Search results for: annual dose limits

Authors: Jee-Young Lee, Joaquim J. Ferreira, Hyeo-il Ma, José-Francisco Rocha, Beomseok Jeon

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The effective management of wearing-off is a key driver of medication changes for patients with Parkinson’s disease (PD) treated with levodopa (L-DOPA). While L-DOPA is well tolerated and efficacious, its clinical utility over time is often limited by the development of complications such as dyskinesia. Still, common first-line option includes adjusting the daily L-DOPA dose followed by adjunctive therapies usually counting for the L-DOPA equivalent daily dose (LEDD). The LEDD conversion formulae are a tool used to compare the equivalence of anti-PD medications. The aim of this work is to compare the effects of opicapone (OPC) 50 mg, a catechol-O-methyltransferase (COMT) inhibitor, and an additional 100 mg dose of L-DOPA in reducing the off time in PD patients with early motor fluctuations receiving different daily L-DOPA doses. OPC was found to be well tolerated and efficacious in advanced PD population. This work utilized patients' home diary data from a 4-week Phase 2 pharmacokinetics clinical study. The Korean ADOPTION study randomized (1:1) patients with PD and early motor fluctuations treated with up to 600 mg of L-DOPA given 3–4 times daily. The main endpoint was change from baseline in off time in the subgroup of patients receiving 300–400 mg/day L-DOPA at baseline plus OPC 50 mg and in the subgroup receiving >300 mg/day L-DOPA at baseline plus an additional dose of L-DOPA 100 mg. Of the 86 patients included in this subgroup analysis, 39 received OPC 50 mg and 47 L-DOPA 100 mg. At baseline, both L-DOPA total daily dose and LEDD were lower in the L-DOPA 300–400 mg/day plus OPC 50 mg group than in the L-DOPA >300 mg/day plus L-DOPA 100 mg. However, at Week 4, LEDD was similar between the two groups. The mean (±standard error) reduction in off time was approximately three-fold greater for the OPC 50 mg than for the L-DOPA 100 mg group, being -63.0 (14.6) minutes for patients treated with L-DOPA 300–400 mg/day plus OPC 50 mg, and -22.1 (9.3) minutes for those receiving L-DOPA >300 mg/day plus L-DOPA 100 mg. In conclusion, despite similar LEDD, OPC demonstrated a significantly greater reduction in off time when compared to an additional 100 mg L-DOPA dose. The effect of OPC appears to be LEDD independent, suggesting that caution should be exercised when employing LEDD to guide treatment decisions as this does not take into account the timing of each dose, onset, duration of therapeutic effect and individual responsiveness. Additionally, OPC could be used for keeping the L-DOPA dose as low as possible for as long as possible to avoid the development of motor complications which are a significant source of disability.

Keywords: opicapone, levodopa, pharmacokinetics, off-time

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Authors: Ahmad Shah Farhat, Anahita Alizadeh Qamsari, Ashraf Mohammadzadeh, Hamid Reza Goldouzian, Ezat Khodashenas

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Introduction: Newborns may be treated with phenobarbital for many reasons. Because in each region, depending on different races and genetic factors, different pharmacokinetic conditions govern the drug. It is essential to control blood levels of certain drugs, especially phenobarbital, and maintain these levels during treatment. Methods: In this study, venous blood was collected from 50 neonates who received intravenous phenobarbital at a loading dose of 20 mg/kg weight and at least three days had passed since the maintenance dose of 5 mg/kg body weight. in 24 hours. and sent to the laboratory. Phenobarbital blood levels were measured, then the results were analyzed descriptively. Results: In this study, the average weight of newborns was 9.93 ± 2.58. The mean blood concentration of phenobarbital, three days after starting the maintenance dose in the group of infants weighing more than 2.5 kg, was 3.33 ± 9.1 micrograms/liter in the group of infants weighing less than 2 kg. and half a kilogram or LBW was 5.9 ± 9.5 micrograms/liter and in the group weighing less than 1.5 kg VLBW was 14.4 ± 15.46 micrograms/liter. There was no significant difference between groups (p>0.05). Three days after starting the maintenance dose in all three groups, the mean blood phenobarbital concentration was 9.86 ± 0.86 micrograms/liter. Conclusion: Blood phenobarbital levels in our newborns are below therapeutic levels, so phenobarbital levels should be evaluated.

Keywords: poisining, neonats, phenobarbital, drug

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Authors: Muhammad Ather Nadeem, Bilal Ahmad Khan, Tasawer Abbas

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Nanoherbicides utilize nanotechnology to enhance the delivery of biological or chemical herbicides using combinations of nanomaterials. The aim of this research was to examine the efficacy of chitosan nanoparticles containing MCPA herbicide as a potential eco-friendly alternative for weed control in wheat crops. Scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and ultraviolet absorbance were used to analyze the developed nanoparticles. The SEM analysis indicated that the average size of the particles was 35 nm, forming clusters with a porous structure. Both nanoparticles of fluroxyper + MCPA exhibited maximal absorption peaks at a wavelength of 320 nm. The compound fluroxyper +MCPA has a strong peak at a 2θ value of 30.55°, which correlates to the 78 plane of the anatase phase. The weeds, including Chenopodium album, Lathyrus aphaca, Angalis arvensis, and Melilotus indica, were sprayed with the nanoparticles while they were in the third or fourth leaf stage. There were seven distinct dosages used: doses (D0 (Check weeds), D1 (Recommended dose of traditional herbicide, D2 (Recommended dose of Nano-herbicide (NPs-H)), D3 (NPs-H with 05-fold lower dose), D4 ((NPs-H) with 10-fold lower dose), D5 (NPs-H with 15-fold lower dose), and D6 (NPs-H with 20-fold lower dose)). The chitosan-based nanoparticles of MCPA at the prescribed dosage of conventional herbicide resulted in complete death and visual damage, with a 100% fatality rate. The dosage that was 5-fold lower exhibited the lowest levels of plant height (3.95 cm), chlorophyll content (5.63%), dry biomass (0.10 g), and fresh biomass (0.33 g) in the broad-leaved weed of wheat. The herbicide nanoparticles, when used at a dosage 10-fold lower than that of conventional herbicides, had a comparable impact on the prescribed dosage. Nano-herbicides have the potential to improve the efficiency of standard herbicides by increasing stability and lowering toxicity.

Keywords: mortality, visual injury, chlorophyl contents, chitosan-based nanoparticles

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Authors: S. Sreeja, Radhakrishnan R. Nair, Noble Gracious, Sreeja S. Nair, M. Radhakrishna Pillai

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Background: Tacrolimus is a potent immunosuppressant clinically used for the long term treatment of antirejection of transplanted organs in liver and kidney transplant recipients though dose optimization is poorly managed. However, So far no study has been carried out on the South Indian kidney transplant patients. The objective of this study is to evaluate the potential influence of a functional polymorphism in CYP3A5*3 gene on tacrolimus physiological availability/dose ratio in South Indian renal transplant patients. Materials and Methods: Twenty five renal transplant recipients receiving tacrolimus were enrolled in this study. Their body weight, drug dosage, and therapeutic concentration of Tacrolimus were observed. All patients were on standard immunosuppressive regime of Tacrolimus-Mycophenolate mofetil along with steroids on a starting dose of Tac 0.1 mg/kg/day. CYP3A5 genotyping was performed by PCR followed with RFLP. Conformation of RFLP analysis and variation in the nucleotide sequence of CYP3A5*3 gene were determined by direct sequencing using a validated automated generic analyzer. Results: A significant association was found between tacrolimus per dose/kg/d and CYP3A5 gene (A6986G) polymorphism in the study population. The CYP3A5 *1/*1, *1/*3 and *3/*3 genotypes were detected in 5 (20 %), 5 (20 %) and 15 (60 %) of the 25 graft recipients, respectively. CYP3A5*3 genotypes were found to be a good predictor of tacrolimus Concentration/Dose ratio in kidney transplant recipients. Significantly higher L/D was observed among non-expressors 9.483 ng/mL(4.5- 14.1) as compared with the expressors 5.154 ng/mL (4.42-6.5 ) of CYP3A5. Acute rejection episodes were significantly higher for CYP3A5*1 homozygotes compared to patients with CYP3A5*1/*3 and CYP3A5*3/*3 genotypes (40 % versus 20 % and 13 %, respectively ). The dose normalized TAC concentration (ng/ml/mg/kg) was significantly lower in patients having CYP3A5*1/*3 polymorphism. Conclusion: This is the first study to extensively determine the effect of CYP3A5*3 genetic polymorphism on tacrolimus pharmacokinetics in South Indian renal transplant recipients and also shows that majority of our patients carry mutant allele A6986G in CYP3A5*3 gene. Identification of CYP3A5 polymorphism prior to transplantation could contribute to evaluate the appropriate initial dosage of tacrolimus for each patient.

Keywords: kidney transplant patients, CYP3A5 genotype, tacrolimus, RFLP

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Authors: Muhammad Isa Khan, Jalil Ur Rehman, Muhammad Afzal Khan Rao, James Chow

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Purpose: This study investigates the dose-volume variations in planning target volume (PTV) and organs-at-risk (OARs) using different collimator angles for smart arc prostate volumetric modulated arc therapy (VMAT). Awareness of the collimator angle for PTV and OARs sparing is essential for the planner because optimization contains numerous treatment constraints producing a complex, unstable and computationally challenging problem throughout its examination of an optimal plan in a rational time. Materials and Methods: Single arc VMAT plans at different collimator angles varied systematically (0°-90°) were performed on a Harold phantom and a new treatment plan is optimized for each collimator angle. We analyzed the conformity index (CI), homogeneity index (HI), gradient index (GI), monitor units (MUs), dose-volume histogram, mean and maximum doses to PTV. We also explored OARs (e.g. bladder, rectum and femoral heads), dose-volume criteria in the treatment plan (e.g. D30%, D50%, V30Gy and V38Gy of bladder and rectum; D5%,V14Gy and V22Gy of femoral heads), dose-volume histogram, mean and maximum doses for smart arc VMAT at different collimator angles. Results: There was no significance difference found in VMAT optimization at all studied collimator angles. However, if 0.5% accuracy is concerned then collimator angle = 45° provides higher CI and lower HI. Collimator angle = 15° also provides lower HI values like collimator angle 45°. It is seen that collimator angle = 75° is established as a good for rectum and right femur sparing. Collimator angle = 90° and collimator angle = 30° were found good for rectum and left femur sparing respectively. The PTV dose coverage statistics for each plan are comparatively independent of the collimator angles. Conclusion: It is concluded that this study will help the planner to have freedom to choose any collimator angle from (0°-90°) for PTV coverage and select a suitable collimator angle to spare OARs.

Keywords: VMAT, dose-volume histogram, collimator angle, organs-at-risk

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Authors: Md Murshed Bhuyan, Hirotaka Okabe, Yoshiki Hidaka, Kazuhiro Hara

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Pectin-Acrylamide- (Vinyl Phosphonic Acid) Hydrogels were prepared from their blend by using gamma radiation of various doses. It was found that the gel fraction of hydrogel increases with increasing the radiation dose reaches a maximum and then started decreasing with increasing the dose. The optimum radiation dose and the composition of raw materials were determined on the basis of equilibrium swelling which resulted in 20 kGy absorbed dose and 1:2:4 (Pectin:AAm:VPA) composition. Differential scanning calorimetry reveals the gel strength for using them as the adsorbent. The FTIR-spectrum confirmed the grafting/ crosslinking of the monomer on the backbone of pectin chain. The hydrogels were applied in adsorption of Al, Ga, and In from multielement solution where the adsorption capacity order for those three elements was found as – In>Ga>Al. SEM images of hydrogels and metal adsorbed hydrogels indicate the gel network and adherence of the metal ions in the interpenetrating network of the hydrogel which were supported by EDS spectra. The adsorption isotherm models were studied and found that the Langmuir adsorption isotherm model was well fitted with the data. Adsorption data were also fitted to different adsorption kinetic and diffusion models. Desorption of metal adsorbed hydrogels was performed in 5% nitric acid where desorption efficiency was found around 90%.

Keywords: hydrogel, gamma radiation, vinyl phosphonic acid, metal adsorption

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Authors: Ahmad Shanei, Milad Baradaran-Ghahfarokhi

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This study aimed to investigate testicular dose (TD) and the associated risk of heritable disease from common pelvis radiotherapy of male patients in Iran. In this work, the relation between TD and changes in beam energy, pelvis size, source to skin distance (SSD) and beam directions (anterior or posterior) were also evaluated. The values of TDs were measured on 67 randomly selected male patients during common pelvis radiotherapy using 1.17 and 1.33 MeV, Theratron Cobalt-60 unit at SSD of 80 cm and 9 MV, Neptun 10 PC and 18 MV, GE Saturne 20 at SSD of 100 cm at Seyed-Al Shohada Hospital, Isfahan, Iran. Results showed that the maximum TD was up to 12% of the tumor dose. Considering the risk factor for radiation-induced heritable disorders of 0.1% per Sv, an excess risk of hereditary disorders of 72 per 10000 births was conservatively calculated. There was a significant difference in the measured TD using different treatment machines and energies (P < 0.001). The TD at 100 cm SSD were much less than that for 80 cm SSD (P <0.001). The Pearson Correlation test showed that, as expected, there was a strong correlation between TD and patient’s pelvis size (r = 0.275, P <0.001). Using the student’s t-tests, it was found that, there was not a significant difference between TD and beam direction (P = 0.231). Iranian male patients undergoing pelvic radiotherapy have the potential of receiving a TD of more than 1 Gy which might result in temporary azoospermia. The risk for induction of hereditary disorders in future generations should be considered as low but not negligible in comparison with the correspondent nominal risk.

Keywords: pelvis radiotherapy, testicular dose, infertility, hereditary effects

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Authors: Chaiyakrit Raoupatham, Ram Hari Dhakal, Chalermchai Wanichlamlert

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This paper is aimed to introduce the solution of concrete slump recovery using chemical admixture type-F (superplasticizer, naphthalene base) to the practice, in order to solve unusable concrete problem due to concrete loss its slump, especially for those tropical countries that have faster slump loss rate. In the other hand, randomly adding superplasticizer into concrete can cause concrete to segregate. Therefore, this paper also develops the estimation model used to calculate amount of second dose of superplasticizer need for concrete slump recovery. Fresh properties of ordinary Portland cement concrete with volumetric ratio of paste to void between aggregate (paste content) of 1.1-1.3 with water-cement ratio zone of 0.30 to 0.67 and initial superplasticizer (naphthalene base) of 0.25%- 1.6% were tested for initial slump and slump loss for every 30 minutes for one and half hour by slump cone test. Those concretes with slump loss range from 10% to 90% were re-dosed and successfully recovered back to its initial slump. Slump after re-dosed was tested by slump cone test. From the result, it has been concluded that, slump loss was slower for those mix with high initial dose of superplasticizer due to addition of superplasticizer will disturb cement hydration. The required second dose of superplasticizer was affected by two major parameter, which were water-cement ratio and paste content, where lower water-cement ratio and paste content cause an increase in require second dose of superplasticizer. The amount of second dose of superplasticizer is higher as the solid content within the system is increase, solid can be either from cement particles or aggregate. The data was analyzed to form an equation use to estimate the amount of second dosage requirement of superplasticizer to recovery slump to its original.

Keywords: estimation model, second superplasticizer dosage, slump loss, slump recovery

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Authors: Reza Reiazi

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Attempts to verify Geant4 hadronic physic to transport antiproton beam using standard physics list have not reach to a reasonable results because of lack of reliable cross section data or non reliable model to predict the final states of annihilated particles. Since most of the antiproton annihilation energy is carried away by recoiling nuclear fragments which are result of pions interactions with surrounding nucleons, it should be investigated if the toolkit verified for pions. Geant4 version 9.4.6.p01 was used. Dose calculation was done using 700 MeV pions hitting a water tank applying standards physic lists. We conclude Geant4 standard physics lists to predict the depth dose of Pion minus beam is not same for all investigated models. Since the nuclear fragments will deposit their energy in a small distance, they are the most important source of dose deposition in the annihilation vertex of antiproton beams.

Keywords: Monte Carlo, Pion, simulation, antiproton beam

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Authors: Sevana Daneghian, Leila Chodari, Sahar Mehranfar, Shadi Mohammadpour-Asl, Diman Mahdi

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Sarcopenia is an age-related muscle disease. Lack of antioxidant protection, and cumulative oxidative damage to skeletal muscle are recognized mechanisms. Curcumin is a hormetin as it has a stimulating effect in low doses and an inhibitory effect in high doses. The purpose of this study was to examine the effects of four weeks of curcumin supplementation in presarcopenic and sarcopenic rats, and likelihood of potential negative effects while co-exist with sarcopenia. The rats were divided into 7 groups: young sham rats, 18 months old; presarcopenic control, supplemented with 400 and 1500 mg/kg/day, 24 months old; Sarcopenia control, sarcopenia supplemented with 400 and 1500 mg/kg/day. MDA levels were significantly reduced in the low-dose pre-sarcopenic group compared to the control group. Compared to the corresponding control groups, SOD levels decreased in the groups treated with low-dose presarcopenic supplementation and increased in the high-dose sarcopenic supplemented. GPx levels increased at both doses only in the sarcopenic group compared to the control group. SIRT-1 only increased at low doses in the sarcopenic groups and PGC-1α in both pre-sarcopenia groups compared to the corresponding control. IGF-1 increased compared to the control group at both doses in the pre-sarcopenic group and at high doses in sarcopenic group. Considering the hormetic effects of curcumin, it can be argued that, curcumin supplementation has some positive effects not only at low but also at high doses in both groups. This means that the high doses of curcumin have no negative synergistic effects in addition to oxidative stress during sarcopenia and high-dose supplementation in patients already suffering from high oxidative stress due to sarcopenia is safe and could be considered hormetic.

Keywords: curcumin, hormesis, sarcopenia, muscular atrophy, PGC protein, Sirtuins

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Authors: Chor Yi Ng, Christine Kong, Loretta Teo, Stephen Yau, FC Cheung, TL Poon, Francis Lee

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Purpose: Dynamic conformal arc (DCA) and intensity modulated radiotherapy (IMRT) are two treatment techniques commonly used for stereotactic radiosurgery/radiotherapy of cranial lesions. IMRT plans usually give better dose conformity while DCA plans have better dose fall off. Rapid dose fall off is preferred for radiotherapy of cranial lesions, but dose conformity is also important. For certain lesions, DCA plans have good conformity, while for some lesions, the conformity is just unacceptable with DCA plans, and IMRT has to be used. The choice between the two may not be apparent until each plan is prepared and dose indices compared. We described a deviation index (DI) which is a measurement of the deviation of the target shape from a sphere, and test its functionality to choose between the two techniques. Method and Materials: From May 2015 to May 2017, our institute has performed stereotactic radiotherapy for 105 patients treating a total of 115 lesions (64 DCA plans and 51 IMRT plans). Patients were treated with the Varian Clinac iX with HDMLC. Brainlab Exactrac system was used for patient setup. Treatment planning was done with Brainlab iPlan RT Dose (Version 4.5.4). DCA plans were found to give better dose fall off in terms of R50% (R50% (DCA) = 4.75 Vs R50% (IMRT) = 5.242) while IMRT plans have better conformity in terms of treatment volume ratio (TVR) (TVR(DCA) = 1.273 Vs TVR(IMRT) = 1.222). Deviation Index (DI) is proposed to better facilitate the choice between the two techniques. DI is the ratio of the volume of a 1 mm shell of the PTV and the volume of a 1 mm shell of a sphere of identical volume. DI will be close to 1 for a near spherical PTV while a large DI will imply a more irregular PTV. To study the functionality of DI, 23 cases were chosen with PTV volume ranged from 1.149 cc to 29.83 cc, and DI ranged from 1.059 to 3.202. For each case, we did a nine field IMRT plan with one pass optimization and a five arc DCA plan. Then the TVR and R50% of each case were compared and correlated with the DI. Results: For the 23 cases, TVRs and R50% of the DCA and IMRT plans were examined. The conformity for IMRT plans are better than DCA plans, with majority of the TVR(DCA)/TVR(IMRT) ratios > 1, values ranging from 0.877 to1.538. While the dose fall off is better for DCA plans, with majority of the R50%(DCA)/ R50%(IMRT) ratios < 1. Their correlations with DI were also studied. A strong positive correlation was found between the ratio of TVRs and DI (correlation coefficient = 0.839), while the correlation between the ratio of R50%s and DI was insignificant (correlation coefficient = -0.190). Conclusion: The results suggest DI can be used as a guide for choosing the planning technique. For DI greater than a certain value, we can expect the conformity for DCA plans to become unacceptably great, and IMRT will be the technique of choice.

Keywords: cranial lesions, dynamic conformal arc, IMRT, image guided radiotherapy, stereotactic radiotherapy

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Authors: Guohua Cao, Xu Dong

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X-ray Fluorescence Molecular Imaging (XFMI) holds great promise as a low-cost molecular imaging modality for biomedical applications with high chemical sensitivity. However, for in vivo biomedical applications, a key technical bottleneck is the relatively low chemical sensitivity of XFMI, especially at a reasonably low radiation dose. In laboratory x-ray source based XFMI, one of the main factors that limits the chemical sensitivity of XFMI is the scattered x-rays. We will present our latest findings on improving the chemical sensitivity of XFMI using excitation beam spectrum optimization. XFMI imaging experiments on two mouse-sized phantoms were conducted at three different excitation beam spectra. Our results show that the minimum detectable concentration (MDC) of iodine can be readily increased by five times via excitation spectrum optimization. Findings from this investigation could find use for in vivo pre-clinical small-animal XFMI in the future.

Keywords: molecular imaging, X-ray fluorescence, chemical sensitivity, X-ray scattering

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Authors: Aid Asma, Dahdouh Nadjib, Amokrane Samira, Ladjali Samir, Nibou Djamel

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The present work has for main objective the elimination of the textile dye Maxilon Red (MR) by two processes, adsorption on activated clay followed by photocatalysis in presence of ZnO as a photocatalyst. The influence of the physical parameters like the initial pH, adsorbent dose of the activated clay, the MR concentration and temperature has been studied. The best adsorption yield occurs at neutral pH ~ 7 within 60 min with an uptake percentage of 97% for a concentration of 25 mg L⁻¹ and a dose of 0.5 g L⁻¹. The adsorption data were suitably fitted by the Langmuir model with a maximum capacity of 176 mg g⁻¹. The MR adsorption is well described by the pseudo second order kinetic. The second part of this work was dedicated to the photocatalytic degradation onto ZnO under solar irradiation of the residual MR concentration, remained after adsorption. The effect of ZnO dose and MR concentration has also been investigated. The parametric study showed that the elimination is very effective by this process, based essentially on the in situ generation of free radicals *OH which are non-selective and very reactive. The photodegradation process follows a first order kinetic model according to the Langmuir-Hinshelwood model.

Keywords: maxilon red, adsorption, photodegradation, ZnO, coupling

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Authors: Muhammad Al Rizqi Dharma Fauzi, Dwi Yulian Fahruddin Shah, Andre Pratama, Ari Hasna Widyapuspa, Ganden Supriyanto

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Diabetes mellitus is still known as one of diseases which give a big amount of death in the world. From 2012 to 2014, diabetes is estimated to have resulted in 1.5 to 4.9 million deaths each year. In this paper, we present our research in the analysis and dose determination of Tenebrio molitor (Mealworm) extract as an anti-diabetic agent which is believed by Indonesian people as a traditional treatment to prevent and treat diabetes. We found that Tenebrio molitor extract has a potential as an anti-diabetic agent by in vitro test to Mus musculus which were divided into six group of treatment. Our dose determination analysis gave a conclusion that at 2,5 g/mL of concentration of the extract would give the optimal result in healing a wound given to Mus musculus which were induced by aloxane monohydrate. These results show that Tenebrio molitor extract is potential to be used as an Anti-Diabetic agent.

Keywords: diabetes, extraction, Tenebrio molitor, traditional medicine

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Authors: K. Rawojć, J. Miszczyk, A. Możdżeń, A. Panek, J. Swakoń, M. Rydygier

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Due to the mitotic delay, poor mitotic index and disappearance of lymphocytes from peripheral blood circulation, assessing the DNA damage after high dose exposure is less effective. Conventional chromosome aberration analysis or cytokinesis-blocked micronucleus assay do not provide an accurate dose estimation or radiosensitivity prediction in doses higher than 6.0 Gy. For this reason, there is a need to establish reliable methods allowing analysis of biological effects after exposure in high dose range i.e., during particle radiotherapy. Lately, Premature Chromosome Condensation (PCC) has become an important method in high dose biodosimetry and a promising treatment modality to cancer patients. The aim of the study was to evaluate the usefulness of drug-induced PCC scoring procedure in an experimental mode, where 100 G2/M cells were analyzed in different dose ranges. To test the consistency of obtained results, scoring was performed by 3 independent persons in the same mode and following identical scoring criteria. Whole-body exposure was simulated in an in vitro experiment by irradiating whole blood collected from healthy donors with 60 MeV protons and 250 keV X-rays, in the range of 4.0 – 20.0 Gy. Drug-induced PCC assay was performed on human peripheral blood lymphocytes (HPBL) isolated after in vitro exposure. Cells were cultured for 48 hours with PHA. Then to achieve premature condensation, calyculin A was added. After Giemsa staining, chromosome spreads were photographed and manually analyzed by scorers. The dose-effect curves were derived by counting the excess chromosome fragments. The results indicated adequate dose estimates for the whole-body exposure scenario in the high dose range for both studied types of radiation. Moreover, compared results revealed no significant differences between scores, which has an important meaning in reducing the analysis time. These investigations were conducted as a part of an extended examination of 60 MeV protons from AIC-144 isochronous cyclotron, at the Institute of Nuclear Physics in Kraków, Poland (IFJ PAN) by cytogenetic and molecular methods and were partially supported by grant DEC-2013/09/D/NZ7/00324 from the National Science Centre, Poland.

Keywords: cell response to radiation exposure, drug induced premature chromosome condensation, premature chromosome condensation procedure, proton therapy

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Authors: V. P. Ramani, K. P. Patel, S. B. Patel

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It is necessary to dispose of generated industrial wastes in the proper way to overcome the further pollution for a safe environment. Waste can be used in agriculture for good quality higher food production. In order to evaluate the effect and rate of processed industrial biomass on yield, contents, uptake and soil status in maize, a field experiment was conducted during 2009 - 2011 at Anand on loamy sand soil for two years. The treatments of different levels of NPK i.e. 100% RD, 75% RD and 50% RD were kept to study the possibility of reduction in fertilizer application with the use of processed biomass (BM) in different proportion with FYM. (Where, RD= Recommended dose, FYM= Farm Yard Manure, BM= Processed Biomass.) The significantly highest grain yield of maize was recorded under the treatment of 75% NPK + BM application @ 10t ha-1. The higher (10t ha-1) and lower (5t ha-1) application rate of BM with full dose of NPK was found beneficial being at par with the treatment 75% NPK along with BM application @ 10t ha-1. There is saving of 25% recommended dose of NPK when combined with BM application @ 10.0t ha-1 or 50% saving of organics when applied with full dose (100%) of NPK. The highest straw yield (7734 kg ha-1) of maize on pooled basis was observed under the treatment of recommended dose of NPK along with FYM application at 7.5t ha-1 coupled with BM application at 2.5t ha-1. It was also observed that highest straw yield was at par under all the treatments except control and application of 100% recommended dose of NPK coupled with BM application at 7.5t ha-1. The Fe content of maize straw were found altered significantly due to different treatments on pooled basis and it was noticed that biomass application at 7.5t ha-1 along with recommended dose of NPK showed significant enhancement in Fe content of straw over other treatments. Among heavy metals, Co, Pb and Cr contents of grain were found significantly altered due to application of different treatments variably during the pooled. While, Ni content of maize grain was not altered significantly due to application of different organics. However, at higher rate of BM application i.e. of 10t ha-1, there was slight increase in heavy metal content of grain/ straw as well as DTPA heavy metals in soil; although the increase was not alarming Thus, the overall results indicated that the application of BM at 5t ha-1 along with full dose of NPK is beneficial to get higher yield of maize without affecting soil / plant health adversely. It also indicated that the 5t BM ha-1 could be utilized in place of 10t FYM ha-1 where FYM availability is scarce. The 10t BM ha-1 helps to reduce a load of chemical fertilizer up to 25 percent in agriculture. The lower use of agro-chemicals always favors safe environment. However, the continuous use of biomass needs periodical monitoring to check any buildup of heavy metals in soil/ plant over the years.

Keywords: alternate use of industrial waste, heavy metals, maize, processed industrial biomass

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Authors: Prateep Wajeetongratana

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This study investigates the management accountant’s roles that link with the creation of corporate shared value to enable more effective decision-making and improve the information needs of stakeholders. Mixed method is employed to collect using triangulation for credibility. A quantitative approach is employed to conduct a survey of 200 Thai companies providing annual reports in the Stock Exchange of Thailand. The results of the study reveal that environmental and social data incorporated in a corporate social responsibility (CSR) disclosure are based on the indicators of the Global Reporting Initiatives (GRI) at a statistically significant level of 0.01. Environmental and social indicators in CSR are associated with environmental and social data disclosed in the annual report to support stakeholders’ and the public’s interests that are addressed and show that a significant relationship between environmental and social in CSR disclosures and the information in annual reports is statistically significant at the 0.01 level.

Keywords: corporate social responsibility, creating shared value, management accountant’s roles, stock exchange of Thailand

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Authors: Yolanda Ramirez, Angel Tejada, Agustin Baidez

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This paper shows the general perceptions of Spanish university stakeholders in relation to the university’s annual reports and the adequacy and potential of intellectual capital reporting. To this end, a questionnaire was designed and sent to every member of the Social Councils of Spanish public universities. It was thought that these participants would provide a good example of the attitude of university stakeholders since they represent the different social groups connected with universities. From the results of this study we are in the position of confirming the need for universities to offer information on intellectual capital in their accounting information model.

Keywords: intellectual capital, disclosure, stakeholders, universities, annual report

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Authors: M. Pawlaczyk-Łuszczyńska, T. Wszołek, A. Dudarewicz, P. Małecki, M. Kłaczyński, A. Bortkiewicz

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Human tolerance to infrasound is defined by the hearing threshold. Infrasound that cannot be heard (or felt) is not annoying and is not thought to have any other adverse or health effects. Recent research has largely confirmed earlier findings. ISO 7196:1995 recommends the use of G-weighted characteristics for the assessment of infrasound. There is a strong correlation between G-weighted SPL and annoyance perception. The aim of this study was to propose exposure limits for infrasound from wind turbines. However, only a few countries have set limits for infrasound. These limits are usually no higher than 85-92 dBG, and none of them are specific to wind turbines. Over the years, a number of studies have been carried out to determine hearing thresholds below 20 Hz. It has been recognized that 10% of young people would be able to perceive 10 Hz at around 90 dB, and it has also been found that the difference in median hearing thresholds between young adults aged around 20 years and older adults aged over 60 years is around 10 dB, irrespective of frequency. This shows that older people (up to about 60 years of age) retain good hearing in the low frequency range, while their sensitivity to higher frequencies is often significantly reduced. In terms of exposure limits for infrasound, the average hearing threshold corresponds to a tone with a G-weighted SPL of about 96 dBG. In contrast, infrasound at Lp,G levels below 85-90 dBG is usually inaudible. The individual hearing threshold can, therefore be 10-15 dB lower than the average threshold, so the recommended limits for environmental infrasound could be 75 dBG or 80 dBG. It is worth noting that the G86 curve has been taken as the threshold of auditory perception of infrasound reached by 90-95% of the population, so the G75 and G80 curves can be taken as the criterion curve for wind turbine infrasound. Finally, two assessment methods and corresponding exposure limit values have been proposed for wind turbine infrasound, i.e. method I - based on G-weighted sound pressure level measurements and method II - based on frequency analysis in 1/3-octave bands in the frequency range 4-20 Hz. Separate limit values have been set for outdoor living areas in the open countryside (Area A) and for noise sensitive areas (Area B). In the case of Method I, infrasound limit values of 80 dBG (for areas A) and 75 dBG (for areas B) have been proposed, while in the case of Method II - criterion curves G80 and G75 have been chosen (for areas A and B, respectively).

Keywords: infrasound, exposure limit, hearing thresholds, wind turbines

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Authors: C. Silvestros, K. Mellou, T. Georgakopoulou, A. Koustenis, E. Kokkinou, C. Botsi, A. Terzidis

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'PHILOS – Emergency health response to refugee crisis' is a programme of the Greek Ministry of Health, implemented by the Hellenic Center for Disease Control and Prevention (HCDCP) funded by the Asylum, Migration and Integration Fund (AMIF) of EU’s DG Migration and Home Affairs. One of the main objectives of the program is the immunization coverage of the target – population to assure the prevention of vaccine-preventable diseases. The program foresees vaccination needs assessment of children hosted at camps at the mainland and implementation of interventions to cover the vaccination gaps in co-operation with the Ministry of Health. The National Immunization Advisory Committee in Greece recommended that MMR (Measles, Mumps, and Rubella), PCV (Pneumococcal conjugate vaccine) and HEXA (diphtheria, tetanus, pertussis, polio, hepatitis B and Haemophilus influenzae type b) vaccines should be performed in priority. Recording was completed at 24 camps (May - June 2017); 3381 children (0-18 years) were recorded. The median number of children hosted at each camp was 95 (range: 5-553). For 68% of the children, the WHO vaccination booklet was available. 44%, 48.5% and 61% of the children were vaccinated with at least one dose of PCV, HEXA, and MMR, respectively. The proportion of vaccinated children for the three vaccines mentioned above is significantly lower for the remaining doses; PCV (second dose 8%, third dose 1.3%), HEXA (second dose 13%, third dose 2.7%, forth dose 0.1%) and MMR (second dose 23%). None of the 37 (10 from Afghanistan, 3 from Bangladesh, 23 from Pakistan, 1 from Syria) recorded unaccompanied children did not have a WHO vaccination booklet and were considered unvaccinated. There is no differentiation in vaccination coverage among different ethnicities. Massive catch up vaccination was performed at 4 camps, and 671 vaccinations were performed (245 PCV, 307 HEXA, and 119 MMR). Similar interventions are planned for all camps of the country. Recording reveled gaps in vaccination coverage of the population, mainly because of the mobility of the population, the influx of refugees- which is still ongoing- and new births. Mass vaccination campaigns are considered vital in order to increase vaccination coverage, and continuous efforts are needed in order all children living at the camps to have full access to the National Childhood Immunization Program.

Keywords: vaccine preventable, refugee–migrants camps, vaccination coverage, PCV, MMR, HEXA

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Authors: Shoukat Ali, Amjad Hussain, Latif-ur-Rehman, Sehrish Inam

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Radiotherapy plays an important role in the management of cancer patients. Approximately 50% of the cancer patients receive radiotherapy at one point or another during the course of treatment. The entire radiotherapy treatment of curative intent is divided into different phases, depending on the histology of the tumor. The established protocols are useful in deciding the total dose, fraction size, and numbers of phases. The objective of this study was to evaluate the dosimetric differences between the conventional treatment protocols and the three-dimensional conformal simultaneously integrated boost (SIB) plans for three different tumors sites (i.e. bladder, breast, and brain). A total of 30 patients with brain, breast and bladder cancers were selected in this retrospective study. All the patients were CT simulated initially. The primary physician contoured PTV1 and PTV2 in the axial slices. The conventional doses prescribed for brain and breast is 60Gy/30 fractions, and 64.8Gy/36 fractions for bladder treatment. For the SIB plans biological effective doses (BED) were calculated for 25 fractions. The two conventional (Phase I and Phase II) and a single SIB plan for each patient were generated on Eclipse™ treatment planning system. Treatment plans were compared and analyzed for coverage index, conformity index, homogeneity index, dose gradient and organs at risk doses.In both plans 95% of PTV volume received a minimum of 95% of the prescribe dose. Dose deviation in the optic chiasm was found to be less than 0.5%. There is no significant difference in lung V20 and heart V30 in the breast plans. In the rectum plans V75%, V50% and V25% were found to be less than 1.2% different. Deviation in the tumor coverage, conformity and homogeneity indices were found to be less than 1%. SIB plans with three dimensional conformal radiotherapy technique reduce the overall treatment time without compromising the target coverage and without increasing dose to the organs at risk. The higher dose per fraction may increase the late effects to some extent. Further studies are required to evaluate the late effects with the intention of standardizing the SIB technique for practical implementation.

Keywords: coverage index, conformity index, dose gradient, homogeneity index, simultaneously integrated boost

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Authors: Raymond Limen Njinga

Abstract:

The comparator factors (Fc) for miniature research reactors are of great importance in the field of nuclear physics as it provide accurate bases for the evaluation of elements in all form of samples via ko-NAA techniques. The Fc was initially simulated theoretically thereafter, series of experiments were performed to validate the results. In this situation, the experimental values were obtained using the alloy of Au(0.1%) - Al monitor foil and a neutron flux setting of 5.00E+11 cm-2.s-1. As was observed in the inner irradiation position, the average experimental value of 7.120E+05 was reported against the theoretical value of 7.330E+05. In comparison, a percentage deviation of 2.86 (from theoretical value) was observed. In the large case of the outer irradiation position, the experimental value of 1.170E+06 was recorded against the theoretical value of 1.210E+06 with a percentage deviation of 3.310 (from the theoretical value). The estimation of equivalent dose rate at 5m from neutron flux of 5.00E+11 cm-2.s-1 within the neutron energies of 1KeV, 10KeV, 100KeV, 500KeV, 1MeV, 5MeV and 10MeV were calculated to be 0.01 Sv/h, 0.01 Sv/h, 0.03 Sv/h, 0.15 Sv/h, 0.21Sv/h and 0.25 Sv/h respectively with a total dose within a period of an hour was obtained to be 0.66 Sv.

Keywords: neutron flux, comparator factor, NAA techniques, neutron energy, equivalent dose

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Authors: Alemayehu Muluneh, Saskia Keesstra, Leo Stroosnijder, Woldeamlak Bewket, Ashenafi Burka

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There are some scientific evidences and a belief by many that forests attract rain and deforestation contributes to a decline of rainfall. However, there is still a lack of concrete scientific evidence on the role of forests in rainfall amount. In this paper, we investigate the forest-rainfall relationships in the environmentally hot spot area of the Central Rift Valley (CRV) of Ethiopia. Specifically, we evaluate long term (1970-2009) rainfall variability and its relationship with historical forest cover and the relationship between existing forest cover and topographical variables and rainfall distribution. The study used 16 long term and 15 short term rainfall stations. The Mann-Kendall test, bi variate and multiple regression models were used. The results show forest and wood land cover continuously declined over the 40 years period (1970-2009), but annual rainfall in the rift valley floor increased by 6.42 mm/year. But, on the escarpment and highlands, annual rainfall decreased by 2.48 mm/year. The increase in annual rainfall in the rift valley floor is partly attributable to the increase in evaporation as a result of increasing temperatures from the 4 existing lakes in the rift valley floor. Though, annual rainfall is decreasing on the escarpment and highlands, there was no significant correlation between this rainfall decrease and forest and wood land decline and also rainfall variability in the region was not explained by forest cover. Hence, the decrease in annual rainfall on the escarpment and highlands is likely related to the global warming of the atmosphere and the surface waters of the Indian Ocean. Spatial variability of number of rainy days from systematically observed two-year’s rainfall data (2012-2013) was significantly (R2=-0.63) explained by forest cover (distance from forest). But, forest cover was not a significant variable (R2=-0.40) in explaining annual rainfall amount. Generally, past deforestation and existing forest cover showed very little effect on long term and short term rainfall distribution, but a significant effect on number of rainy days in the CRV of Ethiopia.

Keywords: elevation, forest cover, rainfall, slope

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Authors: Ana M. Lara, Manuela Llano, Felipe Gaitán, Rosa H. Bustos, Ana Maria Perdomo-Arciniegas, Ximena Bonilla

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Umbilical cord blood is used as a source of progenitor and stem cells for the regeneration of the hematopoietic and immune system to treat patients with different hematological or non-hematological diseases. This stem cell source represents an advantage over the use of bone marrow or mobilized peripheral blood because it has a lower incidence rate of graft-versus-host disease, probably due to fewer immunological compatibility restrictions. However, its low cellular dose limits its use in pediatric patients. This work proposes the standardization of a cell expansion technique to compensate for the dose of infused cells through the ex-vivo manipulation of hematopoietic progenitor cells from umbilical cord blood before transplantation. The expansion model is carried out through co-cultures with mesenchymal stem cells (MSC) from bone marrow (BM) and less explored fetal tissues such as Wharton's jelly (WJ) and umbilical cord blood (UCB). Initially, a master cell bank of primary mesenchymal stem cells isolated from different sources was established and characterized following International Society of Cell Therapies (ISCT) indications. Additionally, we assessed the effect of a short 25 Gy cycle of gamma irradiation on cell cycle arrest of mesenchymal cells over the support capacity for the expansion of hematopoietic stem cells from umbilical cord blood was evaluated. The results show that co-cultures with MSC from WJ and UCB allow the cellular dose of HSPC to be maximized between 5 and 16 times having a similar support capacity as BM. In addition, was evaluated the hematopoietic stem progenitor cell's HSPC functionality through the evaluation of migration capacity, their differentiation capacity during culture time by flow cytometry to evaluate the expression of membrane markers associated with lineage-committed progenitors, their clonogenic potential, and the evaluation of secretome profile in the expansion process was evaluated. So far, the treatment with gamma irradiation maintains the hematopoietic support capacity of mesenchymal stem cells from the three sources studied compared to treatments without irradiation, favoring the use of fetal tissues that are generally waste to obtain mesenchymal cell lines for ex-vivo expansion systems. With the results obtained, a standardized protocol that will contribute to the development of ex-vivo expansion with MSC on a larger scale will be achieved, enabling its clinical use and expanding its application in adults.

Keywords: ex-vivo expansion, hematopoietic stem cells, hematopoietic stem cell transplantation, mesenchymal stem cells, umbilical cord blood

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Authors: Madhu Sudan, G. N. Tiwari

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In this paper, an attempt has been made to analyze the effect of wall window orientation on Daylight Illuminance Ratio (DIR) and energy saving in a building known as “SODHA BERS COMPLEX (SBC)” at Varanasi, UP, India. The building has been designed incorporating all passive concepts for thermal comfort as well daylighting concepts to maximize the use of natural daylighting for the occupants in the day to day activities. The annual average DIR and the energy saving has been estimated by using the DIR model for wall window with different orientations under clear sky condition. It has been found that for south oriented window the energy saving per square meter is more compared to the other orientations due to the higher level of solar insolation for the south window in northern hemisphere whereas energy saving potential is minimum for north oriented wall window. The energy saving potential was 26%, 81% and 51% higher for east, south and west oriented window in comparison to north oriented window. The average annual DIR has same trends of variation as the annual energy saving and it is maximum for south oriented window and minimum for north oriented window.

Keywords: clear sky, daylight factor, energy saving, wall window

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Authors: Kyung Min Kwom, Young Joo Lee

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Purpose: Up to 90% of pancreatic cancer patient suffer from neuropathic pain. In palliative care setting, pain control in a pancreatic cancer patient is one of the major goals. Ketamine is a NMDA receptor antagonist effective in neuropathic pain. Also, there have been studies about opioid sparing effect of ketamine. This study was held in palliative care unit among pancreatic cancer patients to find out the factors related to ketamine use and the opioid sparing effect. Methods: Medical records of pancreatic cancer patients admitted to St. Mary’s hospital palliative care unit from 2013.1 to 2014.12 were reviewed. Patients were divided into two categories according to ketamine use. Also, opioid use before and after ketamine use was compared in ketamine group. Results: Compared to non ketamine use group, patients in ketamine group required a higher dose of opioid. Total opioid dose, daily opioid dose, number of daily rescue medication, daily average rescue dose were statistically significantly higher in ketamine group. Opioid requirement was increased after ketamine administration. Conclusion: In this study, ketamine group required more opioid. Ketamine is frequently considered in patients with severe pain, requiring high amount of opioid. Also, ketamine did not have an opioid sparing effect. Future studies about palliative use of ketamine in a larger number of patients are required.

Keywords: ketamine, opioid sparing, palliative care, pancreatic cancer

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Authors: Maged Assem Soliman Mossallam

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Microsatellites' low available power limits the usage of active thermal control techniques in these categories of satellites. Passive thermal control techniques are preferred due to their high reliability and power saving which increase the satellite's survivability in orbit. Steady-state and transient simulations are applied to the microsatellite design in order to define severe conditions in orbit. Satellite thermal orbital three-dimensional simulation is performed using thermal orbit propagator coupled with Comsol Multiphysics finite element solver. Sensitivity study shows the dependence of the satellite temperatures on the internal heat dissipation and the thermooptical properties of anodization coatings. The critical case is defined as low power orbiting mode at the eclipse zone. Using black anodized aluminum drops the internal temperatures to severe values which exceed the permissible cold limits. Replacement with anodized titanium returns the internal subsystems' temperatures back to adequate temperature fluctuations limits.

Keywords: passive thermal control, thermooptical, anodized titanium, emissivity, absorbtiviy

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Authors: Mohand Yaghi, O. Kehinde

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Background: For the diagnosis of prostate cancer Trans-rectal prostate biopsy (TRPB) is used commonly, the procedure is associated with infective complications. There is evidence that antibiotics (ABx) decrease infective events after TRPB, but different regimens are used. Aim: To systematically review different regimens of prophylactic oral antibiotics in TRPB. Design: Medline, Embase, Clinical trials site, and Cochrane library were searched, experts were consulted about relevant studies. Randomized clinical trials (RCT) conducted in the last twenty years, which investigated different oral antibiotic regimens in TRPB, and compared their efficacy to reduce infectious complications were analyzed. Measurements: Primary outcomes were bacteriuria, urinary tract infection (UTI), fever, bacteremia, sepsis. Secondary outcomes were hospitalization rate, and the prevalence of ABx-resistant bacteria. Results: Nine trials were eligible with 3012 patients. Antibiotics prevented bacteriuria (3.5% vs. 9.88%), UTI (4.46% vs. 9.75%), and hospitalization (0.21% vs. 2.13%) significantly in comparison with placebo or no treatment. No significant difference was found in all outcomes of the review between the single dose regimen and the 3 days. The single dose regimen was as effective as the multiple dose except in Bacteriuria (6.75% vs. 3.25%), and the prevalence of ABx-resistant bacteria (1.57% vs. 0.27%). Quinolones reduced only UTI significantly in comparison with other antibiotics. Lastly, Ciprofloxacin is the best Quinolone to prevent UTI, and hospitalization. Conclusion: it is essential to prescribe prophylactic Antibiotics in TRPB. No conclusive evidence could be claimed about the superiority of the multiple or the 3 days regimens to the single dose regimen. Unexpectedly, ABx-resistant bacteria was identified more often in the single dose cohorts.

Keywords: infection, prostate cancer, sepsis, TRPB

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Authors: Kuan-Jen Lai, Fang-Yi Lin, Shang-Rong Huang, Yun-Zheng Zeng, Po-Chieh Hsu, Jay Wu

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The normalized glandular dose (DgN) estimates the energy deposition of mammography in clinical practice. The Monte Carlo simulations frequently use uniformly mixed phantom for calculating the conversion factor. However, breast tissues are not uniformly distributed, leading to errors of conversion factor estimation. This study constructed a three-layer phantom to estimated more accurate of normalized glandular dose. In this study, MCNP code (Monte Carlo N-Particles code) was used to create the geometric structure. We simulated three types of target/filter combinations (Mo/Mo, Mo/Rh, Rh/Rh), six voltages (25 ~ 35 kVp), six HVL parameters and nine breast phantom thicknesses (2 ~ 10 cm) for the three-layer mammographic phantom. The conversion factor for 25%, 50% and 75% glandularity was calculated. The error of conversion factors compared with the results of the American College of Radiology (ACR) was within 6%. For Rh/Rh, the difference was within 9%. The difference between the 50% average glandularity and the uniform phantom was 7.1% ~ -6.7% for the Mo/Mo combination, voltage of 27 kVp, half value layer of 0.34 mmAl, and breast thickness of 4 cm. According to the simulation results, the regression analysis found that the three-layer mammographic phantom at 0% ~ 100% glandularity can be used to accurately calculate the conversion factors. The difference in glandular tissue distribution leads to errors of conversion factor calculation. The three-layer mammographic phantom can provide accurate estimates of glandular dose in clinical practice.

Keywords: Monte Carlo simulation, mammography, normalized glandular dose, glandularity

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Authors: D. S. Mohale, A. V. Chandewar

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Anxiety is defined as an exaggerated feeling of apprehension, uncertainty and fear. Nerium indicum is a well-known ornamental and medicinal plant belonging to the family Apocynaceae. A wide spectrum of biological activities has been reported with various constituents isolated from different parts of the plant. This study was conducted to investigate antianxiety activity of flower extract. Flowers were collected and dried in shade and coarsely powdered. Powdered mixture was extracted with ethyl acetate by maceration process. Extract of flowers obtained was subsequently dried in oven at 40-50 °C. This extract is then tested for antianxiety activity at low and high dose using Elevated Plus Maze and Light & dark Model. Rats shown increased open arm entries and time spent in open arm in elevated Plus maze with treatment low and high dose of extract of Nerium indicum flower as compared to their respective control groups. In Light & dark Model, light box entries and time spent in light box increased with treatment low and high dose of extract of Nerium indicum flower as compared to their respective control groups. From result it is concluded that Ethyl acetate extract of flower of Nerium indicum possess antianxiety activity at low and high dose.

Keywords: anxiety, anxieolytic, social isolation, nerium indicum, kaner

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