Search results for: drug withdrawal.

Authors: Ching - Yi Lee, I-Hsiung Tseng, Feng-Chuan Pan

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Environment today is featured with aging population, increasing prevalence of chronic disease and complex of medical treatment. Safe use of pharmaceutics relied very much on the efforts made by both the health- related organizations and as well as the government agencies. As far as the specialization concern in providing health services to the patients, the government actively issued and implemented the divisions of medical treatment and pharmaceutical to improve the quality of care and to reduce medication errors and ensure public health. Pharmaceutical sub-sector policy has been implemented for 13 years. This study attempts to explore the factors that affect the patients- behavior intention of refilling a prescription from a NHIB pharmacy. Samples were those patients refilling their prescriptions with the case NHIB pharmacies. A self-administered questionnaire was used to collect respondents- information while the patients or family members visit the pharmacy for the refilling. 1,200 questionnaires were dispatched in 37 pharmacies that randomly selected from Pingtung City, Dongkang, Chaozhou, Hengchun areas. 732 responses were gained with 604 valid samples for further analyses. Results of data analyses indicated that respondents- attitude, subjective norm, perceived behavior control and behavior intentions toward refilling behavior varied from some demographic variables to another. This research also suggested adding actual behavior, either by a self-report or observed, into the research.

Keywords: Separation of dispensing and prescribing, prescriptions refill slip, NHIB contracted pharmacy, drug safety, theory of planned behavior.

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Authors: Mohd. A. M. Rahim, Yahaya Hassan, Mathumalar L. Fahrni

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Second line antiretroviral therapy (ART) regimen is used when patients fail their first line regimen. There are many factors such as non-adherence, drug resistance as well as virological and immunological failure that lead to second line highly active antiretroviral therapy (HAART) regimen treatment failure. This study was aimed at determining predictor factors to treatment failure with second line HAART and analyzing median survival time. An observational, retrospective study was conducted in Sungai Buloh Hospital (HSB) to assess current status of HIV patients treated with second line HAART regimen. Convenience sampling was used and 104 patients were included based on the study’s inclusion and exclusion criteria. Data was collected for six months i.e. from July until December 2013. Data was then analysed using SPSS version 18. Kaplan-Meier and Cox regression analyses were used to measure median survival times and predictor factors for treatment failure. The study population consisted mainly of male subjects, aged 30- 45 years, who were heterosexual, and had HIV infection for less than 6 years. The most common second line HAART regimen given was lopinavir/ritonavir (LPV/r)-based combination. Kaplan-Meier analysis showed that patients on LPV/r demonstrated longer median survival times than patients on indinavir/ritonavir (IDV/r) based combination (p<0.001). The commonest reason for a treatment to fail with second line HAART was non-adherence. Based on Cox regression analysis, other predictor factors for treatment failure with second line HAART regimen were age and mode of HIV transmission.

Keywords: Adherence, antiretroviral therapy, second line, treatment failure.

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Authors: Arash Taheri, Meysam Mohammadi-Amin, Seyed Hossein Moosavy

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Medical applications are among the most impactful areas of microrobotics. The ultimate goal of medical microrobots is to reach currently inaccessible areas of the human body and carry out a host of complex operations such as minimally invasive surgery (MIS), highly localized drug delivery, and screening for diseases at their very early stages. Miniature, safe and efficient propulsion systems hold the key to maturing this technology but they pose significant challenges. A new type of propulsion developed recently, uses multi-flagella architecture inspired by the motility mechanism of prokaryotic microorganisms. There is a lack of efficient methods for designing this type of propulsion system. The goal of this paper is to overcome the lack and this way, a numerical strategy is proposed to design multi-flagella propulsion systems. The strategy is based on the implementation of the regularized stokeslet and rotlet theory, RFT theory and new approach of “local corrected velocity". The effects of shape parameters and angular velocities of each flagellum on overall flow field and on the robot net forces and moments are considered. Then a multi-layer perceptron artificial neural network is designed and employed to adjust the angular velocities of the motors for propulsion control. The proposed method applied successfully on a sample configuration and useful demonstrative results is obtained.

Keywords: Artificial Neural Network, Biomimetic Microrobots, Flagellar Propulsion, Swimming Robots.

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Authors: E. M. Vieira, C. S. Vieira, L. P. Bonifácio, L. M. de Oliveira Ciabati, A. C. A. Franzon, F. S. Zaratini, J. A. C. Sanchez, M. S. Andrade, J. P. Dias de Souza

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The quality of prenatal care is key to reduce maternal morbidity and mortality. Communication between the health service and users can stimulate prevention and care. M-health has been an important and low cost strategy to health education. The PRENACEL programme (prenatal in the cell phone) was developed. It consists of a programme of information via SMS from the 20^th week of pregnancy up to 12^th week after delivery. Messages were about prenatal care, birth, contraception and breastfeeding. Communication of the pregnant woman asking questions about their health was possible. The objective of this study was to evaluate the implementation of PRENACEL as a useful complement to the standard prenatal care. Twenty health clinics were selected and randomized by cluster, 10 as the intervention group and 10 as the control group. In the intervention group, women and their partner were invited to participate. The control group received the standard prenatal care. All women were interviewed in the immediate post-partum and in the 12^th and 24^th week post-partum. Most women were married, had more than 8 years of schooling and visit the clinic more than 6 times during prenatal care. The intervention group presented lowest percentage of higher economic participants (5.6%), less single mothers and no drug user. It also presented more prenatal care visits than the control group and it was less likely to present Severe Acute Maternal Mortality when compared to control group as well as higher percentage of partners (75.4%) was present at the birth compared to control group. Although the study is still being carried out, preliminary data are showing positive results of the compliance of women to prenatal care.

Keywords: Cellphone, health technology, prenatal care, prevention.

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Authors: Sarunyoo Songkro, Naranut Rajatasereekul, Nipapat Cheewasrirungrueng

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The aim of the present study was to evaluate the mucoadhesion and the release of nicotinamide gel formulations using in vitro methods. An agar plate technique was used to investigate the adhesiveness of the gels whereas a diffusion apparatus was employed to determine the release of nicotinamide from the gels. In this respect, 10% w/w nicotinamide gels containing bioadhesive polymers: Carbopol 934P (0.5-2% w/w), hydroxypropylmethyl cellulose (HPMC) (4-10% w/w), sodium carboxymethyl cellulose (SCMC) (4-6% w/w) and methylcellulose 4000 (MC) (3-5% w/w) were prepared. The gel formulations had pH values in the range of 7.14 - 8.17, which were considered appropriate to oral mucosa application. In general, the rank order of pH values appeared to be SCMC > MC4000 > HPMC > Carbopol 934P. Types and concentrations of polymers used somewhat affected the adhesiveness. It was found that anionic polymers (Carbopol 934 and SCMC) adhered more firmly to the agar plate than the neutral polymers (HPMC and MC 4000). The formulation containing 0.5% Carbopol 934P (F1) showed the highest release rate. With the exception of the formulation F1, the neutral polymers tended to give higher relate rates than the anionic polymers. For oral tissue treatment, the optimum has to be balanced between the residence time (adhesiveness) of the formulations and the release rate of the drug. The formulations containing the anionic polymers: Carbopol 934P or SCMC possessed suitable physical properties (appearance, pH and viscosity). In addition, for anionic polymer formulations, justifiable mucoadhesive properties and reasonable release rates of nicotinamide were achieved. Accordingly, these gel formulations may be applied for the treatment of oral mucosal lesions.

Keywords: Nicotinamide, bioadhesive polymer, mucoadhesiveness, release rate, gel.

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Authors: S. Jaramillo, Y. Montoya, W. Agudelo, J. Bustamante

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Cardiovascular diseases (CVD) are related to affectations of the heart and blood vessels, within these are pathologies such as coronary or peripheral heart disease, caused by the narrowing of the vessel wall (atherosclerosis), which is related to the accumulation of Low-Density Lipoproteins (LDL) in the arterial walls that leads to a progressive reduction of the lumen of the vessel and alterations in blood perfusion. Currently, the main therapeutic strategy for this type of alteration is drug treatment with statins, which inhibit the enzyme 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA reductase), responsible for modulating the rate of cholesterol production and other isoprenoids in the mevalonate pathway. This enzyme induces the expression of LDL receptors in the liver, increasing their number on the surface of liver cells, reducing the plasma concentration of cholesterol. On the other hand, when the blood vessel presents stenosis, a surgical procedure with vascular implants is indicated, which are used to restore circulation in the arterial or venous bed. Among the materials used for the development of vascular implants are Dacron® and Teflon®, which perform the function of re-waterproofing the circulatory circuit, but due to their low biocompatibility, they do not have the ability to promote remodeling and tissue regeneration processes. Based on this, the present research proposes the development of a hydrolyzed collagen and polyethylene oxide electrospun membrane reinforced with medium and high-intensity statins, so that in future research it can favor tissue remodeling processes from its microarchitecture.

Keywords: atherosclerosis, medium and high-intensity statins, microarchitecture, electrospun membrane

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Authors: M. Sangeetha, D. Chamundeeswari, C. Saravanababu, C. Rose, V. Gopal

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Rheumatoid arthritis (RA) is a chronic, progressive, systemic inflammatory disorder affecting the synovial joints and typically producing symmetrical arthritis that leads to joint destruction, which is responsible for the deformity and disability. Despite improvements in the treatment of RA over the past decade, there still is a need for new therapeutic agents that are efficacious, less expensive, and free of severe adverse reactions. The present study aimed to investigate role of inflammatory markers in arthritic rats treated with ethanolic bark extract of Albizia procera. The protective effect of ethanolic bark extract of Albizia procera against complete Freund’s adjuvant (CFA) induced arthritis in rats. Arthritis was induced by an intradermal injection of 0.1 ml FCA in the foot pad of left hind limb of rats. ETBE (100 and 200 mg/kg b.wt./p.o) and the reference drug diclofenac (25 mg/kg b.wt./p.o) were administered to arthritic rats. Paw volume was measured for all the animals before inducing arthritis and thereafter once in seven days by using plethysmometer for 42 days. Gene expression of inflammatory markers such as IL-1β and IL-10 were investigated in paw tissues. Up regulation of IL-1β and Down regulation IL-10 were observed in CFA injected rats when compared to normal rats. ETBE attenuated these alterations dose dependently when compared to the vehicle treated rats. These results provide insights into the mechanism of anti-arthritic activity, and unravel potential therapeutic use of Albizia procera in arthritis.

Keywords: CFA-Complete Freund’s adjuvant, ETBE, Ethanolic Bark Extract, IL- Interleukins, RA-Rheumatoid Arthritis.

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Authors: Khalid Pervaiz Akhter, Mahmood Ahmad, Ghulam Murtaza, Ishrat Shafi, Zafar Javed

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The objective of this manuscript is to find area under the plasma concentration- time curve (AUC) for multiple doses of salbutamol sulphate sustained release tablets (Ventolin® oral tablets SR 8 mg, GSK, Pakistan) in the group of 18 healthy adults by using computational mathematics techniques. Following the administration of 4 doses of Ventolin® tablets 12 hourly to 24 healthy human subjects and bioanalysis of obtained plasma samples, plasma drug concentration-time profile was constructed. AUC, an important pharmacokinetic parameter, was measured using integrated equation of multiple oral dose regimens. The approximated AUC was also calculated by using computational mathematics techniques such as repeated rectangular, repeated trapezium and repeated Simpson's rule and compared with exact value of AUC calculated by using integrated equation of multiple oral dose regimens to find best computational mathematics method that gives AUC values closest to exact. The exact values of AUC for four consecutive doses of Ventolin® oral tablets were 150.5819473, 157.8131756, 164.4178231 and 162.78 ng.h/ml while the closest values approximated AUC values were 149.245962, 157.336171, 164.2585768 and 162.289224 ng.h/ml, respectively as found by repeated rectangular rule. The errors in the approximated values of AUC were negligible. It is concluded that all computational tools approximated values of AUC accurately but the repeated rectangular rule gives slightly better approximated values of AUC as compared to repeated trapezium and repeated Simpson's rules.

Keywords: Salbutamol sulphate, Area under curve (AUC), repeated rectangular rule, repeated trapezium rule, repeated Simpson's rule.

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Authors: Siti Nor Hafizah binti Mohd Zaid, Mohamed Abdel-Maguid, Abdel-Hamid Soliman

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An Advance Driver Assistance System (ADAS) is a computer system on board a vehicle which is used to reduce the risk of vehicular accidents by monitoring factors relating to the driver, vehicle and environment and taking some action when a risk is identified. Much work has been done on assessing vehicle and environmental state but there is still comparatively little published work that tackles the problem of driver state. Visual attention is one such driver state. In fact, some researchers claim that lack of attention is the main cause of accidents as factors such as fatigue, alcohol or drug use, distraction and speeding all impair the driver-s capacity to pay attention to the vehicle and road conditions [1]. This seems to imply that the main cause of accidents is inappropriate driver behaviour in cases where the driver is not giving full attention while driving. The work presented in this paper proposes an ADAS system which uses an image based template matching algorithm to detect if a driver is failing to observe particular windscreen cells. This is achieved by dividing the windscreen into 24 uniform cells (4 rows of 6 columns) and matching video images of the driver-s left eye with eye-gesture templates drawn from images of the driver looking at the centre of each windscreen cell. The main contribution of this paper is to assess the accuracy of this approach using Receiver Operating Characteristic analysis. The results of our evaluation give a sensitivity value of 84.3% and a specificity value of 85.0% for the eye-gesture template approach indicating that it may be useful for driver point of regard determinations.

Keywords: Advanced Driver Assistance Systems, Eye-Tracking, Hazard Detection.

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Authors: Surender Singh Jadav, Venkatesan Jayaprakash, Arijit Basu, Barij Nayan Sinha

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Chikungunya virus (CHICKV) is an arboviruses belonging to family Tagoviridae and is transmitted to human through by mosquito (Aedes aegypti and Aedes albopictus) bite. A large outbreak of chikungunya has been reported in India between 2006 and 2007, along with several other countries from South-East Asia and for the first time in Europe. It was for the first time that the CHICKV outbreak has been reported with mortality from Reunion Island and increased mortality from Asian countries. CHICKV affects all age groups, and currently there are no specific drugs or vaccine to cure the disease. The need of antiviral agents for the treatment of CHICKV infection and the success of virtual screening against many therapeutically valuable targets led us to carry out the structure based drug design against Chikungunya nSP2 protease (PDB: 3TRK). Highthroughput virtual screening of publicly available databases, ZINC12 and BindingDB, has been carried out using the Openeye tools and Schrodinger LLC software packages. Openeye Filter program has been used to filter the database and the filtered outputs were docked using HTVS protocol implemented in GLIDE package of Schrodinger LLC. The top HITS were further used for enriching the similar molecules from the database through vROCS; a shape based screening protocol implemented in Openeye. The approach adopted has provided different scaffolds as HITS against CHICKV protease. Three scaffolds: Indole, Pyrazole and Sulphone derivatives were selected based on the docking score and synthetic feasibility. Derivatives of Pyrazole were synthesized and submitted for antiviral screening against CHICKV.

Keywords: Chikungunya, nsP2 protease, ADME filter, HTVS, Docking, Active site.

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Authors: Sadegh Lotfieblisofla, Arash Khodabakhshi

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Tissue plasminogen activator (tPA) as a serine protease plays an important role in the fibrinolytic system and the dissolution of fibrin clots in human body. The production of this drug in plants such as tobacco could reduce its production costs. In this study, expression of tPA gene and protein targeting to different plant cell compartments, using various signal peptides has been investigated. For high level of expression, Kozak sequence was used after CaMV35S in the beginning of the gene. In order to design the final construction, Extensin, KDEL (amino acid sequence including Lys-Asp-Glu-Leu) and SP (γ-zein signal peptide coding sequence) were used as leader signals to conduct this protein into apoplast, endoplasmic reticulum and cytosol spaces, respectively. Cloned human tPA gene under the CaMV (Cauliflower mosaic virus) 35S promoter and NOS (Nopaline Synthase) terminator into pBI121 plasmid was transferred into tobacco explants by Agrobacterium tumefaciens strain LBA₄₄₀₄. The presence and copy number of genes in transgenic tobacco was proved by Southern blotting. Enzymatic activity of the rt-PA protein in transgenic plants compared to non-transgenic plants was confirmed by Zymography assay. The presence and amount of rt-PA recombinant protein in plants was estimated by ELISA analysis on crude protein extract of transgenic tobacco using a specific antibody. The yield of recombinant tPA in transgenic tobacco for SP, KDEL, Extensin signals were counted 0.50, 0.68, 0.69 microgram per milligram of total soluble proteins.

Keywords: Recombinant tissue plasminogen activator, plant cell comportment, leader signals, transgenic tobacco.

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Authors: Syarifah Abd Rahim, Fatinah Ab Rahman, Engku N. E. M. Nasir, Noor A. Ramle

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Co-crystal is believed to improve the solubility and dissolution rates and thus, enhanced the bioavailability of poor water soluble drugs particularly during the oral route of administration. With the existing of poorly soluble drugs in pharmaceutical industry, the screening of co-crystal formation using carbamazepine (CBZ) as a model drug compound with dicarboxylic acids co-crystal formers (CCF) namely fumaric (FA) and succinic (SA) acids in ethanol has been studied. The co-crystal formations were studied by varying the mol ratio values of CCF to CBZ to access the effect of CCF concentration on the formation of the co-crystal. Solvent evaporation, slurry and cooling crystallization which representing the solution based method co-crystal screening were used. Based on the differential scanning calorimetry (DSC) analysis, the melting point of CBZ-SA in different ratio was in the range between 188oC-189oC. For CBZ-FA form A and CBZ-FA form B the melting point in different ratio were in the range of 174oC-175oC and 185oC-186oC respectively. The product crystal from the screening was also characterized using X-ray powder diffraction (XRPD). The XRPD pattern profile analysis has shown that the CBZ co-crystals with FA and SA were successfully formed for all ratios studied. The findings revealed that CBZ-FA co-crystal were formed in two different polymorphs. It was found that CBZ-FA form A and form B were formed from evaporation and slurry crystallization methods respectively. On the other hand, in cooling crystallization method, CBZ-FA form A was formed at lower mol ratio of CCF to CBZ and vice versa. This study disclosed that different methods and mol ratios during the co-crystal screening can affect the outcome of co-crystal produced such as polymorphic forms of co-crystal and thereof. Thus, it was suggested that careful attentions is needed during the screening since the co-crystal formation is currently one of the promising approach to be considered in research and development for pharmaceutical industry to improve the poorly soluble drugs.

Keywords: Carbamazepine, co-crystal, co-crystal former, dicarboxylic acid.

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Authors: Lubna M. Zakaryia Mahmoud, Mohammed A. Dawood, Doaa A. Heiba

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A prospective double-blind placebo controlled trial carried out on 60 children known to be asthmatic who presented to the emergency department at Alexandria University of Children’s Hospital at El-Shatby with acute asthma exacerbations to assess the efficacy of adding inhaled magnesium sulfate to β-agonist, compared with β-agonist in saline, in the management of acute asthma exacerbations in children. The participants in the study were divided in two groups; Group A (study group) received inhaled salbutamol solution (0.15 ml/kg) plus isotonic magnesium sulfate 2 ml in a nebulizer chamber. Group B (control group): received nebulized salbutamol solution (0.15 ml/kg) diluted with placebo (2 ml normal saline). Both groups received inhaled solution every 20 minutes that was repeated for three doses. They were evaluated using the Pediatric Asthma Severity Score (PASS), oxygen saturation using portable pulse oximetry and peak expiratory flow rate using a portable peak expiratory flow meter at initially recorded as zero-minute assessment and every 20 minutes from the end of each nebulization (nebulization lasts 5-10 minutes) recorded as 20, 40 and 60-minute assessments. Regarding PASS, comparison showed non-significant difference with p-value 0.463, 0.472, 0.0766 at 20, 40 and 60 minutes. Regarding oxygen saturation, improvement was more significant towards group A starting from 40 min with significant p-value=0.000. At 60 min p-value=0.000. Although mean PEFR significantly improved from zero-min in both groups; however, improvement was more significant in group A with significant p-value = 0.015, 0.001, 0.001 at 20 min, 40 min and 60 min, respectively. The conclusion this study suggests is that inhaled magnesium sulfate is an efficient add on drug to standard β- agonist inhalation used in the treatment of moderate to severe asthma exacerbations.

Keywords: Nebulized, magnesium sulfate, acute asthma, pediatric.

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Authors: Nassima Elyebdri, Asma Boumediou, Soumia Addoun

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Traditional medicine has been part of the Algerian culture for decades. In particular, the city of Tlemcen still retains practices based on phytotherapy to the present day, as this kind of medicine fulfills the needs of its followers among the local population. The toxic plants contain diverse natural substances which supplied a lot of medicine in the pharmaceutical industry. In order to explore new medicinal sources among toxic plants, an ethnobotanical study was carried out on the use of these plants by the population, at Emir Abdelkader Square of the city of Tlemcen, a rather busy place with a high number of traditional health practitioners and herbalists. This is a descriptive and transversal study aimed at estimating the frequency of using toxic plants among the studied population, for a period of 4 months. The information was collected, using self-anonymous questionnaires, and analyzed by the IBM SPSS Statistics software used for statistical analysis. A sample of 200 people, including 120 women and 80 men, were interviewed. The mean age was 41 ± 16 years. Among those questioned, 83.5% used plants; 8% of them used toxic plants and 35% used plants that can be toxic under certain conditions. Some improvements were observed in 88% of the cases where toxic plants were used. 80 medicinal plants, belonging to 36 botanical families, were listed, identified and classified. The most frequent indications for these plants were for respiratory diseases in 64.7% of cases, and for digestive disorders in 51.5% of cases. 11% of these plants are toxic, 26% could be toxic under certain conditions. Among toxics plants, the most common ones are Berberis vulgaris with 5.4%, indicated in the treatment of uterine fibroids and thyroid, Rhamnus alaternus with 4.8% for hepatic jaundice, Nerium oleander with 3% for hemorrhoids, Ruta chalepensis with 1.2%, indicated for digestive disorders and dysmenorrhea, and Viscum album with 1.2%, indicated for respiratory diseases. The most common plants that could be toxic are Mentha pulegium (15.6%), Eucalyptus globulus (11.4%), and Pimpinella anisum (10.2%). This study revealed interesting results on the use of toxic plants, which are likely to serve as a basis for further ethno-pharmacological investigations in order to get new drug sources.

Keywords: Ethnobotany, phytotherapy, Tlemcen, toxic plants.

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Authors: M. Ardelean, F. Manea, A. Pop, J. Schoonman

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The presence of pharmaceuticals in the environment and especially in water has gained increasing attention. They are included in emerging class of pollutants, and for most of them, legal limits have not been set-up due to their impact on human health and ecosystem was not determined and/or there is not the advanced analytical method for their quantification. In this context, the development of various advanced analytical methods for the quantification of pharmaceuticals in water is required. The electrochemical methods are known to exhibit the great potential for high-performance analytical methods but their performance is in direct relation to the electrode material and the operating techniques. In this study, two types of carbon-based electrodes materials, i.e., boron-doped diamond (BDD) and carbon nanofiber (CNF)-epoxy composite electrodes have been investigated through voltammetric techniques for the detection of naproxen in water. The comparative electrochemical behavior of naproxen (NPX) on both BDD and CNF electrodes was studied by cyclic voltammetry, and the well-defined peak corresponding to NPX oxidation was found for each electrode. NPX oxidation occurred on BDD electrode at the potential value of about +1.4 V/SCE (saturated calomel electrode) and at about +1.2 V/SCE for CNF electrode. The sensitivities for NPX detection were similar for both carbon-based electrode and thus, CNF electrode exhibited superiority in relation to the detection potential. Differential-pulsed voltammetry (DPV) and square-wave voltammetry (SWV) techniques were exploited to improve the electroanalytical performance for the NPX detection, and the best results related to the sensitivity of 9.959 µA·µM^-1 were achieved using DPV. In addition, the simultaneous detection of NPX and fluoxetine -a very common antidepressive drug, also present in water, was studied using CNF electrode and very good results were obtained. The detection potential values that allowed a good separation of the detection signals together with the good sensitivities were appropriate for the simultaneous detection of both tested pharmaceuticals. These results reclaim CNF electrode as a valuable tool for the individual/simultaneous detection of pharmaceuticals in water.

Keywords: Boron-doped diamond electrode, carbon nanofiber-epoxy composite electrode, emerging pollutants, pharmaceuticals.

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Authors: Dhananjay C. Joshi, Jung-Hsin Lin

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Protein-protein interactions (PPI) play a crucial role in many biological processes such as cell signalling, transcription, translation, replication, signal transduction, and drug targeting, etc. Structural information about protein-protein interaction is essential for understanding the molecular mechanisms of these processes. Structures of protein-protein complexes are still difficult to obtain by biophysical methods such as NMR and X-ray crystallography, and therefore protein-protein docking computation is considered an important approach for understanding protein-protein interactions. However, reliable prediction of the protein-protein complexes is still under way. In the past decades, several grid-based docking algorithms based on the Katchalski-Katzir scoring scheme were developed, e.g., FTDock, ZDOCK, HADDOCK, RosettaDock, HEX, etc. However, the success rate of protein-protein docking prediction is still far from ideal. In this work, we first propose a more practical measure for evaluating the success of protein-protein docking predictions,the rate of first success (RFS), which is similar to the concept of mean first passage time (MFPT). Accordingly, we have assessed the ZDOCK bound and unbound benchmarks 2.0 and 3.0. We also createda new benchmark set for protein-protein docking predictions, in which the complexes have experimentally determined binding affinity data. We performed free energy calculation based on the solution of non-linear Poisson-Boltzmann equation (nlPBE) to improve the binding mode prediction. We used the well-studied thebarnase-barstarsystem to validate the parameters for free energy calculations. Besides,thenlPBE-based free energy calculations were conducted for the badly predicted cases by ZDOCK and ZRANK. We found that direct molecular mechanics energetics cannot be used to discriminate the native binding pose from the decoys.Our results indicate that nlPBE-based calculations appeared to be one of the promising approaches for improving the success rate of binding pose predictions.

Keywords: protein-protein docking, protein-protein interaction, molecular mechanics energetics, Poisson-Boltzmann calculations

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Authors: M. G. Cattaneo

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The non-effectiveness of certain codified human rights is particularly apparent with reference to the lack of access to essential drugs in developing countries, which represents a breach of the human right to receive adequate health assistance. This paper underlines the conflict and the legal contradictions between human rights, namely health rights, international Intellectual Property Rights, in particular patent law, as well as international trade law. The paper discusses the crucial links between R&D costs for innovation, patents and new medical drugs, with the goal of reformulating the hierarchies of priorities and of interests at stake in the international intellectual property (IP) law system. Different from what happens today, International patent law should be a legal instrument apt at rebalancing an axiological asymmetry between the (conflicting) needs at stake The core argument in the paper is the proposal of an alternative pathway, namely a feasible proposal for a patent law reform. IP laws tend to balance the benefits deriving from innovation with the costs of the provided monopoly, but since developing countries and industrialized countries are in completely different political and economic situations, it is necessary to (re)modulate such exchange according to the different needs. Based on this critical analysis, the paper puts forward a proposal, called Trading Time for Space (TTS), whereby a longer time for patent exclusive life in western countries (Time) is offered to the patent holder company, in exchange for the latter selling the medical drug at cost price in developing countries (Space). Accordingly, pharmaceutical companies should sell drugs in developing countries at the cost price, or alternatively grant a free license for the sale in such countries, without any royalties or fees. However, such social service shall be duly compensated. Therefore, the consideration for such a service shall be an extension of the temporal duration of the patent’s exclusive in the country of origin that will compensate the reduced profits caused by the supply at the price cost in developing countries.

Keywords: Global health, global justice, patent law reform, access to drugs.

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Authors: Rupinder Bakshi, Geeta Walia, Anita Gupta

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Urinary Tract Infections are considered as one of the most common bacterial infections with an estimated annual global incidence of 150 million. Antimicrobial drug resistance is one of the major threats due to wide spread usage of uncontrolled antibiotics. In this study, a total number of 9149 urine samples were collected from R.H Patiala and processed in the Department of Microbiology G. M. C Patiala (January 2013 to December 2013). Urine samples were inoculated on MacConkey’s and blood agar plates and incubated at 370C for 24 hrs. The organisms were identified by colony characters, Gram’s staining, and biochemical reactions. Antimicrobial susceptibility of the isolates was determined against various antimicrobial agents (Hi – Media Mumbai India) by Kirby Bauer DISK diffusion method on Muller Hinton agar plates. Maximum patients were in the age group of 21-30 yrs followed by 31-40 yrs. Males (34%) are less prone to urinary tract infections than females (66%). Culture was positive in 25% of the samples. Escherichia coli was the most common isolate 60.3% followed by Klebsiella pneumoniae 13.5%, Proteus spp. 9% and Staphylococcus aureus 7.6%. Most of the urinary isolates were sensitive to, carbepenems, Aztreonam, Amikacin, and Piperacillin + Tazobactum. All the isolates showed a good sensitivity towards Nitrofurantoin (82%). ESBL production was found to be 70.6% in Escherichia coli and 29.4% in Klebsiella pneumonia. Susceptibility of ESBL producers to Imipenem, Nitrofurantoin and Amikacin were found to be 100%, 76%, and 75% respectively. Uropathogens are increasingly showing resistance to many antibiotics making empiric management of outpatient UTIs challenging. Ampicillin, Cotrimoxazole and Ciprofloxacin should not be used in empiric treatment. Nitrofurantoin could be used in lower urinary tract infection. Knowledge of uropathogens and their antimicrobial susceptibility pattern in a geographical region will help in appropriate and judicious antibiotic usage in a health care setup.

Keywords: Urinary Tract Infection, UTI, antibiotic susceptibility pattern, ESBL.

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Authors: Anna Pick Kiong Ling, Jia May Chin, Rhun Yian Koh, Ying Pei Wong

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Background: Uncontrolled inflammation may cause serious inflammatory diseases if left untreated. Non-steroidal anti-inflammatory drug (NSAIDs) is commonly used to inhibit pro-inflammatory enzymes, thus, reduce inflammation. However, long term administration of NSAIDs leads to various complications. Medicinal plants are getting more attention as it is believed to be more compatible with human body. One of them is a flavonoid-containing medicinal plants, Strobilanthes crispus which has been traditionally claimed to possess anti-inflammatory and antioxidant activities. Nevertheless, its anti-inflammatory activities are yet to be scientifically documented. Objectives: This study aimed to examine the anti-inflammatory activity of S. crispus by investigating its effects on intracellular oxidative stress and prostaglandin E₂ (PGE₂) levels. Materials and Methods: In this study, the Maximum Non-toxic Dose (MNTD) of methanol extract of both leaves and stems of S. crispus was first determined using 3-(4,5-dimethylthiazolyl-2)-2,5-diphenytetrazolium Bromide (MTT) assay. The effects of S. crispus extracts at MNTD and half MNTD (½MNTD) on intracellular ROS as well as PGE₂ levels in 1.0 µg/mL LPS-stimulated RAW 264.7 macrophages were then be measured using DCFH-DA and a competitive enzyme immunoassay kit, respectively. Results: The MNTD of leaf extract was determined as 700µg/mL while for stem was as low as 1.4µg/mL. When LPS-stimulated RAW 264.7 macrophages were subjected to the MNTD of S. crispus leaf extract, both intracellular ROS and PGE₂ levels were significantly reduced. In contrast, stem extract at both MNTD and ½MNTD did not significantly reduce the PGE₂ level, but significantly increased the intracellular ROS level. Conclusion: The methanol leaf extract of S. crispus may possess anti-inflammatory properties as it is able to significantly reduce the intracellular ROS and PGE₂ levels of LPS-stimulated cells. Nevertheless, further studies such as investigating the interleukin, nitric oxide and cytokine tumor necrosis factor-α (TNFα) levels has to be conducted to further confirm the anti-inflammatory properties of S. crispus.

Keywords: Anti-inflammatory, natural products, prostaglandin E2, reactive oxygen species.

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Authors: S. Vijayakumar, M. Sasikala, T. S. Mohammed Saleem, Gurusharan, K. Gauthaman

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The main objective of our study is to collect data about the profile of the asthmatic patients in Assam and thereby have a comprehensive knowledge of the factors influencing the asthmatic patients of the state and their medication pattern. We developed a search strategy to find any publication about the community based survey asthma related and used. These to search the MEDLINE (1996 to current literature) CINAHL DOAJ pubmed databases using the key phrases, Asthma, Respiratory disorders, Drug therapy of Asthma, database decision support system and asthma. The appropriate literature was printed out from the online source and library (Journal) source. The study was conducted through a set of structured and non-structured questionnaires targeted on the asthmatic patients belonging to the rural and urban areas of Assam, during the month of Dec 2006 to July 2007, 138 cases were studied in Gauwathi Medical College & Hospital located in Bhangagarh, Assam in India. The demographic characteristics a factor in 138 patients with asthma with allergic rhinitis (cases) gives the detail profile of asthmatic patient-s distribution of Assam as classified on the basis of age and sex. It is evident from the study that male populations (66%) are more prone to asthma as compared to the females (34%).Another striking features that emerged from this survey is the maximum prevalence of asthma in the age group of 20- 30 years followed by infants belonging to the age group of 7 (0.05%) 0-10years among both male and female populations of Assam. The high incidence of asthma in the age group of 20-30 years may probably be due to the allergy arising out of sudden exposure to dust and pollen which the children face while playing and going to the school. The rural females in the age group of 30-40 years are more prone to asthma than urban females in the same age group may be due to sex differentiation among the tribal population of the state. Pharmacists should educate the asthmatics how to use inhalers considering growing menace of asthma in the state. Safer drugs should be produced in the form of aerosol so that easy administration by the asthmatic patients and physicians of the state is possible for curing asthma. The health centers should be more equipped with the medicines to cure asthma in the state like Assam.

Keywords: Asthma, Respiratory disease, Smoker.

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Authors: Abdullah Faqihi, John Hedley

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Biosensors play a significant role in the healthcare sectors, scientific and technological progress. Developing electrodes that are easy to manufacture and deliver better electrochemical performance is advantageous for diagnostics and biosensing. They can be implemented extensively in various analytical tasks such as drug discovery, food safety, medical diagnostics, process controls, security and defence, in addition to environmental monitoring. Development of biosensors aims to create high-performance electrochemical electrodes for diagnostics and biosensing. A biosensor is a device that inspects the biological and chemical reactions generated by the biological sample. A biosensor carries out biological detection via a linked transducer and transmits the biological response into an electrical signal; stability, selectivity, and sensitivity are the dynamic and static characteristics that affect and dictate the quality and performance of biosensors. In this research, a developed experimental study for laser scribing technique for graphene oxide inside a vacuum chamber for processing of graphene oxide is presented. The processing of graphene oxide (GO) was achieved using the laser scribing technique. The effect of the laser scribing on the reduction of GO was investigated under two conditions: atmosphere and vacuum. GO solvent was coated onto a LightScribe DVD. The laser scribing technique was applied to reduce GO layers to generate rGO. The micro-details for the morphological structures of rGO and GO were visualised using scanning electron microscopy (SEM) and Raman spectroscopy so that they could be examined. The first electrode was a traditional graphene-based electrode model, made under normal atmospheric conditions, whereas the second model was a developed graphene electrode fabricated under a vacuum state using a vacuum chamber. The purpose was to control the vacuum conditions, such as the air pressure and the temperature during the fabrication process. The parameters to be assessed include the layer thickness and the continuous environment. Results presented show high accuracy and repeatability achieving low cost productivity.

Keywords: Laser scribing, LightScribe DVD, graphene oxide, scanning electron microscopy.

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Authors: Nicole Scott, Emily Dwyer, Cara Patrissy, Samantha Bonventre, Lina Begdache

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Across North America, the use and abuse of Attention Deficit Hyperactivity Disorder (ADHD) medication, cannabis, nicotine, and other psychoactive substances across college campuses have become an increasingly prevalent problem. Students frequently use these substances to aid their studying or deal with their mental health issues. However, it is still unknown what psychoactive substances are likely to be abused when college students illicitly use ADHD medication. In addition, it is not clear which psychoactive substance is associated with mental distress. Thus, the purpose of this study is to fill these gaps by assessing the use of different psychoactive substances when illicit ADHD medication is used; and how this association relates to mental stress. A total of 702 undergraduate students from different college campuses in the US completed an anonymous survey distributed online. Data were self-reported on demographics, the use of ADHD medications, cannabis, nicotine, other psychoactive drugs, and mental distress, and feelings and opinions on the use of illicit study drugs were all included in the survey. Mental distress was assessed using the Kessler Psychological Distress 6 Scale. Data were analyzed in SPSS, Version 25.0, using Pearson’s Correlation Coefficient. Our results show use of ADHD medication, cannabis use (non-frequent and very frequent), and nicotine use (non-frequent and very frequent); there were both statistically significant positive and negative correlations to specific psychoactive substances and their corresponding frequencies. Along the same lines, ADHD medication, cannabis use (non-frequent and very frequent), and nicotine use (non-frequent and very frequent) had statistically significant positive and negative correlations to specific mental distress experiences. As these findings are combined, a vicious loop can initiate a cycle where individuals who abuse psychoactive substances may or may not be inclined to use other psychoactive substances. This may later inhibit brain functions in those main areas of the brain stem, amygdala, and prefrontal cortex where this vicious cycle may or may not impact their mental distress. Addressing the impact of study drug abuse and its potential to be associated with further substance abuse may provide an educational framework and support proactive approaches to promote awareness among college students.

Keywords: Stimulant, depressant, nicotine, ADHD medication, psychoactive substances, mental health, illicit, ecstasy, adrenochrome.

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Authors: Rajan Rajabalaya, Li-Qun Tor, Sheba David

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Transdermal delivery of ondansetron hydrochloride (OdHCl) can prevent the problems encountered with oral ondansetron. In previously conducted studies, effect of amount of polyvinyl pyrrolidone, permeation enhancer and casting solvent on the physicochemical properties on OdHCl were investigated. It is feasible to develop ondansetron transdermal patch by using ethyl cellulose and polyvinyl pyrrolidone with dibutyl pthalate as plasticizer, however, the desired flux is not achieved. The primary aim of this study is to use dimethyl succinate (DMS) and propylene glycol that are not incorporated in previous studies to determine their effect on the physicochemical properties of an OdHCl transdermal patch using ethyl cellulose and polyvinyl pyrrolidone. This study also investigates the effect of permeation enhancer (eugenol and phosphatidylcholine) on the release of OdHCl. The results showed that propylene glycol is a more suitable plasticizer compared to DMS in the fabrication of OdHCl transdermal patch using ethyl cellulose and polyvinyl pyrrolidone as polymers. Propylene glycol containing patch has optimum drug content, thickness, moisture content and water absorption, tensile strength, and a better release profile than DMS. Eugenol and phosphatidylcholine can increase release of OdHCl from the patches. From the physicochemical result and permeation profile, a combination of 350mg of ethyl cellulose, 150mg polyvinyl pyrrolidone, 3% of total polymer weight of eugenol, and 40% of total polymer weight of propylene glycol is the most suitable formulation to develop an OdHCl patch. OdHCl release did not increase with increasing the percentage of plasticiser. DMS 4, PG 4, DMS 9, PG 9, DMS 14, and PG 14 gave better release profiles where using 300mg: 0mg, 300mg: 100mg, and 350mg: 150mg of EC: PVP. Thus, 40% of PG or DMS appeared to be the optimum amount of plasticiser when the above combination where EC: PVP was used. It was concluded from the study that a patch formulation containing 350mg EC, 150mg PVP, 40% PG and 3% eugenol is the best transdermal matrix patch compositions for the uniform and continuous release/permeation of OdHCl over an extended period. This patch design can be used for further pharmacokinetic and pharmacodynamic studies in suitable animal models.

Keywords: Ondansetron hydrochloride, dimethyl succinate, eugenol.

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Authors: Pibool Waijittragum

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The purpose of this research is to analyze the marketing strategies of Thai Halal products which related to the way of life for Thai Muslims. The expected benefit is the marketing strategy for brand building process for Halal products in Thailand. 4 elements of marketing strategies which necessary for the brand identity creation is the research framework: consists of Attributes, Benefits, Values and Personality. The research methodology was applied using qualitative and quantitative; 19 marketing experts with dynamic roles in Thai consumer products were interviewed. In addition, a field survey of 122 Thai Muslims selected from 175 Muslim communities in Bangkok was studied. Data analysis will be according to 5 categories of Thai Halal product: 1) Meat 2) Vegetable and Fruits 3) Instant foods and Garnishing ingredient 4) Beverages, Desserts and Snacks 5) Hygienic daily products; such as soap, shampoo and body lotion. The results will explain some suitable representation in the marketing strategies of Thai Halal products as are: 1) Benefit; the characteristics of the product with its benefit. Consumers will purchase this product with the reason of; it is beneficial nutrients product, there are no toxic or chemical residues. Fresh and clean materials 2) Attribute; the exterior images that attract to consumer. Consumers will purchase this product with the reason of; there is a standard proof mark, food and drug secure proof mark and Halal products mark. Packaging and its materials should be draw attention. Use an attractive graphic. Use outstanding images of product, material or ingredients. 3) Value; the value of products that affect to consumers perception; it is healthy products. Accumulate quality of life. It is a product of expertise, manufacturing of research result. Consumers are important. It’s sincere, honest and reliable to all. 4) Personality; reflection of consumers thought. The Personality feedback to them after they were consumes this product; they are health care persons. They are the rational person, moral person, justice person and thoughtful person like a progressive thinking.

Keywords: Marketing strategies, Product identity, Branding, Thai Halal products.

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Authors: Samar Saadeldin Abdelmotalab Omer, Ikram Mohamed Eltayeb Elsiddig, Amna Beshir Medani Ahmed, Saad Mohamed Hussein Ayoub

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Many herbal medicinal products are considered potential anti-hypercholesterolemic agents with encouraging safety profiles, however only a limited amount of clinical research exists to support their efficacy. The present study was designed to compare the antihypercholesterolemic and antioxidant activities of the crude ethanolic extracts of Citrus reticulata fruit peel, Zingiber officinale rhizome and Sesamum indicum seeds. Forty-five rats were used throughout the experiment which are extended for four weeks. These were divided into nine groups, five rats per each group as follows; group 1 was the normal control group (rats only fed standard normal rat diet), group 2 was the hypercholesterolemic control group (rats fed only hypercholesterolemic diet which contained 1% cholesterol plus 10% saturated animal fat added to the normal rat diet), groups 3 and 4 were fed hypercholesterolemic diet in addition to Citrus reticulata ethanolic extract at doses of (250mg/kg (group 3) and 500mg/kg (group 4)) administered daily via oral route, groups 5 and 6 were given hypercholesterolemic diet in addition to Zingiber officinale ethanolic extract at doses of (250mg/kg (group 5) and 500mg/kg (group 6)) daily through oral route, groups 7 and 8 fed on hypercholesterolemic diet in addition to Sesamum indicum ethanolic extract at doses of (250mg/kg (group 7) and 500mg/kg (group 8)) daily orally; and group 9 rats were given hypercholesterolemic diet in addition to atorvastatin (0.18mg/kg) daily via oral route as a standard reference antihypercholesterolemic drug. Blood samples from all groups were drawn from the retro-orbital venous plexus four weeks following treatment after overnight fasting and the lipid profile (total cholesterol (TC), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C) and triglyceride levels) were measured and the risk ratio (TC/HDL-C) was assessed. The antioxidant activity of the three plants extracts was determined using DPPH free-radical antioxidant assay. Results of in vivo and in vitro antihypercholesterolemic and antioxidant assay respectively, revealed that the three extracts possess comparable antioxidant and antihypercholesterolemic activities.

Keywords: Antihypercholesterolemic effects, Antioxidant activity, HDL, LDL, TC, TGs, Citrus reticulata, Sesamum indicum, Zingiber officinale.

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Authors: Mustafa M. Donma, Orkide Donma

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Obesity is a clinical state associated with low-grade inflammation. It is also a major risk factor for insulin resistance (IR). In its advanced stages, metabolic syndrome (MetS), a much more complicated disease which may lead to life-threatening problems, may develop. Obesity-mediated IR seems to correlate with the inflammation. Human studies performed particularly on pediatric population are scarce. The aim of this study is to detect possible associations between inflammation and IR in terms of some related ratios. 549 children were grouped according to their age- and sex-based body mass index (BMI) percentile tables of WHO. MetS components were determined. Informed consent and approval from the Ethics Committee for Clinical Investigations were obtained. The principles of the Declaration of Helsinki were followed. The exclusion criteria were infection, inflammation, chronic diseases and those under drug treatment. Anthropometric measurements were obtained. Complete blood cell, fasting blood glucose, insulin, and C-reactive protein (CRP) analyses were performed. Homeostasis model assessment of insulin resistance (HOMA-IR), systemic immune inflammation (SII) index, tense index, alanine aminotransferase to aspartate aminotransferase ratio (ALT/AST), neutrophils to lymphocyte (NLR), platelet to lymphocyte, and lymphocyte to monocyte ratios were calculated. Data were evaluated by statistical analyses. The degree for statistical significance was 0.05. Statistically significant differences were found among the BMI values of the groups (p < 0.001). Strong correlations were detected between the BMI and waist circumference (WC) values in all groups. Tense index values were also correlated with both BMI and WC values in all groups except overweight (OW) children. SII index values of children with normal BMI were significantly different from the values obtained in OW, obese, morbid obese and MetS groups. Among all the other lymphocyte ratios, NLR exhibited a similar profile. Both HOMA-IR and ALT/AST values displayed an increasing profile from N towards MetS3 group. BMI and WC values were correlated with HOMA-IR and ALT/AST. Both in morbid obese and MetS groups, significant correlations between CRP versus SII index as well as HOMA-IR versus ALT/AST were found. ALT/AST and HOMA-IR values were correlated with NLR in morbid obese group and with SII index in MetS group, (p < 0.05), respectively. In conclusion, these findings showed that some parameters may exhibit informative differences between the early and late stages of obesity. Important associations among HOMA-IR, ALT/AST, NLR and SII index have come to light in the morbid obese and MetS groups. This study introduced the SII index and NLR as important inflammatory markers for the discrimination of normal and obese children. Interesting links were observed between inflammation and IR in morbid obese children and those with MetS, both being late stages of obesity.

Keywords: Children, inflammation, insulin resistance, metabolic syndrome, obesity.

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Authors: K. Beheshti Maal, R. Shafiee

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According to FDA (Food and Drug Administration of the United States), vinegar is definedas a sour liquid containing at least 4 grams acetic acid in 100 cubic centimeter (4% solution of acetic acid) of solution that is produced from sugary materials by alcoholic fermentation. In the base of microbial starters, vinegars could be contained of more than 50 types of volatile and aromatic substances that responsible for their sweet taste and smelling. Recently the vinegar industry has a great proportion in agriculture, food and microbial biotechnology. The acetic acid bacteria are from the family Acetobacteraceae. Regarding to the latest version of Bergy-s Mannual of Systematic Bacteriology that has categorized bacteria in the base of their 16s RNA differences, the most important acetic acid genera are included Acetobacter (genus I), Gluconacetobacter (genus VIII) and Gluconobacter (genus IX). The genus Acetobacter that is primarily used in vinegar manufacturing plants is a gram negative, obligate aerobe coccus or rod shaped bacterium with the size 0.6 - 0.8 X 1.0 - 4.0 μm, nonmotile or motile with peritrichous flagella and catalase positive – oxidase negative biochemically. Some strains are overoxidizer that could convert acetic acid to carbon dioxide and water.In this research one Acetobacter native strain with high acetic acid productivity was isolated from Iranian white – red cherry. We used two specific culture media include Carr medium [yeast extract, 3%; ethanol, 2% (v/v); bromocresol green, 0.002%; agar, 2% and distilled water, 1000 ml], Frateur medium [yeast extract, 10 g/l; CaCO3, 20 g/l; ethanol, 20 g/l; agar, 20 g/l and distilled water, 1000 ml] and an industrial culture medium. In addition to high acetic acid production and high growth rate, this strain had a good tolerance against ethanol concentration that was examined using modified Carr media with 5%, 7% and 9% ethanol concentrations. While the industrial strains of acetic acid bacteria grow in the thermal range of 28 – 30 °C, this strain was adapted for growth in 34 – 36 °C after 96 hours incubation period. These dramatic characteristics suggest a potential biotechnological strain in production of cherry vinegar with a sweet smell and different nutritional properties in comparison to recent vinegar types. The lack of growth after 24, 48 and 72 hours incubation at 34 – 36 °C and the growth after 96 hours indicates a good and fast thermal flexibility of this strain as a significant characteristic of biotechnological and industrial strains.

Keywords: Acetobacte, acetic acid bacteria, white – red cherry, food and agriculture biotechnology, industrial fermentation, vinegar

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

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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

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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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