MORPHOLOGICAL, GENETIC AND BIOCHEMICAL CHARACTERIZATION OF THE ANTI-MALARIAL HERB, Artemisia annua GERMPLASM COLLECTION AT WEST VIRGINIA UNIVERSITY

Malaria is one of the deadliest diseases in human history. Nearly half of the world’s population, is at the risk in 106 countries. Only in 2016, this disease killed about 445,000 people, 72% of them being children under age five. It also accounts for US $12 billion dollars of direct costs in Africa alone. Five different species of Plasmodium cause malaria but P. falciparum is the most detrimental one, causing 50% of all malaria cases and is considered as the deadliest parasite in humans. Artemisinin (ART), a 15 C sesquiterpenoid is currently the only precursor to the most effective anti-malarial drugs. The World Health Organization (WHO) recommends the use of ART-derived drugs in combination with other anti-malarial drugs (collectively called as Artemisinin-based Combination Therapies, ACT), to prevent the development of ART resistance by the parasite. The natural source of ART is Artemisia annua, an Asteraceae plant native to East Asia. ART is synthesized in 10-cell glandular trichomes and accumulates extra-cellularly in the sub cuticular space. ART is synthesized in A. annua in low quantities, about 0.01-3% DW and, due to its complex molecular structure, it cannot be synthesized chemically in an economically viable way. Even though the semi-synthesis of ART has been successful in bioreactors, ART extraction from A. annua is much more economically viable. Therefore, it is important to understand the A. annua genetic contribution to ART synthesis to improve the ART yield of the plants. We characterized a collection of 12 different genotypes of Artemisia annua at West Virginia University in terms of developmental traits, biochemical profile, and gene expression to better understand the phenotypical differences of the germplasm in the collection. Plants were analyzed for height, biomass, leaf shape and leaf size, adaxial and abaxial trichome densities for morphological characterization. Freeze dried leaf material was extracted with hexane and an internal standard and the extractions were analyzed with GC-MS. Flash frozen leaf material were used to extract total RNA and analyzed for the gene expression of 15 genes with qRT-PCR. Based on the results, it was revealed that there is high phenotypical and metabolic variation among the genotypes. Monoterpenes made up for a large component of the hexane-extracted metabolome. Camphor and endo-borneol contributed significantly to differentiate the genotypes. Out of the all the genes analyzed, gene expression of three genes (FPS, CPR, and DBR2) were significantly different among the genotypes. Based on data, genotype J has the highest accumulation of ART and DHAA with anatomical characteristics supporting towards high ART and DHAA yield. Next, I and G genotypes also showed anatomical features supporting towards high ART and DHAA accumulation. The genotypes can be used to further investigate ideal genetic variations and allelic combinations for crop improvement in future

Acceptable use policy and employee computer usage: case of Sri Lankan software development industry

Organizations introduce acceptable use policies to deter employee computer misuse. Despite the controlling, monitoring and other forms of interventions employed, some employees misuse the organizational computers to carry out their personal work such as sending emails, surfing internet, chatting, playing games etc. These activities not only waste productive time of employees but also bring a risk to the organization. A questionnaire was administrated to a random sample of employees selected from large and medium scale software development organizations, which measured the work computer misuse levels and the factors that influence such behavior. The presence of guidelines provided no evidence of significant effect on the level of employee computer misuse. Not having access to Internet /email away from work and organizational settings were identified to be the most significant influences of work computer misuse

Associated risk factors in Breast cancer: A comparative Sri Lankan perspective

Breast cancer (BC) is the commonest carcinoma among women in Sri Lanka. Various modifiable and non-modifiable risk factors are reported as causatives of BC, even though studies on the incidence and relevance of these risk factors to the Sri Lankan context are not comprehensively documented. Thus, objectives of the present study were to assess the odds related to the incidence of known and unknown risk factors in BC development in Sri Lanka. The risk factors including age at diagnosis of BC, age at menarche, age at menopause, parity, duration of breastfeeding, history of abortions, usage of hormonal contraceptives, smoking, involvement of exercises, frequency of consumption of selected foods etc. were collected from an interviewer-administered questionnaire from 355 participants (255 BC patients and 150 healthy women). Ethical approval for the study was obtained. The majority (63%) of the BC patients were postmenopausal and the commonest age group at diagnosis of the carcinoma was 51-60 years. A woman was observed to have 3.6 (Odds Ratio= 3.58, Confidence Interval 1.37-9.34) and 2.1 (Odds Ratio 2.13, Confidence Interval 1.0-4.95) times risk in developing BC when_having first-order relatives and second-order relatives with breast cancer respectively. A woman had three times the odds (Odds Ratio= 3.02, Confidence Interval 1.59-5.75) of developing BC with the use of hormonal contraceptives for more than two consecutive years and three times the risk of _having BC (Odds Ratio= 3.12, Confidence Interval 1.63-5.98) if she has had one or more spontaneous or induced abortions. Factors including consumption of selected food, use of bottled water and usage of microwave ovens with inappropriate containers (plastic containers) among BC patients were not significantly different compared to healthy. The risk factors including a woman in the age close to or soon after menopause, having a family history of BC, having used hormonal contraceptives and having experienced one or more abortions showed a higher risk compared to other factors studied. KEYWORDS: Breast cancer, risk factors, family history, abortions, menopausal statu

Nano-lactoferrin in diagnostic, imaging and targeted delivery for cancer and infectious diseases

Lactoferrin (Lf) is a natural occurring iron binding protein present in many mammalian excretions and involved in various physiological processes. Lf is used in the transport of iron along with other molecules and ions from the digestive system. However its the modulatory functions exhibited by Lf in connection to immune response, disease regression and diagnosis that has made this protein an attractive therapeutic against chronic diseases. Further, the exciting potentials of employing nanotechnology in advancing drug delivery systems, active disease targeting and prognosis have also shown some encouraging outcomes. This review focuses on the role of Lf in diagnosing infection, cancer, neurological and inflammatory diseases and the recent nanotechnology based strategies

Comparison of Calibration Approaches of the Soil and Water Assessment Tool (SWAT) Model in a Tropical Watershed

Hydrologic models are indispensable tools for water resource planning and management. Accurate model predictions are critical for better water resource development and management decisions. Single-site model calibration and calibrating a watershed model at the watershed outlet are commonly adopted strategies. In the present study, for the first time, a multi-site calibration for the Soil and Water Assessment Tool (SWAT) in the Kelani River Basin with a catchment area of about 2340 km2 was carried out. The SWAT model was calibrated at five streamflow gauging stations, Deraniyagala, Kithulgala, Holombuwa, Glencourse, and Hanwella, with drainage areas of 183, 383, 155, 1463, and 1782 km2, respectively, using three distinct calibration strategies. These strategies were, utilizing (1) data from downstream and (2) data from upstream, both categorized here as single-site calibration, and (3) data from downstream and upstream (multi-site calibration). Considering the performance of the model during the calibration period, which was examined using the statistical indices R2 and NSE, the model performance at Holombuwa was upgraded from “good” to “very good” with the multi-site calibration technique. Simultaneously, the PBIAS at Hanwella and Kithulgala improved from “unsatisfactory” to “satisfactory” and “satisfactory” to “good” model performance, while the RSR improved from “good” to “very good” model performance at Deraniyagala, indicating the innovative multi-site calibration approach demonstrated a significant improvement in the results. Hence, this study will provide valuable insights for hydrological modelers to determine the most appropriate calibration strategy for their large-scale watersheds, considering the spatial variation of the watershed characteristics, thereby reducing the uncertainty in hydrologic predictions.publishedVersio

Impact of insulin sensitisation on metabolic and fertility outcomes in women with polycystic ovary syndrome and overweight or obesity - a systematic review, meta-analysis, and meta-regression

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-age women. This systematic review, meta-analysis and meta-regression aims to compare the effect of insulin sensitiser pharmacotherapy on metabolic and reproductive outcomes in women with PCOS and overweight or obesity. We searched online databases MEDLINE via OVID, EMBASE, Clinicaltrials.gov and EudraCT for trials published from inception to 13th November 2023. Inclusion criteria were double-blind, randomised controlled trials in women diagnosed with PCOS, body mass index (BMI) ≥ 25 kg/m2, which reported metabolic or reproductive outcomes. The intervention was insulin sensitisation pharmacotherapy versus placebo or other agents. The primary outcomes were the changes from baseline BMI, fasting blood glucose and menstrual frequency. Nineteen studies were included in this review. Metformin had the most significant effect on the fasting plasma glucose and body mass index. Insulin sensitiser pharmacotherapy significantly reduced fasting plasma glucose, body mass index, fasting serum insulin, HOMA-IR, sex hormone binding globulin and total testosterone, but the effect size was small. There was a lack of menstrual frequency and live birth data. The results indicate a role for insulin sensitisers in improving the metabolic and, to a lesser degree, reproductive profile in these women. Further research should examine insulin sensitisers' effects on objective measures of fecundity

Species Composition and Diversity in two Selected Lowland Tropical Rainforests in Sri Lanka and their Relationships to Temperature and Precipitation

Tropical rainforests are characterised by high species diversity, which may be due to a range of factors such as climate, topography, soil properties and the level of disturbance, both natural and anthropogenic. This study focused on investigating the species composition, richness, diversity and their conservation status in lowland tropical rainforests at two selected locations in Sri Lanka and determining their relationships to temperature and precipitation. Two permanent one-hectare sampling plots each were established at the Kanneliya (KDN1 and KDN2) and Pitadeniya-Sinharaja (PTD1 and PTD2) Forest Reserves. All trees with dbh≥10 cm were enumerated. A total of 3,303 trees were recorded, representing 158 species from 91 genera and 53 families, with a total basal area of 196.26 m2. Most abundant plant species were Alstonia macrophylla in KDN1 (11.7% of trees with dbh≥10 cm), Syzygium grande in KDN2 (9.8%), Shorea affinis in PTD1 (15.8%) Mesua thwaitesii in PTD2 (17.5%). Cullenia rosayroana (7.2%) is the most abundant species within the whole study area. While 25 species were recorded in all four plots, 70 species were found in only one location. Genus Shorea (18.6%) is the most common including 12 different species and Dipterocarpaceae (21.9%) is the most common family including 19 species. KDN1 recorded 1,011 plants from 108 species, with 74.3% endemic, 12.8% native and 11.9% exotic species. Other study sites recorded only endemic (88% at KDN2, 83.7% at PTD1 and 82.3% at PTD2) and native species. In comparison to PTD, KDN recorded higher numbers of trees with dbh≥10 cm (Chi-square p<0.0001), species (p<0.0001) and genera (p=0.0091). KDN also recorded a higher number of families but the difference was not significant (p=0.358). All indices of species diversity (Shannon index, H and Simpson index, D), evenness (J) and richness (R) are higher at KDN. However, only the difference in D was statistically-significant at p=0.05. Multiple regression analysis using the stepwise procedure showed that the number of trees with dbh≥10 cm and the species number increased with increasing average annual air temperature (T) but decreased with annual total precipitation (P). On the other hand, the numbers of genera and families increased with decreasing P with T not having a significant influence. The two diversity indices, H and D, increased with decreasing P and increasing T. In contrast, increasing P decreased J and R whereas variation in T did not have a significant influence. These findings provide important insights in to dynamics plant diversity in response to environmental changes.Keywords: Species composition, Species diversity, Tropical rainforest

Clinical Utility of Radiologic Disease Reassessment in the Management of Pediatric B-Cell Non-Hodgkin Lymphoma

Although outcomes for children with B-cell non-Hodgkin lymphoma are excellent, between 20% and 40% demonstrate residual radiologic abnormalities at disease assessment during consolidation therapy, the significance of which remains uncertain. The authors report the outcomes for all children treated for B-cell non-Hodgkin lymphoma at our center over an 11-year period. Twenty-four of 64 (38%) children had residual radiologic abnormalities at disease remission assessment. Seven (29%) underwent histologic biopsies that were normal. No children with residual radiologic abnormalities experienced disease relapse or death, suggesting that imaging at this time point creates clinical uncertainty without indicating residual disease or predicting relapse

A simple Affymetrix ratio-transformation method yields comparable expression level quantifications with cDNA data

Gene expression profiling is rapidly evolving into a powerful technique for investigating tumor malignancies. The researchers are overwhelmed with the microarray-based platforms and methods that confer them the freedom to conduct large-scale gene expression profiling measurements. Simultaneously, investigations into cross-platform integration methods have started gaining momentum due to their underlying potential to help comprehend a myriad of broad biological issues in tumor diagnosis, prognosis, and therapy. However, comparing results from different platforms remains to be a challenging task as various inherent technical differences exist between the microarray platforms. In this paper, we explain a simple ratio-transformation method, which can provide some common ground for cDNA and Affymetrix platform towards cross-platform integration. The method is based on the characteristic data attributes of Affymetrix- and cDNA- platform. In the work, we considered seven childhood leukemia patients and their gene expression levels in either platform. With a dataset of 822 differentially expressed genes from both these platforms, we carried out a specific ratio-treatment to Affymetrix data, which subsequently showed an improvement in the relationship with the cDNA data