life. Our objective was to (1) understand the proportion of patients discharged to hospice after hip fracture surgery and their 30-day mortality rates and (2) identify the independent predictors of discharge to hospice.We retrospectively queried the American College of Surgeons National Surgical Quality Improvement Program for all hip fracture surgeries between the years of 2016 and 2018. Included cases were stratified into two cohorts: cases involving a discharge to hospice and nonhospice discharge. Variables assessed included patient demographics, comorbidities, perioperative characteristics, and postoperative outcomes. Differences between hospice and nonhospice patients were compared using chi-squared analysis or the Fisher exact test for categorical variables and Student t -tests for continuous variables. A binary logistic regression model was used to assess independent predictors of hospice discharge with 30-day mortality.Overall, 31,531 surgically treated hip fractures were identified, of which only 281 (0.9%) involved a discharge to hospice. Patients discharged to hospice had a 67% 30-day mortality rate in comparison with 5.6% of patients not discharged to hospice ( P0.001). Disseminated cancer, dependent functional status,10% weight loss over 6 months preoperatively, and preoperative cognitive deficit were the strongest predictors of hospice discharge with 30-day mortality after hip fracture surgery.Current hospice utilization in hip fracture patients remains low, but 30-day mortality in these patients is high. An awareness of the associations between patient characteristics and discharge to hospice with 30-day mortality is important for surgeons to consider when discussing postoperative expectations and outcomes with these patients.Level III, retrospective comparative study.

Temesgen Sidamo,1 Prakruti S Rao,2 Eleni Aklillu,3 Workineh Shibeshi,1 Yumi Park,4,5 Yong-soon Cho,4,5 Jae-Gook Shin,4,5 Scott K Heysell,2 Stellah G Mpagama,6 Ephrem Engidawork1 1Department of Pharmacology and Clinical Pharmacy, School of Pharmacy, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia; 2Division of Infectious Diseases and International Health, University of Virginia, Charlottesville, VA, USA; 3Department of Laboratory of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden; 4Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Busan, Republic of Korea; 5Center for Personalized Precision Medicine of Tuberculosis (cPMTb), Inje University College of Medicine, Busan, Republic of Korea; 6Kibong’oto Infectious Diseases Hospital, Sanya Juu, TanzaniaCorrespondence: Ephrem Engidawork, Department of Pharmacology and Clinical Pharmacy, School of Pharmacy, College of Health Sciences, Addis Ababa University, P.O. Box 9086, Addis Ababa, Ethiopia, Email ephrem.engidawork@aau.edu.etObjective: This study aimed to explore the population pharmacokinetic modeling (PopPK) of levofloxacin (LFX) and moxifloxacin (MXF), as well as the percent probability of target attainment (PTA) as defined by the ratio of the area under the plasma concentration-time curve over 24 h and the in vitro minimum inhibitory concentration (AUC0-24/MIC) in Ethiopian multidrug resistant tuberculosis (MDR-TB) patients.Methods: Steady state-plasma concentration of the drugs in MDR-TB patients were determined using optimized liquid chromatography-tandem mass spectrometry. PopPK and simulations were run at various doses, and pharmacokinetic parameters were estimated. The effect of covariates on the PK parameters and PTA for maximum mycobacterial kill and resistance prevention was also investigated.Results: LFX and MXF both fit in a one-compartment model with adjustments. Serum-creatinine (Cr) influenced (p = 0.01) the clearance of LFX, whereas body mass index (BMI) influenced (p = 0.01) the apparent volume of distribution (V) of MXF. The PTA for LFX maximal mycobacterial kill at the critical MIC of 0.5 mg/L with the simulated 750 mg, 1000 mg, and 1500 mg doses were 29%, 62%, and 95%, respectively, whereas the PTA for resistance prevention at 1500 mg was only 4.8%, with none of the lower doses achieving this target. At the critical MIC of 0.25 mg/L, there was no change in the PTA for maximum bacterial kill when the MXF dose was increased (600 mg, 800 mg, and 1000 mg), but the PTA for resistance prevention was improved.Conclusion: The standard doses of LFX and MXF may not provide adequate drug exposure. PopPK of LFX is more predictable for maximum mycobacterial kill, whereas MXF’s resistance prevention target increases with dose. Cr and BMI are likely important covariates for dose optimization in Ethiopian patients.Keywords: population pharmacokinetics, probability of target attainment, moxifloxacin, levofloxacin, MDR-TB patients, Ethiopia

Traumatic brain injury (TBI) remains a leading cause of mortality and morbidity in young adults. The role of iron in potentiating neurodegeneration following TBI has gained recent interest as iron deposition has been detected in the injured brain in the weeks to months post-TBI, in both the preclinical and clinical setting. A failure in iron homeostasis can lead to oxidative stress, inflammation and excitotoxicity; and whether this is a cause or consequence of the long-term effects of TBI remains unknown.We investigated the role of iron and the effect of therapeutic intervention using a brain-permeable iron chelator, deferiprone, in a controlled cortical impact mouse model of TBI. An extensive assessment of cognitive, motor and anxiety/depressive outcome measures were examined, and neuropathological and biochemical changes, over a 3-month period post-TBI.Lesion volume was significantly reduced at 3 months, which was preceded by a reduction in astrogliosis, microglia/macrophages and preservation of neurons in the injured brain at 2 weeks and/or 1 month post-TBI in mice receiving oral deferiprone. Deferiprone treatment showed significant improvements in neurological severity scores, locomotor/gait performance and cognitive function, and attenuated anxiety-like symptoms post-TBI. Deferiprone reduced iron levels, lipid peroxidation/oxidative stress and altered expression of neurotrophins in the injured brain over this period.Our findings support a detrimental role of iron in the injured brain and suggest that deferiprone (or similar iron chelators) may be promising therapeutic approaches to improve survival, functional outcomes and quality of life following TBI.

Background: Typically, oxytocin is used to induce uterine contractions during caesarean delivery. The intravenous administration of oxytocin is known to have negative side effects, including tachycardia, hypotension, and alterations in electrocardiograms (EKGs), which can be harmful in high-risk patients. In this study, we contrasted the outcomes of two oxytocin dosages. Methods: A total of 70 patients—35 in each group—were receiving an I.V. bolus of 2 or 5 units of oxytocin while undergoing elective caesarean sections under spinal anaesthesia. An hourly infusion of ve units of oxytocin was then administered. Evaluation of uterine tone, the need for further uterotonic drugs, changes in hemodynamics, and adverse pharmacological effects were compared between the two groups. Results: The two groups' patients had similar characteristics. At two minutes, uterine tone ratings remained similar. The difference between the two groups at the fth minute was statistically signicant. At the fth minute, there was a substantial change in the clinically acceptable uterine tone measured over the entire trial time. At the rst minute, the percentage rise in the mean maternal HR was observed to differ signicantly (p=0.002). No signicant difference in maternal tachycardia existed across the groups. When the systolic blood pressure was compared to the baseline at 1, 2, 3, 4, 15, 18, and 21 minutes, there was a discernible difference in the percent drop. There was a noticeable difference in the diastolic blood pressure during the entire trial period. Only few cases had side effects like nausea and vomiting, there was no appreciable difference. Conclusion: In healthy adult women having an elective caesarean section, a 2-unit oxytocin bolus followed by an infusion of 5 units per hour had a positive effectiveness and safety prole.

bstract: Optical Character Recognition (OCR) is the electronic conversion of images of typed, handwritten or printed text into machine encoded text, whether from scanned document, a photo of a document, a scene photo. The Optical Character Recognition is emerging as a useful technology for data entry, digital data storage and as an aid to visually impaired people. The Devanagari script is composed of 47 primary characters including 14 vowels and 33 consonants. It is fourth most widely adopted writing system in the world being used for 120 languages. Convolution Neural Network (CNN) are a specialized type of artificial neural networks that use a mathematical operation called convolution in place of general matrix multiplication in at least one of their layers. They are specifically designed to process pixel data and are used in

>Objective: To study the hepatoprotective activity of 3 Ca++ channel blockers namely felodipine (FEL), lercanidipine (LER), and isradipine (ISR) with three selected doses i.e; 1/4th TD, 1/2nd TD, and TD in paracetamol (PCM) and alcohol (ALC)-induced hepatotoxicity in rats both at preventing and curative aspects. Further, it was also reported that PCM and ALC producing hepatotoxicity by facilitating accumulation of excess Ca++ in hepatocyte. Ca++ channel blockers block the entry of Ca++ into the cells. Hence the present study is planned to evaluate the hepatoprotective activity of Ca++ channel blockers in the above-mentioned models. Materials and Methods: In rats, the hepatoprotective activity of Ca++ channel blockers is evaluated in PCM (2 g/Kg) and ALC (3.76 g/Kg) induced hepatotoxic models. Thiopental-induced sleeping time (TST), physical parameters like liver weight and liver volume, and biochemical parameters like alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum alkaline phosphatase (ALP), serum direct bilirubin (BILD), serum total bilirubin (BILT), serum albumin (ALB), and serum total proteins (PRO), were estimated by Erba chem. Standard reference SIL produced significant hepatoprotective activity. Results: All three drugs significantly reduced liver weight to 6.07, 4.87, 5.51, 4.28, 6.10, and 5.02 g, respectively. Three drugs produced a significant reduction in liver volume noted as 6.03, 4.83, 5.45, 4.23, 6.05, and 4.96 mL, respectively, in paracetamol-induced hepatotoxicity. All three drugs significantly reduced liver weight, as 6.42, 5.65, 6.66, 6.34, 5.30, and 5.85 g, respectively. A significant reduction in liver volume was noted at 6.35, 5.53, 6.23, 5.18, and 5.80 mL, respectively, in alcohol-induced hepatotoxicity. Conclusion: Ca++ channel blockers too at three different doses at preventive and curative aspects produced a significant hepatoprotective activity in PCM and ALC-induced hepatotoxic models..

Managing the composition of the bacterial communities in the digestive tract with the use of probiotics that enhance protective microflora could result in positive effects on health and performance of calves. The objective of this study was to evaluate a 2-step probiotic program (added to colostrum and milk) on the digestive health and growth of preweaning Holstein heifers. A randomized clinical trial was conducted from July to October 2020 in a calf rearing facility in Colorado. Calves were housed in pairs sharing the same treatment in 2 polyethylene hutches within a common area of 4.50 m

Human African Trypanosomiasis (HAT) is a vector-borne disease caused by kinetoplastid parasites of the Trypanosoma genus. The disease proceeds in two stages, with a hemolymphatic blood stage and a meningo-encephalic brain stage. In the latter stage, the parasite causes irreversible damage to the brain leading to sleep cycle disruption and is fatal if untreated. An orally bioavailable treatment is highly desirable. In this study, we present a brain-penetrant, parasite-selective 20S proteasome inhibitor that was rapidly optimized from an HTS singleton hit to drug candidate compound 7 that showed cure in a stage II mouse efficacy model. Here, we describe hit expansion and lead optimization campaign guided by cryo-electron microscopy and an in silico model to predict the brain-to-plasma partition coefficient Kp as an important parameter to prioritize compounds for synthesis. The model combined with in vitro and in vivo experiments allowed us to advance compounds with favorable unbound brain-to-plasma ratios (Kp,uu) to cure a CNS disease such as HAT.