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A practical scheme for the estimation of serum total protein and albumin

Kua See Lai, Chew Yin La, De Witt GF, Buttery JE

Med J Malaysia, 1973 Dec;28(2):115-7.
PMID: 4276227
Fulltext The Effect of 5-Min Mindful Breathing on Pain in Palliative Care Cancer Patients: A Randomized Controlled Study

Guan NC, Beng TS, Sue-Yin L, Kanagasundram S

Indian J Palliat Care, 2021 02 17;27(1):83-88.
PMID: 34035622 DOI: 10.4103/IJPC.IJPC_122_20

Context: While pain is a common complaint among palliative cancer patients, there is little research looking into nonpharmacological methods for the reduction of pain in the palliative setting.
Aim: This study aims to study the efficacy of 5-min mindful breathing for rapid reduction of pain in a palliative care setting.
Methods: This is a sub-analysis of the previous randomized controlled study on distress reduction. Sixty patients were recruited and randomly assigned to either the intervention (5-min mindful breathing) or the control (5-min normal listening) group. Participants reported their pain on a 10-item analog scale at baseline, immediately after intervention and 10 min postintervention. Changes in pain scores were further analyzed.
Results: Pain scores decreased for both the intervention and control groups. However, the reduction of pain did not reach statistical difference in both groups (P > 0.05).
Conclusion: Five-minute mindful breathing is a quick and easy to administer therapy but does not have significant effects in terms of pain reduction in palliative settings. Future research and directions are nonetheless suggested and encouraged to look for short-term mindfulness-based therapies on pain reduction for this population.
Fulltext Quantification of intracellular payload release from polymersome nanoparticles

Scarpa E, Bailey JL, Janeczek AA, Stumpf PS, Johnston AH, Oreffo RO, et al.

Sci Rep, 2016 07 11;6:29460.
PMID: 27404770 DOI: 10.1038/srep29460

Polymersome nanoparticles (PMs) are attractive candidates for spatio-temporal controlled delivery of therapeutic agents. Although many studies have addressed cellular uptake of solid nanoparticles, there is very little data available on intracellular release of molecules encapsulated in membranous carriers, such as polymersomes. Here, we addressed this by developing a quantitative assay based on the hydrophilic dye, fluorescein. Fluorescein was encapsulated stably in PMs of mean diameter 85 nm, with minimal leakage after sustained dialysis. No fluorescence was detectable from fluorescein PMs, indicating quenching. Following incubation of L929 cells with fluorescein PMs, there was a gradual increase in intracellular fluorescence, indicating PM disruption and cytosolic release of fluorescein. By combining absorbance measurements with flow cytometry, we quantified the real-time intracellular release of a fluorescein at a single-cell resolution. We found that 173 ± 38 polymersomes released their payload per cell, with significant heterogeneity in uptake, despite controlled synchronisation of cell cycle. This novel method for quantification of the release of compounds from nanoparticles provides fundamental information on cellular uptake of nanoparticle-encapsulated compounds. It also illustrates the stochastic nature of population distribution in homogeneous cell populations, a factor that must be taken into account in clinical use of this technology.
Controversies around COVID-19 Vaccines and Antidepressants: Scope and Perspective in Malaysia

Chong Guan N, Weng Hou S, Abousheishaa AA, Sue Yin L, Sulaiman ARB, Chee Khin K

Curr Drug Res Rev, 2022 Nov 23.
PMID: 36420879 DOI: 10.2174/2589977515666221123093522

BACKGROUND: Individuals with severe mental illness are prone to severe COVID-19 infection with increased morbidity and mortality. Psychiatric patients are often concerned about the potential interactions between the newly approved COVID-19 vaccines in Malaysia and psychotropic drugs like antidepressants. To date, such data are unavailable.
OBJECTIVES: This review aims to clear the polemics of COVID-19 vaccine-antidepressants interaction in these 3 aspects: (1) cytokines and cytochrome P450 pathway, (2) blood-brain barrier (BBB) involvement and (3) and its interaction with polyethylene glycol (PEG), the potential allergenic culprit following COVID-19 vaccination.
METHODS: A systemic scoping approach was employed to search for peer-reviewed journal articles across four healthcare and scientific databases (PubMed, MEDLINE, PsycINFO and Cumulative Index to Nursing and Allied Health Literature (CINAHL)).
RESULTS: Antidepressants metabolism often involve the CYP450 enzymes. Vaccine-antidepressants interactions are probable, likely to be triggered by interactions of CYP450 enzymes and inflammatory cytokines, resulting in diminished drug metabolism and chemical detoxification. Aside, PEG, the excipient in mRNA-based COVID-19 vaccines and antidepressants, has been reported as the anaphylaxis causative allergen. However, whether it leads to a synergistic, potentiation or antagonistic effects when used in combination, remains to be elucidated.
CONCLUSION: Psychotropic medications, including antidepressants, showed potentially relevant safety risk for COVID-19 patients. These vulnerable patient group must be prioritized for early access to safe and efficacious COVID-19 vaccines, as vaccination remains the most important public health intervention to tackle the ongoing COVID-19 pandemic.
Fulltext Surface fractures in pre-crystallized and crystallized zirconia-containing lithium silicate glass-ceramics generated in ultrasonic vibration-assisted machining

Juri AZ, Song XF, Nakanishi Y, Dudley J, Jamieson L, Yin L

J Mech Behav Biomed Mater, 2023 Nov;147:106132.
PMID: 37776763 DOI: 10.1016/j.jmbbm.2023.106132

Machining-induced surface fractures in ceramic restorations is a long-standing problem in dentistry, affecting the restorations' functionality and reliability. This study approached a novel ultrasonic vibration-assisted machining technique to zirconia-containing lithium silicate glass-ceramics (ZLS) and characterized its induced surface fracture topographies and morphologies to understand the microstructure-property-processing relations. The materials were processed using a digitally controlled ultrasonic milling machine at a harmonic vibration frequency with different amplitudes. Machining-induced surface fracture topographies were measured with a 3D white light optical profilometer using the arithmetic mean, peak and valley, and maximum heights, as well as the kurtosis and skewness height distributions, and the texture aspect ratios. Fracture morphologies were analysed using scanning electron microscopy (SEM). The surface fracture topographies were significantly dependent on the material microstructure, the mechanical properties, and the ultrasonic machining vibration amplitudes. Larger scale fractures with higher arithmetic mean, peak and valley heights, and kurtosis and skewness height distributions were induced in higher brittleness indexed pre-crystallized ZLS than lower indexed crystallized ZLS by conventional machining. Conchoidal fractures occurred in pre-crystallized ZLS while microcracks were found in crystallized state although brittle fractures mixed with localized ductile flow deformations dominated all machined ZLS surfaces. Ultrasonic machining at an ideal vibration amplitude resulted in more ductile removal, reducing fractured-induced peaks and valleys for both materials than conventional processing. This research demonstrates the microstructure-property-processing interdependence for ZLS materials and the novel machining technique to be superior to current processing, reducing fractures in the materials and potentially advancing dental CAD/CAM techniques.
Fulltext Unraveling varying spatiotemporal patterns of dengue and associated exposure-response relationships with environmental variables in Southeast Asian countries before and during COVID-19

Luo W, Liu Z, Ran Y, Li M, Zhou Y, Hou W, et al.

medRxiv, 2024 Mar 26.
PMID: 38585938 DOI: 10.1101/2024.03.25.24304825

The enforcement of COVID-19 interventions by diverse governmental bodies, coupled with the indirect impact of COVID-19 on short-term environmental changes (e.g. plant shutdowns lead to lower greenhouse gas emissions), influences the dengue vector. This provides a unique opportunity to investigate the impact of COVID-19 on dengue transmission and generate insights to guide more targeted prevention measures. We aim to compare dengue transmission patterns and the exposure-response relationship of environmental variables and dengue incidence in the pre- and during-COVID-19 to identify variations and assess the impact of COVID-19 on dengue transmission. We initially visualized the overall trend of dengue transmission from 2012-2022, then conducted two quantitative analyses to compare dengue transmission pre-COVID-19 (2017-2019) and during-COVID-19 (2020-2022). These analyses included time series analysis to assess dengue seasonality, and a Distributed Lag Non-linear Model (DLNM) to quantify the exposure-response relationship between environmental variables and dengue incidence. We observed that all subregions in Thailand exhibited remarkable synchrony with a similar annual trend except 2021. Cyclic and seasonal patterns of dengue remained consistent pre- and during-COVID-19. Monthly dengue incidence in three countries varied significantly. Singapore witnessed a notable surge during-COVID-19, particularly from May to August, with cases multiplying several times compared to pre-COVID-19, while seasonality of Malaysia weakened. Exposure-response relationships of dengue and environmental variables show varying degrees of change, notably in Northern Thailand, where the peak relative risk for the maximum temperature-dengue relationship rose from about 3 to 17, and the max RR of overall cumulative association 0-3 months of relative humidity increased from around 5 to 55. Our study is the first to compare dengue transmission patterns and their relationship with environmental variables before and during COVID-19, showing that COVID-19 has affected dengue transmission at both the national and regional level, and has altered the exposure-response relationship between dengue and the environment.
Fulltext Clinical and Mutational Analysis of the GCDH Gene in Malaysian Patients with Glutaric Aciduria Type 1

Abdul Wahab SA, Yakob Y, Abdul Azize NA, Md Yunus Z, Huey Yin L, Mohd Khalid MK, et al.

Biomed Res Int, 2016;2016:4074365.
PMID: 27672653

Glutaric aciduria type 1 (GA1) is an autosomal recessive metabolic disorder caused by deficiency of glutaryl-CoA dehydrogenase enzyme encoded by the GCDH gene. In this study, we presented the clinical and molecular findings of seven GA1 patients in Malaysia. All the patients were symptomatic from infancy and diagnosed clinically from large excretion of glutaric and 3-hydroxyglutaric acids. Bidirectional sequencing of the GCDH gene revealed ten mutations, three of which were novel (Gln76Pro, Glu131Val, and Gly390Trp). The spectrum of mutations included eight missense mutations, a nonsense mutation, and a splice site mutation. Two mutations (Gln76Pro and Arg386Gln) were homozygous in two patients with parental consanguinity. All mutations were predicted to be disease causing by MutationTaster2. In conclusion, this is the first report of both clinical and molecular aspects of GA1 in Malaysian patients. Despite the lack of genotype and phenotype correlation, early diagnosis and timely treatment remained the most important determinant of patient outcome.
Complete genome sequences of Lactococcus lactis D1_2, a bacterium with antimicrobial properties isolated from peat soil

Isaac P, Mutusamy P, Su Yin L, Jing Wei Y, Mohd Salleh F, Abu Bakar MALb, et al.

Microbiol Resour Announc, 2023 Nov 07.
PMID: 37933991 DOI: 10.1128/MRA.00680-23

Lactococcus lactis is a beneficial lactic acid bacterium commonly studied for its probiotic properties and role in dairy production. Here, we present a complete genome of Lactococcus lactis D1_2, isolated from peat swamp forests. To discover the potential antimicrobial properties, the complete genome of the strain was sequenced and analyzed.
Fulltext Phenotypic Characterization and Comparative Genomic Analysis of Novel Salmonella Bacteriophages Isolated from a Tropical Rainforest

Mutusamy P, Banga Singh KK, Su Yin L, Petersen B, Sicheritz-Ponten T, Clokie MRJ, et al.

Int J Mol Sci, 2023 Feb 12;24(4).
PMID: 36835084 DOI: 10.3390/ijms24043678

Salmonella infections across the globe are becoming more challenging to control due to the emergence of multidrug-resistant (MDR) strains. Lytic phages may be suitable alternatives for treating these multidrug-resistant Salmonella infections. Most Salmonella phages to date were collected from human-impacted environments. To further explore the Salmonella phage space, and to potentially identify phages with novel characteristics, we characterized Salmonella-specific phages isolated from the Penang National Park, a conserved rainforest. Four phages with a broad lytic spectrum (kills >5 Salmonella serovars) were further characterized; they have isometric heads and cone-shaped tails, and genomes of ~39,900 bp, encoding 49 CDSs. As the genomes share a <95% sequence similarity to known genomes, the phages were classified as a new species within the genus Kayfunavirus. Interestingly, the phages displayed obvious differences in their lytic spectrum and pH stability, despite having a high sequence similarity (~99% ANI). Subsequent analysis revealed that the phages differed in the nucleotide sequence in the tail spike proteins, tail tubular proteins, and portal proteins, suggesting that the SNPs were responsible for their differing phenotypes. Our findings highlight the diversity of novel Salmonella bacteriophages from rainforest regions, which can be explored as an antimicrobial agent against MDR-Salmonella strains.
Fulltext Impaired coronary metabolic dilation in the metabolic syndrome is linked to mitochondrial dysfunction and mitochondrial DNA damage

Guarini G, Kiyooka T, Ohanyan V, Pung YF, Marzilli M, Chen YR, et al.

Basic Res Cardiol, 2016 May;111(3):29.
PMID: 27040114 DOI: 10.1007/s00395-016-0547-4

Mitochondrial dysfunction in obesity and diabetes can be caused by excessive production of free radicals, which can damage mitochondrial DNA. Because mitochondrial DNA plays a key role in the production of ATP necessary for cardiac work, we hypothesized that mitochondrial dysfunction, induced by mitochondrial DNA damage, uncouples coronary blood flow from cardiac work. Myocardial blood flow (contrast echocardiography) was measured in Zucker lean (ZLN) and obese fatty (ZOF) rats during increased cardiac metabolism (product of heart rate and arterial pressure, i.v. norepinephrine). In ZLN increased metabolism augmented coronary blood flow, but in ZOF metabolic hyperemia was attenuated. Mitochondrial respiration was impaired and ROS production was greater in ZOF than ZLN. These were associated with mitochondrial DNA (mtDNA) damage in ZOF. To determine if coronary metabolic dilation, the hyperemic response induced by heightened cardiac metabolism, is linked to mitochondrial function we introduced recombinant proteins (intravenously or intraperitoneally) in ZLN and ZOF to fragment or repair mtDNA, respectively. Repair of mtDNA damage restored mitochondrial function and metabolic dilation, and reduced ROS production in ZOF; whereas induction of mtDNA damage in ZLN reduced mitochondrial function, increased ROS production, and attenuated metabolic dilation. Adequate metabolic dilation was also associated with the extracellular release of ADP, ATP, and H2O2 by cardiac myocytes; whereas myocytes from rats with impaired dilation released only H2O2. In conclusion, our results suggest that mitochondrial function plays a seminal role in connecting myocardial blood flow to metabolism, and integrity of mtDNA is central to this process.
Fulltext Mitochondrial DNA integrity and function are critical for endothelium-dependent vasodilation in rats with metabolic syndrome

Kiyooka T, Ohanyan V, Yin L, Pung YF, Chen YR, Chen CL, et al.

Basic Res Cardiol, 2022 Jan 17;117(1):3.
PMID: 35039940 DOI: 10.1007/s00395-021-00908-1

Endothelial dysfunction in diabetes is generally attributed to oxidative stress, but this view is challenged by observations showing antioxidants do not eliminate diabetic vasculopathy. As an alternative to oxidative stress-induced dysfunction, we interrogated if impaired mitochondrial function in endothelial cells is central to endothelial dysfunction in the metabolic syndrome. We observed reduced coronary arteriolar vasodilation to the endothelium-dependent dilator, acetylcholine (Ach), in Zucker Obese Fatty rats (ZOF, 34 ± 15% [mean ± standard deviation] 10-3 M) compared to Zucker Lean rats (ZLN, 98 ± 11%). This reduction in dilation occurred concomitantly with mitochondrial DNA (mtDNA) strand lesions and reduced mitochondrial complex activities in the endothelium of ZOF versus ZLN. To demonstrate endothelial dysfunction is linked to impaired mitochondrial function, administration of a cell-permeable, mitochondria-directed endonuclease (mt-tat-EndoIII), to repair oxidatively modified DNA in ZOF, restored mitochondrial function and vasodilation to Ach (94 ± 13%). Conversely, administration of a cell-permeable, mitochondria-directed exonuclease (mt-tat-ExoIII) produced mtDNA strand breaks in ZLN, reduced mitochondrial complex activities and vasodilation to Ach in ZLN (42 ± 16%). To demonstrate that mitochondrial function is central to endothelium-dependent vasodilation, we introduced (via electroporation) liver mitochondria (from ZLN) into the endothelium of a mesenteric vessel from ZOF and restored endothelium-dependent dilation to vasoactive intestinal peptide (VIP at 10-5 M, 4 ± 3% vasodilation before mitochondrial transfer and 48 ± 36% after transfer). Finally, to demonstrate mitochondrial function is key to endothelium-dependent dilation, we administered oligomycin (mitochondrial ATP synthase inhibitor) and observed a reduction in endothelium-dependent dilation. We conclude that mitochondrial function is critical for endothelium-dependent vasodilation.
Fulltext Single-cell profile reveals the landscape of cardiac immunity and identifies a cardio-protective Ym-1hi neutrophil in myocardial ischemia-reperfusion injury

Dong Y, Kang Z, Zhang Z, Zhang Y, Zhou H, Liu Y, et al.

Sci Bull (Beijing), 2024 Apr 15;69(7):949-967.
PMID: 38395651 DOI: 10.1016/j.scib.2024.02.003

Myocardial ischemia-reperfusion injury (MIRI) is a major hindrance to the success of cardiac reperfusion therapy. Although increased neutrophil infiltration is a hallmark of MIRI, the subtypes and alterations of neutrophils in this process remain unclear. Here, we performed single-cell sequencing of cardiac CD45+ cells isolated from the murine myocardium subjected to MIRI at six-time points. We identified diverse types of infiltrating immune cells and their dynamic changes during MIRI. Cardiac neutrophils showed the most immediate response and largest changes and featured with functionally heterogeneous subpopulations, including Ccl3hi Neu and Ym-1hi Neu, which were increased at 6 h and 1 d after reperfusion, respectively. Ym-1hi Neu selectively expressed genes with protective effects and was, therefore, identified as a novel specific type of cardiac cell in the injured heart. Further analysis indicated that neutrophils and their subtypes orchestrated subsequent immune responses in the cardiac tissues, especially instructing the response of macrophages. The abundance of Ym-1hi Neu was closely correlated with the therapeutic efficacy of MIRI when neutrophils were specifically targeted by anti-Lymphocyte antigen 6 complex locus G6D (Ly6G) or anti-Intercellular cell adhesion molecule-1 (ICAM-1) neutralizing antibodies. In addition, a neutrophil subtype with the same phenotype as Ym-1hi Neu was detected in clinical samples and correlated with prognosis. Ym-1 inhibition exacerbated myocardial injury, whereas Ym-1 supplementation significantly ameliorated injury in MIRI mice, which was attributed to the tilt of Ym-1 on the polarization of macrophages toward the repair phenotype in myocardial tissue. Overall, our findings reveal the anti-inflammatory phenotype of Ym-1hi Neu and highlight its critical role in myocardial protection during the early stages of MIRI.
Fulltext Genome-wide association studies identify susceptibility loci for epithelial ovarian cancer in east Asian women

Lawrenson K, Song F, Hazelett DJ, Kar SP, Tyrer J, Phelan CM, et al.

Gynecol Oncol, 2019 05;153(2):343-355.
PMID: 30898391 DOI: 10.1016/j.ygyno.2019.02.023

OBJECTIVE: Genome-wide association studies (GWASs) for epithelial ovarian cancer (EOC) have focused largely on populations of European ancestry. We aimed to identify common germline variants associated with EOC risk in Asian women.
METHODS: Genotyping was performed as part of the OncoArray project. Samples with >60% Asian ancestry were included in the analysis. Genotyping was performed on 533,631 SNPs in 3238 Asian subjects diagnosed with invasive or borderline EOC and 4083 unaffected controls. After imputation, genotypes were available for 11,595,112 SNPs to identify associations.
RESULTS: At chromosome 6p25.2, SNP rs7748275 was associated with risk of serous EOC (odds ratio [OR] = 1.34, P = 8.7 × 10-9) and high-grade serous EOC (HGSOC) (OR = 1.34, P = 4.3 × 10-9). SNP rs6902488 at 6p25.2 (r2 = 0.97 with rs7748275) lies in an active enhancer and is predicted to impact binding of STAT3, P300 and ELF1. We identified additional risk loci with low Bayesian false discovery probability (BFDP) scores, indicating they are likely to be true risk associations (BFDP <10%). At chromosome 20q11.22, rs74272064 was associated with HGSOC risk (OR = 1.27, P = 9.0 × 10-8). Overall EOC risk was associated with rs10260419 at chromosome 7p21.3 (OR = 1.33, P = 1.2 × 10-7) and rs74917072 at chromosome 2q37.3 (OR = 1.25, P = 4.7 × 10-7). At 2q37.3, expression quantitative trait locus analysis in 404 HGSOC tissues identified ESPNL as a putative candidate susceptibility gene (P = 1.2 × 10-7).
CONCLUSION: While some risk loci were shared between East Asian and European populations, others were population-specific, indicating that the landscape of EOC risk in Asian women has both shared and unique features compared to women of European ancestry.
Fulltext Long-term exposure to outdoor and household air pollution and blood pressure in the Prospective Urban and Rural Epidemiological (PURE) study

Arku RE, Brauer M, Ahmed SH, AlHabib KF, Avezum Á, Bo J, et al.

Environ Pollut, 2020 Jul;262:114197.
PMID: 32146361 DOI: 10.1016/j.envpol.2020.114197

Exposure to air pollution has been linked to elevated blood pressure (BP) and hypertension, but most research has focused on short-term (hours, days, or months) exposures at relatively low concentrations. We examined the associations between long-term (3-year average) concentrations of outdoor PM2.5 and household air pollution (HAP) from cooking with solid fuels with BP and hypertension in the Prospective Urban and Rural Epidemiology (PURE) study. Outdoor PM2.5 exposures were estimated at year of enrollment for 137,809 adults aged 35-70 years from 640 urban and rural communities in 21 countries using satellite and ground-based methods. Primary use of solid fuel for cooking was used as an indicator of HAP exposure, with analyses restricted to rural participants (n = 43,313) in 27 study centers in 10 countries. BP was measured following a standardized procedure and associations with air pollution examined with mixed-effect regression models, after adjustment for a comprehensive set of potential confounding factors. Baseline outdoor PM2.5 exposure ranged from 3 to 97 μg/m3 across study communities and was associated with an increased odds ratio (OR) of 1.04 (95% CI: 1.01, 1.07) for hypertension, per 10 μg/m3 increase in concentration. This association demonstrated non-linearity and was strongest for the fourth (PM2.5 > 62 μg/m3) compared to the first (PM2.5
Fulltext Joint association of urinary sodium and potassium excretion with cardiovascular events and mortality: prospective cohort study

O'Donnell M, Mente A, Rangarajan S, McQueen MJ, O'Leary N, Yin L, et al.

BMJ, 2019 03 13;364:l772.
PMID: 30867146 DOI: 10.1136/bmj.l772

OBJECTIVE: To evaluate the joint association of sodium and potassium urinary excretion (as surrogate measures of intake) with cardiovascular events and mortality, in the context of current World Health Organization recommendations for daily intake (<2.0 g sodium, >3.5 g potassium) in adults.
DESIGN: International prospective cohort study.
SETTING: 18 high, middle, and low income countries, sampled from urban and rural communities.
PARTICIPANTS: 103 570 people who provided morning fasting urine samples.
MAIN OUTCOME MEASURES: Association of estimated 24 hour urinary sodium and potassium excretion (surrogates for intake) with all cause mortality and major cardiovascular events, using multivariable Cox regression. A six category variable for joint sodium and potassium was generated: sodium excretion (low (<3 g/day), moderate (3-5 g/day), and high (>5 g/day) sodium intakes) by potassium excretion (greater/equal or less than median 2.1 g/day).
RESULTS: Mean estimated sodium and potassium urinary excretion were 4.93 g/day and 2.12 g/day, respectively. After a median follow-up of 8.2 years, 7884 (6.1%) participants had died or experienced a major cardiovascular event. Increasing urinary sodium excretion was positively associated with increasing potassium excretion (unadjusted r=0.34), and only 0.002% had a concomitant urinary excretion of <2.0 g/day of sodium and >3.5 g/day of potassium. A J-shaped association was observed of sodium excretion and inverse association of potassium excretion with death and cardiovascular events. For joint sodium and potassium excretion categories, the lowest risk of death and cardiovascular events occurred in the group with moderate sodium excretion (3-5 g/day) and higher potassium excretion (21.9% of cohort). Compared with this reference group, the combinations of low potassium with low sodium excretion (hazard ratio 1.23, 1.11 to 1.37; 7.4% of cohort) and low potassium with high sodium excretion (1.21, 1.11 to 1.32; 13.8% of cohort) were associated with the highest risk, followed by low sodium excretion (1.19, 1.02 to 1.38; 3.3% of cohort) and high sodium excretion (1.10, 1.02 to 1.18; 29.6% of cohort) among those with potassium excretion greater than the median. Higher potassium excretion attenuated the increased cardiovascular risk associated with high sodium excretion (P for interaction=0.007).
CONCLUSIONS: These findings suggest that the simultaneous target of low sodium intake (<2 g/day) with high potassium intake (>3.5 g/day) is extremely uncommon. Combined moderate sodium intake (3-5 g/day) with high potassium intake is associated with the lowest risk of mortality and cardiovascular events.
Association of Sitting Time With Mortality and Cardiovascular Events in High-Income, Middle-Income, and Low-Income Countries

Li S, Lear SA, Rangarajan S, Hu B, Yin L, Bangdiwala SI, et al.

JAMA Cardiol, 2022 Aug 01;7(8):796-807.
PMID: 35704349 DOI: 10.1001/jamacardio.2022.1581

IMPORTANCE: High amounts of sitting time are associated with increased risks of cardiovascular disease (CVD) and mortality in high-income countries, but it is unknown whether risks also increase in low- and middle-income countries.
OBJECTIVE: To investigate the association of sitting time with mortality and major CVD in countries at different economic levels using data from the Prospective Urban Rural Epidemiology study.
DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study included participants aged 35 to 70 years recruited from January 1, 2003, and followed up until August 31, 2021, in 21 high-income, middle-income, and low-income countries with a median follow-up of 11.1 years.
EXPOSURES: Daily sitting time measured using the International Physical Activity Questionnaire.
MAIN OUTCOMES AND MEASURES: The composite of all-cause mortality and major CVD (defined as cardiovascular death, myocardial infarction, stroke, or heart failure).
RESULTS: Of 105 677 participants, 61 925 (58.6%) were women, and the mean (SD) age was 50.4 (9.6) years. During a median follow-up of 11.1 (IQR, 8.6-12.2) years, 6233 deaths and 5696 major cardiovascular events (2349 myocardial infarctions, 2966 strokes, 671 heart failure, and 1792 cardiovascular deaths) were documented. Compared with the reference group (<4 hours per day of sitting), higher sitting time (≥8 hours per day) was associated with an increased risk of the composite outcome (hazard ratio [HR], 1.19; 95% CI, 1.11-1.28; Pfor trend < .001), all-cause mortality (HR, 1.20; 95% CI, 1.10-1.31; Pfor trend < .001), and major CVD (HR, 1.21; 95% CI, 1.10-1.34; Pfor trend < .001). When stratified by country income levels, the association of sitting time with the composite outcome was stronger in low-income and lower-middle-income countries (≥8 hours per day: HR, 1.29; 95% CI, 1.16-1.44) compared with high-income and upper-middle-income countries (HR, 1.08; 95% CI, 0.98-1.19; P for interaction = .02). Compared with those who reported sitting time less than 4 hours per day and high physical activity level, participants who sat for 8 or more hours per day experienced a 17% to 50% higher associated risk of the composite outcome across physical activity levels; and the risk was attenuated along with increased physical activity levels.
CONCLUSIONS AND RELEVANCE: High amounts of sitting time were associated with increased risk of all-cause mortality and CVD in economically diverse settings, especially in low-income and lower-middle-income countries. Reducing sedentary time along with increasing physical activity might be an important strategy for easing the global burden of premature deaths and CVD.
Urbanization and physical activity in the global Prospective Urban and Rural Epidemiology study

Boakye K, Bovbjerg M, Schuna J, Branscum A, Varma RP, Ismail R, et al.

Sci Rep, 2023 Jan 06;13(1):290.
PMID: 36609613 DOI: 10.1038/s41598-022-26406-5

Urbanization may influence physical activity (PA) levels, although little evidence is available for low- and middle- income countries where urbanization is occurring fastest. We evaluated associations between urbanization and total PA, as well as work-, leisure-, home-, and transport-specific PA, for 138,206 adults living in 698 communities across 22 countries within the Prospective Urban and Rural Epidemiology (PURE) study. The 1-week long-form International PA Questionnaire was administered at baseline (2003-2015). We used satellite-derived population density and impervious surface area estimates to quantify baseline urbanization levels for study communities, as well as change measures for 5- and 10-years prior to PA surveys. We used generalized linear mixed effects models to examine associations between urbanization measures and PA levels, controlling for individual, household and community factors. Higher community baseline levels of population density (- 12.4% per IQR, 95% CI - 16.0, - 8.7) and impervious surface area (- 29.2% per IQR, 95% CI - 37.5, - 19.7), as well as the rate of change in 5-year population density (- 17.2% per IQR, 95% CI - 25.7, - 7.7), were associated with lower total PA levels. Important differences in the associations between urbanization and PA were observed between PA domains, country-income levels, urban/rural status, and sex. These findings provide new information on the complex associations between urbanization and PA.
Associations of Antibiotics, Hormonal Therapies, Oral Contraceptives, and Long-Term NSAIDS With Inflammatory Bowel Disease: Results From the Prospective Urban Rural Epidemiology (PURE) Study

Narula N, Wong ECL, Pray C, Marshall JK, Rangarajan S, Islam S, et al.

Clin Gastroenterol Hepatol, 2023 Sep;21(10):2649-2659.e16.
PMID: 36528284 DOI: 10.1016/j.cgh.2022.11.037

BACKGROUND & AIMS: Several medications have been suspected to contribute to the etiology of inflammatory bowel disease (IBD). This study assessed the association between medication use and the risk of developing IBD using the Prospective Urban Rural Epidemiology cohort.
METHODS: This was a prospective cohort study of 133,137 individuals between the ages of 20 and 80 from 24 countries. Country-specific validated questionnaires documented baseline and follow-up medication use. Participants were followed up prospectively at least every 3 years. The main outcome was the development of IBD, including Crohn's disease (CD) and ulcerative colitis (UC). Short-term (baseline but not follow-up use) and long-term use (baseline and subsequent follow-up use) were evaluated. Results are presented as adjusted odds ratios (aORs) with 95% CIs.
RESULTS: During a median follow-up period of 11.0 years (interquartile range, 9.2-12.2 y), there were 571 incident IBD cases (143 CD and 428 UC). Incident IBD was associated significantly with baseline antibiotic (aOR, 2.81; 95% CI, 1.67-4.73; P = .0001) and hormonal medication use (aOR, 4.43; 95% CI, 1.78-11.01; P = .001). Among females, previous or current oral contraceptive use also was associated with IBD development (aOR, 2.17; 95% CI, 1.70-2.77; P < .001). Nonsteroidal anti-inflammatory drug users also were observed to have increased odds of IBD (aOR, 1.80; 95% CI, 1.23-2.64; P = .002), which was driven by long-term use (aOR, 5.58; 95% CI, 2.26-13.80; P < .001). All significant results were consistent in direction for CD and UC with low heterogeneity.
CONCLUSIONS: Antibiotics, hormonal medications, oral contraceptives, and long-term nonsteroidal anti-inflammatory drug use were associated with increased odds of incident IBD after adjustment for covariates.
Fulltext Association of dairy consumption with metabolic syndrome, hypertension and diabetes in 147 812 individuals from 21 countries

Bhavadharini B, Dehghan M, Mente A, Rangarajan S, Sheridan P, Mohan V, et al.

BMJ Open Diabetes Res Care, 2020 04;8(1).
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.
Association of dairy intake with cardiovascular disease and mortality in 21 countries from five continents (PURE): a prospective cohort study

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).

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