Search results for: Rajani Ghimire

Authors: Dipendra Kumar Yadav, Rajani Ghimire, Saroj Yadav

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Background: The concern about adolescent on reproductive health has grown due to unprecedented increasing rates of early pregnancies and sexually transmitted Infections and they do not have adequate awareness and knowledge about it. Access to these services as well as information about them is, therefore, crucial for adolescents to utilize and benefit from sexual and reproductive health services. The objective of the study was to assess the reproductive health knowledge, attitude and health services utilization among adolescents in rural and urban areas of Kaski district. Materials and Methods: A community-based descriptive cross-sectional study was conducted among adolescents (10-19 years of age) in rural and urban areas of Kaski district, Nepal. The period of data collection was October to November, 2014. Altogether 419 participants were taken for the study. Results: The mean age of the respondents was 15.86 and standard deviation was ±2.305. More than half (58.7 %) of the respondents were females and 41.3 % were males. Out of 419, majority (78.8%) of the respondents were known about family planning, among them only 70 % of respondents were aware about family planning methods. Fifty-one percentages of the respondents were aware about the sexually transmitted diseases. Before giving a birth there is need to consult with partner with this fact 68.7 % of the respondents were agree, 23.6 % of them were neutral and very few (7.6%) of them were disagree. Nearly twenty six percentage of the respondents were faced the reproductive health problems within one month. Out of 107 respondents, 57.9 % did not utilize reproductive health services because of different reasons. Conclusions: The overall level of knowledge towards reproductive health among adolescents was found low. However, levels of attitude towards different reproductive health components were found favorable. Only 42.1% of the respondents were utilized reproductive health services among those who was faced the reproductive health problems within one month which was low coverage of reproductive health services utilization.

Keywords: reproductive health knowledge, reproductive health attitudes, adolescent, service utilization

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Authors: Rajan Ghimire

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One of the diseases caused by the coronavirus shook the whole world. This situation challenged the education system across the world and compelled educators to shift to an online mode of teaching. Many academic institutions that were persistent to keep their traditional pedagogical approach were also forced to change their teaching methods. This study aims to assess science education students' experiences and perceptions of this global issue, especially on the science teaching and learning process. The study is based on qualitative research and through in-depth interviews with respondents and data is analyzed. Online distance teaching and learning processes meet the requirements of students who cannot or prefer not to participate in conventional classroom settings. But there are some challenges for the students and teachers in the science teaching learning process. This study recommends some points to all stakeholders.

Keywords: electronic devices, internet, online and distance learning, science education, educational policy

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Authors: Rajani Vishal, C. P. Mishra

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Background: Self-perception of an individual about own body has a strong influence on their food preference and thereby on their nutritional status. Body image is gaining importance in social theory. Globally, women in particular seem to be favour of one ideal body type (Viz A slim, tall and perfectly proportionate body). Beauty and body image ideals among research scholars can play a significant influence on their own actions. Objectives: 1) To assess perception of study subjects about body image; 2)To analyze the relationship between body image and residential status of study subjects. Material and Method: 176 female research scholars of Banaras Hindu University were selected through multistage sampling. They were interviewed with pre designed and pre-tested proforma about area of residence and perception about body image. Result: As much as 86.4% subjects were happy with the way they looked whereas 83.0% subjects considered themselves as attractive. In case of 13.6%, 27.3%, 31.8%, 14.2% and 13.1% subjects, best-described body shapes were thin, normal, curvy, athletic and overweight, respectively. Area of residence was significantly (p< o.o5) associated with perception of attractiveness and description of body shape. Conclusion: In spite of varied description of body image, majority of subjects had positive perception about their body image.

Keywords: attractiveness, body image, body shape, nutritional status

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Authors: Kailash Ghimire, Manoj Thapa

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This study focuses on early identification of deficiencies in pre-required areas of students who are enrolled in College Algebra and Calculus I classes. The students were given pre-diagnostic tests on the first day of the class before they are provided with the syllabus. The tests consist of prerequisite, uniform and advanced content outlined by the University System of Georgia (USG). The results show that 48% of students in College Algebra are lacking prerequisite skills while 52% of Calculus I students are lacking prerequisite skills but, interestingly these students are prior exposed to uniform content and advanced content. The study is still in progress and this paper contains the outcome from Fall 2017 and Spring 2018. In this paper, early intervention used in these classes: two days vs three days meeting a week and students’ self-assessment using exam wrappers and their effectiveness on students’ learning will also be discussed. A result of this study shows that there is an improvement on Drop, Fail and Withdraw (DFW) rates by 7%-10% compared to those in previous semesters.

Keywords: student at risk, diagnostic tests, identification, intervention, normalization gain, validity of tests

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Authors: Gayatri Nahak, Satyajit Kanungo, Rajani Kanta Sahu

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Holarrhena antidysenterica Linn. (Apocynaceae) is a typical Indian medicinal plant popularly known as “Indrajav”. Traditionally the plant has been considered a popular remedy for the treatment of dysentery, diarrhea, intestinal worms and the seeds of this plant are also used as an anti-diabetic remedy. In the present study axillary shoot multiplication, callus induction and shoot regeneration from callus culture were obtained on Murashige and Skoog (MS) medium supplemented with different concentrations and combinations of plant growth regulators. Then in vivo and in vitro grown healthy plants were selected for study of antioxidant activity through DPPH and OH methods. Significantly higher antioxidant activity and phenol contents were observed in vitro raised plant in comparison to in vivo plants. The findings indicated the greater amount of phenolic compounds leads to more potent radical scavenging effect as shown in in vitro raised plant in comparison to in vivo plants which showed the ability to utilize tissue culture techniques towards development of desired bioactive metabolites from in vitro culture as an alternative way to avoid using endangered plants in pharmaceutical purposes.

Keywords: Holarrhena antidysenterica, in vitro, in vivo, antioxidant activity

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Authors: Rajani Bogati, Gopini Pathak

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Women living in husband’s home (second home) after getting married is a common culture in Nepalese society. Most of the marriages are arranged between the mutual understandings of their parents as per their cultural practice. Culturally, arranged marriage system protects women in the society. Even though, women domestic violence is also still alive in the society. It depends upon the family class, ethnicity, caste, religion etc. Lower class (poor) family always try to get marriage from the higher class (rich) family of girl and also try to send their girl in higher class family. This study analysis the freedom of women of Armala Village Development Committee, Kaski district on the base of the family class of girl where she born (First home). 88% women are getting more respect in their second home if their family class of first home and second homes are same. They feel more comfortable and freedom in their second home. 79% of Women are suffering from domestic violence while the marriage between the boys from higher class and the girls from lower class. But less than 10% women are getting distress from violence if the marriage is accompanied between the girls from higher class and the boys from lower class. Less domestic violence is seem where the both families are educated, even though they are from different class. This study recommends that the society should be educated first to reduce women domestic violence.

Keywords: arranged marriage, women, family class, domestic violence

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Authors: Sunita Singh, Rajani Srivastava

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For natural resource management and in other applications about earth observation revolutionary remote sensing technology plays a significant role. One of such application in monitoring and classification of crop types at spatial and temporal scale, as it provides latest, most precise and cost-effective information. Present study emphasizes the use of three different vegetation indices of Rapid Eye imagery on crop type classification. It also analyzed the effect of each indices on classification accuracy. Rapid Eye imagery is highly demanded and preferred for agricultural and forestry sectors as it has red-edge and NIR bands. The three indices used in this study were: the Normalized Difference Vegetation Index (NDVI), the Green Normalized Difference Vegetation Index (GNDVI), and the Normalized Difference Red Edge Index (NDRE) and all of these incorporated the Red Edge band. The study area is Varanasi district of Uttar Pradesh, India and Radial Basis Function (RBF) kernel was used here for the Support Vector Machines (SVMs) classification. Classification was performed with these three vegetation indices. The contribution of each indices on image classification accuracy was also tested with single band classification. Highest classification accuracy of 85% was obtained using three vegetation indices. The study concluded that NDRE has the highest contribution on classification accuracy compared to the other vegetation indices and the Rapid Eye imagery can get satisfactory results of classification accuracy without original bands.

Keywords: GNDVI, NDRE, NDVI, rapid eye, vegetation indices

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Authors: Rajani S. Pujar, Pandurangarao N. Kulkarni

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Increased temporal masking affects the speech perception in persons with sensorineural hearing impairment especially under adverse listening conditions. This paper presents a cascaded scheme, which employs a noise reduction algorithm as well as temporal splitting of the speech signal. Earlier investigations have shown that by splitting the speech temporally and presenting alternate segments to the two ears help in reducing the effect of temporal masking. In this technique, the speech signal is processed by two fading functions, complementary to each other, and presented to left and right ears for binaural dichotic presentation. In the present study, half cosine signal is used as a fading function with crossover gain of 6 dB for the perceptual balance of loudness. Temporal splitting is combined with noise reduction algorithm to improve speech perception in the background noise. Two noise reduction schemes, namely spectral subtraction and Wiener filter are used. Listening tests were conducted on six normal-hearing subjects, with sensorineural loss simulated by adding broadband noise to the speech signal at different signal-to-noise ratios (∞, 3, 0, and -3 dB). Objective evaluation using PESQ was also carried out. The MOS score for VCV syllable /asha/ for SNR values of ∞, 3, 0, and -3 dB were 5, 4.46, 4.4 and 4.05 respectively, while the corresponding MOS scores for unprocessed speech were 5, 1.2, 0.9 and 0.65, indicating significant improvement in the perceived speech quality for the proposed scheme compared to the unprocessed speech.

Keywords: MOS, PESQ, spectral subtraction, temporal splitting, wiener filter

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Authors: Dhruba Khatri, Uttam Ghimire, Nabin Kumar Thapalia

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Protected area management in Indonesia is based on MAB program and ICDPs have become Indonesia’s main approach to biodiversity conservation since the early 1990s. However, very few ICDPs have realized the importance of biodiversity conservation in Indonesia and significantly enhanced as a result of currently planned project activities. Gunung Palung National Park in West Kalimantan was damaged illegal logging after decentralization. It made clear through the field survey: (1) Agroforestry did not make reduce to deforestation on regional level and (2) local people who engaging illegal logging activities have two characteristics that for their life and for vent of surplus labor in village. From these results, it became clear that a local resident had a bilateral character as an actor of conservation and the deforestation and also it confirmed that a market also was working on both of the conservation and deforestation. Therefore, surplus labor can be the key actors for future program design and at the same time it is necessary corroborative system which central government, local government, and local people are concerned with the process of policy making under the situation that management body of national park and buffer zone was separated.

Keywords: buffer zone, decentralization, Gunung Palung National Park, illegal logging, Indonesia

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Authors: Rajani Kant Rai, Jayakrishnan Athipet

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There have been several attempts to prepare polymers with antimicrobial properties by doping with various N-halamines. Hydantoins (Cyclic N-halamine) is of importance due to their stability rechargeable chloroamide function, broad-spectrum anti-microbial action and ability to prevent resistance to the organisms. Polymerizable hydantoins are synthesized by tethering vinyl moieties to 5,5,-dialkyl hydantoin sacrificing the imide hydrogen in the molecule thereby restricting the halogen capture only to the amide nitrogen that results in compromised antibacterial activity. In order to increase the activity of the antimicrobial polymer, we have developed a scheme to maximize the attachment of chlorine to the amide and the imide moieties of hydantoin. Vinyl hydantoin monomer, (Z)-5-(4-((3-methylbuta-1,3-dien-2-yl)oxy)benzylidene)imidazolidine-2,4-dione (MBBID) was synthesized and copolymerized with a commercially available monomer, methyl methacrylate, by free radical polymerization. The antimicrobial activity of hydantoin is strongly dependent on their surface area and hence their microbial activity increases when incorporated in microspheres or nanoparticles as compared to their bulk counterpart. In this regard, smooth and rough surface microsphere of the vinyl monomer (MBBID) with commercial monomer was synthesized. The oxidative chlorine content of the copolymer ranged from 1.5 to 2.45 %. Further, to demonstrate the water purification potential, the thin column was packed with smooth or rough microspheres and challenged with simulated contaminated water that exhibited 6 log kill (total kill) of the bacteria in 20 minutes of exposure with smooth (25 mg/ml) and rough microsphere (15.0 mg/ml).

Keywords: cyclic N-halamine, vinyl hydantoin monomer, rough surface microsphere, simulated contaminated water

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Authors: Ghimire K., Mehta R. S., Parajuli P., Chettri R.

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Background: Malnutrition is a common hallmark of Human Immuno Virus (HIV) disease. It plays a synergistic role in immunosuppression which is initiated by Human Immuno Virus itself, and malnutrition forms an independent risk factor for disease progression. Objectives: The objective of the study is to assess the nutritional status of the people living with Human Immuno Virus/Acquired Immune Deficiency Syndrome attending the Anti-Retro viral Treatment Clinic and find the association of nutritional status with different socio-demographic variables. Methods: A total of 101 people living with HIV/AIDS (PLWHA) were selected by convenient sampling technique. The study was conducted at the ART clinic of BPKIHS. A subjective global assessment tool was used for data collection. Descriptive and inferential statistics were used for data analysis. Results: The study demonstrated that the mean age of the respondents was 40.97+8.650 years. 65.3% were well-nourished, and 34.7% of the participants were mildly/moderately malnourished, whereas none of them were severely malnourished. BMI was statistically significant with education status, family income, and duration of illness of the participants, and nutritional status was statistically significant with gender, marital status, education status, and family history of HIV. Conclusion: On the basis of the result, it can be concluded that more than half of the respondents were well nourished. Gender, marital status, and education are associated with nutritional status.

Keywords: nutritional status, people living with HIV/AIDS, ART treatment, Nepal

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Authors: Kanupreiya, Rajani Sharma

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Construction of a single underground structure is itself a challenging task, and it becomes more critical in tectonically active young mountains such as the Himalayas which are highly anisotropic. The Himalayan geology mostly comprises of incompetent and sheared rock mass in addition to fold/faults, rock burst, and water ingress. Underground tunnels form the most essential and important structure in run-of-river hydroelectric projects. Punatsangchhu I hydroelectric project (PHEP-I), Bhutan (1200 MW) is a run-of-river scheme which has four parallel underground desilting chambers. The Punatsangchhu River carries a large quantity of silt load during monsoon season. Desilting chambers were provided to remove the silt particles of size greater than and equal to 0.2 mm with 90% efficiency, thereby minimizing the rate of damage to turbines. These chambers are 330 m long, 18 m wide at the center and 23.87 m high, with a 5.87 m hopper portion. The geology of desilting chambers was known from an exploratory drift which exposed low dipping foliation joint and six joint sets. The RMR and Q value in this reach varied from 40 to 60 and 1 to 6 respectively. This paper describes different rock engineering principles undertaken for safe excavation and rock support of the moderately jointed, blocky and thinly foliated biotite gneiss. For the design of rock support system of desilting chambers, empirical and numerical analysis was adopted. Finite element analysis was carried out for cavern design and finalization of pillar width using Phase2. Phase2 is a powerful tool for simulation of stage-wise excavation with simultaneous provision of support system. As the geology of the region had 7 sets of joints, in addition to FEM based approach, safety factors for potentially unstable wedges were checked using UnWedge. The final support recommendations were based on continuous face mapping, numerical modelling, empirical calculations, and practical experiences.

Keywords: dam siltation, Himalayan geology, hydropower, rock support, numerical modelling

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Authors: Guna Raj Dhungana, Roshan Nepal, Apshara Parajuli, , Archana Maharjan, Shyam K. Mishra, Pramod Aryal, Rajani Malla

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Introduction: Klebsiella pneumoniae is a well-known opportunistic human pathogen, primarily causing healthcare-associated infections. The global emergence of carbapenemase-producing K. pneumoniaeis a major public health burden, which is often extensively multidrug resistant.Thus, because of the difficulty to treat these ‘superbug’ and menace and some term as ‘apocalypse’ of post antibiotics era, an alternative approach to controlling this pathogen is prudent and one of the approaches is phage mediated control and/or treatment. Objective: In this study, we aimed to isolate novel bacteriophage against carbapenemase-producing K. pneumoniaeand characterize for potential use inphage therapy. Material and Methods: Twenty lytic phages were isolated from river water using double layer agar assay and purified. Biological features, physiochemical characters, burst size, host specificity and activity spectrum of phages were determined. One most potent phage: Phage TU_Kle10O was selected and characterized by electron microscopy. Whole genome sequences of the phage were analyzed for presence/absence of virulent factors, and other lysin genes. Results: Novel phage TU_Kle10O showed multiple host range within own genus and did not induce any BIM up to 5th generation of host’s life cycle. Electron microscopy confirmed that the phage was tailed and belonged to Caudovirales family. Next generation sequencing revealed its genome to be 166.2 Kb. bioinformatical analysis further confirmed that the phage genome ‘did not’ contain any ‘bacterial genes’ within phage genome, which ruled out the concern for transfer of virulent genes. Specific 'lysin’ enzyme was identified phages which could be used as 'antibiotics'. Conclusion: Extensively multidrug resistant bacteria like carbapenemase-producing K. pneumoniaecould be treated efficiently by phages.Absence of ‘virulent’ genes of bacterial origin and presence of lysin proteins within phage genome makes phages an excellent candidate for therapeutics.

Keywords: bacteriophage, Klebsiella pneumoniae, MDR, phage therapy, carbapenemase,

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Authors: Arpit Kumar Shrivastava, Subrat Kumar, Rajani Kanta Mohapatra, Priyadarshi Soumyaranjan Sahu

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Computational approaches to predict structure, function and other biological characteristics of proteins are becoming more common in comparison to the traditional methods in drug discovery. Cryptosporidiosis is a major zoonotic diarrheal disease particularly in children, which is caused primarily by Cryptosporidium hominis and Cryptosporidium parvum. Currently, there are no vaccines for cryptosporidiosis and recommended drugs are not effective. With the availability of complete genome sequence of C. hominis, new targets have been recognized for the development of effective and better drugs and/or vaccines. We identified a unique hypothetical epitopic protein in C. hominis genome through BLASTP analysis. A 3D model of the hypothetical protein was generated using I-Tasser server through threading methodology. The quality of the model was validated through Ramachandran plot by PROCHECK server. The functional annotation of the hypothetical protein through DALI server revealed structural similarity with human Transportin 3. Phylogenetic analysis for this hypothetical protein also showed C. hominis hypothetical protein (CUV04613) was the closely related to human transportin 3 protein. The 3D protein model is further subjected to virtual screening study with inhibitors from the Zinc Database by using Dock Blaster software. Docking study reported N-(3-chlorobenzyl) ethane-1,2-diamine as the best inhibitor in terms of docking score. Docking analysis elucidated that Leu 525, Ile 526, Glu 528, Glu 529 are critical residues for ligand–receptor interactions. The molecular dynamic simulation was done to access the reliability of the binding pose of inhibitor and protein complex using GROMACS software at 10ns time point. Trajectories were analyzed at each 2.5 ns time interval, among which, H-bond with LEU-525 and GLY- 530 are significantly present in MD trajectories. Furthermore, antigenic determinants of the protein were determined with the help of DNA Star software. Our study findings showed a great potential in order to provide insights in the development of new drug(s) or vaccine(s) for control as well as prevention of cryptosporidiosis among humans and animals.

Keywords: cryptosporidium hominis, hypothetical protein, molecular docking, molecular dynamics simulation

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Authors: Kishor Prasad Bhatta, Suman Ghimire, Durga Prasad Joshi

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Invasive Alien Species (IAS) are considered waste forest resources in Nepal. The rapid expansion of IAS is one of the nine main drivers of forest degradation, though the extent and distribution of this species are not well known. Further, the knowledge of the impact of IAS removal on forest plant diversity is hardly known, and the possibilities of income generation from them at the grass-root communities are rarely documented. Systematic sampling of 1% with nested circular plots of 500 square meters was performed in IAS removed and non-removed area, each of 30 hectares in Udayapur Community Forest User Group (CFUG), Chitwan, central Nepal to observe whether the removal of IAS contributed to an increase in plant diversity. In addition, ten entrepreneurs of Udaypur CFUG, involved in the charcoal production, briquette making and marketing were interviewed and interacted as well as their record keeping booklets were reviewed to understand if the charcoal production contributed to their income and employment. The average annual precipitation and temperature of the study area is 2100 mm and 34 degree Celsius respectively with Shorea robusta as main tree species and Eupatorium odoratum as dominant IAS. All the interviewed households were from the ̔below-poverty-line’ category as per Community Forestry Guidelines. A higher Shannon-Weiner plant diversity index at regeneration level was observed in IAS removed areas (2.43) than in control site (1.95). Furthermore, the number of tree seedlings and saplings in the IAS harvested blocks were significantly higher (p < 0.005) compared to the unharvested one. The sale of charcoal produced through the pyrolysis of IAS in ̔ Bio-energy kilns’ contributed for an average increased income of 30.95 % (Nepalese rupees 31,000) of the involved households. Despite above factors, some operational policy hurdles related to charcoal transport and taxation existed at field level. This study suggests that plant diversity could be increased through the removal of IAS, and considerable economic benefits could be achieved if charcoal is substantially produced and utilized.

Keywords: briquette, economic benefits, pyrolysis, regeneration

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Authors: Keshav Prasad Kandel, Balaram Khadka, Karan Bhatta, Basu Dev Ghimire

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Earthquakes still exist as a threating disaster. Being able to predict earthquakes will certainly help prevent substantial loss of life and property. Perhaps, Very Low Frequency/Low Frequency (VLF/LF) signal band (3-30 kHz), which is effectively reflected from D-layer of ionosphere, can be established as a tool to predict earthquake. On May 20 and May 29, 2012, earthquakes of magnitude 6.1 and 5.8 respectively struck Emilia-Romagna of Italy. A year back, on August 24, 2016, an earthquake of magnitude 6.2 struck Central Italy (42.7060 N and 13.2230 E) at 1:36 UT. We present the results obtained from the US Navy VLF Transmitter’s NSY signal of 45.9 kHz transmitted from Niscemi, in the province of Sicily, Italy and received at the Kiel Longwave Monitor, Germany for 2012 and 2016. We analyzed the terminator times, their individual differences and nighttime fluctuation counts. We also analyzed trends, dispersion and nighttime fluctuation which gave us a possible precursors to these earthquakes. Since perturbations in VLF amplitude could also be due to various other factors like lightning, geomagnetic activities (storms, auroras etc.) and solar activities (flares, UV flux, etc.), we filtered the possible perturbations due to these agents to guarantee that the perturbations seen in VLF/LF amplitudes were as a precursor to Earthquakes. As our TRGCP path is North-south, the sunrise and sunset time in transmitter and receiver places matches making pathway for VLF/LF smoother and therefore hoping to obtain more natural data. To our surprise, we found many clear anomalies (as precursors) in terminator times 5 days to 16 days before the earthquakes. Moreover, using night time fluctuation method, we found clear anomalies 5 days to 13 days prior to main earthquakes. This exactly correlates with the findings of previous authors that ionospheric perturbations are seen few days to one month before the seismic activity. In addition to this, we were amazed to observe unexpected decrease of dispersion on certain anomalies where it was supposed to increase, thereby not supporting our finding to some extent. To resolve this problem, we devised a new parameter called dispersion nighttime (dispersion). On analyzing, this parameter decreases significantly on days of nighttime anomalies thereby supporting our precursors to much extent.

Keywords: D-layer, TRGCP (Transmitter Receiver Great Circle Path), terminator times, VLF/LF

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Authors: Rubisha Adhikari, Rajani Shah

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Introduction: Aging is a natural, global and inevitable phenomenon every single person has to go through, and nobody can escape the process. One of the emerging challenges to public health is to improve the quality of later years of life as life expectancy continues to increase. Quality of life (QoL) has grown to be a key goal for many public health initiatives. Population aging has become a global phenomenon as they are growing more quickly in emerging nations than they are in industrialized nations, leaving minimal opportunities to regulate the consequences of the demographic shift. Methods: A community-based descriptive analytical approach was used to examine the quality of life and associated factors among elderly people. A mixed method was chosen for the study. For the quantitative data collection, a household survey was conducted using the WHOQOL-OLD tool. In-depth interviews were conducted among twenty participants for qualitative data collection. Data generated through in-depth interviews were transcribed verbatim. In-depth interviews lasted about an hour and were audio recorded. The in-depth interview guide had been developed by the research team and pilot-tested before actual interviews. Results: This study result showed the association between quality of life and socio-demographic variables. Among all the variables under socio-demographic variable of this study, age (ꭓ2=14.445, p=0.001), gender (ꭓ2=14.323, p=<0.001), marital status (ꭓ2=10.816, p=0.001), education status (ꭓ2=23.948, p=<0.001), household income (ꭓ2=13.493, p=0.001), personal income (ꭓ2=14.129, p=0.001), source of personal income (ꭓ2=28.332,p=<0.001), social security allowance (ꭓ2=18.005,p=<0.001), alcohol consumption (ꭓ2=9.397,p=0.002) are significantly associated with quality of life of elderly. In addition, affordability (ꭓ2=12.088, p=0.001), physical activity (ꭓ2=9.314, p=0.002), emotional support (ꭓ2=9.122, p=0.003), and economic support (ꭓ2=8.104, p=0.004) are associated with quality of life of elderly people. Conclusion: In conclusion, this mixed method study provides insight into the attributes of the quality of life of elderly people in Nepal and similar settings. As the geriatric population is growing in full swing, maintaining a high quality of life has become a major challenge. This study showed that determinants such as age, gender, marital status, education status, household income, personal income, source of personal income, social security allowance and alcohol consumption, economic support, emotional support, affordability and physical activity have an association with quality of life of the elderly.

Keywords: ageing, chitwan, elderly, health status, quality of life

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Authors: Markus Bredel, Sindhu Nair, Hoa Q. Trummell, Rajani Rajbhandari, Christopher D. Willey, Lewis Z. Shi, Zhuo Zhang, William J. Placzek, James A. Bonner

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Purpose: EGFR-targeted monoclonal antibodies (mAbs) provide clinical benefit in some patients with H&N squamous cell carcinoma (HNSCC), but others progress with minimal response. Missense mutations in the EGFR ectodomain (ECD) can be acquired under mAb therapy by mimicking the effect of large deletions on receptor untethering and activation. Little is known about the contribution of EGFR ECD mutations to EGFR activation and anti-EGFR response in HNSCC. Methods: We selected patient-derived HNSCC cells (UM-SCC-1) for resistance to mAb Cetuximab (CTX) by repeated, stepwise exposure to mimic what may occur clinically and identified two concurrent EGFR ECD mutations (UM-SCC-1R). We examined the competence of the mutants to bind EGF ligand or CTX. We assessed the potential impact of the mutations through visual analysis of space-filling models of the native sidechains in the original structures vs. their respective side-chain mutations. We performed CRISPR in combination with site-directed mutagenesis to test for the effect of the mutants on ligand-independent EGFR activation and sorting. We determined the effects on receptor internalization, endocytosis, downstream signaling, and radiation sensitivity. Results: UM-SCC-1R cells carried two non-synonymous missense mutations (G33S and N56K) mapping to domain I in or near the EGF binding pocket of the EGFR ECD. Structural modeling predicted that these mutants restrict the adoption of a tethered, inactive EGFR conformation while not permitting association of EGFR with the EGF ligand or CTX. Binding studies confirmed that the mutant, untethered receptor displayed a reduced affinity for both EGF and CTX but demonstrated sustained activation and presence at the cell surface with diminished internalization and sorting for endosomal degradation. Single and double-mutant models demonstrated that the G33S mutant is dominant over the N56K mutant in its effect on EGFR activation and EGF binding. CTX-resistant UM-SCC-1R cells demonstrated cross-resistance to mAb Panitumuab but, paradoxically, remained sensitive to the reversible receptor tyrosine kinase inhibitor Erlotinib. Conclusions: HNSCC cells can select for EGFR ECD mutations under EGFR mAb exposure that converge to trap the receptor in an open, constitutively activated state. These mutants impede the receptor’s competence to bind mAbs and EGF ligand and alter its endosomal trafficking, possibly explaining certain cases of clinical mAb and radiation resistance.

Keywords: head and neck cancer, EGFR mutation, resistance, cetuximab

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