Displaying publications 41 - 60 of 331 in total

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  1. Haghvirdizadeh P, Ramachandran V, Etemad A, Heidari F, Ghodsian N, Bin Ismail N, et al.
    J Diabetes Res, 2015;2015:289846.
    PMID: 26451383 DOI: 10.1155/2015/289846
    BACKGROUND: Type 2 diabetes mellitus (T2DM) is a complex polygenic disorder characterized by impaired insulin resistance, insulin secretion, and dysregulation of lipid and protein metabolism with environmental and genetic factors. ATP-binding cassette transporter A1 (ABCA1) gene polymorphisms are reported as the one of the genetic risk factors for T2DM in various populations with conflicting results. This study was conducted based on PCR-HRM to determine the frequency of ABCA1 gene by rs2230806 (R219K), rs1800977 (C69T), and rs9282541 (R230C) polymorphisms Malaysian subjects.

    METHODS: A total of 164 T2DM and 165 controls were recruited and their genotypes for ABCA1 gene polymorphisms were determined based on the real time high resolution melting analysis.

    RESULTS: There was a significant difference between the subjects in terms of age, BMI, FPG, HbA1c, HDL, LDL, and TG (P < 0.05). There was a significant association between HOM of R219K (P = 0.005), among Malaysian subjects; moreover, allele frequency revealed the significant difference in A allele of R219K (P = 0.003). But, there was no significant difference in genotypic and allelic frequencies of C69T and R230C polymorphism.

    CONCLUSION: R219K polymorphism of ABCA1 gene can be considered as a genetic risk factor for T2DM subjects among Malaysians.

  2. Bhavadharini B, Dehghan M, Mente A, Rangarajan S, Sheridan P, Mohan V, et al.
    PMID: 32423962 DOI: 10.1136/bmjdrc-2019-000826
    OBJECTIVE: Our aims were to assess the association of dairy intake with prevalence of metabolic syndrome (MetS) (cross-sectionally) and with incident hypertension and incident diabetes (prospectively) in a large multinational cohort study.

    METHODS: The Prospective Urban Rural Epidemiology (PURE) study is a prospective epidemiological study of individuals aged 35 and 70 years from 21 countries on five continents, with a median follow-up of 9.1 years. In the cross-sectional analyses, we assessed the association of dairy intake with prevalent MetS and its components among individuals with information on the five MetS components (n=112 922). For the prospective analyses, we examined the association of dairy with incident hypertension (in 57 547 individuals free of hypertension) and diabetes (in 131 481 individuals free of diabetes).

    RESULTS: In cross-sectional analysis, higher intake of total dairy (at least two servings/day compared with zero intake; OR 0.76, 95% CI 0.71 to 0.80, p-trend<0.0001) was associated with a lower prevalence of MetS after multivariable adjustment. Higher intakes of whole fat dairy consumed alone (OR 0.72, 95% CI 0.66 to 0.78, p-trend<0.0001), or consumed jointly with low fat dairy (OR 0.89, 95% CI 0.80 to 0.98, p-trend=0.0005), were associated with a lower MetS prevalence. Low fat dairy consumed alone was not associated with MetS (OR 1.03, 95% CI 0.77 to 1.38, p-trend=0.13). In prospective analysis, 13 640 people with incident hypertension and 5351 people with incident diabetes were recorded. Higher intake of total dairy (at least two servings/day vs zero serving/day) was associated with a lower incidence of hypertension (HR 0.89, 95% CI 0.82 to 0.97, p-trend=0.02) and diabetes (HR 0.88, 95% CI 0.76 to 1.02, p-trend=0.01). Directionally similar associations were found for whole fat dairy versus each outcome.

    CONCLUSIONS: Higher intake of whole fat (but not low fat) dairy was associated with a lower prevalence of MetS and most of its component factors, and with a lower incidence of hypertension and diabetes. Our findings should be evaluated in large randomized trials of the effects of whole fat dairy on the risks of MetS, hypertension, and diabetes.

  3. Dehghan M, Mente A, Rangarajan S, Sheridan P, Mohan V, Iqbal R, et al.
    Lancet, 2018 11 24;392(10161):2288-2297.
    PMID: 30217460 DOI: 10.1016/S0140-6736(18)31812-9
    BACKGROUND: Dietary guidelines recommend minimising consumption of whole-fat dairy products, as they are a source of saturated fats and presumed to adversely affect blood lipids and increase cardiovascular disease and mortality. Evidence for this contention is sparse and few data for the effects of dairy consumption on health are available from low-income and middle-income countries. Therefore, we aimed to assess the associations between total dairy and specific types of dairy products with mortality and major cardiovascular disease.

    METHODS: The Prospective Urban Rural Epidemiology (PURE) study is a large multinational cohort study of individuals aged 35-70 years enrolled from 21 countries in five continents. Dietary intakes of dairy products for 136 384 individuals were recorded using country-specific validated food frequency questionnaires. Dairy products comprised milk, yoghurt, and cheese. We further grouped these foods into whole-fat and low-fat dairy. The primary outcome was the composite of mortality or major cardiovascular events (defined as death from cardiovascular causes, non-fatal myocardial infarction, stroke, or heart failure). Hazard ratios (HRs) were calculated using multivariable Cox frailty models with random intercepts to account for clustering of participants by centre.

    FINDINGS: Between Jan 1, 2003, and July 14, 2018, we recorded 10 567 composite events (deaths [n=6796] or major cardiovascular events [n=5855]) during the 9·1 years of follow-up. Higher intake of total dairy (>2 servings per day compared with no intake) was associated with a lower risk of the composite outcome (HR 0·84, 95% CI 0·75-0·94; ptrend=0·0004), total mortality (0·83, 0·72-0·96; ptrend=0·0052), non-cardiovascular mortality (0·86, 0·72-1·02; ptrend=0·046), cardiovascular mortality (0·77, 0·58-1·01; ptrend=0·029), major cardiovascular disease (0·78, 0·67-0·90; ptrend=0·0001), and stroke (0·66, 0·53-0·82; ptrend=0·0003). No significant association with myocardial infarction was observed (HR 0·89, 95% CI 0·71-1·11; ptrend=0·163). Higher intake (>1 serving vs no intake) of milk (HR 0·90, 95% CI 0·82-0·99; ptrend=0·0529) and yogurt (0·86, 0·75-0·99; ptrend=0·0051) was associated with lower risk of the composite outcome, whereas cheese intake was not significantly associated with the composite outcome (0·88, 0·76-1·02; ptrend=0·1399). Butter intake was low and was not significantly associated with clinical outcomes (HR 1·09, 95% CI 0·90-1·33; ptrend=0·4113).

    INTERPRETATION: Dairy consumption was associated with lower risk of mortality and major cardiovascular disease events in a diverse multinational cohort.

    FUNDING: Full funding sources are listed at the end of the paper (see Acknowledgments).

  4. Mente A, Dehghan M, Rangarajan S, McQueen M, Dagenais G, Wielgosz A, et al.
    Lancet Diabetes Endocrinol, 2017 10;5(10):774-787.
    PMID: 28864143 DOI: 10.1016/S2213-8587(17)30283-8
    BACKGROUND: The relation between dietary nutrients and cardiovascular disease risk markers in many regions worldwide is unknown. In this study, we investigated the effect of dietary nutrients on blood lipids and blood pressure, two of the most important risk factors for cardiovascular disease, in low-income, middle-income, and high-income countries.

    METHODS: We studied 125 287 participants from 18 countries in North America, South America, Europe, Africa, and Asia in the Prospective Urban Rural Epidemiology (PURE) study. Habitual food intake was measured with validated food frequency questionnaires. We assessed the associations between nutrients (total fats, saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids, carbohydrates, protein, and dietary cholesterol) and cardiovascular disease risk markers using multilevel modelling. The effect of isocaloric replacement of saturated fatty acids with other fats and carbohydrates was determined overall and by levels of intakes by use of nutrient density models. We did simulation modelling in which we assumed that the effects of saturated fatty acids on cardiovascular disease events was solely related to their association through an individual risk marker, and then compared these simulated risk marker-based estimates with directly observed associations of saturated fatty acids with cardiovascular disease events.

    FINDINGS: Participants were enrolled into the study from Jan 1, 2003, to March 31, 2013. Intake of total fat and each type of fat was associated with higher concentrations of total cholesterol and LDL cholesterol, but also with higher HDL cholesterol and apolipoprotein A1 (ApoA1), and lower triglycerides, ratio of total cholesterol to HDL cholesterol, ratio of triglycerides to HDL cholesterol, and ratio of apolipoprotein B (ApoB) to ApoA1 (all ptrend<0·0001). Higher carbohydrate intake was associated with lower total cholesterol, LDL cholesterol, and ApoB, but also with lower HDL cholesterol and ApoA1, and higher triglycerides, ratio of total cholesterol to HDL cholesterol, ratio of triglycerides to HDL cholesterol, and ApoB-to-ApoA1 ratio (all ptrend<0·0001, apart from ApoB [ptrend=0·0014]). Higher intakes of total fat, saturated fatty acids, and carbohydrates were associated with higher blood pressure, whereas higher protein intake was associated with lower blood pressure. Replacement of saturated fatty acids with carbohydrates was associated with the most adverse effects on lipids, whereas replacement of saturated fatty acids with unsaturated fats improved some risk markers (LDL cholesterol and blood pressure), but seemed to worsen others (HDL cholesterol and triglycerides). The observed associations between saturated fatty acids and cardiovascular disease events were approximated by the simulated associations mediated through the effects on the ApoB-to-ApoA1 ratio, but not with other lipid markers including LDL cholesterol.

    INTERPRETATION: Our data are at odds with current recommendations to reduce total fat and saturated fats. Reducing saturated fatty acid intake and replacing it with carbohydrate has an adverse effect on blood lipids. Substituting saturated fatty acids with unsaturated fats might improve some risk markers, but might worsen others. Simulations suggest that ApoB-to-ApoA1 ratio probably provides the best overall indication of the effect of saturated fatty acids on cardiovascular disease risk among the markers tested. Focusing on a single lipid marker such as LDL cholesterol alone does not capture the net clinical effects of nutrients on cardiovascular risk.

    FUNDING: Full funding sources listed at the end of the paper (see Acknowledgments).

  5. Dehghan M, Mente A, Rangarajan S, Mohan V, Lear S, Swaminathan S, et al.
    Am J Clin Nutr, 2020 04 01;111(4):795-803.
    PMID: 31965140 DOI: 10.1093/ajcn/nqz348
    BACKGROUND: Eggs are a rich source of essential nutrients, but they are also a source of dietary cholesterol. Therefore, some guidelines recommend limiting egg consumption. However, there is contradictory evidence on the impact of eggs on diseases, largely based on studies conducted in high-income countries.

    OBJECTIVES: Our aim was to assess the association of egg consumption with blood lipids, cardiovascular disease (CVD), and mortality in large global studies involving populations from low-, middle-, and high-income countries.

    METHODS: We studied 146,011 individuals from 21 countries in the Prospective Urban Rural Epidemiology (PURE) study. Egg consumption was recorded using country-specific validated FFQs. We also studied 31,544 patients with vascular disease in 2 multinational prospective studies: ONTARGET (Ongoing Telmisartan Alone and in Combination with Ramipril Global End Point Trial) and TRANSCEND (Telmisartan Randomized Assessment Study in ACEI Intolerant Subjects with Cardiovascular Disease). We calculated HRs using multivariable Cox frailty models with random intercepts to account for clustering by study center separately within each study.

    RESULTS: In the PURE study, we recorded 14,700 composite events (8932 deaths and 8477 CVD events). In the PURE study, after excluding those with history of CVD, higher intake of egg (≥7 egg/wk compared with <1 egg/wk intake) was not significantly associated with blood lipids, composite outcome (HR: 0.96; 95% CI: 0.89, 1.04; P-trend = 0.74), total mortality (HR: 1.04; 95% CI: 0.94, 1.15; P-trend = 0.38), or major CVD (HR: 0.92; 95% CI: 0.83, 1.01; P-trend = 0.20). Similar results were observed in ONTARGET/TRANSCEND studies for composite outcome (HR 0.97; 95% CI: 0.76, 1.25; P-trend = 0.09), total mortality (HR: 0.88; 95% CI: 0.62, 1.24; P-trend = 0.55), and major CVD (HR: 0.97; 95% CI: 0.73, 1.29; P-trend = 0.12).

    CONCLUSIONS: In 3 large international prospective studies including ∼177,000 individuals, 12,701 deaths, and 13,658 CVD events from 50 countries in 6 continents, we did not find significant associations between egg intake and blood lipids, mortality, or major CVD events. The ONTARGET and TRANSCEND trials were registered at clinicaltrials.gov as NCT00153101. The PURE trial was registered at clinicaltrials.gov as NCT03225586.

  6. Wang C, Bangdiwala SI, Rangarajan S, Lear SA, AlHabib KF, Mohan V, et al.
    Eur Heart J, 2019 05 21;40(20):1620-1629.
    PMID: 30517670 DOI: 10.1093/eurheartj/ehy695
    AIMS: To investigate the association of estimated total daily sleep duration and daytime nap duration with deaths and major cardiovascular events.

    METHODS AND RESULTS: We estimated the durations of total daily sleep and daytime naps based on the amount of time in bed and self-reported napping time and examined the associations between them and the composite outcome of deaths and major cardiovascular events in 116 632 participants from seven regions. After a median follow-up of 7.8 years, we recorded 4381 deaths and 4365 major cardiovascular events. It showed both shorter (≤6 h/day) and longer (>8 h/day) estimated total sleep durations were associated with an increased risk of the composite outcome when adjusted for age and sex. After adjustment for demographic characteristics, lifestyle behaviours and health status, a J-shaped association was observed. Compared with sleeping 6-8 h/day, those who slept ≤6 h/day had a non-significant trend for increased risk of the composite outcome [hazard ratio (HR), 1.09; 95% confidence interval, 0.99-1.20]. As estimated sleep duration increased, we also noticed a significant trend for a greater risk of the composite outcome [HR of 1.05 (0.99-1.12), 1.17 (1.09-1.25), and 1.41 (1.30-1.53) for 8-9 h/day, 9-10 h/day, and >10 h/day, Ptrend < 0.0001, respectively]. The results were similar for each of all-cause mortality and major cardiovascular events. Daytime nap duration was associated with an increased risk of the composite events in those with over 6 h of nocturnal sleep duration, but not in shorter nocturnal sleepers (≤6 h).

    CONCLUSION: Estimated total sleep duration of 6-8 h per day is associated with the lowest risk of deaths and major cardiovascular events. Daytime napping is associated with increased risks of major cardiovascular events and deaths in those with >6 h of nighttime sleep but not in those sleeping ≤6 h/night.

  7. Lopez-Jaramillo P, Gomez-Arbelaez D, Martinez-Bello D, Abat MEM, Alhabib KF, Avezum Á, et al.
    Lancet Healthy Longev, 2023 Jan;4(1):e23-e33.
    PMID: 36521498 DOI: 10.1016/S2666-7568(22)00247-1
    BACKGROUND: The triglyceride glucose (TyG) index is an easily accessible surrogate marker of insulin resistance, an important pathway in the development of type 2 diabetes and cardiovascular diseases. However, the association of the TyG index with cardiovascular diseases and mortality has mainly been investigated in Asia, with few data available from other regions of the world. We assessed the association of insulin resistance (as determined by the TyG index) with mortality and cardiovascular diseases in individuals from five continents at different levels of economic development, living in urban or rural areas. We also examined whether the associations differed according to the country's economical development.

    METHODS: We used the TyG index as a surrogate measure for insulin resistance. Fasting triglycerides and fasting plasma glucose were measured at the baseline visit in 141 243 individuals aged 35-70 years from 22 countries in the Prospective Urban Rural Epidemiology (PURE) study. The TyG index was calculated as Ln (fasting triglycerides [mg/dL] x fasting plasma glucose [mg/dL]/2). We calculated hazard ratios (HRs) using a multivariable Cox frailty model with random effects to test the associations between the TyG index and risk of cardiovascular diseases and mortality. The primary outcome of this analysis was the composite of mortality or major cardiovascular events (defined as death from cardiovascular causes, and non-fatal myocardial infarction, or stroke). Secondary outcomes were non-cardiovascular mortality, cardiovascular mortality, all myocardial infarctions, stroke, and incident diabetes. We also did subgroup analyses to examine the magnitude of associations between insulin resistance (ie, the TyG index) and outcome events according to the income level of the countries.

    FINDINGS: During a median follow-up of 13·2 years (IQR 11·9-14·6), we recorded 6345 composite cardiovascular diseases events, 2030 cardiovascular deaths, 3038 cases of myocardial infarction, 3291 cases of stroke, and 5191 incident cases of type 2 diabetes. After adjusting for all other variables, the risk of developing cardiovascular diseases increased across tertiles of the baseline TyG index. Compared with the lowest tertile of the TyG index, the highest tertile (tertile 3) was associated with a greater incidence of the composite outcome (HR 1·21; 95% CI 1·13-1·30), myocardial infarction (1·24; 1·12-1·38), stroke (1·16; 1·05-1·28), and incident type 2 diabetes (1·99; 1·82-2·16). No significant association of the TyG index was seen with non-cardiovascular mortality. In low-income countries (LICs) and middle-income countries (MICs), the highest tertile of the TyG index was associated with increased hazards for the composite outcome (LICs: HR 1·31; 95% CI 1·12-1·54; MICs: 1·20; 1·11-1·31; pinteraction=0·01), cardiovascular mortality (LICs: 1·44; 1·15-1·80; pinteraction=0·01), myocardial infarction (LICs: 1·29; 1·06-1·56; MICs: 1·26; 1·10-1·45; pinteraction=0·08), stroke (LICs: 1·35; 1·02-1·78; MICs: 1·17; 1·05-1·30; pinteraction=0·19), and incident diabetes (LICs: 1·64; 1·38-1·94; MICs: 2·68; 2·40-2·99; pinteraction <0·0001). In contrast, in high-income countries, higher TyG index tertiles were only associated with an increased hazard of incident diabetes (2·95; 2·25-3·87; pinteraction <0·0001), but not of cardiovascular diseases or mortality.

    INTERPRETATION: The TyG index is significantly associated with future cardiovascular mortality, myocardial infarction, stroke, and type 2 diabetes, suggesting that insulin resistance plays a promoting role in the pathogenesis of cardiovascular and metabolic diseases. Potentially, the association between the TyG index and the higher risk of cardiovascular diseases and type 2 diabetes in LICs and MICs might be explained by an increased vulnerability of these populations to the presence of insulin resistance.

    FUNDING: Full funding sources are listed at the end of the paper (see Acknowledgments).

  8. Swaminathan S, Dehghan M, Raj JM, Thomas T, Rangarajan S, Jenkins D, et al.
    BMJ, 2021 02 03;372:m4948.
    PMID: 33536317 DOI: 10.1136/bmj.m4948
    OBJECTIVE: To evaluate the association between intakes of refined grains, whole grains, and white rice with cardiovascular disease, total mortality, blood lipids, and blood pressure in the Prospective Urban and Rural Epidemiology (PURE) study.

    DESIGN: Prospective cohort study.

    SETTING: PURE study in 21 countries.

    PARTICIPANTS: 148 858 participants with median follow-up of 9.5 years.

    EXPOSURES: Country specific validated food frequency questionnaires were used to assess intakes of refined grains, whole grains, and white rice.

    MAIN OUTCOME MEASURE: Composite of mortality or major cardiovascular events (defined as death from cardiovascular causes, non-fatal myocardial infarction, stroke, or heart failure). Hazard ratios were estimated for associations of grain intakes with mortality, major cardiovascular events, and their composite by using multivariable Cox frailty models with random intercepts to account for clustering by centre.

    RESULTS: Analyses were based on 137 130 participants after exclusion of those with baseline cardiovascular disease. During follow-up, 9.2% (n=12 668) of these participants had a composite outcome event. The highest category of intake of refined grains (≥350 g/day or about 7 servings/day) was associated with higher risk of total mortality (hazard ratio 1.27, 95% confidence interval 1.11 to 1.46; P for trend=0.004), major cardiovascular disease events (1.33, 1.16 to 1.52; P for trend<0.001), and their composite (1.28, 1.15 to 1.42; P for trend<0.001) compared with the lowest category of intake (<50 g/day). Higher intakes of refined grains were associated with higher systolic blood pressure. No significant associations were found between intakes of whole grains or white rice and health outcomes.

    CONCLUSION: High intake of refined grains was associated with higher risk of mortality and major cardiovascular disease events. Globally, lower consumption of refined grains should be considered.

  9. Iqbal R, Dehghan M, Mente A, Rangarajan S, Wielgosz A, Avezum A, et al.
    Am J Clin Nutr, 2021 09 01;114(3):1049-1058.
    PMID: 33787869 DOI: 10.1093/ajcn/nqaa448
    BACKGROUND: Dietary guidelines recommend limiting red meat intake because it is a major source of medium- and long-chain SFAs and is presumed to increase the risk of cardiovascular disease (CVD). Evidence of an association between unprocessed red meat intake and CVD is inconsistent.

    OBJECTIVE: The study aimed to assess the association of unprocessed red meat, poultry, and processed meat intake with mortality and major CVD.

    METHODS: The Prospective Urban Rural Epidemiology (PURE) Study is a cohort of 134,297 individuals enrolled from 21 low-, middle-, and high-income countries. Food intake was recorded using country-specific validated FFQs. The primary outcomes were total mortality and major CVD. HRs were estimated using multivariable Cox frailty models with random intercepts.

    RESULTS: In the PURE study, during 9.5 y of follow-up, we recorded 7789 deaths and 6976 CVD events. Higher unprocessed red meat intake (≥250 g/wk vs. <50 g/wk) was not significantly associated with total mortality (HR: 0.93; 95% CI: 0.85, 1.02; P-trend = 0.14) or major CVD (HR: 1.01; 95% CI: 0.92, 1.11; P-trend = 0.72). Similarly, no association was observed between poultry intake and health outcomes. Higher intake of processed meat (≥150 g/wk vs. 0 g/wk) was associated with higher risk of total mortality (HR: 1.51; 95% CI: 1.08, 2.10; P-trend = 0.009) and major CVD (HR: 1.46; 95% CI: 1.08, 1.98; P-trend = 0.004).

    CONCLUSIONS: In a large multinational prospective study, we did not find significant associations between unprocessed red meat and poultry intake and mortality or major CVD. Conversely, a higher intake of processed meat was associated with a higher risk of mortality and major CVD.

  10. Wan Jamaludin WF, Mohamad Yusoff F, Ismail NA, Mohd Idris MR, Palaniappan S, Ng CKK, et al.
    Malays J Pathol, 2018 Apr;40(1):61-67.
    PMID: 29704386 MyJurnal
    INTRODUCTION: Immunosuppressive state due to haematological malignancies and chemotherapy may cause disruption to wound healing despite optimum conventional treatment and standard wound dressing. Non-healing wounds are predisposed to infection whereas chemotherapy dose reductions or interruptions are associated with poor survival.

    BACKGROUND: Mononuclear cells contain progenitor cells including haematopoietic and mesenchymal stem cells, endothelial progenitor cells and fibroblasts which facilitate wound healing through cytokines, growth factor secretions, cell-cell interactions and provision of extracellular matrix scaffolding. Clinical applications of autologous mononuclear cells therapy in wound healing in non-malignant patients with critical limb ischaemia have been reported with remarkable outcome.

    METHODS: We report three patients with haematological malignancies undergoing chemotherapy, who received autologous mononuclear cells implantation to treat non-healing wound after optimum conventional wound care. The sources of mononuclear cells (MNC) were from bone marrow (BM), peripheral blood (PB) and mobilised PB cells (mPB-MNC) using granulocyte colony stimulating factor (G-CSF). The cells were directly implanted into wound and below epidermis. Wound sizes and adverse effects from implantation were assessed at regular intervals.

    RESULTS: All patients achieved wound healing within three months following autologous mononuclear cells implantation. No implantation adverse effects were observed.

    CONCLUSIONS: Autologous mononuclear cells therapy is a feasible alternative to conventional wound care to promote complete healing in non-healing wounds compounded by morbid factors such as haematological malignancies, chemotherapy, diabetes mellitus (DM), infections and prolonged immobility.

  11. Khatib R, McKee M, Shannon H, Chow C, Rangarajan S, Teo K, et al.
    Lancet, 2016 Jan 2;387(10013):61-9.
    PMID: 26498706 DOI: 10.1016/S0140-6736(15)00469-9
    BACKGROUND: WHO has targeted that medicines to prevent recurrent cardiovascular disease be available in 80% of communities and used by 50% of eligible individuals by 2025. We have previously reported that use of these medicines is very low, but now aim to assess how such low use relates to their lack of availability or poor affordability.
    METHODS: We analysed information about availability and costs of cardiovascular disease medicines (aspirin, β blockers, angiotensin-converting enzyme inhibitors, and statins) in pharmacies gathered from 596 communities in 18 countries participating in the Prospective Urban Rural Epidemiology (PURE) study. Medicines were considered available if present at the pharmacy when surveyed, and affordable if their combined cost was less than 20% of household capacity-to-pay. We compared results from high-income, upper middle-income, lower middle-income, and low-income countries. Data from India were presented separately given its large, generic pharmaceutical industry.
    FINDINGS: Communities were recruited between Jan 1, 2003, and Dec 31, 2013. All four cardiovascular disease medicines were available in 61 (95%) of 64 urban and 27 (90%) of 30 rural communities in high-income countries, 53 (80%) of 66 urban and 43 (73%) of 59 rural communities in upper middle-income countries, 69 (62%) of 111 urban and 42 (37%) of 114 rural communities in lower middle-income countries, eight (25%) of 32 urban and one (3%) of 30 rural communities in low-income countries (excluding India), and 34 (89%) of 38 urban and 42 (81%) of 52 rural communities in India. The four cardiovascular disease medicines were potentially unaffordable for 0·14% of households in high-income countries (14 of 9934 households), 25% of upper middle-income countries (6299 of 24,776), 33% of lower middle-income countries (13,253 of 40,023), 60% of low-income countries (excluding India; 1976 of 3312), and 59% households in India (9939 of 16,874). In low-income and middle-income countries, patients with previous cardiovascular disease were less likely to use all four medicines if fewer than four were available (odds ratio [OR] 0·16, 95% CI 0·04-0·57). In communities in which all four medicines were available, patients were less likely to use medicines if the household potentially could not afford them (0·16, 0·04-0·55).
    INTERPRETATION: Secondary prevention medicines are unavailable and unaffordable for a large proportion of communities and households in upper middle-income, lower middle-income, and low-income countries, which have very low use of these medicines. Improvements to the availability and affordability of key medicines is likely to enhance their use and help towards achieving WHO's targets of 50% use of key medicines by 2025.
    FUNDING: Population Health Research Institute, the Canadian Institutes of Health Research, Heart and Stroke Foundation of Ontario, AstraZeneca (Canada), Sanofi-Aventis (France and Canada), Boehringer Ingelheim (Germany and Canada), Servier, GlaxoSmithKline, Novartis, King Pharma, and national or local organisations in participating countries.
  12. Chow CK, Ramasundarahettige C, Hu W, AlHabib KF, Avezum A, Cheng X, et al.
    Lancet Diabetes Endocrinol, 2018 10;6(10):798-808.
    PMID: 30170949 DOI: 10.1016/S2213-8587(18)30233-X
    BACKGROUND: Data are scarce on the availability and affordability of essential medicines for diabetes. Our aim was to examine the availability and affordability of metformin, sulfonylureas, and insulin across multiple regions of the world and explore the effect of these on medicine use.

    METHODS: In the Prospective Urban Rural Epidemiology (PURE) study, participants aged 35-70 years (n=156 625) were recruited from 110 803 households, in 604 communities and 22 countries; availability (presence of any dose of medication in the pharmacy on the day of audit) and medicine cost data were collected from pharmacies with the Environmental Profile of a Community's Health audit tool. Our primary analysis was to describe the availability and affordability of metformin and insulin and also commonly used and prescribed combinations of two medicines for diabetes management (two oral drugs, metformin plus a sulphonylurea [either glibenclamide (also known as glyburide) or gliclazide] and one oral drug plus insulin [metformin plus insulin]). Medicines were defined as affordable if the cost of medicines was less than 20% of capacity-to-pay (the household income minus food expenditure). Our analyses included data collected in pharmacies and data from representative samples of households. Data on availability were ascertained during the pharmacy audit, as were data on cost of medications. These cost data were used to estimate the cost of a month's supply of essential medicines for diabetes. We estimated affordability of medicines using income data from household surveys.

    FINDINGS: Metformin was available in 113 (100%) of 113 pharmacies from high-income countries, 112 (88·2%) of 127 pharmacies in upper-middle-income countries, 179 (86·1%) of 208 pharmacies in lower-middle-income countries, 44 (64·7%) of 68 pharmacies in low-income countries (excluding India), and 88 (100%) of 88 pharmacies in India. Insulin was available in 106 (93·8%) pharmacies in high-income countries, 51 (40·2%) pharmacies in upper-middle-income countries, 61 (29·3%) pharmacies in lower-middle-income countries, seven (10·3%) pharmacies in lower-income countries, and 67 (76·1%) of 88 pharmacies in India. We estimated 0·7% of households in high-income countries and 26·9% of households in low-income countries could not afford metformin and 2·8% of households in high-income countries and 63·0% of households in low-income countries could not afford insulin. Among the 13 569 (8·6% of PURE participants) that reported a diagnosis of diabetes, 1222 (74·0%) participants reported diabetes medicine use in high-income countries compared with 143 (29·6%) participants in low-income countries. In multilevel models, availability and affordability were significantly associated with use of diabetes medicines.

    INTERPRETATION: Availability and affordability of essential diabetes medicines are poor in low-income and middle-income countries. Awareness of these global differences might importantly drive change in access for patients with diabetes.

    FUNDING: Full funding sources listed at the end of the paper (see Acknowledgments).

  13. Miller V, Yusuf S, Chow CK, Dehghan M, Corsi DJ, Lock K, et al.
    Lancet Glob Health, 2016 10;4(10):e695-703.
    PMID: 27567348 DOI: 10.1016/S2214-109X(16)30186-3
    BACKGROUND: Several international guidelines recommend the consumption of two servings of fruits and three servings of vegetables per day, but their intake is thought to be low worldwide. We aimed to determine the extent to which such low intake is related to availability and affordability.

    METHODS: We assessed fruit and vegetable consumption using data from country-specific, validated semi-quantitative food frequency questionnaires in the Prospective Urban Rural Epidemiology (PURE) study, which enrolled participants from communities in 18 countries between Jan 1, 2003, and Dec 31, 2013. We documented household income data from participants in these communities; we also recorded the diversity and non-sale prices of fruits and vegetables from grocery stores and market places between Jan 1, 2009, and Dec 31, 2013. We determined the cost of fruits and vegetables relative to income per household member. Linear random effects models, adjusting for the clustering of households within communities, were used to assess mean fruit and vegetable intake by their relative cost.

    FINDINGS: Of 143 305 participants who reported plausible energy intake in the food frequency questionnaire, mean fruit and vegetable intake was 3·76 servings (95% CI 3·66-3·86) per day. Mean daily consumption was 2·14 servings (1·93-2·36) in low-income countries (LICs), 3·17 servings (2·99-3·35) in lower-middle-income countries (LMICs), 4·31 servings (4·09-4·53) in upper-middle-income countries (UMICs), and 5·42 servings (5·13-5·71) in high-income countries (HICs). In 130 402 participants who had household income data available, the cost of two servings of fruits and three servings of vegetables per day per individual accounted for 51·97% (95% CI 46·06-57·88) of household income in LICs, 18·10% (14·53-21·68) in LMICs, 15·87% (11·51-20·23) in UMICs, and 1·85% (-3·90 to 7·59) in HICs (ptrend=0·0001). In all regions, a higher percentage of income to meet the guidelines was required in rural areas than in urban areas (p<0·0001 for each pairwise comparison). Fruit and vegetable consumption among individuals decreased as the relative cost increased (ptrend=0·00040).

    INTERPRETATION: The consumption of fruit and vegetables is low worldwide, particularly in LICs, and this is associated with low affordability. Policies worldwide should enhance the availability and affordability of fruits and vegetables.

    FUNDING: Population Health Research Institute, the Canadian Institutes of Health Research, Heart and Stroke Foundation of Ontario, AstraZeneca (Canada), Sanofi-Aventis (France and Canada), Boehringer Ingelheim (Germany and Canada), Servier, GlaxoSmithKline, Novartis, King Pharma, and national or local organisations in participating countries.

  14. Chukwuma OB, Rafatullah M, Tajarudin HA, Ismail N
    Life (Basel), 2021 May 28;11(6).
    PMID: 34071172 DOI: 10.3390/life11060493
    Omics have given rise to research on sparsely studied microbial communities such as the landfill, lignocellulolytic microorganisms and enzymes. The bacterial diversity of Municipal Solid Waste sediments was determined using the illumina MiSeq system after DNA extraction and Polymerase chain reactions. Data analysis was used to determine the community's richness, diversity, and correlation with environmental factors. Physicochemical studies revealed sites with mesophilic and thermophilic temperature ranges and a mixture of acidic and alkaline pH values. Temperature and moisture content showed the highest correlation with the bacteria community. The bacterial analysis of the community DNA revealed 357,030 effective sequences and 1891 operational taxonomic units (OTUs) assigned. Forty phyla were found, with the dominant phyla Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidota, while Aerococcus, Stenotrophomonas, and Sporosarcina were the dominant species. PICRUSt provided insight on community's metabolic function, which was narrowed down to search for lignocellulolytic enzymes' function. Cellulase, xylanase, esterase, and peroxidase were gene functions inferred from the data. This article reports on the first phylogenetic analysis of the Pulau Burung landfill bacterial community. These results will help to improve the understanding of organisms dominant in the landfill and the corresponding enzymes that contribute to lignocellulose breakdown.
  15. Ismail N, Ismail M, Azmi NH, Bakar MFA, Yida Z, Stanslas J, et al.
    Chem Biol Interact, 2017 Sep 25;275:61-73.
    PMID: 28734741 DOI: 10.1016/j.cbi.2017.07.014
    The study determined the effect of thymoquinone rich fraction (TQRF) and thymoquinone (TQ) in the forms of nano- and conventional emulsions on learning and memory, lipid peroxidation, total antioxidant status, antioxidants genes expression and soluble β-amyloid (Aβ) levels in rats fed with a high fat-cholesterol diet (HFCD). The TQRF was extracted from Nigella sativa seeds using a supercritical fluid extraction system and prepared into nanoemulsion, which later named as TQRF nanoemulsion (TQRFNE). Meanwhile, TQ was acquired commercially and prepared into thymoquinone nanoemulsion (TQNE). The TQRF and TQ conventional emulsions (CE), named as TQRFCE and TQCE, respectively were studied for comparison. Statin (simvastatin) and non-statin (probucol) cholesterol-lowering agents, and a mild-to-severe Alzheimer's disease drug (donepezil) were served as control drugs. The Sprague Dawley rats were fed with HFCD for 6 months, and treated with the intervention groups via oral gavage daily for the last 3 months. As a result, HFCD-fed rats exhibited hypercholesterolaemia, accompanied by memory deficit, increment of lipid peroxidation and soluble Aβ levels, decrement of total antioxidant status and down-regulation of antioxidants genes expression levels. TQRFNE demonstrated comparable effects to the other intervention groups and control drugs in serum biomarkers as well as in the learning and memory test. Somehow, TQRFNE was more prominent than those intervention groups and control drugs in brain biomarkers concomitant to gene and protein expression levels. Supplementation of TQRFNE into an HFCD thus could ameliorate memory deficit, lipid peroxidation and soluble Aβ levels as well as improving the total antioxidant status and antioxidants genes expression levels.
  16. Ahmad Mohd Zain MR, Abdul Kari Z, Dawood MAO, Nik Ahmad Ariff NS, Salmuna ZN, Ismail N, et al.
    Appl Biochem Biotechnol, 2022 Oct;194(10):4587-4624.
    PMID: 35579740 DOI: 10.1007/s12010-022-03952-2
    A novel coronavirus disease (COVID-19) or severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), transmitted from person to person, has quickly emerged as the pandemic responsible for the current global health crisis. This infection has been declared a global pandemic, resulting in a concerning number of deaths as well as complications post-infection, primarily among vulnerable groups particularly older people and those with multiple comorbidities. In this article, we review the most recent research on the role of date palm (Phoenix dactylifera L.) fruits (DPFs) to prevent or treat COVID-19 infection. The mechanisms underlying this preventive or therapeutic effect are also discussed in terms of bioactivity potentials in date palm, e.g., antimicrobial, antioxidant, anticancer, anti-diabetic, anti-inflammatory, neuroprotective, and hemolytic potential, as well as prospect against COVID-19 disease and the potential product development. Therefore, it can be concluded that regular consumption of DPFs may be associated with a lower risk of some chronic diseases. Indeed, DPFs have been widely used in folk medicine since ancient times to treat a variety of health conditions, demonstrating the importance of DPFs as a nutraceutical and source of functional nourishment. This comprehensive review aims to summarize the majority of the research on DPFs in terms of nutrient content and biologically active components such as phenolic compounds, with an emphasis on their roles in improving overall health as well as the potential product development to ensure consumers' satisfaction in a current pandemic situation. In conclusion, DPFs can be given to COVID-19 patients as a safe and effective add-on medication or supplement in addition to routine treatments.
  17. Umar MF, Rafatullah M, Abbas SZ, Ibrahim MNM, Ismail N
    J Hazard Mater, 2021 10 05;419:126469.
    PMID: 34192640 DOI: 10.1016/j.jhazmat.2021.126469
    Xylene, a recalcitrant compound present in wastewater from activities of petrochemical and chemical industries causes chronic problems for living organisms and the environment. Xylene contaminated wastewater may be biodegraded through a benthic microbial fuel cell (BMFC) as seen in this study. Xylene was oxidized into intermediate 3-methyl benzoic acid and entirely converted into non-toxic carbon dioxide. The highest voltage of the BMFC reactor was generated at 410 mV between 23 and 90 days when cell potential was 1 kΩ. The reactor achieved a maximum power density of about 63 mW/m2, and a current of 0.4 mA which was optimized from variable resistance (20 Ω - 1 kΩ). However, the maximum biodegradation efficiency of the BMFC was at 87.8%. The cyclic voltammetry curve helped to determine that the specific capacitance was 0.124 F/g after 30 days of the BMFC operation. Furthermore, the fitting equivalent circuit was observed with the help of Nyquist plot for calculating overall internal resistance of 65.82 Ω on 30th day and 124.5 Ω on 80th day. Staphylococcus edaphicus and Staphylococcus sparophiticus were identified by 16S rRNA sequencing as the dominant species in the control and BMFC electrode, presumably associated with xylene biodegradation.
  18. Abu Bakar SA, Syed Mohamed Shahruddin SNS, Ismail N, Wan Md Adnan WAH
    PeerJ, 2022;10:e13694.
    PMID: 35935256 DOI: 10.7717/peerj.13694
    The estimation of biological age (BA) is an important asymptomatic measure that can be used to understand the physical changes and the aging process of a living being. Factors that contribute towards profiling the human biological age can be diverse. Therefore, this study focuses on developing a BA model for patients with Chronic Kidney Disease (CKD). The procedure commences with the selection of significant biomarkers using a correlation test. Appropriate weighting is then assigned to each selected biomarker using the indexing method to produce a BA index. The BA index is matched to the age variation within the sample to acquire additional terms for the chronological age leading ultimately to the estimated BA. From a sample of 190 patients (133 trained data and 57 testing data) obtained from the University of Malaya Medical Centre (UMMC), Malaysia, the intensity of the BA is found to be between three to nine years from the chronological age. Visual observations further validate the high similarities between the training and testing data sets.
  19. Hossain K, Quaik S, Ismail N, Rafatullah M, Avasan M, Shaik R
    Iran J Biotechnol, 2016 Sep;14(3):154-162.
    PMID: 28959331 DOI: 10.15171/ijb.1216
    BACKGROUND: Application of membrane technology to wastewater treatment has expanded over the last decades due to increasingly stringent legislation, greater opportunities for water reuse/recycling processes and continuing advancement in membrane technology.

    OBJECTIVES: In the present study, a bench-scale submerged microfiltration membrane bioreactor (MBR) was used to assess the treatment of textile wastewater.

    MATERIALS AND METHODS: The decolorization capacity of white-rot fungus coriolus versicolor was confirmed through agar plate and liquid batch studies. The temperature and pH of the reactor were controlled at 29±1°C and 4.5±2, respectively. The bioreactor was operated with an average flux of 0.05 m.d(-1) (HRT=15hrs) for a month.

    RESULTS: Extensive growth of fungi and their attachment to the membrane led to its fouling and associated increase of the transmembrane pressure requiring a periodic withdrawal of sludge and membrane cleaning. However, stable decoloration activity (approx. 98%), BOD (40-50%), COD (50-67%) and total organic carbon (TOC) removal (>95%) was achieved using the entire system (fungi + membrane), while the contribution of the fungi culture alone for TOC removal, as indicated by the quality of the reactor supernatant, was 35-50% and 70%, respectively.

    CONCLUSIONS: The treated wastewater quality satisfied the requirement of water quality for dyeing and finishing process excluding light coloration. Therefore, textile wastewater reclamation and reuse is a promising alternative, which can both conserve or supplement the available water resource and reduce or eliminate the environmental pollution.

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