Changes in serum lipids following consumption of coconut oil and palm olein oil: A sequential feeding crossover clinical trial.

BACKGROUND: High incidence of cardiovascular disease (CVD) in South Asia is linked to genetic predisposition and diets high in saturated fatty acids (SFAs). Increased CVD prevalence correlates with rising palm oil consumption in some South Asian countries, where coconut oil and palm olein oil are primary SFA sources. OBJECTIVE: Compare the effects of coconut oil and palm olein oil on serum lipoprotein lipids and biochemical parameters in healthy adults. METHODS: A sequential feeding crossover clinical trial with two feeding periods of 8 weeks each was conducted among 40 healthy adults. Participants were provided palm olein oil in the first feeding period followed by coconut oil with a 16-week washout period in between. The outcomes measured were the difference in serum low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C), TC/HDL-C ratio, triglycerides (TG), very-low-density lipoprotein cholesterol (VLDL-C), fasting plasma glucose (FPG), and liver enzymes. RESULTS: Thirty-seven participants completed the study. LDL-C decreased by 13.0 % with palm olein oil (p < 0.001) and increased by 5.6 % with coconut oil (p = 0.044), showing a significant difference (p < 0.001). TC decreased by 9.9 % with palm olein oil (p < 0.001) and increased by 4.0 % with coconut oil (p = 0.044). CONCLUSION: Palm olein oil consumption resulted in more favorable changes in lipid-related CVD risk factors (TC, LDL-C, TC:HDL-C, and FPG) compared to coconut oil. Clinical Trial Registry number and website where it was obtained: (SLCTR/2019/034); https://slctr.lk/trials/slctr-2019-034.

Impact of an oral nutritional supplement on the body composition of older adults with or at risk of malnutrition in an institutionalised setting: A randomised controlled trial.

BACKGROUND: Malnutrition often manifests as a body weight (BW) reduction and unhealthy alteration in body composition. The present study aimed to assess the efficacy of an oral nutritional supplement (ONS) in improving BW and body composition among older adults with malnutrition. METHODS: An open-label randomised controlled, parallel-group study was conducted among older adults (age ≥ 60 years) with/at risk of malnutrition (mini nutrition assessment-short form score ≤ 11). In total, 50 participants were randomly assigned to the intervention (IG) and control (CG) groups (1:1 ratio). The IG received the ONS (57 g/day; 247 kcal/serving, 12 g protein) before bedtime for 12 weeks. CG received 200 mL of water. Anthropometric measurements, body composition analysis, and dietary and physical activity assessments were performed at the beginning and end of the study. RESULTS: Forty-two participants (IG: 20, CG: 22) completed the study. The mean ± SD ages of the IG and CG were 75.4 ± 6.1 and 74.8 ± 5.2 years, respectively (p = 0.73). The IG had a significant increase in BW (+1.68 ± 1.16 vs. -0.46 ± 0.95 kg; p < 0.001), lean mass (+1.23 ± 0.93 vs. -0.45 ± 0.90 kg; p < 0.001) and fat mass (+0.54 ± 0.82 vs. -0.06 ± 0.82 kg; p = 0.02) compared to the CG. One-quarter of the IG (n = 5) achieved a weight gain > 5% of BW, whereas none in the CG did (p = 0.01). No significant changes were observed in bone mineral content in either group. CONCLUSIONS: For malnourished older adults, supplementing with an ONS, along with regular food intake, significantly increased BW, lean mass and fat mass compared to control following the regular diet without supplementation.

Frequency of pharmacogenomic variants affecting efficacy and safety of anti-cancer drugs in a south Asian population from Sri Lanka.

BACKGROUND: Therapy with anti-cancer drugs remain the cornerstone of treating cancer. The effectiveness and safety of anti-cancer drugs vary significantly among individuals due to genetic factors influencing the drug response and metabolism. Data on the pharmacogenomic variations in Sri Lankans related to anti-cancer therapy is sparse. As current treatment guidelines in Sri Lanka often do not consider local pharmacogenomic variants, this study aimed to explore the diversity of pharmacogenomic variants in the Sri Lankan population to pave the way for personalized treatment approaches and improve patient outcomes. METHODS: Pharmacogenomic data regarding variant-drug pairs of genes CYP2D6, DPYD, NUDT15, EPAS1, and XRCC1 with clinical annotations labelled as evidence levels 1A-2B were obtained from the Pharmacogenomics Knowledgebase database. Their frequencies in Sri Lankans were obtained from an anonymized database that was derived from 541 Sri Lankans who underwent exome sequencing at the Human Genetics Unit, Faculty of Medicine, University of Colombo. Variations in DPYD, NUDT15, and EPAS1 genes are related to increased toxicity to fluoropyrimidines, mercaptopurines, and sorafenib respectively. Variations in CYP2D6 and XRCC1 genes are related to changes in efficacy of tamoxifen and platinum compounds, respectively. Minor allele frequencies of these variants were calculated and compared with other populations. RESULTS: MAFs of rs1065852 c.100 C > T (CYP2D6), rs3918290 c.1905 + 1G > A (DPYD), rs56038477 c.1236G > A (DPYD), rs7557402 c.1035-7 C > G (EPAS1), rs116855232 c.415 C > T (NUDT15*3), and rs25487 c.1196 A > G (XRCC1) were: 12.9% [95%CI:10.9-14.9], 1.5% [95%CI:0.8-2.2], 1.2% [95%CI:0.5-1.8], 37.7% [95%CI:34.8-40.6], 8.3% [95%CI:6.7-10.0], and 64.0% [95%CI:61.1-66.8], respectively. Frequencies of rs1065852 c.100 C > T (CYP2D6), rs7557402 c.1035-7 C > G (EPAS1), and rs25487 (XRCC1) were significantly lower in Sri Lankans, while frequencies of rs116855232 c.415 C > T (NUDT15*3) and rs56038477 c.1236G > A (DPYD) were significantly higher in Sri Lankans when compared to some Western and Asian populations. CONCLUSION: Sri Lankans are likely to show lower toxicity risk with sorafenib (rs7557402 c.84,131 C > G) and, higher toxicity risk with fluoropyrimidines (rs56038477 c.1236G > A) and mercaptopurine (rs116855232 c.415 C > T), and reduced effectiveness with tamoxifen (rs1065852 c.100 C > T) and platinum compounds (rs25487). These findings highlight the potential contribution of these genetic variations to the individual variability in anti-cancer dosage requirements among Sri Lankans.

Dilated cardiomyopathy due to hypocalcaemia: a case report.

BACKGROUND: Hypocalcaemia is a rare, but reversible, cause of dilated cardiomyopathy causing heart failure. Several case reports have been reported on reversible cardiomyopathy secondary to hypocalcaemia. CASE PRESENTATION: We report a case of 54-year-old female Sri Lankan patient who presented with shortness of breath and was diagnosed with heart failure with reduced ejection fraction due to dilated cardiomyopathy. The etiology for dilated cardiomyopathy was identified as hypocalcemic cardiomyopathy, secondary to primary hypoparathyroidism, which was successfully treated with calcium and vitamin D replacement therapy. CONCLUSION: This adds to literature of this rare cause of reversible cardiomyopathy secondary to hypocalcemia reported from the South Asian region of the world. This case highlights the impact of proper treatment improving the heart failure in patients with hypocalcemic cardiomyopathy.

The effect of coconut oil and palm oil on anthropometric parameters: a clinical trial.

BACKGROUND: During recent years several studies have investigated the impact of different dietary oils on body weight. They have shown differential positive and negative effects on anthropometry. We investigated the effects of palm and coconut oils on body weight and other anthropometric parameters, considering their importance as a primary source of saturated fat, controlling for other confounding variable such as total energy intake. METHODS: The study was conducted as a sequential feeding clinical trial with 40 healthy men and women divided into two feeding periods of initial palm oil (8 weeks) and subsequent coconut oil (8 weeks), with a 16-week washout period in between. Each participant received a pre-determined volume of each oil, which were integrated into their routine main meals and snacks during the respective study periods. Changes in body weight, body mass index (BMI), waist circumference (WC), hip circumference (HC), and waist-to-hip ratio (WHR) were evaluated. Physical activity levels and dietary intake were also evaluated as potential confounding factors. RESULTS: Thirty-seven participants completed both oil treatment periods. The mean (± SD) age of the participants was 39 (± 13.1) years. There were no significant differences in any of the anthropometric parameters between the initial point of feeding coconut oil and the initial point of feeding palm oil. Following both oil treatment phases, no significant changes in the subjects' body weight, BMI, or other anthropometric measurements (WC, HC, and WHR) were observed. CONCLUSION: Neither coconut oil nor palm oil significantly changed anthropometry-related cardiovascular risk factors such as body weight, BMI, WC, HC, and WHR. TRIAL REGISTRATION: Sri Lankan Clinical Trial Registry: SLCTR/2019/034 on 4th October 2019 ( https://slctr.lk/trials/slctr-2019-034 ).

A national survey on registered products, availability, prices, and affordability of 100 essential medicines in community pharmacies across Sri Lanka.

INTRODUCTION: Availability of essential medicines that meet the expected quality standards, in appropriate dosage forms at affordable prices is a fundamental prerequisite to fulfill healthcare needs of given a population. This study assessed available products, prices and affordability of essential medicines (EM) in community pharmacies in Sri Lanka with comparison of registration status from the National Medicines Regulatory Authority(NMRA). METHODS: A cross-sectional island-wide survey of 80 pharmacies was conducted according to World Health Organization and Health Action International Manual (WHO/HAI). Hundred medicines were selected from the global core list(n = 14), regional core list(n = 16) and the Sri Lanka Essential Medicine List (SL-EML) (n = 70) based on healthcare needs. Number of registered products in 2015 and 2021 were compared. FINDINGS: Average availability was 85.4%(± 12.31) and availability was lowest in the Northern province (69.38 ± 21.18%)(p = 0.008). Availability between the state owned, franchise and privately owned pharmacies was not significantly different (p > 0.05). 89.4% medicines were affordable except for amiodarone, hydroxychloroquine, sitagliptin, soluble insulin, isophane insulin, losartan, levodopa carbidopa combination, clonazepam and ceftriaxone. The median price ratio (MPR) of 33.7% of medicines was less than 1 and MPR of 37.1% originator brands (OB) was over 3. Median number of generic brands in the market was 8(range 2-44), 9% of medicines had 20 or more products in the market and 72.7% medicines had more products available than the number registered in 2015. The average number of registered products were similar in 2015 (8.27) and 2021(7.59) (p = 0.15). CONCLUSION: The overall availability of EMs in Sri Lanka was high in all categories of community pharmacies. Medicines were largely affordable and reasonably priced in 2015, although OBs were generally more expensive. Majority of medicines had more products in the market than the number of registered products.

Emerging insights and future prospects for therapeutic application of siRNA targeting angiotensinogen in hypertension.

INTRODUCTION: Hypertension is the main global risk factor for cardiovascular disease. Despite this, less than half of treated hypertensive patients are controlled. One reason for this is nonadherence, a major unmet need in hypertension pharmacotherapy. Small interfering RNA (small interfering ribonucleic acid) therapies inhibit protein translation, and, when linked to N-acetylgalactosamine, allow liver-specific targeting, and durability over several months. Targeted knockdown of hepatic angiotensinogen, the source of all angiotensins, offers a precision medicine approach. AREAS COVERED: This article describes the molecular basis for durability over months and the 24-h tonic target inhibition observed after one administration. We present an analysis of the published phase I trials using zilebesiran, a siRNA targeting hepatic angiotensinogen, which reduces blood pressure (BP) by up to 20 mmHg, lasting 24 weeks. Finally, we examine data evaluating reversibility of angiotensinogen knockdown and its relevance to the future clinical utility of zilebesiran. EXPERT OPINION: Further studies should assess safety, efficacy, and outcomes in larger, more broadly representative groups. An advantage of zilebesiran is the potential for bi-annual dosing, thereby reducing nonadherence and improving control rates. It may also reduce nighttime BP due to 24-h tonic control. The provision of adherence assessment services will maximize the clinical value of zilebesiran.

Pharmacogenomic variants affecting efficacy and toxicity of statins in a south Asian population from Sri Lanka.

Aim: To describe the diversity of pharmacogenetic variants of statins among Sri Lankans. Materials & methods: Variant data of relevant genes were obtained from an anonymized database of 426 Sri Lankans. Minor allele frequencies (MAFs) were compared with published data from other populations. Results: The MAF of SLCO1B1*5 (rs4149056 [T>C]) was 18.19% (95% CI: 14.53-21.85). MAFs of CYP2C9*2 (rs1799853 [C>T]) and CYP2C9*3 (rs1057910 [A>C]) were 2.58% (95% CI: 1.08-4.08) and 10.30% (95% CI: 7.75-13.61), respectively. MAFs of rs2231142 (G>T) (ABCG2), rs7412 (C>T) (APOE) and rs20455 (A>G) (KIF6) variants were 10.68% (95% CI: 7.76-13.60), 3.52% (95% CI: 1.77-5.27) and 50.7% (95% CI: 45.96-55.45), respectively. Compared with western/other Asian populations, rs20455 (A>G), CYP2C9*3 (A>C) and SLCO1B1*5 (T>C) variants were significantly higher in Sri Lankans. Conclusion: Variants that affect efficacy of statins (KIF6 [rs20455], CYP2C9*3) and increase risk of statin-induced myotoxicity (SLCO1B1*5 and CYP2C9*3) were prevalent in higher frequencies among Sri Lankans compared with western populations.

The impact of an oral nutritional supplement on body weight gain in older adults with malnutrition: an open-label randomized controlled trial.

BACKGROUND: The global aging population is expanding rapidly and many individuals have a particularly higher risk of malnutrition. Malnutrition can lead to impaired body function, morbidity, and mortality. Meeting nutritional requirements is a key strategy to minimize multiple debilitating adverse outcomes associated with malnutrition in the elderly. Oral nutritional supplements (ONS) have been widely used as a dietary intervention for malnutrition in older adults. These supplements provide additional nutrients and calories to support nutritional requirements and have been shown to improve nutritional status, physical function, and quality of life in malnourished older adults. METHODS: This is an open-label, randomized controlled, parallel-group study including 50 institutionalized older adults (aged > 60 years) with malnutrition or at risk of malnutrition, living in a selected elderly care institution in Colombo, Sri Lanka. The aim is to assess improvement in healthy body weight gain and body composition in older adults with malnutrition at risk of malnutrition by using an ONS. Older adults will be screened for malnutrition using the Mini Nutrition Assessment (MNA) tool and eligible participants randomized using the simple random sampling technique to intervention and control groups (1:1 allocation ratio). The intervention group will consume 200 mL of ONS before bed continuously for 12 weeks. The primary outcome is the percentage who achieved at least 5% weight gain in the intervention group compared to the control group. Nutritional status (anthropometric, biochemical, clinical, and dietary), body composition (dual-energy X-ray absorptiometry), frailty, functional capacity (hand grip strength, knee extension, and Barthel index) cognitive status (Montreal Cognitive Assessment), and physical activity will be assessed as secondary outcomes at baseline and at the end of the 12-week intervention. Some measurements (anthropometry, dietary, and functional assessments) will also be performed at the end of the 4th week. Data will be analyzed using SPSS V-23. DISCUSSION: This study will determine whether the use of an ONS is effective in promoting healthy weight gain in older adults with malnutrition or at risk of malnutrition. In addition, investigating the impact of an ONS on multiple outcomes via clinical, nutritional, functional, and cognitive function will provide a more comprehensive understanding of the potential benefits of these supplements. TRIAL REGISTRATION: Sri Lanka Clinical Trail Registry SLCTR/2022/021. Oct. 6, 2022.

Novel Pharmacological Approaches in the Treatment of Hypertension: A Focus on RNA-Based Therapeutics.

Hypertension remains the leading cause of cardiovascular disease and premature death globally, affecting half of US adults. A high proportion of hypertensive patients exhibit uncontrolled blood pressure (BP), associated with poor adherence, linked to pill burden and adverse effects. Novel pharmacological strategies are urgently needed to improve BP control. Dysregulation of the renin-angiotensin system increases BP through its primary effector, Ang II (angiotensin II), which results in tissue remodeling and end-organ damage. Silencing liver angiotensinogen (the sole source of Ang II) has been achieved using novel RNA therapeutics, including the antisense oligonucleotide, IONIS-AGT (angiotensinogen)-LRX, and the small-interfering RNA, zilebesiran. Conjugation to N-acetylgalactosamine enables targeted delivery to hepatocytes, where endosomal storage, slow leakage, and small-interfering RNA recycling (for zilebesiran) result in knockdown over several months. Indeed, zilebesiran has an impressive and durable effect on systolic BP, reduced by up to 20 mm Hg and sustained for 6 months after a single administration, likely due to its very effective knockdown of angiotensinogen, without causing acute kidney injury or hyperkalemia. By contrast, IONIS-AGT-LRX caused less knockdown and marginal effects on BP. Future studies should evaluate any loss of efficacy relating to antidrug antibodies, safety issues associated with long-term angiotensinogen suppression, and broader benefits, especially in the context of common comorbidities such as type 2 diabetes and chronic kidney disease.

Coconut oil consumption and bodyweight reduction: a systematic review and meta-analysis.

INTRODUCTION: Due to the composition and biological properties of coconut oil, there is still considerable debate regarding potential benefits for the management of obesity, including the specific impact on body weight (BW) reduction. This systematic review and meta-analysis of clinical trials aims to assess the impact of coconut oil on BW reduction in comparison to other oils and fats. EVIDENCE ACQUISITION: The databases, PubMed®, Web of Science®, EMBASE®, and SciVerse Scopus® were systematically searched. A combination of medical subject headings and words linked to coconut oil and obesity parameters were utilized. Any clinical trials comparing coconut oil to any other form of oil or fat, with more than one month feeding period among adults were considered. EVIDENCE SYNTHESIS: From the 540 potentially relevant papers, 9 were included. The period of coconut oil intake varied from four to twelve weeks, apart from one long-term trial where coconut oil was consumed for two years. When compared to other oils and fats, coconut oil substantially decreased BW (N.=546), Body Mass Index (BMI) (N.=551), and percentage of fat mass (FM%) (N.=491) by 0.75 kg (P=0.04), 0.28 kg/m2 (P=0.03), and 0.35% (P=0.008), respectively. Coconut oil consumption did not result in any significant alteration in waist circumference (WC) (N.=385) (-0.61 cm; P=0.30), waist-to-hip ratio (WHR) (N.=330) (-0.01; P=0.39) and FM (N.=86) (-0.25 kg; P=0.29). CONCLUSIONS: Results indicate a small statistically significant reduction in BW, BMI, and FM% in the coconut oil group. In contrast, consumption of coconut oil had no statistically significant effect on WC, WHR, or FM.

Small interfering RNA: Discovery, pharmacology and clinical development-An introductory review.

Post-transcriptional gene silencing targets and degrades mRNA transcripts, silencing the expression of specific genes. RNA interference technology, using synthetic structurally well-defined short double-stranded RNA (small interfering RNA [siRNA]), has advanced rapidly in recent years. This introductory review describes the utility of siRNA, by exploring the underpinning biology, pharmacology, recent advances and clinical developments, alongside potential limitations and ongoing challenges. Mediated by the RNA-induced silencing complex, siRNAs bind to specific complementary mRNAs, which are subsequently degraded. siRNA therapy offers advantages over other therapeutic approaches, including ability of specifically designed siRNAs to potentially target any mRNA and improved patient adherence through infrequent administration associated with a very long duration of action. Key pharmacokinetic and pharmacodynamic challenges include targeted administration, poor tissue penetration, nuclease inactivation, rapid renal elimination, immune activation and off-target effects. These have been overcome by chemical modification of siRNA and/or by utilising a range of delivery systems, increasing bioavailability and stability to allow successful clinical translation. Patisiran (hereditary transthyretin-mediated amyloidosis) was the first licensed siRNA, followed by givosiran (acute hepatic porphyria), lumasiran (primary hyperoxaluria type 1) and inclisiran (familial hypercholesterolaemia), which all use N-acetylgalactosamine (GalNAc) linkage for effective liver-directed delivery. Others are currently under development for indications varying from rare genetic diseases to common chronic non-communicable diseases (hypertension, cancer). Technological advances are paving the way for broader clinical use. Ongoing challenges remain in targeting organs beyond the liver and reaching special sites (e.g., brain). By overcoming these barriers, siRNA therapy has the potential to substantially widen its therapeutic impact.

Half a century of Sri Lanka research: Subjects, researchers, institutions, journals and impact (1973-2019) / Medio siglo de investigación en Sri Lanka: temas, investigadores, instituciones, revistas e impacto (1973-2019)

Abstract Introduction: Bibliometric analyses of research in Sri Lanka, a lower-middle income island nation in South Asia, has focused mainly on medical research, concluding that there is a need for increased research productivity and impact, and for local solutions to health concerns. There has been no general bibliometric analysis across scientific disciplines in the nation, or any study that covers a long period of time to identify general time trends. Objective: To measure and analyse Sri Lanka research by focusing on subjects, authors, institutions, journals and citation for half a century. Methods: We used an advanced search method to extract publications with the word "Sri Lanka" in the SCI-EXPANDED, and calculated indicators such as total citations from Web of Science Core Collection since publication year to the end of 2019, citations in 2019, and mean citations per publication. Journal data were taken from 2019 Journal Citation Report. Affiliation re-classification was done to ensure consistency regarding the origin of all publications. Publications were further analysed based on collaboration, and first and corresponding authorship. Results: We retrieved 16 069 publications in 19 document types (77 % articles). Corrections had the highest number of authors per publication (616) followed by articles (116). Four articles had more than 5 000 authors and 593 articles had more than 1 000 authors. The highest citations in this database were for international megaprojects where Sri Lanka authors played minor roles. The UK had the most collaborative articles with Sri Lanka (19 %). The articles were published in 3 051 journals across 177 Web of Science categories. The category of Public, environmental and occupational health, with 193 journals, had 6.7 % of all articles, followed by environmental sciences (6.6 %). Conclusion: Sri Lanka has an unusually strong pattern of participating as small role players in international megaprojects about health and physics. Sri Lanka authors should be encouraged to expand their horizons by researching non-applied fields that are the basis of all innovation; to strengthen their own journals so that they have better visibility and impact, and to improve their positions in international projects that are published in larger journals.

Resumen Introducción: Los análisis bibliométricos de la investigación en Sri Lanka, una nación insular de ingresos mediano-bajos en el sur de Asia, se han centrado principalmente en la investigación médica, concluyendo que existe la necesidad de aumentar la productividad y el impacto de la investigación, y de soluciones locales a los problemas de salud. No ha habido un análisis bibliométrico general de disciplinas científicas o algún estudio que cubra un período largo de tiempo para identificar tendencias generales. Objetivo: Medir y analizar la investigación de Sri Lanka centrándose en temas, autores, instituciones, revistas y citas, durante medio siglo. Métodos: Utilizamos un método de búsqueda avanzada para extraer publicaciones con las palabras "Sri Lanka" en el SCI-EXPANDED, y calculamos indicadores como el total de citas de Web of Science Core Collection desde el año de publicación hasta finales de 2019, citas solo en 2019, y media de citas por publicación. Los datos de revistas son del Journal Citation Report 2019. Revisamos manualmente las afiliaciones para garantizar su coherencia, y, de todos los tipos de publicación, analizamos en detalle los artículos en función de la colaboración y la autoría. Resultados: Hallamos 16 069 publicaciones en 19 tipos de documentos (77 % artículos). Las correcciones tuvieron el mayor número de autores por publicación (616), seguidas de los artículos (116 autores en promedio); cuatro artículos tenían más de 5 000 autores y 593 artículos tenían más de 1 000 autores. Las citas más altas en esta base de datos fueron para megaproyectos internacionales en los que los autores de Sri Lanka desempeñaron papeles menores. El Reino Unido tuvo más artículos colaborativos con Sri Lanka (19 %). Los artículos se publicaron en 3 051 revistas de 177 categorías del Web of Science. La categoría d Salud pública, ambiental y ocupacional, con 193 revistas, tuvo el 6.7 % del total de artículos, seguida de Ciencias ambientales (6.6 %). Conclusión: En Sri Lanka hay una tendencia inusual a participar como pequeños actores en megaproyectos internacionales sobre salud y física. Debería alentarse a quienes hacen ciencia en Sri Lanka a ampliar sus horizontes investigando campos no aplicados, que son la base de la innovación; a fortalecer sus propias revistas para lograr mayor visibilidad e impacto, y a mejorar su ubicación en proyectos internacionales que se publican en revistas más grandes.

Diversity of pharmacogenomic variants affecting warfarin metabolism in Sri Lankans.

Aims: To describe the diversity of pharmacogenomic variants affecting warfarin metabolism in Sri Lankans. Materials & methods: Genotype data were filtered out from an anonymized database of 400 Sri Lankans, and minor allele frequencies (MAF) were calculated. Variants of CYP2C9, VKORC1 and CYP4F2 genes were studied. Results: Overall, CYP2C9*2 and CYP2C9*3 alleles had MAFs of 2.25% (95% CI: 0.80-3.70) and 10.38% (95% CI: 7.50-13.50), respectively. CYP2C9*11 and CYP2C9*14 alleles had MAFs of 0.13% (95% CI: 0-0.74) and 2.50% (95% CI: 0.97-4.03), respectively. MAFs of VKORC1 variants rs7294, rs9934438, rs8050894 and rs2884737 were 47.25% (95% CI: 42.36-52.14), 10.13% (95% CI: 7.28-13.22), 9.88% (95% CI: 7.06-12.94) and 4.88% (95% CI: 2.86-7.14), respectively. MAF of CYP4F2 variant rs2108622 was 45.63% (95% CI: 40.87-50.63). Conclusion: Compared with other populations, the frequencies of some studied variants were significantly different in Sri Lankans, and these are likely to account for variability in warfarin dosage requirements.

The effect of zinc supplementation on glucose homeostasis: a randomised double-blind placebo-controlled trial.

AIMS: The burden and health costs of Type 2 Diabetes Mellitus continue to increase globally and prevention strategies in at-risk people need to be explored. Previous work, in both animal models and humans, supports the role of zinc in improving glucose homeostasis. We, therefore, aimed to test the effectiveness of zinc supplementation on glycaemic control in pre-diabetic adults. METHODS: We conducted a randomized, double-blind, placebo-controlled trial across 10 General Practitioner (GP) practices in NSW, Australia. The trial is known as Zinc in Preventing the Progression of pre-Diabetes (ZIPPeD)Study. Pre-diabetic (haemoglobin A1c [HbA1c] 5.7-6.4%, 39-46 mmol/mol) men and women (N = 98) were all assigned to a free state government telephone health coaching service (New South Wales Get Healthy Information and Coaching Service) and then randomised to either daily 30 mg zinc gluconate or placebo. Blood tests were collected at baseline, 1, 6 and 12 months for the primary outcomes (HbA1c, fasting blood glucose (FBG)); secondary outcomes included Homeostasis Model Assessment 2 (HOMA 2) parameters, lipids, body weight, height, waist circumference, blood pressure and pulse. RESULTS: The baseline-adjusted mean group difference at 6 months, expressed as treatment-placebo, (95% CI) was -0.02 (-0.14, 0.11, p = 0.78) for HbA1c and 0.17 (-0.07, 0.42; p = 0.17) for FBG, neither of which were statistically significant. There were also no significant differences between groups in any of the secondary outcomes. Zinc was well tolerated, and compliance was high (88%). CONCLUSION: We believe our results are consistent with other Western clinical trial studies and do not support the use of supplemental zinc in populations with a Western diet. There may still be a role for supplemental zinc in the developing world where diets may be zinc deficient. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry, ACTRN12618001120268. Registered on 6 July 2018.

Gestational obesity: An unconventional endocrine disruptor for the fetus.

Obesity has reached pandemic proportions and is a growing concern throughout the world. A parallel trend has also been observed among women in reproductive age, leading to the increasing global prevalence of gestational obesity (GO). The well-known obesity-related health problems also extend to pregnancy, where they are responsible for giving rise to a variety of medical and obstetrical complications, resulting in an increased incidence of adverse maternal and fetal outcomes. In this context, several epidemiological and clinical studies have shown that nutritional changes through different stages of gestation can have a substantial impact on the future health and development of the child. Therefore, it is clear that GO is a modifiable endocrine disruptor that negatively influences the health of the fetus and the newborn, with long-term metabolic implications. This review aims to describe the impact of GO on maternal and fetal outcomes using the available scientific literature and highlighting the evidence-based nutritional approaches currently recommended for the management of GO.

Is the proportion of per capita fat supply associated with the prevalence of overweight and obesity? an ecological analysis.

BACKGROUND: Although it is reported in numerous interventional and observational studies, that a low-fat diet is an effective method to combat overweight and obesity, the relationship at the global population level is not well established. This study aimed to quantify the associations between worldwide per capita fat supply and prevalence of overweight and obesity and further classify this association based on per capita Gross National Income (GNI). METHODS: A total of 93 countries from four GNI groups were selected. Country-specific overweight and obesity prevalence data were retrieved from the most recent WHO Global Health Observatory database. Per capita supply of fat and calories were obtained from the United Nations Food and Agricultural Organization database; FAOSTAT, Food Balance Sheet for years 2014-2016. The categorizations of countries were done based on GNI based classification by the World Bank. RESULTS: Among the selected countries, the overweight prevalence ranged from 3.9% (India) to 78.8% (Kiribati), while obesity prevalence ranged from 3.6% (Bangladesh) to 46.0% (Kiribati). The highest and the lowest per capita fat supply from total calorie supply were documented in Australia (41.2%) and Madagascar (10.5%) respectively. A significant strong positive correlation was observed between the prevalence of overweight (r = 0.64, p < 0.001) and obesity (r = 0.59, p < 0.001) with per capita fat supply. The lower ends of both trend lines were densely populated by the low- and lower-middle-income countries and the upper ends of both lines were greatly populated by the high-income countries. CONCLUSIONS: Per capita fat supply per country is significantly associated with both prevalence of overweight and obesity.

Zinc supplementation in prediabetes mellitus.

INTRODUCTION: Certain pharmacological and lifestyle interventions have been shown to reduce progression of prediabetes. We aimed to perform a systematic review and meta-analyses of studies assessing the outcomes of zinc supplementation in individuals with prediabetes. EVIDENCE ACQUISITION: A comprehensive search was conducted in PubMed, SciVerse Scopus and Web of Science databases. Controlled clinical trials in prediabetics individuals, on zinc supplementation with or without other nutrients, assessing at least one accepted glycemic parameter as an outcome were deemed eligible. EVIDENCE SYNTHESIS: Three papers were included in the systematic review and meta-analysis, with a total of 265 participants. Duration of zinc supplementation ranged from 6-12 months. The zinc dose ranged from 20-30 mg/day. In the pooled analysis, zinc supplementation significantly reduced FBG both when given alone (-10.86 mg/dL; 95% CI, -14.74 to -6.98; P<0.001) and with other micronutrients (-11.77 mg/dL; P<0.001). Similarly, 2hr-OGTT blood glucose was reduced by 21.08 mg/dL (95% CI, -40.05 to -2.11; P=0.03) in the pooled analysis of studies using zinc alone and in combination with other micronutrients. One study demonstrated a significant reduction of HbA1c by 0.5% with combined supplementation, while another reported a significant reduction in CRP with zinc supplementation. When all trials were considered, TC, HDL-c and HOMA-ß showed significant improvement. Zinc supplementation significantly improved the zinc status from baseline. CONCLUSIONS: Zinc supplementation demonstrated beneficial effects on glycemic and lipid parameters in individuals with prediabetes. It may have the potential to reduce the prevalence of prediabetes and control associated morbidity and mortality.