Evidence of a Hardening in the Cosmic Ray Proton Spectrum at around 166 TeV Observed by the GRAPES-3 Experiment.

We present the measurement of the cosmic ray proton spectrum from 50 TeV to 1.3 PeV using 7.81×10^{6} extensive air shower events recorded by the ground-based GRAPES-3 experiment between 1 January 2014 and 26 October 2015 with a live time of 460 day. Our measurements provide an overlap with direct observations by satellite and balloon-based experiments. The electromagnetic and muon components in the shower were measured by a dense array of plastic scintillator detectors and a tracking muon telescope, respectively. The relative composition of the proton primary from the air shower data containing all primary particles was extracted using the multiplicity distribution of muons which is a sensitive observable for mass composition. The observed proton spectrum suggests a spectral hardening at ∼166 TeV and disfavors a single power law description of the spectrum up to the Knee energy (∼3 PeV).

Refractive Error Prevalence among School Children in Dadeldhura District of Nepal.

Background Uncorrected refractive error is the major cause of visual impairment worldwide. There is no data on refractive error prevalence among school children in hilly region of Far West Nepal. Objective The prevalence of refractive error has been found to vary among children of different caste/ethnic groups and geographical regions. The purpose of this study is to determine the prevalence of refractive error among school children from different caste/ethnic groups in Dadeldhura district of Far West Nepal. Method This is a cross sectional study of refractive error among secondary school children from 2 schools in Dadeldhura district. All children underwent a vision screening consisting of visual acuity, ocular examination and refraction. Myopia was diagnosed for an eye with spherical equivalent refraction (SER) ≤ -0.5 D whereas an eye with SER ≥ +2.0 D was diagnosed as hyperopic. Ethnicity was reported through self administered questionnaire. Result Among children aged 12 to 16 years (14.07 ± 1.4) prevalence of myopia was 3.5%, hyperopia 0.33% and astigmatism 1%. All except three children had spherical equivalent refraction (SER) within ±2 D. Caste/ethnicity was not associated significantly with myopia in either eye (χ2 = 0.27, df= 2, p= 0.87). Conclusion The prevalence of refractive error among secondary school children in Dadeldhura district of Far West Nepal is very low in comparison to myopia prevalence reported in studies from other parts of the world, but slightly lower than myopia prevalence found in other, eastern parts of Nepal.

The Prevalence of Diabetic Retinopathy Among Known Diabetic Population in Nepal.

Background The worldwide prevalence of diabetic retinopathy (DR) was found to be 34.6%. WHO estimates that DR is responsible for 4.8% of the 37 million cases of blindness throughout the world. In a study undertaken in urban population in Nepal, M.D. Bhattarai found the prevalence of diabetes among people aged 20 years and above to be 14.6% and the prevalence among people aged 40 years and above to be 19%. Studies on DR, to our knowledge, have mostly been hospital based in Nepal. Little information is available about prevalence of DR at the community level in Nepal. Objective To investigate the prevalence of diabetic retinopathy and associated risk factors among known diabetic population of Nepal. Method A descriptive cross sectional study was conducted among individuals aged 30 and more using cluster sampling method. The study sites were Kathmandu metropolitan city and Birgunj sub-metropolitan city. A sample size of 5400 was calculated assuming 5% prevalence rate with 95% confidence level, 5% worst acceptable level and 1.5 cluster sampling design effect. Study participants were interviewed, anthropometric measurements and fundus photograph was taken from participants with diabetes. Fundus photographs were used to grade retinopathy. Result Around 12% of the respondents were diabetic, mean age 55.43±11.86 years, of which slightly more than half were females (50.2%). Among these diabetic respondents 9.9% had some forms of diabetic retinopathy, mean age 54.08±10.34 years, 56.7% were male. When severe grade of retinopathy in any eye was considered as overall grade of retinopathy for the individual, prevalence of Non-proliferative Diabetic Retinopathy, Proliferative Diabetic Retinopathy and complete vision loss was found to be 9.1%, 0.5% and 0.3%. Prevalence of Diabetic Macular Edema was 5.5%. Duration of diabetes, family history of diabetes and blood pressure at the day of survey was found to be associated with having any retinopathy. Conclusion Diabetic retinopathy is emerging as a public health threat in Nepal. With increasing diabetes, DR can be expected to increase more. Existing eye care services may require upgrading to provide quality and affordable retinopathy services to address this emerging problem.

Reduced vision and refractive errors, results from a school vision screening program in Kanchanpur District of far western Nepal.

BACKGROUND: At present there is no data available on reduced vision and refractive errors in school children of far western Nepal. So, school screening records were used to obtain data useful for planning of refractive services. METHODS: Data are provided from school screening conducted by Geta Eye Hospital during February/March 2008. The cases with complete data sets on visual acuity, refractive error and age were included and analyzed using computer software. RESULTS: Of 1165 children (mean age 11.6 ± 2.5 years) examined, 98.8% (n = 1151) had uncorrected visual acuity of 6/9 and better in at least one eye whereas 1.2% (n = 14) had acuity 6/12 and worse in both eyes. Among them, either eye of 9 children improved to 6/9 and better with correction. However, visual acuity was 6/12 and worse in both eyes of 5 children even after correction. There were 24 children with refractive errors (myopia, 1.54%; n = 18 and hypermetropia, 0.51%; n = 6) in at least one eye. The spherical equivalent refraction was not significantly different with age and gender. CONCLUSIONS: The incidence of reduced vision and refractive errors among school children of this semi rural district were low.

Refractive status among the students presenting to Geta Eye Hospital, Kailali, Nepal.

A retrospective hospital based study was designed in order to evaluate the refractive status of students presenting to Geta Eye Hospital. All the hospital record of secondary level school students were collected from the record unit of the hospital. Children below 5 years of age and those with incomplete record were excluded from the study. All students who visited Geta Eye hospital during May 1 to July 30, 2007 AD were included in the study. Out of 328 students presenting to Geta Eye Hospital, presenting visual acuity was normal (6/6) in 67.4% students, while 32.6% had reduced presenting visual acuity. Altogether 7.0% students had presenting visual acuity worse than 6/18 in the better eye and 2.4% improved to better than 6/18 with correction. Significant refractive error (>0.50 D Spherical Equivalent) was found in total of 32.0% students. Myopia was present in 11.89% students, whereas Astigmatism and hypermetropia were present in 11.3% and 8.8% of the total students respectively. Out of total students, 95.4% students were found to have best corrected visual acuity of 6/6-6/18 in the better eye. There were 4.0% students in MVI category and 0.6% in SVI category after correction. Altogether 7.6% cases of amblyopia were found. Hyperopia was most commonly associated with amblyopia. Associated ocular morbidity in either eye was assessed and was found in 25.0% students. 6.4% cases had convergence insufficiency. About one third of the students presenting to hospital had significant refractive error. Thus, School can be our peripheral referral unit if we could train teachers to detect abnormal vision.

The efficacy of monoisoamyl ester of dimercaptosuccinic acid in chronic experimental arsenic poisoning in mice.

The therapeutic efficacy of monoisoamyl meso-2,3-dimercaptosuccinic acid (MiADMSA), a new monoester of 2,3-dimercaptosuccinic acid on arsenic induced oxidative stress in liver and kidneys, alterations in hematopoietic system and depletion of arsenic burden was assessed, in mice. Three different doses of MiADMSA (25, 50 or 100 mg/kg) for five consecutive days were administered in chronically arsenic exposed mice (10 ppm in drinking water for six months). Oral administration of MiADMSA particularly at a dose of 50 mg/kg, produced relatively more pronounced beneficial effects on the inhibited blood delta-aminolevulinic acid dehydratase (ALAD), biochemical variables indicative of hepatic and renal oxidative stress and depletion of arsenic concentration in blood, liver and kidneys, compared with intraperitoneal administration of the drug. The treatment with MiADMSA although, produced essential metals imbalance which could be a restrictive factor for the possible therapeutic use of this compound in chronic arsenic poisoning and thus require further exploration.

Haematological, hepatic and renal alterations after repeated oral or intraperitoneal administration of monoisoamyl DMSA. I. Changes in male rats.

Monoisoamyl 2,3-dimercaptosuccinic acid (MiADMSA), a vicinal thiol chelator, is gaining recognition recently as a better chelator than meso 2,3-dimercaptosuccinic acid (DMSA) in decreasing heavy metal burden in tissues because of its lipophilic character. There is, however, little information available on the toxicological properties of this chelator after repeated administration in animals. In the present study, we investigated the dose-dependent effect of MiADMSA on various biochemical parameters suggestive of alterations in haem biosynthesis and hepatic, renal and brain oxidative stress after 21 days of repeated intraperitoneal (i.p.) or oral (p.o.) administration to rats. The concentration of essential metals in blood and soft tissues was determined along with histopathological observations of hepatic and renal tissues. The results suggest that MiADMSA administration had no effect on blood delta-aminolevulinic acid dehydratase activity. However, an increase in zinc protoporphyrin and a decrease in haemoglobin levels were noted in animals given MiADMSA i.p. A moderate increase in serum alkaline phosphatase suggested mild hepatotoxicity at the highest dose (100 mg kg(-1), i.p.). This was confirmed by histopathological examinations, which identified basophilic stippling, granulation of the cytoplasm, haemorrhage and congestion. At the highest dose, levels of hepatic thiobarbituric acid reactive substance and oxidized glutathione were increased above those of control values. Levels of hepatic reduced glutathione were decreased. Taken together, these observations point to oxidative stress. In animals administered MiADMSA i.p. there was an increase in the brain malondialdehyde levels at the two higher doses (50 and 100 mg kg(-1)). Essential metal status revealed a significant effect of MiADMSA (p.o.) in increasing blood zinc while significantly decreasing the kidney zinc level. The most significant adverse effect of MiADMSA was on copper concentration, which showed significant depletion from almost all major organs. Magnesium levels in blood decreased but increased in liver of MiADMSA-administered rats. Histopathological observations of liver and kidneys suggest few moderate lesions. It can be concluded that repeated administration of MiADMSA is compromised with some mild toxic effect, particularly the loss of copper. The effects during oral administration are comparatively less pronounced than by the i.p. route.

Meso 2,3-dimercaptosuccinic acid (DMSA) and monoisoamyl DMSA effect on gallium arsenide induced pathological liver injury in rats.

The effect of meso 2,3-dimercaptosuccinic acid (DMSA) and monoisoamyl DMSA (MiADMSA) on gallium arsenide (GaAs) induced liver damage was studied. The oral feeding rat model was used in this study. The animals were exposed to 10 mg/kg GaAs, orally, once daily, 5 days a week for 24 weeks and treated thereafter with single oral daily dose of either 0.3 mmol/kg DMSA or MiADMSA for two course of 5 days treatment. The animals were sacrificed thereafter. Lipid peroxidation was assessed by measuring liver thiobarbituric acid reactive substance (TBARS). Liver damage was assessed by number of biochemical variables and by light microscopy. The activity of superoxide dismutase (SOD) and delta-aminolevulinic acid dehydratase (ALAD) beside reduced glutathione (GSH) concentration was measured in blood. Exposure to GaAs produced a significant reduction in GSH while, increased the oxidized glutathione (GSSG) concentration. Hepatic glutathione peroxidase (GPx) and catalase activity increased significantly while level of serum transaminase increased moderately. Gallium arsenide exposure also produced marked hepatic histopathological lesions. Overall, treatment with MiADMSA proved to be better than DMSA in the mobilization of arsenic and in the turnover of some of the above mentioned GaAs sensitive biochemical alterations. Histopathological lesions also, responded more favorably to chelation treatment with MiADMSA than DMSA.

Combined administration of a chelating agent and an antioxidant in the prevention and treatment of acute lead intoxication in rats.

The administration of chelating agents, meso 2,3-dimercaptosuccinic acid (DMSA), monoisoamyl DMSA (MiADMSA) either individually or in combination with an antioxidant, n-acetylcysteine (NAC) in the prevention and treatment of acute lead intoxication in rats, was investigated. The results suggest that concomitant oral supplementation of DMSA with lead was most effective in preventing the inhibition of lead sensitive blood delta-aminolevulinic acid dehydratase (ALAD) activity in blood, elevation of zinc protoporphyrin level and the alterations in hepatic reduced and oxidized glutathione (GSH and GSSG) contents. A number of other biochemical variables either remained insensitive to lead exposure or responded moderately to chelation treatment. Combined administrations of NAC plus DMSA was most effective when given during lead exposure or post exposure, followed by DMSA and MiADMSA alone or NAC plus MiADMSA treatment, in reducing the accumulation of lead in blood and liver. Administration of NAC alone was only mildly effective in preventing lead absorption in the blood and tissues. The results suggest that combined administration of DMSA and NAC could be a more effective treatment protocol for acute lead toxicity, keeping in view its beneficial effect on oxidative injury.

Arsenic-induced changes in certain neurotransmitter levels and their recoveries following chelation in rat whole brain.

Arsenic as sodium arsenite (100 ppm in drinking water) was administered to male rats for 16 weeks. Animals were then treated either with meso-2,3-dimercaptosuccinic acid (DMSA), sodium 2,3-dimercaptopropane 1-sulfonate (DMPS), dimethyl DMSA (DmDMSA), or diisopropyl DMSA (DiPDMSA) twice daily (50 mg/kg) intraperitoneally for 5 days. After 5 days of rest period, the animals were again given a second course of chelation therapy. The animals were sacrificed subsequently for the determination of whole brain biogenic amines levels, acetylcholinesterase (AChE), monoamine oxidase (MAO) and delta-aminolevulinic acid dehydratase (ALAD) activities. A number of biochemical parameters and arsenic concentrations in some tissues were also determined. The results suggest a significant increase in brain arsenic concentration accompanied by alterations in neurotransmitters levels following As(III) exposure. Although chelation treatment was effective in reducing As burden, the altered biochemical variables responded less favorably to chelation therapy. The DMSA-diesters, particularly DiPDMSA, produced a more pronounced increase in brain arsenic burden, as well as alterations in a few neurotransmitters. It can be concluded that the lipophilic character of As antidotes may lead to unfavorable results following intraperitoneal administration.

Evaluation of two compounds as possible radioprotectors.

Radioprotecting effectiveness of S-[2-(diethylamino)ethyl] 4-methylbenzothiohydroximate hydrochloride (Dev-B-9) and S-[2-(diethylamino)ethyl]alpha-keto 4-methyl benzothiohydroximate hydrochloride (Dev-B 43) were evaluated by both survival studies in mice exposed to 10.5 Gy whole body gamma-irradiation and 24 hours deoxycytidine (CdR) excretion in urine of rats following 5 Gy irradiation. The drugs were tested after intraperitoneal (i.p.) administration. The drugs rendered significant protection in sublethal (5 Gy) irradiation but could not protect against 10.5 Gy exposure.

Studies on the efficacy of diethyxime as an antidote against organophosphorus intoxication in rats.

Diethyxime, a non-quaternary cholinesterase reactivator was evaluated for its antidotal efficacy against organophosphorus intoxication in rats using the protection index, cholinesterase reactivation and neuromuscular function as the experimental protocol. Diethyxime along with atropine produced a marked antidotal effect against dimethyl dichlorovinyl phosphate (DDVP) poisoning on all the parameters studied. The action of diethyxime was mainly peripheral. The protective efficacy against diisopropyl fluorophosphate (DFP) poisoning was not observed with this reactivator.