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Authors: R. U. Hamzah, H. L. Muhammad, A. Sayyadi, M. B Busari, R. Garba, M. B. Umar, A. N Abubakar

Abstract:

Lead (Pb) and Cadmium (Cd) are toxic, non-essential transition metals that pose many health risks for both humans and animals. They are environmental toxicants which contribute to testicular damage resulting to infertility problem among male populace worldwide. Chelating agents used for lead and cadmium toxicity are not readily available, toxic, expensive and unable to mop up most of the toxic metals accumulated in various organs. In this study, the effect of crude extract (CE), ethyl acetate fraction (EF) and acetone fraction (AF) of Pterocarpus mildbraedii leaf extract was assessed on cadmium-lead chloride induced testicular damaged in male albino Wistar rats. CE of the leaf was obtained by extracting in absolute methanol which was further subjected to solvent partitioning via vacuum liquid chromatographic (VLC) techniques using ethyl acetate, acetone and 70% methanol. A preliminary phytochemical screening and in vitro antioxidants guided activities on the CE and fractions were determined using standard methods. EF, AF and CE which exhibited significant in vitro activity were subjected to an in vivo study using Wistar rats. In vivo antioxidant markers, male reproductive hormones, testicular enzymes and DNA damage markers were analyzed on the rats’ testes supernatant. AF had the highest quantities of phenols (319.00 mg/g), flavonoids (8.87 mg/g) and tannins (8.87 mg/g) while methanol and EFs were richer in saponins (135.32 µg/g) and alkaloids (38.34 µg/g) respectively. A dose dependent 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, ferric reducing antioxidant power (FRAP) and lipid peroxidation were observed in all the extract with high antioxidants power in CE and AF. Administration of lead-cadmium chloride solution significantly (p > 0.05) decreases the testicular superoxide dismutase (SOD) activity to 6.82 unit/mg protein, Catalase (CAT) activity to 8.07 of H2O2 consumed/unit/mg protein and Glutathione (GSH) concentration to 31.30 ug/mg protein. There was a concomitant increase in the level of Malondialdehyde (MDA) to a value of 23.70 mmol/mg protein. In addition, lead-cadmium chloride solution significantly (p > 0.05) increases the testicular marker enzymes (Alkaline phosphatase (119.57 u/L), lactate dehydrogenase (357.05 u/L), Acid phosphatase (98.65 u/L)) and DNA damage markers (conjugated dienes (93.39 nmol/mg protein), carbonyl protein (35.39 nmol/mg protein), DNA fragmentation percentage (32.12%)) with lowered testicular hormones (Testosterone (3.1 ng/mL), Follicle stimulating (0.35 IU/mL) and Luteinizing hormones (0.15 IU/mL)) of the animals in negative control group when compared with other treated groups. Treatment with Pterocarpus mildbraedii leaf extract reverts the observed changes with the best activities found in the CE and AFs in a dose dependent manner. Pterocarpus mildbraedii leaf extract ameliorated the lead/cadmium induced testicular damage in male albino rats. The restoration of the aforementioned parameters by some of the extract dosages were comparable to the standard drug with higher activities in the crude and AF. Therefore, Pterocarpus mildbraedii leaf extract can be explored further for the management of lead/cadmium induced toxicity.

Keywords: Cadmium, lead, Pterocarpus mildbraedii, testicular damage.

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Authors: Sotirios Raptis

Abstract:

Health and Social care (HSc) services planning and scheduling are facing unprecedented challenges, due to the pandemic pressure and also suffer from unplanned spending that is negatively impacted by the global financial crisis. Data-driven approaches can help to improve policies, plan and design services provision schedules using algorithms that assist healthcare managers to face unexpected demands using fewer resources. The paper discusses services packing using statistical significance tests and machine learning (ML) to evaluate demands similarity and coupling. This is achieved by predicting the range of the demand (class) using ML methods such as Classification and Regression Trees (CART), Random Forests (RF), and Logistic Regression (LGR). The significance tests Chi-Squared and Student’s test are used on data over a 39 years span for which data exist for services delivered in Scotland. The demands are associated using probabilities and are parts of statistical hypotheses. These hypotheses, as their NULL part, assume that the target demand is statistically dependent on other services’ demands. This linking is checked using the data. In addition, ML methods are used to linearly predict the above target demands from the statistically found associations and extend the linear dependence of the target’s demand to independent demands forming, thus, groups of services. Statistical tests confirmed ML coupling and made the prediction statistically meaningful and proved that a target service can be matched reliably to other services while ML showed that such marked relationships can also be linear ones. Zero padding was used for missing years records and illustrated better such relationships both for limited years and for the entire span offering long-term data visualizations while limited years periods explained how well patients numbers can be related in short periods of time or that they can change over time as opposed to behaviours across more years. The prediction performance of the associations were measured using metrics such as Receiver Operating Characteristic (ROC), Area Under Curve (AUC) and Accuracy (ACC) as well as the statistical tests Chi-Squared and Student. Co-plots and comparison tables for the RF, CART, and LGR methods as well as the p-value from tests and Information Exchange (IE/MIE) measures are provided showing the relative performance of ML methods and of the statistical tests as well as the behaviour using different learning ratios. The impact of k-neighbours classification (k-NN), Cross-Correlation (CC) and C-Means (CM) first groupings was also studied over limited years and for the entire span. It was found that CART was generally behind RF and LGR but in some interesting cases, LGR reached an AUC = 0 falling below CART, while the ACC was as high as 0.912 showing that ML methods can be confused by zero-padding or by data’s irregularities or by the outliers. On average, 3 linear predictors were sufficient, LGR was found competing well RF and CART followed with the same performance at higher learning ratios. Services were packed only when a significance level (p-value) of their association coefficient was more than 0.05. Social factors relationships were observed between home care services and treatment of old people, low birth weights, alcoholism, drug abuse, and emergency admissions. The work found  that different HSc services can be well packed as plans of limited duration, across various services sectors, learning configurations, as confirmed by using statistical hypotheses.

Keywords: Class, cohorts, data frames, grouping, prediction, probabilities, services.

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