Search results for: Sanjiv Shrestha
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 55

Search results for: Sanjiv Shrestha

25 Integrated Modeling of Transformation of Electricity and Transportation Sectors: A Case Study of Australia

Authors: T. Aboumahboub, R. Brecha, H. B. Shrestha, U. F. Hutfilter, A. Geiges, W. Hare, M. Schaeffer, L. Welder, M. Gidden

Abstract:

The proposed stringent mitigation targets require an immediate start for a drastic transformation of the whole energy system. The current Australian energy system is mainly centralized and fossil fuel-based in most states with coal and gas-fired plants dominating the total produced electricity over the recent past. On the other hand, the country is characterized by a huge, untapped renewable potential, where wind and solar energy could play a key role in the decarbonization of the Australia’s future energy system. However, integrating high shares of such variable renewable energy sources (VRES) challenges the power system considerably due to their temporal fluctuations and geographical dispersion. This raises the concerns about flexibility gap in the system to ensure the security of supply with increasing shares of such intermittent sources. One main flexibility dimension to facilitate system integration of high shares of VRES is to increase the cross-sectoral integration through coupling of electricity to other energy sectors alongside the decarbonization of the power sector and reinforcement of the transmission grid. This paper applies a multi-sectoral energy system optimization model for Australia. We investigate the cost-optimal configuration of a renewable-based Australian energy system and its transformation pathway in line with the ambitious range of proposed climate change mitigation targets. We particularly analyse the implications of linking the electricity and transport sectors in a prospective, highly renewable Australian energy system.

Keywords: decarbonization, energy system modelling, renewable energy, sector coupling

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24 Coagulase Negative Staphylococci: Phenotypic Characterization and Antimicrobial Susceptibility Pattern

Authors: Lok Bahadur Shrestha, Narayan Raj Bhattarai, Basudha Khanal

Abstract:

Introduction: Coagulase-negative staphylococci (CoNS) are the normal commensal of human skin and mucous membranes. The study was carried out to study the prevalence of CoNS among clinical isolates, to characterize them up to species level and to compare the three conventional methods for detection of biofilm formation. Objectives: to characterize the clinically significant coagulase-negative staphylococci up to species level, to compare the three phenotypic methods for the detection of biofilm formation and to study the antimicrobial susceptibility pattern of the isolates. Methods: CoNS isolates were obtained from various clinical samples during the period of 1 year. Characterization up to species level was done using biochemical test and study of biofilm formation was done by tube adherence, congo red agar, and tissue culture plate method. Results: Among 71 CoNS isolates, seven species were identified. S. epidermidis was the most common species followed by S. saprophyticus, S. haemolyticus. Antimicrobial susceptibility pattern of CoNS documented resistance of 90% to ampicillin. Resistance to cefoxitin and ceftriaxone was observed in 55% of the isolates. We detected biofilm formation in 71.8% of isolates. The sensitivity of tube adherence method was 82% while that of congo red agar method was 78%. Conclusion: Among 71 CoNS isolated, S. epidermidis was the most common isolates followed by S. saprophyticus and S. haemolyticus. Biofilm formation was detected in 71.8% of the isolates. All of the methods were effective at detecting biofilm-producing CoNS strains. Biofilm former strains are more resistant to antibiotics as compared to biofilm non-formers.

Keywords: CoNS, congo red agar, bloodstream infections, foreign body-related infections, tissue culture plate

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23 Effect of Honey on Rate of Healing of Socket after Tooth Extraction in Rabbits

Authors: Deependra Prasad Sarraf, Ashish Shrestha, Mehul Rajesh Jaisani, Gajendra Prasad Rauniar

Abstract:

Background: Honey is the worlds’ oldest known wound dressing. Its wound healing properties are not fully established till today. Concerns about antibiotic resistance, and a renewed interest in natural remedies have prompted the resurgence in the antimicrobial and wound healing properties of Honey. Evidence from animal studies and some trials has suggested that honey may accelerate wound healing in burns, infected wounds and open wounds. None of these reports have documented the effect of honey on the healing of socket after tooth extraction. Therefore, the present experimental study was planned to evaluate the efficacy of honey on the healing of socket after tooth extraction in rabbits. Materials and Methods: An experimental study was conducted in six New Zealand White rabbits. Extraction of first premolar tooth on both sides of the lower jaw was done under anesthesia produced by Ketamine and Xylazine followed by application of honey on one socket (test group) and normal saline (control group) in the opposite socket. The intervention was continued for two more days. On the 7th day, the biopsy was taken from the extraction site, and histopathological examination was done. Student’s t-test was used for comparison between the groups and differences were considered to be statistically significant at p-value less than 0.05. Results: There was a significant difference between control group and test group in terms of fibroblast proliferation (p = 0.0019) and bony trabeculae formation (p=0.0003). Inflammatory cells were also observed in both groups, and it was not significant (p=1.0). Overlying epithelium was hyperplastic in both the groups. Conclusion: The study showed that local application of honey promoted the rapid healing process particularly by increasing fibroblast proliferation and bony trabeculae.

Keywords: honey, extraction wound, Nepal, healing

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22 Potential Impacts of Warming Climate on Contributions of Runoff Components from Two Catchments of Upper Indus Basin, Karakoram, Pakistan

Authors: Syed Hammad Ali, Rijan Bhakta Kayastha, Ahuti Shrestha, Iram Bano

Abstract:

The hydrology of Upper Indus basin is not recognized well due to the intricacies in the climate and geography, and the scarcity of data above 5000 meters above sea level where most of the precipitation falls in the form of snow. The main objective of this study is to measure the contributions of different components of runoff in Upper Indus basin. To achieve this goal, the Modified positive degree-day model (MPDDM) was used to simulate the runoff and investigate its components in two catchments of Upper Indus basin, Hunza and Gilgit River basins. These two catchments were selected because of their different glacier coverage, contrasting area distribution at high altitudes and significant impact on the Upper Indus River flow. The components of runoff like snow-ice melt and rainfall-base flow were identified by the model. The simulation results show that the MPDDM shows a good agreement between observed and modeled runoff of these two catchments and the effects of snow-ice are mainly reliant on the catchment characteristics and the glaciated area. For Gilgit River basin, the largest contributor to runoff is rain-base flow, whereas large contribution of snow-ice melt observed in Hunza River basin due to its large fraction of glaciated area. This research will not only contribute to the better understanding of the impacts of climate change on the hydrological response in the Upper Indus, but will also provide guidance for the development of hydropower potential, water resources management and offer a possible evaluation of future water quantity and availability in these catchments.

Keywords: future discharge projection, positive degree day, regional climate model, water resource management

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21 Lignin Pyrolysis to Value-Added Chemicals: A Mechanistic Approach

Authors: Binod Shrestha, Sandrine Hoppe, Thierry Ghislain, Phillipe Marchal, Nicolas Brosse, Anthony Dufour

Abstract:

The thermochemical conversion of lignin has received an increasing interest in the frame of different biorefinery concepts for the production of chemicals or energy. It is needed to better understand the physical and chemical conversion of lignin for feeder and reactor designs. In-situ rheology reveals the viscoelastic behaviour of lignin upon thermal conversion. The softening, re-solidification (char formation), swelling and shrinking behaviours are quantified during pyrolysis in real-time [1]. The in-situ rheology of an alkali lignin (Protobind 1000) was conducted in high torque controlled strain rheometer from 35°C to 400°C with a heating rate of 5°C.min-1. The swelling, through glass phase transition overlapped with depolymerization, and solidification (crosslinking and “char” formation) are two main phenomena observed during lignin pyrolysis. The onset of temperatures for softening and solidification for this lignin has been found to be 141°C and 248°C respectively. An ex-situ characterization of lignin/char residues obtained at different temperatures after quenching in the rheometer gives a clear understanding of the pathway of lignin degradation. The lignin residues were sampled from the mid-point temperatures of the softening range and solidification range to study the chemical transformations undergoing. Elemental analysis, FTIR and solid state NMR were conducted after quenching the solid residues (lignin/char). The quenched solid was also extracted by suitable solvent and followed by acetylation and GPC-UV analysis. The combination of 13C NMR and GPC-UV reveals the depolymerization followed by crosslinking of lignin/char. NMR and FTIR provide the evolution of functional moieties upon temperature. Physical and chemical mechanisms occurring during lignin pyrolysis are accounted in this study. Thanks to all these complementary methods.

Keywords: pyrolysis, bio-chemicals, valorization, mechanism, softening, solidification, cross linking, rheology, spectroscopic methods

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20 Seminal Attributes, Cooling Procedure and Post Thaw Quality of Semen of Indigenous Khari Bucks (Capra hircus) of Nepal

Authors: Pankaj Kumar Jha, Saroj Sapkota, Dil Bahadur Gurung, Raju Kadel, Neena Amatya Gorkhali, Bhola Shankar Shrestha

Abstract:

The study was conducted to evaluate the seminal attributes, effectiveness of cooling process and post-thawed semen quality of a Nepalese indigenous Khari buck. Thirty-two ejaculates, 16 from each buck were studied for seminal attributes of fresh semen: volume, color, mass activity, motility, viability, sperm concentration, and morphology. The pooled mean values for each seminal attributes were: volume 0.7±0.3 ml; colour 3.1±0.3 (milky white); mass activity 3.8±0.4 (rapid wave motion with formation of eddies at the end of waves to very rapid wave motion with distinct eddies formation); sperm motility 80.9±5.6%; sperm viability 94.6±2.0%; sperm concentration 2597.0±406.8x106/ml; abnormal acrosome, mid-piece and tail 10.7±1.8% and abnormal head 5±1.7%. For freezing semen, further 6 ejaculates from each buck were studied with Tris based egg yolk citrate extender. The pooled mean values of motility and viability of post diluted semen for 90 and 120 minutes each for cooling and glycerol equilibration were 73.8±4.8%, 88.1±2.6% and 69.2±6.0%, 85.0±1.7%, respectively. The pooled mean values of post thaw motility and viability with advancement of preservation time were: 0hour 49.0±4.6%, 81.2±1.9%; 2nd day 41±2.2%, 79±1%; 5th day 41±2.2%, 78.6±0.9% and 10th day 41±2.2%, 78.6±0.9%. We concluded from the above study that the seminal attributes and results of post-thaw semen quality were satisfactory and in accordance with other work in foreign countries, which indicated the feasibility of cryopreserving buck semen. For more validation, research with large number of bucks, different types of diluents and freezing trials by removing seminal plasma followed by pregnancy rate is recommended.

Keywords: cryopreservation, Nepalese indigenous Khari (Hill goat) buck, post-thaw semen quality, seminal attributes

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19 Efficacy and Safety of Combination Therapy in Androgenetic Alopecia: Randomized Uncontrolled Evaluator, Blind Study

Authors: Shivani Dhande, Sanjiv Choudhary, Adarshlata Singh

Abstract:

Introduction: Early age of onset of baldness has marked psychological impact on personality. Combination therapies have better efficacy than monotherapy in androgenetic alopecia. Although medical, surgical treatment and cosmetic aids are available for treatment of pattern baldness, medical is first preferred the line of treatment. Although only 5% topical minoxidil is USFDA approved, 10% is available in India since 2007. Efficacy of tablet finasteride is well established in male pattern baldness. 5% topical minoxidil is effective and safe in female pattern baldness. There is a role of saw palmetto in regrowth of scalp hair. With this background research was undertaken to study efficacy and safety of topical minoxidil 10% + tab. Finesteride (1mg) + dermaroller in male pattern baldness and topical minoxidil 5% + cap. Saw palmetto (320 mg) + dermaroller in female pattern baldness. Methods and Materials: It was a randomized uncontrolled evaluator blind study consisting of total 21 patients, 15 of male pattern baldness and 6 of female pattern baldness within 20-35 yrs of age were enrolled. Male patients had Hamilton grade 2-4 MPB and females had Ludwig grade 2 FPB. Male patients were treated with Tab Finesteride 1mg once daily + 10% topical Minoxidil 1ml twice daily for 6 months. Female patients were treated with Cap. Saw palmetto 320 mg once daily + 5% topical Minoxidil twice daily for 6 months. In both male & female patients dermaroller therapy was used once in 10 days for 4 sittings followed by once in 15 days for next 5 months. Blood pressure and possible side effects were monitored in every follow up visits. Pre and post treatment photographs were taken. Assessment of hair growth was done at baseline and at the end of 6 months. Patients satisfactory grading scale and Physician assessment of hair growth scale were used to assessing the results. Trichoscan was done for assessment of hair-shaft diameter and density. Pre and post treatment photographs and Trichoscan hair growth analysis (by diameter and density) was done by physician (dermatologist) not directly involved in this study (evaluator blind). Result: This combination therapy showed moderate response in female pattern alopecia and good to excellent results in male pattern alopecia at the end of 6 months. During therapy none of the patients showed side effects like hypotension, headache and loss of libido, hirsuitism. Mild irritation due to crystal deposition was noted by 3 patients. Conclusion: Effective and early treatment using combination therapy with higher percent of Minoxidil for rapid hair growth is necessary in initial period since it will boost up the self-confidence in patients leading to better treatment compliance. Subsequent maintenance of hair growth can be done with lower concentration. No significant side effects with treatment are observed in both group of patients.

Keywords: androgenetic alopecia, dermaroller, finasteride, minoxidil, saw palmetto

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18 Media-Based Interventions to Influence English Language Learning: A Case of Bangladesh

Authors: Md. Mizanoor Rahman, Md. Zakir Hossain Talukder, M. Mahruf C. Shohel, Prithvi Shrestha

Abstract:

In Bangladesh, classroom practice and English Learning (EL) competencies acquired both by the teacher and learner in primary and secondary schools are still very weak. Therefore, English is the most commonly failed examination subject at the school level; in addition, there are severe problems in communicative English by the Bangladeshi nationals– this has been characterized as a constraint to economic development. Job applicants and employees often lack English language skills necessary to work effectively. As a result; both government and its international development partners such as DFID, UNESCO, and CIDA have been very active to uplift the quality of the English language learning and implementing projects with innovative approaches. Recently; the economy has been increasing and in line with this, the technology has been deployed in English learning to improve reading, writing, speaking and listening skills. Young Bangladeshi creative, from a variety of backgrounds including film, animation, photography, and digital media are being trained to develop ideas for English Language Teaching (ELT) media. They are being motivated to develop a wide range of ideas for low cost English learning media products. English Language education policy in Bangladesh supports communicative language teaching practices and accordingly, actors have been influencing curriculum, textbook, deployment of technology and assessment changes supporting communicative ELT. The various projects are also being implemented to reform the curriculum, revise the textbook and adjust the assessment mechanism so that the country can increase in proficiency in communicative English among the population. At present; the numbers of teachers, students and adult learners classified at higher levels of proficiency because of deployment of technology and motivation for learning and using English among school population of Bangladesh. The current paper discusses the various interventions in Bangladesh with appropriate media to improve the competencies of the ELT among population.

Keywords: English learning, technology, education, psychological sciences

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17 Estimation of Snow and Ice Melt Contributions to Discharge from the Glacierized Hunza River Basin, Karakoram, Pakistan

Authors: Syed Hammad Ali, Rijan Bhakta Kayastha, Danial Hashmi, Richard Armstrong, Ahuti Shrestha, Iram Bano, Javed Hassan

Abstract:

This paper presents the results of a semi-distributed modified positive degree-day model (MPDDM) for estimating snow and ice melt contributions to discharge from the glacierized Hunza River basin, Pakistan. The model uses daily temperature data, daily precipitation data, and positive degree day factors for snow and ice melt. The model is calibrated for the period 1995-2001 and validated for 2002-2013, and demonstrates close agreements between observed and simulated discharge with Nash–Sutcliffe Efficiencies of 0.90 and 0.88, respectively. Furthermore, the Weather Research and Forecasting model projected temperature, and precipitation data from 2016-2050 are used for representative concentration pathways RCP4.5 and RCP8.5, and bias correction was done using a statistical approach for future discharge estimation. No drastic changes in future discharge are predicted for the emissions scenarios. The aggregate snow-ice melt contribution is 39% of total discharge in the period 1993-2013. Snow-ice melt contribution ranges from 35% to 63% during the high flow period (May to October), which constitutes 89% of annual discharge; in the low flow period (November to April) it ranges from 0.02% to 17%, which constitutes 11 % of the annual discharge. The snow-ice melt contribution to total discharge will increase gradually in the future and reach up to 45% in 2041-2050. From a sensitivity analysis, it is found that the combination of a 2°C temperature rise and 20% increase in precipitation shows a 10% increase in discharge. The study allows us to evaluate the impact of climate change in such basins and is also useful for the future prediction of discharge to define hydropower potential, inform other water resource management in the area, to understand future changes in snow-ice melt contribution to discharge, and offer a possible evaluation of future water quantity and availability.

Keywords: climate variability, future discharge projection, positive degree day, regional climate model, water resource management

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16 Imaging Spectrum of Central Nervous System Tuberculosis on Magnetic Resonance Imaging: Correlation with Clinical and Microbiological Results

Authors: Vasundhara Arora, Anupam Jhobta, Suresh Thakur, Sanjiv Sharma

Abstract:

Aims and Objectives: Intracranial tuberculosis (TB) is one of the most devastating manifestations of TB and a challenging public health issue of considerable importance and magnitude world over. This study elaborates on the imaging spectrum of neurotuberculosis on magnetic resonance imaging (MRI) in 29 clinically suspected cases from a tertiary care hospital. Materials and Methods: The prospective hospital based evaluation of MR imaging features of neuro-tuberculosis in 29 clinically suspected cases was carried out in Department of Radio-diagnosis, Indira Gandhi Medical Hospital from July 2017 to August 2018. MR Images were obtained on a 1.5 T Magnetom Avanto machine and were analyzed to identify any abnormal meningeal enhancement or parenchymal lesions. Microbiological and Biochemical CSF analysis was performed in radio-logically suspected cases and the results were compared with the imaging data. Clinical follow up of the patients started on anti-tuberculous treatment was done to evaluate the response to treatment and clinical outcome. Results: Age range of patients in the study was between 1 year to 73 years. The mean age of presentation was 11.5 years. No significant difference in the distribution of cerebral tuberculosis was noted among the two genders. Imaging findings of neuro-tuberculosis obtained were varied and non specific ranging from lepto-meningeal enhancement, cerebritis to space occupying lesions such as tuberculomas and tubercular abscesses. Complications presenting as hydrocephalus (n= 7) and infarcts (n=9) was noted in few of these patients. 29 patients showed radiological suspicion of CNS tuberculosis with meningitis alone observed in 11 cases, tuberculomas alone were observed in 4 cases, meningitis with parenchymal tuberculomas in 11 cases. Tubercular abscess and cerebritis were observed in one case each. Tuberculous arachnoiditis was noted in one patient. Gene expert positivity was obtained in 11 out of 29 radiologically suspected patients; none of the patients showed culture positivity. Meningeal form of the disease alone showed higher positivity rate of gene Xpert (n=5) followed by combination of meningeal and parenchymal forms of disease (n=4). The parenchymal manifestation of disease alone showed least positivity rates (n= 3) with gene xpert testing. All 29 patients were started on anti tubercular treatment based on radiological suspicion of the disease with clinical improvement observed in 27 treated patients. Conclusions: In our study, higher incidence of neuro- tuberculosis was noted in paediatric population with predominance of the meningeal form of the disease. Gene Xpert positivity obtained was low due to paucibacillary nature of cerebrospinal fluid (CSF) with even lower positivity of CSF samples in parenchymal form of the manifestation. MRI showed high accuracy in detecting CNS lesions in neuro-tuberculosis. Hence, it can be concluded that MRI plays a crucial role in the diagnosis because of its inherent sensitivity and specificity and is an indispensible imaging modality. It caters to the need of early diagnosis owing to poor sensitivity of microbiological tests more so in the parenchymal manifestation of the disease.

Keywords: neurotuberculosis, tubercular abscess, tuberculoma, tuberculous meningitis

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15 Honey Intoxication: A Unique Cause of Sudden Cardiac Collapse

Authors: Bharat Rawat, Shekhar Rajbhandari, Yadav Bhatta, Jay Prakash Jaiswal, Shivaji Bikram Silwal, Rajiv Shrestha, Shova Sunuwar

Abstract:

Introduction: The honey produced by the bees fed on Rhobdodendron species containing grayanotoxin is known as mad honey. Grayanotoxin is found in honey obtained from the nectar of Rhododendron species growing on the mountains of the Black Sea region of Turkey and also in Japan, Nepal, Brazil, parts of North America, and Europe. Although the incidence of grayanotoxin poisoning is rare, there is concern that the number of cases per year will rise with the increasing demand for organic products. Mad honey intoxication might present with mild symptoms of cardiovascular, gastrointestinal and neurological systems or might also present with a life-threatening form with AV block and cardiovascular collapse. In this article, we describe the summary of five cases, which came to our hospital with mad honey related cardiac complications. Findings: In last one year, five cases presented in the emergency department with sudden onset of Loss of consciousness, dizziness, shortness of breath. They felt difficulty after the consumption of 1-3 teaspoonful of wild honey. The honey was brought from most of the rural parts of Nepal like khotang. Some of them also came with vomiting, dizziness, and loose stool. On examination, most of them had severe bradycardia and low blood pressure. No abnormalities were detected on systemic examinations. In one patient, ECG and cardiac enzymes showed features of the acute coronary syndrome, but his treadmill test done few days later was normal. All patients were managed with inj. Atropine, I/V normal saline, and other supportive measures and discharged in a stable condition within one or two days. Conclusions: Rhododendrons is the national flower of Nepal. The specific species of rhododendron found in Nepal which contains the toxin is not known. Bees feeding on these rhododendrons are known to transfer the grayanotoxin to the honey they produce. Most symptoms are mild and resolve themselves without medical intervention. Signs and symptoms of grayanotoxin poisoning rarely last more than 24 hours and are usually not fatal. Some signs of mad honey poisoning include Bradycardia, Cardiac arrhythmia, Hypotension, Nausea and Vomiting. They respond to close monitoring and appropriate supportive treatment. Normally, patients recover completely with no residual damage to the heart or its conduction system.

Keywords: rhobdodendron, honey, grayanotoxin, bradycardia

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14 A Comparative Study of Efficacy and Safety of Salicylic Acid, Trichloroacetic Acid and Glycolic Acid in Various Facial Melanosis

Authors: Shivani Dhande, Sanjiv Choudhary, Adarshlata Singh

Abstract:

Introduction: Chemical peeling is a popular, relatively inexpensive day procedure and generally safe method for treatment of pigmentary skin disorders and for skin rejuvenation. Chemical peels are classified by the depth of action into superficial, medium, and deep peels.Various facial pigmentary conditions have significant impact on quality of life causing psychological stress, necessitating its safe and effective treatment.Aim & Objectives:To compare the efficacy of Salicylic acid, Trichloroaceticacid & Glycolic Acid in facial melanosis(melasma,photomelanosis& post acne pigmentation).To study the side effects of above mentioned peeling agents. Method and Materials:It was a randomized parallel control single blind study consisting of total of 36 cases, 12 cases each of melasma, photo melanosis and post acne pigmentation within age group 20-50 years having fitzpatrick’s skin type4. Woods lamp examination was done to confirm the type of melasma.Patients with keloidal tendency, active herpes infection or past history of hypersensitivity to salicylic acid, trichloroaceticand glycolic acid as well aspatients on systemic isotretinoin were excluded.Clinical photographs at the beginning of therapy and then serially, were taken to assess the clinical response. Prior to application a written informed consent was obtained. A post auricular test peel was performed. Patients were divided into 3 groups, containing 12 patients each of melasma, photomelanosis and post acnepigmentation.All the three peels SA peel 20% (done once in 2 weeks), GA peel 50% (done once in 3 weeks) and TCA 15% (done once in 3 weeks) were used with total six settings for each patient. Before application of peel patients were counseled to wash the face with soap and water. Then face was dried and cleaned with spirit and acetone to remove all cutaneous oils. GA, TCA, SA were applied with cotton buds/gauze withmild strokes. After a contact period off 5-10mins neutralization was done with cold water. Post peel topical sunscreen application was mandatory. MASI was used pre and post treatment to assess melasma. Investigator’s global improvement scale- overall hyperpigmentation (4-significant, 3-moderate, 2-mild, 1-minimal, 0-no change ) and Patient’s satisfaction grading scale (>70%- excellent response, 50-70%- good response, <50%- average response) was used to assess improvement in all the three facial melanosis.Results:In our study of 12 patients of melasma, 4 (33.33%)patients showed excellent results;3 (25%) with GAand 1(8.33%) of TCA.Good response was seen in 4 (33.33%) patients;1(8.33%) each for GA & SA and 2(16.66%) for TCA.Poor response was seen in 4(33.33%) patients;1(8.33%) for TCA and 3 (25%) for SA.Of 12 patients of photomelanosis, excellent resultswas seen in 3(25%)patients of TCA. Good response was seen in 4 (33.33%) patients, 1(8.33%) each of TCA &SA and 2(16.66%) of GA.Poor responsewas seen in 5(41.66%) patients;3 (25%) for SA and 2(16.66%) of GA.Of 12 patients of post acne pigmentation, excellent responsein 3 (25%) patients;2(16.66%) of SA and 1(8.33%) of TCA.Good responsewas seen in 5(41.66%) patients;2(16.66%) of SA and GA and1(8.33%) of TCA.Poor response was seen in 4 (33.33%) patients; 2 (16.66%) for SA and TCA both. No major side effects in the form of scarring or persistant pigmentation was seen. Transient blackening of skin with burning sensation was seen in cases treated with TCA and SA. Post procedural itching and redness was noted with GA peel. Conclusion- In our study GA(50%),TCA(15%) & SA(20%) peels showed excellent response in melasma, photomelanosis and post-acne pigmentation respectively.All the 3 peeling agents were well tolerated without any significant side-effects in the above specified concentrations.

Keywords: facial melanosis, gycolic acid, salicylic acid, trichloroacetic acid

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13 Investigation of Chemical Effects on the Lγ2,3 and Lγ4 X-ray Production Cross Sections for Some Compounds of 66dy at Photon Energies Close to L1 Absorption-edge Energy

Authors: Anil Kumar, Rajnish Kaur, Mateusz Czyzycki, Alessandro Migilori, Andreas Germanos Karydas, Sanjiv Puri

Abstract:

The radiative decay of Li(i=1-3) sub-shell vacancies produced through photoionization results in production of the characteristic emission spectrum comprising several X-ray lines, whereas non-radiative vacancy decay results in Auger electron spectrum. Accurate reliable data on the Li(i=1-3) sub-shell X-ray production (XRP) cross sections is of considerable importance for investigation of atomic inner-shell ionization processes as well as for quantitative elemental analysis of different types of samples employing the energy dispersive X-ray fluorescence (EDXRF) analysis technique. At incident photon energies in vicinity of the absorption edge energies of an element, the many body effects including the electron correlation, core relaxation, inter-channel coupling and post-collision interactions become significant in the photoionization of atomic inner-shells. Further, in case of compounds, the characteristic emission spectrum of the specific element is expected to get influenced by the chemical environment (coordination number, oxidation state, nature of ligand/functional groups attached to central atom, etc.). These chemical effects on L X-ray fluorescence parameters have been investigated by performing the measurements at incident photon energies much higher than the Li(i=1-3) sub-shell absorption edge energies using EDXRF spectrometers. In the present work, the cross sections for production of the Lk(k= γ2,3, γ4) X-rays have been measured for some compounds of 66Dy, namely, Dy2O3, Dy2(CO3)3, Dy2(SO4)3.8H2O, DyI2 and Dy metal by tuning the incident photon energies few eV above the L1 absorption-edge energy in order to investigate the influence of chemical effects on these cross sections in presence of the many body effects which become significant at photon energies close to the absorption-edge energies. The present measurements have been performed under vacuum at the IAEA end-station of the X-ray fluorescence beam line (10.1L) of ELETTRA synchrotron radiation facility (Trieste, Italy) using self-supporting pressed pellet targets (1.3 cm diameter, nominal thicknesses ~ 176 mg/cm2) of 66Dy compounds (procured from Sigma Aldrich) and a metallic foil of 66Dy (nominal thickness ~ 3.9 mg/cm2, procured from Good Fellow, UK). The present measured cross sections have been compared with theoretical values calculated using the Dirac-Hartree-Slater(DHS) model based fluorescence and Coster-Kronig yields, Dirac-Fock(DF) model based X-ray emission rates and two sets of L1 sub-shell photoionization cross sections based on the non-relativistic Hartree-Fock-Slater(HFS) model and those deduced from the self-consistent Dirac-Hartree-Fock(DHF) model based total photoionization cross sections. The present measured XRP cross sections for 66Dy as well as for its compounds for the L2,3 and L4 X-rays, are found to be higher by ~14-36% than the two calculated set values. It is worth to be mentioned that L2,3 and L4 X-ray lines are originated by filling up of the L1 sub-shell vacancies by the outer sub-shell (N2,3 and O2,3) electrons which are much more sensitive to the chemical environment around the central atom. The present observed differences between measured and theoretical values are expected due to combined influence of the many-body effects and the chemical effects.

Keywords: chemical effects, L X-ray production cross sections, Many body effects, Synchrotron radiation

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12 A Dynamic Cardiac Single Photon Emission Computer Tomography Using Conventional Gamma Camera to Estimate Coronary Flow Reserve

Authors: Maria Sciammarella, Uttam M. Shrestha, Youngho Seo, Grant T. Gullberg, Elias H. Botvinick

Abstract:

Background: Myocardial perfusion imaging (MPI) is typically performed with static imaging protocols and visually assessed for perfusion defects based on the relative intensity distribution. Dynamic cardiac SPECT, on the other hand, is a new imaging technique that is based on time varying information of radiotracer distribution, which permits quantification of myocardial blood flow (MBF). In this abstract, we report a progress and current status of dynamic cardiac SPECT using conventional gamma camera (Infinia Hawkeye 4, GE Healthcare) for estimation of myocardial blood flow and coronary flow reserve. Methods: A group of patients who had high risk of coronary artery disease was enrolled to evaluate our methodology. A low-dose/high-dose rest/pharmacologic-induced-stress protocol was implemented. A standard rest and a standard stress radionuclide dose of ⁹⁹ᵐTc-tetrofosmin (140 keV) was administered. The dynamic SPECT data for each patient were reconstructed using the standard 4-dimensional maximum likelihood expectation maximization (ML-EM) algorithm. Acquired data were used to estimate the myocardial blood flow (MBF). The correspondence between flow values in the main coronary vasculature with myocardial segments defined by the standardized myocardial segmentation and nomenclature were derived. The coronary flow reserve, CFR, was defined as the ratio of stress to rest MBF values. CFR values estimated with SPECT were also validated with dynamic PET. Results: The range of territorial MBF in LAD, RCA, and LCX was 0.44 ml/min/g to 3.81 ml/min/g. The MBF between estimated with PET and SPECT in the group of independent cohort of 7 patients showed statistically significant correlation, r = 0.71 (p < 0.001). But the corresponding CFR correlation was moderate r = 0.39 yet statistically significant (p = 0.037). The mean stress MBF value was significantly lower for angiographically abnormal than that for the normal (Normal Mean MBF = 2.49 ± 0.61, Abnormal Mean MBF = 1.43 ± 0. 0.62, P < .001). Conclusions: The visually assessed image findings in clinical SPECT are subjective, and may not reflect direct physiologic measures of coronary lesion. The MBF and CFR measured with dynamic SPECT are fully objective and available only with the data generated from the dynamic SPECT method. A quantitative approach such as measuring CFR using dynamic SPECT imaging is a better mode of diagnosing CAD than visual assessment of stress and rest images from static SPECT images Coronary Flow Reserve.

Keywords: dynamic SPECT, clinical SPECT/CT, selective coronary angiograph, ⁹⁹ᵐTc-Tetrofosmin

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11 Personal Exposure to Respirable Particles and Other Selected Gases among Cyclists near and Away from Busy Roads of Perth Metropolitan Area

Authors: Anu Shrestha, Krassi Rumchev, Ben Mullins, Yun Zhao, Linda Selvey

Abstract:

Cycling is often promoted as a means of reducing vehicular congestion, noise and greenhouse gas and air pollutant emissions in urban areas. It is also indorsed as a healthy means of transportation in terms of reducing the risk of developing a range of physical and psychological conditions. However, people who cycle regularly may not be aware that they can become exposed to high levels of Vehicular Air Pollutants (VAP) emitted by nearby traffics and therefore experience adverse health effects as a result. The study will highlight the present scenario of ambient air pollution level in different cycling routes in Perth and also highlight significant contribution to the understanding of health risks that cyclist may face from exposure to particulate air pollution. Methodology: This research was conducted in Perth, Western Austral and consisted of two groups of cyclists cycling near high (2 routes) and low (two routes) vehicular traffic roads, at high and low levels of exertion, during the cold and warm seasons. A sample size of 123 regular cyclists who cycled at least 80 km/week, aged 20-55, and non-smoker were selected for this study. There were altogether 100 male and 23 female who were asked to choose one or more routes among four different routes, and each participant cycled the route for warm or cold or both seasons. Cyclist who reported cardiovascular and other chronic health conditions (excluding asthma) were not invited into the study. Exposures to selected air pollutants were assessed by undertaking background and personal measurements alone with the measurement of heart and breathe rate of each participant. Finding: According to the preliminary study findings, the cyclists who used cycling route close to high traffic route were exposed to higher levels of measured air pollutants Nitrogen Oxide (NO₂) =0.12 ppm, sulfur dioxide (SO₂)=0.06 ppm and carbon monoxide (CO)=0.25 PPM compared to those who cycled away from busy roads. However, we measured high concentrations of particulate air pollution near one of the low traffic route which we associate with the close proximity to ferry station. Concluding Statement: As a conclusion, we recommend that cycling routes should be selected away from high traffic routes. If possible, we should also consider that if the cycling route is surrounded by the dense populated infrastructures, it can trap the pollutants and always facilitate in increasing inhalation of particle count among the cyclists.

Keywords: air pollution, carbon monoxide, cyclists' health, nitrogen dioxide, nitrogen oxide, respirable particulate matters

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10 Simple and Effective Method of Lubrication and Wear Protection

Authors: Buddha Ratna Shrestha, Jimmy Faivre, Xavier Banquy

Abstract:

By precisely controlling the molecular interactions between anti-wear macromolecules and bottle-brush lubricating molecules in the solution state, we obtained a fluid with excellent lubricating and wear protection capabilities. The reason for this synergistic behavior relies on the subtle interaction forces between the fluid components which allow the confined macromolecules to sustain high loads under shear without rupture. Our results provide rational guides to design such fluids for virtually any type of surfaces. The lowest friction coefficient and the maximum pressure that it can sustain is 5*10-3 and 2.5 MPa which is close to the physiological pressure. Lubricating and protecting surfaces against wear using liquid lubricants is a great technological challenge. Until now, wear protection was usually imparted by surface coatings involving complex chemical modifications of the surface while lubrication was provided by a lubricating fluid. Hence, we here research for a simple, effective and applicable solution to the above problem using surface force apparatus (SFA). SFA is a powerful technique with sub-angstrom resolution in distance and 10 nN/m resolution in interaction force while performing friction experiment. Thus, SFA is used to have the direct insight into interaction force, material and friction at interface. Also, we always know the exact contact area. From our experiments, we found that by precisely controlling the molecular interactions between anti-wear macromolecules and lubricating molecules, we obtained a fluid with excellent lubricating and wear protection capabilities. The reason for this synergistic behavior relies on the subtle interaction forces between the fluid components which allow the confined macromolecules to sustain high loads under shear without rupture. The lowest friction coefficient and the maximum pressure that it can sustain in our system is 5*10-3 and 2.5 GPA which is well above the physiological pressure. Our results provide rational guides to design such fluids for virtually any type of surfaces. Most importantly this process is simple, effective and applicable method of lubrication and protection as until now wear protection was usually imparted by surface coatings involving complex chemical modifications of the surface. Currently, the frictional data that are obtained while sliding the flat mica surfaces are compared and confirmed that a particular mixture of solution was found to surpass all other combination. So, further we would like to confirm that the lubricating and antiwear protection remains the same by performing the friction experiments in synthetic cartilages.

Keywords: bottle brush polymer, hyaluronic acid, lubrication, tribology

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9 From Stigma to Solutions: Harnessing Innovation and Local Wisdom to Tackle Harms Associated with Menstrual Seclusion (Chhaupadi) in Nepal

Authors: Sara E. Baumann, Megan A. Rabin, Mary Hawk, Bhimsen Devkota, Kajol Upadhyaya, Guna Raj Shrestha, Brigit Joseph, Annika Agarwal, Jessica G. Burke

Abstract:

In Nepal, prevailing sociocultural norms associated with menstruation prompt adherence to stringent rules that limit participation in daily activities. Chhaupadi is a specific menstrual tradition in Nepal in which women and girls segregate themselves and follow a series of restrictions during menstruation. Despite having numerous physical and mental health implications, extant interventions have yet to sustainably address the harms associated with chhaupadi. In this study, the authors describe insights garnered from a collaboration with community members in Dailekh district, who formulated their own approaches to mitigate the adverse facets of chhaupadi. Envisaged as an entry point to improve women’s menstrual health experiences, this investigation employed an approach that uses Human-centered Design and a community-engaged approach. The authors conducted a four-day design workshop which unfolded in two phases: The Discovery Phase, to uncover chhaupadi context and key stakeholders, and the Design Phase, to design contextually relevant interventions. Diverse community-members, including those with lived experience practicing chhaupadi, developed five intervention concepts: 1) harnessing Female Community Health Volunteers as role models, for counseling, and raising awareness; 2) focusing on mothers and mother’s groups to instigate behavioral shifts; 3) engaging the broader community in behavior change efforts; 4) empowering fathers to effect change in their homes through counseling and education; and 5) training and emboldening youth to advocate for positive change through advocacy in their schools and homes. This research underscores the importance of employing multi-level approaches tailored to specific stakeholder groups, given Nepal’s rich cultural diversity. The engagement of Female Community Health Volunteers emerged as a promising yet underexplored intervention concept for chhaupadi, warranting broader implementation. Crucially, it is also imperative for interventions to prioritize tackling deleterious aspects of the chhaupadi tradition, emphasizing safety considerations, all while acknowledging chhaupadi’s entrenched cultural history; for some, there are positive aspects of the tradition that women and girls wish to preserve.

Keywords: human-centered design, menstrual health, Nepal, community-engagement, intervention development, women's health, rural health

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8 Outcome of Naive SGLT2 Inhibitors Among ICU Admitted Acute Stroke with T2DM Patients a Prospective Cohort Study in NCMultispecialty Hospital, Biratnagar, Nepal

Authors: Birendra Kumar Bista, Rhitik Bista, Prafulla Koirala, Lokendra Mandal, Nikrsh Raj Shrestha, Vivek Kattel

Abstract:

Introduction: Poorly controlled diabetes is associated with cause and poor outcome of stroke. High blood sugar reduces cerebral blood flow, increases intracranial pressure, cerebral edema and neuronal death, especially among patients with poorly controlled diabetes.1 SGLT2 inhibitors are associated with 50% reduction in hemorrhagic stroke compared with placebo. SGLT2 inhibitors decrease cardiovascular events via reducing glucose, blood pressure, weight, arteriosclerosis, albuminuria and reduction of atrial fibrillation.2,3 No study has been documented in low income countries to see the role of post stroke SGLT2 inhibitors on diabetic patients at and after ICU admission. Aims: The aim of the study was to measure the 12 months outcome of diabetic patients with acute stroke admitted in ICU set up with naïve SGLT2 inhibitors add on therapy. Method: It was prospective cohort study carried out in a 250 bedded tertiary neurology care hospital at the province capital Biratnagar Nepal. Diabetic patient with acute stroke admitted in ICU from 1st January 2022 to 31st December 2022 who were not under SGLT2 inhibitors were included in the study. These patients were managed as per hospital protocol. Empagliflozin was added to the alternate enrolled patients. Empagliflozin was continued at the time of discharged and during follow up unless contraindicated. These patients were followed up for 12 months. Outcome measured were mortality, morbidity requiring readmission or hospital visit other than regular follow up, SGLT2 inhibitors related adverse events, neuropsychiatry comorbidity, functional status and biochemical parameters. Ethical permission was taken from hospital administration and ethical board. Results: Among 147 diabetic cases 68 were not treated with empagliflozin whereas 67 cases were started the SGLT2 inhibitors. HbA1c level and one year mortality was significantly low among patients on empaglifozin arm. Over a period of 12 months 427 acute stroke patients were admitted in the ICU. Out of them 44% were female, 61% hypertensive, 34% diabetic, 57% dyslipidemia, 26% smoker and with median age of 45 years. Among 427 cases 4% required neurosurgical interventions and 76% had hemorrhagic CVA. The most common reason for ICU admission was GCS<8 (51%). The median ICU stay was 5 days. ICU mortality was 21% whereas 1 year mortality was 41% with most common reason being pneumonia. Empaglifozin related adverse effect was seen in 11% most commonly lower urinary tract infection in 6%. Conclusion: Empagliflozin can safely be started among acute stroke with better Hba1C control and low mortality outcome compared to treatment without SGLT2 inhibitor.

Keywords: diabetes, ICU, mortality, SGLT2 inhibitors, stroke

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7 Local Community's Response on Post-Disaster and Role of Social Capital towards Recovery Process: A Case Study of Kaminani Community in Bhaktapur Municipality after 2015 Gorkha Nepal Earthquake

Authors: Lata Shakya, Toshio Otsuki, Saori Imoto, Bijaya Krishna Shrestha, Umesh Bahadur Malla

Abstract:

2015 Gorkha Nepal earthquake have damaged the human settlements in 14 districts of Nepal. Historic core areas of three principal cities namely Kathmandu, Lalitpur and Bhaktapur including numerous traditional ‘newari’ settlements in the peripheral areas have been either collapsed or severely damaged. Despite Government of Nepal and (international) non-government organisations’ attempt towards disaster risk management through the preparation of policies and guidelines and implementation of community-based activities, the recent ‘Gorkha’ earthquake has demonstrated the inadequate preparedness, poor implementation of a legal instrument, resource constraints, and managerial weakness. However, the social capital through community based institutions, self-help attitude, and community bond has helped a lot not only in rescue and relief operation but also in a post-disaster temporary shelter living thereby exhibiting the resilient power of the local community. Conducting a detailed case study of ‘Kaminani’ community with 42 houses at ward no. 16 of Bhaktapur municipality, this paper analyses the local community’s response and activities on the Gorkha earthquake in rescue and relief operation as well as in post disaster work. Leadership, the existence of internal/external aid, physical and human support are also analyzed. Social resource and networking are also explained through critical review of the existing community organisation and their activities. The research methodology includes literature review, field survey, and interview with community leaders and residents based on a semi-structured questionnaire. The study reveals that community carried their recovery process in four different phases: (i) management of emergency evacuation, (ii) constructing community owed temporary shelter for individuals, (iii) demolishing upper floors of the damaged houses, and (iv) planning for collaborative housing reconstruction. As territorial based organization, religion based agency and aim based institution exist in the survey area from pre-disaster time, it can be assumed that the community activists including leaders are well experienced to create aim-based group and manage teamwork to deal with various issues and problems collaboratively. Physical and human support including partial financial aid from external source as a result of community leader’s personal networking is extended to the community members. Thus, human/social resource and personal/social network play a crucial role in the recovery process. And to build such social capital, community should have potential from pre-disaster time.

Keywords: Gorkha Nepal earthquake, local community, recovery process, social resource, social network

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6 Formulation and Optimization of Self Nanoemulsifying Drug Delivery System of Rutin for Enhancement of Oral Bioavailability Using QbD Approach

Authors: Shrestha Sharma, Jasjeet K. Sahni, Javed Ali, Sanjula Baboota

Abstract:

Introduction: Rutin is a naturally occurring strong antioxidant molecule belonging to bioflavonoid category. Due to its free radical scavenging properties, it has been found to be beneficial in the treatment of various diseases including inflammation, cancer, diabetes, allergy, cardiovascular disorders and various types of microbial infections. Despite its beneficial effects, it suffers from the problem of low aqueous solubility which is responsible for low oral bioavailability. The aim of our study was to optimize and characterize self-nanoemulsifying drug delivery system (SNEDDS) of rutin using Box-Behnken design (BBD) combined with a desirability function. Further various antioxidant, pharmacokinetic and pharmacodynamic studies were performed for the optimized rutin SNEDDS formulation. Methodologies: Selection of oil, surfactant and co-surfactant was done on the basis of solubility/miscibility studies. Sefsol+ Vitamin E, Solutol HS 15 and Transcutol P were selected as oil phase, surfactant and co-surfactant respectively. Optimization of SNEDDS formulations was done by a three-factor, three-level (33)BBD. The independent factors were Sefsol+ Vitamin E, Solutol HS15, and Transcutol P. The dependent variables were globule size, self emulsification time (SEF), % transmittance and cumulative percentage drug released. Various response surface graphs and contour plots were constructed to understand the effect of different factor, their levels and combinations on the responses. The optimized Rutin SNEDDS formulation was characterized for various parameters such as globule size, zeta potential, viscosity, refractive index , % Transmittance and in vitro drug release. Ex vivo permeation studies and pharmacokinetic studies were performed for optimized formulation. Antioxidant activity was determined by DPPH and reducing power assays. Anti-inflammatory activity was determined by using carrageenan induced rat paw oedema method. Permeation of rutin across small intestine was assessed using confocal laser scanning microscopy (CLSM). Major findings:The optimized SNEDDS formulation consisting of Sefsol+ Vitamin E - Solutol HS15 -Transcutol HP at proportions of 25:35:17.5 (w/w) was prepared and a comparison of the predicted values and experimental values were found to be in close agreement. The globule size and PDI of optimized SNEDDS formulation was found to be 16.08 ± 0.02 nm and 0.124±0.01 respectively. Significant (p˂0.05) increase in percentage drug release was achieved in the case of optimized SNEDDS formulation (98.8 %) as compared to rutin suspension. Furthermore, pharmacokinetic study showed a 2.3-fold increase in relative oral bioavailability compared with that of the suspension. Antioxidant assay results indicated better efficacy of the developed formulation than the pure drug and it was found to be comparable with ascorbic acid. The results of anti-inflammatory studies showed 72.93 % inhibition for the SNEDDS formulation which was significantly higher than the drug suspension 46.56%. The results of CLSM indicated that the absorption of SNEDDS formulation was considerably higher than that from rutin suspension. Conclusion: Rutin SNEDDS have been successfully prepared and they can serve as an effective tool in enhancing oral bioavailability and efficacy of Rutin.

Keywords: rutin, oral bioavilability, pharamacokinetics, pharmacodynamics

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5 Pharmacognostical, Phytochemical and Biological Studies of Leaves and Stems of Hippophae Salicifolia

Authors: Bhupendra Kumar Poudel, Sadhana Amatya, Tirtha Maiya Shrestha, Bharatmani Pokhrel, Mohan Prasad Amatya

Abstract:

Background: H. salicifolia is a dense, branched, multipurpose, deciduous, nitrogen fixing, thorny willow-like small to moderate tree, restricted to the Himalaya. Among the two species of Nepal (Hippophae salicifolia and H. tibetana), it has been traditionally used as food additive, anticancer (bark), and treating toothache, tooth inflammation (anti-inflammatory) and radiation injury; while people of Western Nepal have largely undermined its veiled treasure by using it for fuel, wood and soil stabilization only. Therefore, the main objective of this study was to explore biological properties (analgesic, antidiabetic, cytotoxic and anti-inflammatory properties of this plant. Methodology: The transverse section of leaves and stems were viewed under microscope. Extracts obtained from soxhlation subjected to tests for phytochemical and biological studies. Rats (used to study antidiabetic and anti-inflammatory properties) and mice (used to study analgesic, CNS depressant, muscle relaxant and locomotor properties) were assumed to be normally distributed; then ANOVA and post hoc tukey test was used to find significance. The data obtained were analyzed by SPSS 17 and Excel 2007. Results and Conclusion: Pharmacognostical analysis revealed the presence of long stellate trichomes, double layered vascular bundle 5-6 in number and double layered compact sclerenchyma. The preliminary phytochemical screening of the extracts was found to exhibit the positive reaction tests for glycoside, steroid, tannin, flavonoid, saponin, coumarin and reducing sugar. The brine shrimp lethality bioassay tested in 1000, 100 and 10 ppm revealed cytotoxic activity inherent in methanol, water, chloroform and ethyl acetate extracts with LC50 (μg/ml) values of 61.42, 99.77, 292.72 and 277.84 respectively. The cytotoxic activity may be due to presence of tannins in the constituents. Antimicrobial screening of the extracts by cup diffusion method using Staphylococcus aereus, Escherichia coli and Pseudomonas aeruginosa against standard antibiotics (oxacillin, gentamycin and amikacin respectively) portrayed no activity against the microorganisms tested. The methanol extract of the stems and leaves showed various pharmacological properties: and antidiabetic, anti-inflammatory, analgesic [chemical writhing method], CNS depressant, muscle relaxant and locomotor activities in a dose-dependent fashion, indicating the possibility of the presence of different constituents in the stems and leaves responsible for these biological activities. All the effects when analyzed by post hoc tukey test were found to be significant at 95% confidence level. The antidiabetic activity was presumed to be due to flavonoids present in extract. Therefore, it can be concluded that this plant’s secondary metabolites possessed strong antidiabetic, anti-inflammatory and cytotoxic activity which could be isolated for further investigation.

Keywords: Hippophae salicifolia, constituents, antidiabetic, inflammatory, brine shrimp

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4 A Novel Upregulated circ_0032746 on Sponging with MIR4270 Promotes the Proliferation and Migration of Esophageal Squamous Cell Carcinoma

Authors: Sachin Mulmi Shrestha, Xin Fang, Hui Ye, Lihua Ren, Qinghua Ji, Ruihua Shi

Abstract:

Background: Esophageal squamous cell carcinoma (ESCC) is a tumor arising from esophageal epithelial cells and is one of the major disease subtype in Asian countries, including China. Esophageal cancer is the 7th highest incidence based on the 2020 data of GLOBOCAN. The pathogenesis of cancer is still not well understood as many molecular and genetic basis of esophageal carcinogenesis has yet to be clearly elucidated. Circular RNAs are RNA molecules that are formed by back-splicing covalently joined 3′- and 5′-endsrather than canonical splicing, and recent data suggest circular RNAs could sponge miRNAs and are enriched with functional miRNA binding sites. Hence, we studied the mechanism of circular RNA, its biological function, and the relationship between microRNA in the carcinogenesis of ESCC. Methods: 4 pairs of normal and esophageal cancer tissues were collected in Zhongda hospital, affiliated to Southeast University, and high-throughput RNA sequencing was done. The result revealed that circ_0032746 was upregulated, and thus we selected circ_0032746 for further study. The backsplice junction of circRNA was validated by sanger sequence, and stability was determined by RNASE R assay. The binding site of circRNA and microRNA was predicted by circinteractome,mirandaand RNAhybrid database. Furthermore, circRNA was silenced by siRNA and then by lentivirus. The regulatory axis of circ0032746/miR4270 was validated by shRNA, mimic, and inhibitor transfection. Then, in vitro experiments were performed to assess the role of circ0032746 on proliferation (CCK-8 assay and colon formation assay), migration and invasion (Transewell assay), and apoptosis of ESCC. Results: The upregulated circ0032746 was validated in 9 pairs of tissues and 5 types of cell lines by qPCR, which showed high expression and was statistically significant (P<0.005) ). Upregulated circ0032746 was silenced by shRNA, which showed significant knockdown in KYSE 30 and TE-1 cell lines expression compared to control. Nuclear and cytoplasmic mRNA fraction experiment displayed the cytoplasmic location of circ0032746. The sponging of miR4270 was validated by co-transfection of sh-circ0032746 and mimic or inhibitor. Transfection with mimic showed the decreased expression of circ_0032746, whereas inhibitor inhibited the result. In vitro experiments showed that silencing of circ_0032746 inhibited the proliferation, migration, and invasion compared to the negative control group. The apoptosis was seen higher in a knockdown group than in the control group. Furthermore, 11 common mircoRNA target mRNAs were predicted by Targetscan, MirTarbase, and miRanda database, which may further play role in the pathogenesis. Conclusion: Our results showed that novel circ_0032746 is upregulated in ESCC and plays role in itsoncogenicity. Silencing of circ_0032746 inhibits the proliferation and migration of ESCC whereas increases the apoptosis of cancer cells. Hence, circ0032746 acts as an oncogene in ESCC by sponging with miR4270 and could be a potential biomarker in the diagnosis of ESCC in the future.

Keywords: circRNA, esophageal squamous cell carcinoma, microRNA, upregulated

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3 Effect of Climate Change on Rainfall Induced Failures for Embankment Slopes in Timor-Leste

Authors: Kuo Chieh Chao, Thishani Amarathunga, Sangam Shrestha

Abstract:

Rainfall induced slope failures are one of the most damaging and disastrous natural hazards which occur frequently in the world. This type of sliding mainly occurs in the zone above the groundwater level in silty/sandy soils. When the rainwater begins to infiltrate into the vadose zone of the soil, the negative pore-water pressure tends to decrease and reduce the shear strength of soil material. Climate change has resulted in excessive and unpredictable rainfall in all around the world, resulting in landslides with dire consequences to human lives and infrastructure. Such problems could be overcome by examining in detail the causes for such slope failures and recommending effective repair plans for vulnerable locations by considering future climatic change. The selected area for this study is located in the road rehabilitation section from Maubara to Mota Ain road in Timor-Leste. Slope failures and cracks have occurred in 2013 and after repairs reoccurred again in 2017 subsequent to heavy rains. Both observed and future predicted climate data analyses were conducted to understand the severe precipitation conditions in past and future. Observed climate data were collected from NOAA global climate data portal. CORDEX data portal was used to collect Regional Climate Model (RCM) future predicted climate data. Both observed and RCM data were extracted to location-based data using ArcGIS Software. Linear scaling method was used for the bias correction of future data and bias corrected climate data were assigned to GeoStudio Software. Precipitations of wet seasons (December to March ) in 2007 to 2013 is higher than 2001-2006 period and it is more than nearly 40% higher precipitation than usual monthly average precipitation of 160mm.The results of seepage analyses which were carried out using SEEP/W model with observed climate, clearly demonstrated that the pore water pressure within the fill slope was significantly increased due to the increase of the infiltration during the wet season of 2013.One main Regional Climate Models (RCM) was analyzed in order to predict future climate variation under two Representative Concentration Pathways (RCPs).In the projected period of 76 years ahead from 2014, shows that the amount of precipitation is considerably getting higher in the future in both RCP 4.5 and RCP 8.5 emission scenarios. Critical pore water pressure conditions during 2014-2090 were used in order to recommend appropriate remediation methods. Results of slope stability analyses indicated that the factor of safety of the fill slopes was reduced from 1.226 to 0.793 during the dry season to wet season in 2013.Results of future slope stability which were obtained using SLOPE/W model for the RCP emissions scenarios depict that, the use of tieback anchors and geogrids in slope protection could be effective in increasing the stability of slopes to an acceptable level during the wet seasons. Moreover, methods and procedures like monitoring of slopes showing signs or susceptible for movement and installing surface protections could be used to increase the stability of slopes.

Keywords: climate change, precipitation, SEEP/W, SLOPE/W, unsaturated soil

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2 WASH Governance Opportunity for Inspiring Innovation and a Circular Economy in Karnali Province of Nepal

Authors: Nirajan Shrestha

Abstract:

Karnali is one of the most vulnerable provinces in Nepal, facing challenges from climate change, poverty, and natural calamities across different regions. In recent years, the province has been severely impacted by climate change stress such as temperature rises in glacier lake of mountainous region and spring source water shortages, particularly in hilly areas where settlements are located, and water sources have depleted from their original ground levels. As a result, Karnali could face a future without enough water for all. Deep causes of sustainable safe water supply have always been neglected in rural areas of Nepal, and communities are unfairly burdened with a challenge of keeping water facilities functioning in areas affected by frequent natural disasters where there is a substantial, well-documented funding gap between the revenues from user payments and the full cost of sustained services. The key importance of a permanent system to support communities in service delivery has been always underrated so far. The complexity of water service sustainability as a topic should be simplified to one clear indicator: the functionality rate, which can be expressed as uptime or the percentage of time that the service is delivered over the total time. For example, a functionality rate of 80% means that the water service is operational 80% of the time, while 20% of the time the system is not functioning. This represents 0.2 multiplied by 365, which equals 73 days every year, or roughly two and a half months without water. This percentage should be widely understood and used in Karnali. All local governments should report their targets and performance in improving it, and there should be a broader discussion about what target is acceptable and what can be realistically achieved. In response to these challenges, the Sustainable WASH for All (SUSWA) project has introduced innovative models and policy formulation strategies in various working local government. SUSWA’s approach, which delegates rural water supply and sanitation responsibilities to local governments, has been instrumental in addressing these issues. To keep pace with the growing demand, the province has adopted a service support center model, linking local governments with federal authorities to ensure effective service delivery to the communities By enhancing WASH governance through local governments engagement, capacity building and inclusive WASH policy frameworks, there is potential to address WASH gaps while fostering a circular economy. This strategy emphasizes resource recovery, waste minimization and the creation of local employment generation opportunities. The research highlights key governance mechanisms, innovative practices and policy interventions that can be scaled up across other regions. It also provides recommendations on how to leverage Karnali’s unique socio-economic and environmental context nature-based solutions to inspire innovation and drive sustainable WASH solutions. Key findings suggest that with strong ownership and leadership of local governments, community engagement and appropriate technology, Karnali Province can become a model for integrating WASH governance with circular economy concept, providing broader lessons for other regions in Nepal.

Keywords: vulnerable provinces, natural calamities, climate change stres, spring source depletion, resources recovery, governance mechanisms, appropriate technology, community engagement, innovation

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1 Drug Reaction with Eosinophilia and Systemic Symptoms (Dress) Syndrome Presenting as Multi-Organ Failure

Authors: Keshari Shrestha, Philip Vatterott

Abstract:

Introduction: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare and potentially fatal drug-related syndrome. DRESS classically presents with a diffuse maculopapular rash, fevers, and eosinophilia more than three weeks after drug exposure. DRESS can present with multi-organ involvement, with liver damage being the most common and severe. Pulmonary involvement is a less common manifestation and is associated with poor clinical outcomes. Chest imaging is often nonspecific, and symptoms can range from mild cough to acute respiratory distress syndrome (ARDS) . This is a case of a 49-year-old female with a history of recent clostridium difficile colitis status post treatment with oral vancomycin who presented with rash, acute liver and kidney failure, as well as diffuse nodular alveolar lung opacities concerning for DRESS syndrome with multi-organ involvement. Clinical Course: This patient initially presented to an outside hospital with clostridium difficile colitis, acute liver injury, and acute kidney injury. She developed a desquamating maculopapular rash in the setting of recent oral vancomycin, meloxicam, and furosemide initiation. She was hospitalized on two additional occasions with worsening altered mental status, liver injury, and acute kidney injury and was initiated on intermittent hemodialysis. Notably, she was found to have systemic eosinophilia (4100 cells/microliter) several weeks prior. She was transferred to this institution for further management where she was found to have encephalopathy, jaundice, lower extremity edema, and diffuse bilateral rhonchorous breath sounds on pulmonary examination. The patient was started on methylprednisolone for suspected DRESS syndrome. She underwent an evaluation for alternative causes of her organ failure. Her workup included a negative infectious, autoimmune, metabolic, toxic, and malignant work-up. Abdominal computed tomography (CT) and ultrasound were remarkable for evidence of hepatic steatosis and possible cirrhotic morphology. Additionally, a chest CT demonstrated diffuse and symmetric nodular alveolar lung opacities with peripheral sparing not consistent with acute respiratory distress syndrome or edema. Ultimately, her condition continued to decline, and she required intubation on several occasions. On hospital day 25 she succumbed to distributive shock in the setting of probable sepsis and multi-organ failure. Discussion: DRESS syndrome occurs in 1 in 1,000 to 10,000 patients with a mortality rate of around 10%. Anti-convulsant, anti-bacterial, anti-viral, and sulfonamide drugs are the most common drugs implicated in the development of DRESS syndrome; however, the list of offending agents is extensive . The diagnosis of DRESS syndrome is made after excluding other causes of disease such as infectious and autoimmune etiologies. The RegiSCAR scoring system is used to diagnose DRESS syndrome with 2-3 points indicating possible disease, 4-5 probable disease, and >5 definite disease. This patient scored a 7 on the RegiSCAR scale for eosinophilia, rash, organ involvement, and exclusion of other causes (infectious and autoimmune). While the pharmacologic trigger in this case is unknown, it is speculated to be caused by vancomycin, meloxicam, or furosemide due to the favorable timeline of initiation. Despite aggressive treatment, DRESS syndrome can often be fatal. Because of this, early diagnosis and treatment of patients with suspected DRESS syndrome is imperative.

Keywords: drug reaction with eosinophilia and systemic symptoms, multi-organ failure, pulmonary involvement, renal failure

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