Transfusion of incompatible blood to a patient with alloanti-Sc1.

Sc1 is a high-prevalence blood group antigen that is part of the Scianna blood group system. The clinical significance of Scianna antibodies is not well understood because of their rarity; there are only a handful of cases in the literature. This scarcity of information can make it difficult to decide on the best course of action when transfusing a patient with alloantibodies to Scianna blood group antigens. We describe a case of an 85-year-old woman presenting with melena and a hemoglobin of 66 g/L. Upon request for crossmatched blood, a panreactive antibody was found, later elucidated to be alloanti-Sc1. Because of the urgent nature of the transfusion, the patient was transfused with 2 incompatible, presumed Sc1+, red blood cell units with no evidence of an acute or delayed transfusion reaction. This case has been shared with the International Society of Blood Transfusion Rare Donor Working Party, via their Outcome of Incompatible Transfusion form, and adds to the body of evidence on clinical significance of antibodies to the antigens of the Scianna blood group system.

Availability of rehabilitation services for communication disorders in Sri Lanka: a cross-sectional survey.

OBJECTIVES: To describe the rehabilitation services available for communication disorders in Sri Lanka and to estimate the adequacy of the services in provinces and districts of the country. SETTING: The study considered government and private institutions, which provide rehabilitation services for communication disorders in Sri Lanka. PARTICIPANTS: Institutions providing services of speech-language pathologists, audiologists and audiology technicians in Sri Lanka. PRIMARY AND SECONDARY OUTCOME MEASURES: We investigated the number of government hospitals and private institutions, which provide speech-language pathology and audiology services in Sri Lanka as the primary outcome measure. A number of speech-language pathologists, audiologists and audiology technicians working in the institutions were obtained from records and institution-based inquiries to identify the adequacy of the services in the country as the secondary outcome measure. RESULTS: Of the 647 government hospitals that provide free healthcare services in the country, 45 and 33 hospitals had speech and language therapy and audiology units, respectively. Government hospitals do not have audiologists but only have audiology technicians. The number of speech and language therapists and audiology technicians in the government sector per 100 000 population in the country was 0.44 and 0.18, respectively. There were wide variations in specialist to population ratio between districts. 77 private centres provide speech therapy services in 15 out of the 25 districts; 36 private centres provide audiological evaluations in 9 districts. CONCLUSIONS: The number of specialist speech and language therapists and audiologists is not sufficient to provide adequate rehabilitation services for communications disorder for the Sri Lankan population. Not recruiting audiologists to the government sector affects the management of hearing impairment in the affected.

REACh for the preschoolers; a developmental assessment tool for 2-5 year old children in Sri Lanka.

BACKGROUND: Preschool children in low resource settings are at higher risk of missing developmental potential due to the lack of standardized and validated methods for the timely detection of children with developmental delays or neurodevelopmental disorders. The preschool teacher is a non-specialist resourceful link within the community to detect and offer interventions early. This paper discusses the preliminary iteration of designing and testing the psychometric properties of a developmental assessment for children aged 24 to 60 months in Sri Lanka. This assessment is designed to be conducted by preschool teachers in their preschool setting. METHODS: Three processes followed: 1. Designing and development of the Ragama Early Assessment for Children (REACh) complete preschool developmental assessment and a tool kit 2. Testing and training teachers on conducting the REACh assessment 3. Preliminary assessment of the psychometric properties including content validity, internal consistency, interrater reliability and concurrent validity. RESULTS: A literature search identified 11 assessments and 542 items representing cognitive, social-emotional and adaptive, language and motor domains. Content validity was assessed to select and adapt items. A complete assessment tool was designed to be administered in four settings within the preschool. This was further improved during pre and pilot testing and teacher training. Cronbach's alpha measuring internal consistency was > 0.70 for cognitive, language, social-emotional and adaptive domains across all three age groups in 1809 children. Interrater reliability was > 65% for age groups 36-47 and 47- 60 months. Concurrent validity using a clinical gold standard demonstrated sensitivity of more than 0.75 for all age groups with variable specificities (24-35 months: 0.71, 36- 47 months: 0.43 and 48-60 months: 0.67) assessed in 75 children. CONCLUSIONS: This culturally and linguistically adapted tool was tested nationally in Sri Lanka. The inte-rrater reliability between teachers and research assistants was higher than 65% for all domains in children more than 36 months. The preliminary iteration confirms it as an acceptable screening assessment for all age groups but with significantly lower specificity in the 36-47 month age group. Further improvement in certain domains together with intense teacher training is likely to enhance the validity and reliability of the assessment. TRIAL REGISTRATION: Ethics clearance for the procedure was granted prospectively from the Ethics Review Committee, Faculty of Medicine, University of Kelaniya (ERC no. P 131/06/2018).

Adrenal carcinoma: a case report.

BACKGROUND: Adrenocortical carcinoma is a rare malignancy (0.5-2 cases/million/year) with a poor prognosis. Hypercortisolism, virilization, and compressive features are among the common presentations of adrenocortical carcinoma. Hematuria is one of the rare initial presentations of adrenocortical carcinoma reported in the literature. We report a case of adrenal carcinoma presenting with microscopic hematuria. CASE PRESENTATION: A 67-year-old Sri Lankan patient with diabetes, hypertension, and ischemic heart disease presented with an acute coronary event. During the routine evaluation, microscopic hematuria was detected without proteinuria or active sediments. She denied any painful micturition, previous similar episodes, or abdominal pain. Further evaluation revealed a hypokalemia with biochemical evidence of hypercortisolism and high testosterone levels with suppressed adrenocorticotropic hormone levels. On imaging, there was evidence of a right suprarenal mass 7 cm × 3 cm × 6 cm in size that was hypoechoic and lobulated and suggestive of a lipid-poor tumor. She underwent adrenalectomy. By the time of surgery 3 weeks later, significant weight gain with features of Cushing syndrome, including hirsutism, skin atrophy, easy bruising without virilization, and proximal myopathy, were noted. Histology identified a right-sided adrenal tumor with capsular and vascular invasion. Hypercortisolism and hematuria disappeared after surgery. The patient was referred for further oncological management. CONCLUSION: This case illustrates a rare presentation of adrenal carcinoma. Awareness of this presentation may facilitate early evaluation and management.

Acceptability, simplicity, and relevance of the new human papillomavirus/DNA test among 35-year-old ever-married women in a district of Sri Lanka: focus group discussions.

BACKGROUND: Two major drawbacks of the present cervical cancer screening programme in Sri Lanka are, the suboptimal sensitivity of the pap smear and the low coverage. The sensitivity of the HPV/DNA screening test is high. The objective of the study was to explore the acceptability relevance and simplicity of the new HPV/DNA screening implementation among ever-married women in a district of Sri Lanka. METHODS: Focus group discussions (FGD) (n = 3) in the public health divisions of the Kalutara district were used to collect data during December 2018. The study population comprised of ever-married women 35 years old, who, carried out an HPV/DNA test at a community Well Woman Clinics (WWCs) (n = 89). A list of WWCs was prepared according to an alphabetical order under urban, rural, and estate sector categories and allocated a number. One WWC was selected from each sector randomly for the three FGDs representing the estate, rural, and urban clinics. A convenient sampling technique was used to select participants for each FGD (n = 8). The information collected at each interview was summarized at the end of each interview. The analysis was done with manual content. RESULTS: Most of the participants were Sinhalese (n = 17, 70.9%), Buddhist (n = 18, n = 75%), and non-working (n = 18, n = 75%). The community awareness of HPV/DNA screening and field staff performance were highly appreciated by most of the participants. Most were aware of the high sensitivity of the HPV/DNA test, therefore the early detection rate of cervical cancer precursors is high. Most of the participants expressed the HPV/DNA test as a convenient and neutral test. Most were mentioned the necessity of repeated clinic visits for the pap test and colposcopy in HPV/DNA screened positive follow-up but there was marked acceptability (n = 23, 95.8%) for HPV/DNA test. CONCLUSIONS: Acceptability of the new HPV/DNA screening test was high. Most of the participants perceived the HPV/DNA test to be simple and also relevant. Therefore, the HPV/DNA screening test can be recommended to be incorporated into the National Cervical Cancer Screening Programme as its suitability was well explored in the Sri Lankan setting.

A Novel In Silico Benchmarked Pipeline Capable of Complete Protein Analysis: A Possible Tool for Potential Drug Discovery.

Current in silico proteomics require the trifecta analysis, namely, prediction, validation, and functional assessment of a modeled protein. The main drawback of this endeavor is the lack of a single protocol that utilizes a proper set of benchmarked open-source tools to predict a protein's structure and function accurately. The present study rectifies this drawback through the design and development of such a protocol. The protocol begins with the characterization of a novel coding sequence to identify the expressed protein. It then recognizes and isolates evolutionarily conserved sequence motifs through phylogenetics. The next step is to predict the protein's secondary structure, followed by the prediction, refinement, and validation of its three-dimensional tertiary structure. These steps enable the functional analysis of the macromolecule through protein docking, which facilitates the identification of the protein's active site. Each of these steps is crucial for the complete characterization of the protein under study. We have dubbed this process the trifecta analysis. In this study, we have proven the effectiveness of our protocol using the cystatin C and AChE proteins. Beginning with just their sequences, we have characterized both proteins' structures and functions, including identifying the cystatin C protein's seven-residue active site and the AChE protein's active-site gorge via protein-protein and protein-ligand docking, respectively. This process will greatly benefit new and experienced scientists alike in obtaining a strong understanding of the trifecta analysis, resulting in a domino effect that could expand drug development.

Curative-Intent Radiotherapy for Squamous Cell Carcinoma of the Head and Neck in Sri Lanka: The Impact of Radiotherapy Technique on Survival.

AIMS: We conducted a retrospective analysis of patients with squamous cell carcinoma of the head and neck (SCCHN) treated with curative-intent radiotherapy at the National Cancer Institute of Sri Lanka to determine the impact of the treatment technique on disease-free survival (DFS). MATERIALS AND METHODS: SCCHN patients treated with radical radiotherapy or adjuvant postoperative radiotherapy from 2016 to 2017 were included in the study. Data on the following variables were collected by reviewing clinical and radiotherapy treatment records: age, gender, tumour site, stage, time to delivery of radiotherapy, use of neoadjuvant chemotherapy, use of concurrent radiosensitising chemotherapy and treatment technique. DFS, defined as the time to death, tumour recurrence or loss to follow-up, was the primary end point and outcomes were compared between patients treated with intensity-modulated radiotherapy (IMRT) in linear accelerators and those treated with conventional radiotherapy in cobalt teletherapy units. Univariate and multivariate analyses were carried out on known prognostic variables. RESULTS: In total, 408 patients were included in the study, with 138 (34%) being treated with IMRT in the linear accelerator. More than 75% of patients were of stage III or IV at diagnosis. The 2-year DFS of the whole cohort was 25% (95% confidence interval 21-30%). Patients treated with IMRT in the linear accelerator had a superior DFS in comparison with those treated with conventional radiotherapy in the cobalt teletherapy units (P < 0.001, hazard ratio 0.64, 95% confidence interval 0.5-0.82). Higher stage, cobalt treatment and use of neoadjuvant chemotherapy were adversely associated with DFS on multivariate analysis. CONCLUSION: A large proportion of patients with SCCHN treated with curative-intent radiotherapy in Sri Lanka had locally advanced disease and DFS was superior in patients treated with IMRT in the linear accelerator.

Experiences of Patients on Natural Herbal Treatments for Diabetes Mellitus at the Diabetes Clinic in Base Hospital - Matara, Sri Lanka.

The prevalence of diabetes mellitus has become a global public health issue. Natural herbal treatments for type 2 diabetes mellitus have been widely used in traditional societies but has recently become popular among western societies as well. The aim of this study was to explore the experience of type 2 patients with diabetes mellitus who are currently on natural herbal treatment. A qualitative, phenomenological design has been used. Twelve participants from both males and females, aged between 25 and 75 years, who were on medical treatment, were selected for sampling. In-depth interviews were conducted at the diabetes clinic in a selected hospital in southern Sri Lanka. The athematic analysis was conducted, and 6 themes were derived. The majority of participants (75%) were motivated to use natural herbal treatments other than oral glycemic therapy. Experiences have been identified as the most influential factors in the use of natural herbal treatments. The need for educational interventions on natural herbal treatments and to propose the integration of herbal medicine into current medical systems is recommended.

Development of Coconut Milk-Based Spicy Ice Cream as a Nondairy Alternative with Desired Physicochemical and Sensory Attributes.

Spices have been a major influence on Sri Lankan cuisine since times immemorial. Spices are identified as one of the most distinctive ingredients for their indigenous flavor, aroma, and medicinal properties. In this study, coconut milk-based spicy ice cream was developed in compliance with the Sri Lankan standards to introduce a new perception of flavor using spices to the ice cream industry. Although coconut ice cream is commercially available in the local market, spicy flavored coconut ice cream is not yet available. Cinnamon (Cinnamomum verum), ginger (Zingiber officinale), and white pepper (Piper nigrum) are the spices used in the preparation of the ice cream as they are freely available and used as complementary spices in Sri Lanka. Physicochemical characteristics and sensory attributes of coconut milk-based spicy ice cream were compared with the existing normal coconut ice cream. In preparation of the ice cream, the same ice cream manufacturing process was followed with some modifications. Three different formulas (0.010%, 0.018%, and 0.025%) were developed by changing the percentage of spices added. The 0.018% spice-added sample was selected as the most acceptable ice cream with desired sensory attributes. pH (6.33 ± 0.01), titratable acidity (0.33 ± 0.05%), moisture (61.86 ± 0.33%), ash (0.41 ± 0.25%), total solids (38.02 ± 0.14%), overrun (66.76 ± 1.44%), protein (4.18 ± 0.16%), and fat content (11.66 ± 0.60%) were evaluated as physicochemical properties. Total phenolic content of the ice cream was expressed as 0.093 ± 0.002 mg gallic acid equivalents (GAE) per gram of sample in dry weight (mg/g). DPPH radical scavenging activity was 60.39 ± 0.02 mg ascorbic acid equivalents per gram of sample in dry weight (mg/g), and total antioxidant capacity was expressed as 0.36 ± 0.04 mmol ascorbic acid equivalent (AAE)/g of dry weight. Physicochemical properties of spicy coconut ice cream were more or less similar to that of normal coconut ice cream and in compliance with the Sri Lankan standards. Coconut milk-based spicy ice cream could be introduced to the market as a potential marketable nondairy product with spicy flavor, aroma, and smooth texture.

The feasibility of new HPV/DNA test as a primary cervical cancer screening method among 35- years- old ever-married women in Kalutara district; a cross-sectional study.

BACKGROUND: Cervical cancer is the second commonest female cancer in Sri Lanka. Two major drawbacks of the present cervical cancer screening programme are the suboptimal sensitivity of the pap smear and the low coverage. The objective of the study is to determine the feasibility of a new HPV/DNA test among 35 -years -old ever-married women in a district of Sri Lanka. METHOD: A community based descriptive cross-sectional study was conducted from 1stof July 2018 to 30th November 2018 in the public health divisions called Medical Officer of Health (MOH) areas of Kalutara district. The study population is comprised of ever-married women 35 years of age. Three women from each cluster (n = 413) were selected by consecutive sampling. A total of 918 women were recruited. HPV/DNA cervical specimen collection (n = 822) was carried out. Cervical specimens were tested by two cytoscreeners with the cobas 4800 PCR based screening machine. Clients' perceptions and prevalence were assessed. The follow-up of women with positive HPV/DNA screening results was carried out. The operational and technical feasibility of the screening test were assessed. Data entry was done by using the statistical package IBM SPSS version 20. RESULTS: Overall response rate was 91.1% (n = 836). Clients' perception was highly positive for HPV/DNA screening test procedure (99.9%, n = 821) and 99.6% (n = 819) of clients had mentioned that the HPV/DNA screening test is worthwhile to be incorporated into the National Cervical Cancer Screening program. The prevalence of HPV was 6.2% (95%CI: 6.18-6.22%). The coverage of the HPV/DNA screening was 89.5%(n = 822). Invalid results reported were 0.12% (n = 1). The percentage of HPV/DNA test positive women who underwent pap test within 3 months of the initial screening was 100% (n = 51), while the percentage of women who attempted to get a colposcopy within the 1 month of referral was 86.7% (n = 13). CONCLUSIONS: HPV/DNA test implementation as a primary cervical cancer screening method is feasible among the 35- year age cohort of ever- married women in Kalutara district. It is necessary to further attempt alternative methods of cobas 4800 HPV/DNA test, which would be much suitable for resource-limited settings.

Vaccine-induced thrombosis and thrombocytopenia (VITT) in Ireland: A review of cases and current practices.

Since the beginning of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2) virus pandemic, several highly effective and safe vaccines have been produced at remarkable speed. Following global implementation of vaccination programmes, cases of thrombosis with thrombocytopenia following administration of adenoviral vector-based vaccines started being reported. In this review we discuss the known pathogenesis and epidemiology of so-called vaccine induced thrombocytopenia and thrombosis (VITT). We consider the available guidelines, diagnostic laboratory tests and management options for these patients. Finally, we discuss important unanswered questions and areas for future research in this novel pathoclinical entity.

Statin treatment and accrual of covert cerebral ischaemia on neuroimaging: a systematic review and meta-analysis of randomized trials.

BACKGROUND AND PURPOSE: Prevention of ischaemic stroke and cardiovascular events is an established benefit of statin therapy, but the effects of statin treatment on the accrual of magnetic resonance imaging (MRI) markers of ischaemic cerebral injury remain unknown. A systematic review was performed to identify all studies that randomized patients with cardiovascular risk factors to statin treatment and assessed the effect of statin treatment on covert infarcts (asymptomatic, evident only on neuroimaging) and white matter hyperintensity (WMH) accrual on MRI. METHODS: A systematic review in MEDLINE and Scopus from inception to 23 October 2019 was performed. A random-effects model was used to calculate the pooled estimates of the crude risk ratios and standardized mean differences. RESULTS: Data from three randomized controlled trials (1430 participants) were included evaluating the effect of rosuvastatin (10 mg/day) in 668 hypertensive patients older than 60 years of age over 5 years, pravastatin (40 mg/day) in 554 elderly people more than 70 years of age over 3 years and simvastatin (20 mg/day) in 208 patients with asymptomatic middle cerebral artery stenosis over 2 years. Patients randomized to statin treatment had decreased accrual of new covert infarcts (risk ratio 0.63, 95% confidence interval 0.46-0.88) during a mean follow-up of 2-6 years. Only one study reported WMH decreased volume change in patients randomized to statin treatment compared to patients randomized to non-statin treatment (standardized mean difference -1.17; 95% confidence interval -1.33, -1.00). CONCLUSION: Our findings suggest that, in addition to stroke prevention, statin treatment can reduce the accrual of covert MRI markers of ischaemic cerebral injury.

Rivaroxaban versus aspirin for secondary prevention of ischaemic stroke in patients with cancer: a subgroup analysis of the NAVIGATE ESUS randomized trial.

BACKGROUND AND PURPOSE: Cancer is a frequent finding in ischaemic stroke patients. The frequency of cancer amongst participants in the NAVIGATE ESUS randomized trial and the distribution of outcome events during treatment with aspirin and rivaroxaban were investigated. METHODS: Trial participation required a recent embolic stroke of undetermined source. Patients' history of cancer was recorded at the time of study entry. During a mean follow-up of 11 months, the effects of aspirin and rivaroxaban treatment on recurrent ischaemic stroke, major bleeding and all-cause mortality were compared between patients with cancer and patients without cancer. RESULTS: Amongst 7213 randomized patients, 543 (7.5%) had cancer. Of all patients, 3609 were randomized to rivaroxaban [254 (7.0%) with cancer] and 3604 patients to aspirin [289 (8.0%) with cancer]. The annual rate of recurrent ischaemic stroke was 4.5% in non-cancer patients in the rivaroxaban arm and 4.6% in the aspirin arm [hazard ratio (HR) 0.98, 95% confidence interval (CI) 0.78-1.24]. In cancer patients, the rate of recurrent ischaemic stroke was 7.7% in the rivaroxaban arm and 5.4% in the aspirin arm (HR 1.43, 95% CI 0.71-2.87). Amongst cancer patients, the annual rate of major bleeds was non-significantly higher for rivaroxaban than aspirin (2.9% vs. 1.1%; HR 2.57, 95% CI 0.67-9.96; P for interaction 0.95). All-cause mortality was similar in both groups. CONCLUSIONS: Our exploratory analyses show that patients with embolic stroke of undetermined source and a history of cancer had similar rates of recurrent ischaemic strokes and all-cause mortality during aspirin and rivaroxaban treatments and that aspirin appeared safer than rivaroxaban in cancer patients regarding major bleeds. www.clinicaltrials.gov (NCT02313909).

Curcumin loaded zinc oxide nanoparticles for activity-enhanced antibacterial and anticancer applications.

Zinc oxide nanoparticles and curcumin have been shown to be excellent antimicrobial agents and promising anticancer agents, both on their own as well as in combination. Together, they have potential as alternatives/supplements to antibiotics and traditional anticancer drugs. In this study, different morphologies of zinc oxide-grafted curcumin nanocomposites (ZNP-Cs) were synthesized and characterized using SEM, TGA, FTIR, XRD and UV-vis spectrophotometry. Antimicrobial assays were conducted against both Gram negative and Gram-positive bacterial stains. Spherical ZnO-curcumin nanoparticles (SZNP-Cs) and rod-shaped ZnO-curcumin nanoparticles showed the most promising activity against tested bacterial strains. The inhibition zones for these curcumin-loaded ZnO nanocomposites were consistently larger than their bare counterparts or pure curcumin, revealing an additve effect between the ZnO and curcumin components. The potential anticancer activity of the synthesized nanocomposites was studied on the rhabdomyosarcoma RD cell line via MTT assay, while their cytotoxic effects were tested against human embryonic kidney cells using the resazurin assay. SZNP-Cs exhibited the best balance between the two, showing the lowest toxicity against healthy cells and good anticancer activity. The results of this investigation demonstrate that the nanomatrix synthesized can act as an effective, additively-enhanced combination delivery/therapeutic agent, holding promise for anticancer therapy and other biomedical applications.

Genetic characterization of Aedes aegypti (Diptera: Culicidae) in Sri Lanka based on COI gene.

BACKGROUND & OBJECTIVES: Aedes aegypti is the most prominent vector for dengue virus worldwide. Accurate identification of the species and understanding its colonization pattern are essential prerequisites in vector control. Thus, the present study was aimed to genetically characterize Ae. aegypti mosquitoes collected from different regions of Sri Lanka based on mitochondrial COI gene. METHODS: Thirty-three Ae. aegypti larval samples were collected from 19 districts. A 735bp region of the mitochondrial COI gene was amplified and analyzed for genetic diversity indices. Phylogenetic trees were constructed using Sri Lankan samples and also including mosquito samples reported from other parts of the world. RESULTS: High genetic diversity was observed within the samples analysed (gene diversity: 0.949; average number of nucleotide differences: 6.371). There were 20 haplotypes presented within the 19 localities investigated. The phylogenetic tree derived two main clades. However, no distinguishable clustering pattern was observed in the phylogenetic tree except for the districts in the northern corner indicating extensive admixing among different populations. When samples from other countries were included in the phylogenetic tree, Anuradhapura, and Mannar samples were clustered together with samples from India, Venezuela, USA, Portugal and Cambodia while Rathnapura was clustered with Bolivia and France. INTERPRETATION & CONCLUSION: Our results suggest that Sri Lanka has undergone multiple invasions of Ae. aegypti from various parts of the world over an extensive period. Further, the mosquito control campaigns had not caused a significant effect on the Ae. aegypti populations which is existing in mutation-drift equilibrium.

Non-resolution of non-alcoholic fatty liver disease (NAFLD) among urban, adult Sri Lankans in the general population: A prospective, cohort follow-up study.

BACKGROUND: There are few studies investigating the natural course of non-alcoholic fatty liver disease (NAFLD) in the community. We assessed resolution of NAFLD in a general population cohort of urban Sri Lankans adults. METHODS: Participants were selected by age-stratified random sampling from electoral lists. They were initially screened in 2007 and re-evaluated in 2014. On both occasions structured interview, anthropometric-measurements, liver ultrasonography, and biochemical/serological tests were performed. NAFLD was diagnosed on ultrasound criteria for fatty liver, safe-alcohol consumption (<14-units/week for men, <7-units/week for women) and absence of hepatitis B/C markers. Non-NAFLD was diagnosed on absence of any ultrasound criteria for fatty liver and safe-alcohol consumption. Resolution of NAFLD was defined as absence of ultrasound criteria for fatty liver. Changes in anthropometric indices [Weight, Body-Mass-Index (BMI), waist-circumference (WC), waist-hip ratio (WHR)], clinical [systolic blood pressure (SBP), diastolic blood pressure (DBP)] and biochemical measurements [Triglycerides (TG), High Density Lipoprotein (HDL), Total Cholesterol (TC), HbA1c%] at baseline and follow-up were compared. RESULTS: Of the 2985 original study participants, 2148 (71.9%) attended follow-up after 7 years. This included 705 who had NAFLD in 2007 and 834 who did not have NAFLD in 2007. Out of 705 who had NAFLD in 2007, 11(1.6%) changed their NAFLD status due to excess alcohol consumption. After controlling for baseline values, NAFLD patients showed significant reduction in BMI, weight, WHR, HDL and TC levels and increase in HbA1c levels compared to non-NAFLD people. Despite this, none of them had complete resolution of NAFLD. CONCLUSION: We did not find resolution of NAFLD in this general population cohort. The observed improvements in anthropometric, clinical and biochemical measurements were inadequate for resolution of NAFLD.

Percentage of small platelets on peripheral blood smear and Child-Turcott-Pugh class can predict the presence of oesophageal varices in newly diagnosed patients with cirrhosis: development of a prediction model for resource limited settings.

BACKGROUND: In cirrhosis upper-gastrointestinal-endoscopy (UGIE) identifies oesophageal varices (OV). UGIE is unavailable in most resource-limited settings. Therefore, we assessed prediction of presence of OV using hematological parameters (HP) and Child-Turcott-Pugh (CTP) class. METHODS: A prospective study was carried out on consecutive, consenting, newly-diagnosed patients with cirrhosis, in the University Medical Unit, Colombo North Teaching Hospital, Ragama, Sri Lanka from April 2014-April 2016. All patients had UGIE to evaluate presence and degree of OV, prior to appropriate therapy. HP (full blood count with indices using automated analyzer and peripheral blood smear using Leishmann stain) and CTP class were assessed on admission. Linear logistic regression model was developed to predict OV using HP and CTP class. RESULTS: 54-patients with cirrhosis were included [14(26%), 24(44%) and 16(30%) belonged to CTP class A, B and C respectively]. 37 had varices [CTP-A 4/14(26.6%), CTP-B 19/24(79.2%), CTP-C 14/16(87.5%)] on UGIE. Generalized linear model fitting showed decreasing percentage of small platelets (%SP) (P = 0.002), CTP-B (P = 0.003) and CTP-C (P = 0.003) compared to CTP-A had higher probability of having OV. The model predicts the log odds for having OV = - 0.189 - (0.046*%SP) + 2.9 [if CTP-B] + 3.7 [if CTP-C]. Based on receiver operating characteristic (ROC) analysis, a model value > - 0.19 was selected as the cutoff point to predict OV with 89%-sensitivity, 76%-specificity, 89%-positive predictive value and 76%-negative predictive value. CONCLUSIONS: We constructed a model using %SP on peripheral blood smear and CTP class. This model may be used to predict the presence of OV, in newly diagnosed patients with cirrhosis, with acceptable sensitivity and specificity, to prioritize the patients who deserve early UGIE in limited resource settings.

Lean non-alcoholic fatty liver disease (lean NAFLD): characteristics, metabolic outcomes and risk factors from a 7-year prospective, community cohort study from Sri Lanka.

INTRODUCTION: While patients with non-alcoholic fatty liver disease (NAFLD) are mostly overweight or obese, some are lean. METHODS: In a community-based follow-up study (baseline and follow-up surveys performed in 2007 and 2014), we investigated and compared the clinical characteristics, body composition, metabolic associations and outcomes, and other risk factors among individuals with lean (BMI < 23 kg/m2) NAFLD, non-lean (BMI ≥ 23 kg/m2) NAFLD and those without NAFLD. To investigate associations of selected genetic variants, we performed a case-control study between lean NAFLD cases and lean non-NAFLD controls. RESULTS: Of the 2985 participants in 2007, 120 (4.0%) had lean NAFLD and 816 (27.3%) had non-lean NAFLD. 1206 (40.4%) had no evidence of NAFLD (non-NAFLD). Compared to non-lean NAFLD, lean NAFLD was commoner among males (p < 0.001), and had a lower prevalence of hypertension (p < 0.001) and central obesity (WC < 90 cm for males, < 80 cm for females) (p < 0.001) without prominent differences in the prevalence of other metabolic comorbidities at baseline survey. Of 2142 individuals deemed as either NAFLD or non-NAFLD in 2007, 704 NAFLD individuals [84 lean NAFLD, 620 non-lean NAFLD] and 834 individuals with non-NAFLD in 2007 presented for follow-up in 2014. There was no difference in the occurrence of incident metabolic comorbidities between lean NAFLD and non-lean NAFLD. Of 294 individuals who were non-NAFLD in 2007 and lean in both 2007 and 2014, 84 (28.6%) had developed lean NAFLD, giving an annual incidence of 4.1%. Logistic regression identified the presence of diabetes at baseline, increase in weight from baseline to follow-up and a higher educational level as independent risk factors for the development of incident lean NAFLD. NAFLD association of PNPLA3 rs738409 was more pronounced among lean individuals (one-tailed p < 0.05) compared to the whole cohort sample. CONCLUSION: Although lean NAFLD constitutes a small proportion of NAFLD, the risk of developing incident metabolic comorbidities is similar to that of non-lean NAFLD. A PNPLA3 variant showed association with lean NAFLD in the studied population. Therefore, lean NAFLD also warrants careful evaluation and follow-up.

Epidemiology and clinical course of inflammatory bowel disease in the Central Province of Sri Lanka: A hospital-based study.

BACKGROUND AND AIM: There is increasing prevalence of inflammatory bowel disease (IBD) in Asia, but Sri Lankan data on the state of epidemiology and clinical course of IBD are scarce. METHODS: A hospital-based study was done by recruiting IBD patients who permanently reside in the Central Province (population 2.57 million, 12.6% of Sri Lankan population) of Sri Lanka. Cases were confirmed by standard criteria and data were collected from health records and patient interviews at clinic visits and hospital admissions. RESULTS: There were 200 cases of IBD; (ulcerative colitis [UC]-140, Crohn's disease [CD]-60, microscopic colitis-7). The crude prevalence rate of UC was 5.44/100 000 (95% CI 5.41-5.47/100 000) and CD was 2.33/100 000 (95% CI 2.31-2.35/100 000). Female to male ratios were 1:0.8 for UC but 1:1.5 for CD.Mean age at diagnosis was 42.0 and 31.9 years for UC and CD, respectively. One UC and one CD patient had positive family history of IBD. Among the UC patients, 60.7%, 24.3%, and 15% had proctitis, left sided, and extensive disease, respectively. At presentation, 62.1% of the UC patients have had moderately severe disease. 60% of the CD patients had only large bowel involvement and 80% had nonstricturing and nonpenetrating disease. Extra intestinal manifestations were present in 45.7% and 60.0% of UC and CD patients, respectively, in which peripheral arthralgia and arthritis being the commonest. 6.4% of UC and 23.3% of the CD patients (total of 23) required infliximab for induction of remission. CONCLUSION: The prevalence of IBD in the Central Province of Sri Lanka is lower than other Asian and Western populations. There is a predominance of male gender and isolated colonic disease in CD patients. UC patients have an equal gender distribution and a higher proportion of proctitis. CD needed induction with infliximab than UC.

Synthesis and evaluation of 4-cycloheptylphenols as selective Estrogen receptor-ß agonists (SERBAs).

A short and efficient route to 4-(4-hydroxyphenyl)cycloheptanemethanol was developed, which resulted in the preparation of a mixture of 4 stereoisomers. The stereoisomers were separated by preparative HPLC, and two of the stereoisomers identified by X-ray crystallography. The stereoisomers, as well as a small family of 4-cycloheptylphenol derivatives, were evaluated as estrogen receptor-beta agonists. The lead compound, 4-(4-hydroxyphenyl)cycloheptanemethanol was selective for activating ER relative to seven other nuclear hormone receptors, with 300-fold selectivity for the ß over α isoform and with EC50 of 30-50 nM in cell-based and direct binding assays.