Accuracy of Glucose Meter Among Adults in a Semi-urban Area in Kathmandu, Nepal

Introduction: Glucose meters are gaining popularity in monitoring of blood glucose at household levels and in health care set-ups due to their portability, affordability and convenience of use over the laboratory based reference methods. Still they are not free of limitations. Operator’s technique, extreme temperatures, humidity, patients’ medication, hematocrit values can affect the reliability of glucose meter results. Hence, the accuracy of glucose meter has been the topic of concern since years. Therefore, present study aims to evaluate the analytical and clinical accuracy of glucose meter using International Organization for Standardization 15197 guideline. Methods: A community based descriptive cross-sectional study was conducted in Kapan, Kathmandu, Nepal in April 2018. Glucose levels were measured using glucose meter and reference laboratory method simultaneously among 203 adults ≥20 years, after an overnight fasting and two hours of ingestion of 75 grams glucose. Modified Bland-Altman plots were created by incorporating ISO 15197 guidelines to check the analytical accuracy and Park error grid was used to evaluate the clinical accuracy of the device. Results: Modified Bland-Altman plots showed>95% of the test results were beyond the acceptable analytical criteria of ISO 15197:2003 and 2013. Park Error Grid-Analysis showed 99% of the data within zones A and B of the consensus error grid. Conclusions: Glucose meter readings were within clinically acceptable parameters despite discrepancies on analytical merit. Possible sources of interferences must be avoided during the measurement to minimize the disparities and the values should be interpreted with caution.

Synthesis and anti-norovirus activity of pyranobenzopyrone compounds

During the last decade, noroviruses have gained media attention as the cause of large scale outbreaks of gastroenteritis on cruise ships, dormitories, nursing homes, etc. Although noroviruses do not multiply in food or water, they can cause large outbreaks because approximately 10–100 virions are sufficient to cause illness in a healthy adult. Recently, it was shown that the activity of acyl-coenzyme A:cholesterol acyltransferase-1 (ACAT1) enzyme may be important in norovirus infection. In search of anti-noroviral agents based on the inhibition of ACAT1, we synthesized and evaluated the inhibitory activities of a class of pyranobenzopyrone molecules containing amino, pyridine, substituted quinolines, or 7,8-benzoquinoline nucleus. Three of the sixteen evaluated compounds possess ED[subscript]5[subscript]0 values in the low micrometer range. 2-Quinolylmethyl derivative 3A and 4-quinolylmethyl derivative 4A showed ED[subscript]5[subscript]0 values of 3.4 and 2.4 [mu]M and TD[subscript]5[subscript]0 values of >200 and 96.4 [mu]M, respectively. The identified active compounds are suitable for further modification for the development of anti-norovirus agents

Design, synthesis, and biological evaluation of tricyclic pyrones and thiouridine nucleosides

Doctor of PhilosophyDepartment of ChemistryDuy H. HuaThe first chapter in this thesis includes the design, synthesis, and evaluation of anti-Alzheimer and anti-norovirus activities of tricyclic pyrones (TPs). Alzheimer’s disease is a major cause of dementia and sixth leading cause of death; it is a growing problem all over the world. On the other hand, norovirus, a highly contagious agent is responsible for more than 90% of non-bacterial gastroenteritis causing severity mainly in the closed environments. No drugs exist to eradicate the symptoms developed by both of these disorders. Studies have shown that the development of Alzheimer’s disease and the infection of norovirus are dependent on cholesterol metabolism. More specifically, the inhibition of acyl-CoA: cholesterol acyltrasferase (ACAT) led to the reduction of plaques in Alzheimer’s disease as well as reduced the infection of norovirus. Mimicking the structure of CP2, a TP with promising anti-Alzheimer activities, a library of tricyclic pyrones containing phenyl, naphthyl, heterocyclic, and dipeptidyl moieties were synthesized and evaluated for their anti-Alzheimer and anti-norovirus efficacies. Several TPs containing phenyl and naphthyl groups showed sub-micromolar to nanomolar potencies for the protection of neuronal MC65 cells from Aβ-oligomers induced death. Similarly, the TPs containing pyrrolyl, imidazolyl, and quinolinyl moieties were effective to inhibit the norovirus replication in low micromolar range. The most effective TPs from MC65 cells protection assay were also effective in the inhibition ACAT and up-regulation ABCA1 gene. The second chapter in this thesis includes the design, synthesis, and anti-norovirus activity of thiouridine nucleosides. Many nucleosides have demonstrated effective inhibition of viral RNA polymerase, and some are progressing at different level of clinical trials for the treatment of hepatitis C virus. Some of the nucleosides, including 2’-C-methyl and 2’-amino substituted analogs, were found to effectively inhibit the norovirus replication. In the search of more potent anti-noroviral compounds, two thiouridine nucleosides were synthesized and evaluated as anti-norovirus agents. Both of these analogs were ineffective up to 50 μM for the inhibition of norovirus replication in cell based assay. Proposed work of converting these nucleosides to their phosphoramidate derivatives is also described

STRATEGIC HUMAN RESOURCE MANAGEMENT AND ITS IMPACT ON BANK’S PERFORMANCE

The importance of strategic planning and management as increased significantly in recent times. It is a means of enhancing organizational competitive advantage. In a swiftly changing competitive environment, human resources are one important source of competitive lead for an organization. However, linking to strategic planning and management, human resource management should be strategic that guarantees positive firm performance outcome. It has become even more necessary in the financial sector, especially for the banking and financial institutions, because of the integration of global financial systems and the resultant increase in competitiveness. Nepal has an established banking system with main challenge to strategic management of human resources and directly implicating to survival of the banks depend on its performance. In this view this study aims at exploring strategic human resource management practices and examining the impact of strategic human resource management practices on organizational performance of commercial banks in Nepal. This study uses a quantitative approach towards descriptive and explanatory casual research design with 6 numbers of banks and 507 numbers of employee as sample. It was found that strategic human resource management practices are a vital element in consideration of increasing the financial performance, business performance, organizational effectiveness, employee job performance, and benchmarked performance achievement

Investigation of HCAR2 antagonists as a potential strategy to modulate bovine leukocytes

Abstract Background Dairy cows experiencing ketosis after calving suffer greater disease incidence and are at greater risk of leaving the herd. In vitro administration of beta-hydroxybutyric acid (BHBA; the primary blood ketone) has inhibitory effects on the function of bovine leukocytes. BHBA is a ligand of HCAR2 and the activation of these receptors promotes an anti-inflammatory response which may be related with immunosuppression observed in transition dairy cattle. The objective of this study was to identify and test antagonists for HCAR2 in bovine immune cells cultured with BHBA. Results We observed expression of HCAR2 at the protein level within lymphocytes, monocytes, and granulocytes. The proportion of cells expressing HCAR2 tended to be greater in mid-lactation compared to early lactation cows; the increase was a result of increased proportion of T and B cells expressing HCAR2. Stimulation of HCAR2 with niacin or BHBA promoted Ca2+ mobilization in neutrophils and mononuclear cells. Mononuclear cells treated with BHBA had diminished intracellular Ca2+ responses when HCAR2 was knocked down by siRNA silencing, indicating Ca2+ mobilization was mediated by HCAR2 signaling. Two candidate antagonists for HCAR2, synthesized from niacin (NA-1 and NA-5), were tested; monocytes and neutrophils pre-treated with NA-1 and NA-5 had reduced Ca2+ mobilization after incubation with BHBA. Furthermore, NA-5 but not NA-1 prevented BHBA-associated reductions in cyclic AMP. Conclusions We demonstrated that HCAR2 is present on bovine leukocytes and has greater expression later in lactation. We confirmed that BHBA and niacin derived HCAR2 antagonists alter bovine leukocyte activity. Our results demonstrate that both BHBA and niacin affect bovine leukocyte Ca2+ mobilization in a HCAR2-dependent manner

Screening of Maize Genotypes against Southern Leaf Blight (Bipolaris maydis) during Summer Season in Nepal

Abstract A study was conducted from 29 March 2014 to 27 July 2014 at the Institute of Agriculture and Animal Science, Paklihawa, Rupandehi with the objective of screening 13 maize genotypes against southern leaf blight caused by Bipolaris maydis. Field experiment was laid out in a randomized complete block design with three replications. Disease scoring was done as percentage of leaf area infected on individual plant at 5 days intervals starting from 63 days after sowing, for 3 times, and disease severity and mean AUDPC were calculated and yield was recorded. Among the tested genotypes, disease severity varies significantly. Disease symptoms appeared first in Yellow Popcorn, 64.00 days after sowing (DAS) with the highest severity and at last in RML-32/RML-17 (79.00 DAS) with the least score in field. The 13 genotypes differed significantly in mean AUDPC values. RML-32/RML-17 (AUDPC value 5.90) appeared most resistant, followed by RML-4/RML-17 (AUDPC value 11.50), while Yellow Popcorn (AUDPC value 71.99) was most susceptible among the tested genotypes. Highest maize yield (3.43 metric ton ha ) on Yellow Popcorn. Maximum SPAD value above cob was recorded in RML-4/RML-17 (45.62) followed by S03TLYQ-AB-01 (44.88) while minimum in Yellow popcorn (30.60). So, Yellow popcorn has the highest (3.16) and RML-32/RML-17 (0.08) lowest total AUDPC above cob. Similarly maximum SPAD value below cob was recorded in RML-4/RML-17 (44.37), while minimum in Yellow popcorn (28.82). So, Yellow popcorn has the highest (8.75) and RML-32/RML-17 (0.41) has lowest total AUDPC below cob. The genotypes RML-4/RML-17 and RML-32/RML-17 appeared resistant to SLB with maximum yield. These genotypes could be used as the sources of resistance in breeding program and could be developed to resistant varieties grown under tropical and subtropical climatic conditions during summer season. The genotype Yellow popcorn being highly susceptible to SLB with a maximum mean AUDPC and minimum yield, can be used as susceptible check for breeding purpose and different varietal screening

Inhibition of Acyl-CoA: Cholesterol Acyltransferase (ACAT), Overexpression of Cholesterol Transporter Gene, and Protection of Amyloid β (Aβ) Oligomers-Induced Neuronal Cell Death by Tricyclic Pyrone Molecules

A major effort in Alzheimer’s disease therapeutic development has targeted Aβ and downstream events. We have synthesized a small library of tricyclic pyrone compounds. Their protective action in MC65 cells and inhibition of ACAT along with the upregulation of cholesterol transporter gene were investigated. Five active compounds exhibited potencies in the nanomolar ranges. The multiple effects of the compounds on Aβ and cellular cholesterol pathways could be potential mechanisms underlying the protective effects in vivo

Inhibition of Acyl-CoA: Cholesterol acyltransferase (ACAT), overexpression of cholesterol transporter gene, and protection of amyloid β (Aβ) oligomers-induced neuronal cell death by tricyclic pyrone molecules

Alzheimer’s disease (AD) is the most common cause of dementia in the elderly. A major effort in AD therapeutic development has targeted Aβ and downstream events. We have taken a rational design approach and synthesized a small library of tricyclic pyrone compounds based on CP2. Their protective action in MC65 cells and the inhibition of acyl‐CoA:cholesterol acyltransferase along with the upregulation of cholesterol transporter gene were investigated. Five most active compounds exhibited potencies in the nanomolar to low micromolar ranges. The multiple effects of the compounds on Aβ and cellular cholesterol pathways could be potential mechanisms underlying the protective effects in vivo