Faculty Bibliography
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176
Repositioning of the global epicentre of non-optimal cholesterol
High blood cholesterol is typically considered a feature of wealthy western countries. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol-which is a marker of cardiovascular risk-changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million-4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.
PMID: 32494083
ISSN: 1476-4687
CID: 4481132
Public Health Is Not Afraid of Pleasure [Editorial]
PMID: 31913673
ISSN: 1541-0048
CID: 4258372
Concentrations of trace elements and KRAS mutations in pancreatic ductal adenocarcinoma
Trace elements are a possible risk factor for pancreatic ductal adenocarcinoma (PDAC). However, their role in the occurrence and persistence of KRAS mutations remains unstudied. There appear to be no studies analyzing biomarkers of trace elements and KRAS mutations in any human cancer. We aimed to determine whether patients with KRAS mutated and nonmutated tumors exhibit differences in concentrations of trace elements. Incident cases of PDAC were prospectively identified in five hospitals in Spain. KRAS mutational status was determined through polymerase chain reaction from tumor tissue. Concentrations of 12 trace elements were determined in toenail samples by inductively coupled plasma mass spectrometry. Concentrations of trace elements were compared in 78 PDAC cases and 416 hospital-based controls (case-control analyses), and between 17 KRAS wild-type tumors and 61 KRAS mutated tumors (case-case analyses). Higher levels of iron, arsenic, and vanadium were associated with a statistically nonsignificant increased risk of a KRAS wild-type PDAC (OR for higher tertile of arsenic = 3.37, 95% CI 0.98-11.57). Lower levels of nickel and manganese were associated with a statistically significant higher risk of a KRAS mutated PDAC (OR for manganese = 0.34, 95% CI 0.14-0.80). Higher levels of selenium appeared protective for both mutated and KRAS wild-type PDAC. Higher levels of cadmium and lead were clear risk factors for both KRAS mutated and wild-type cases. This is the first study analyzing biomarkers of trace elements and KRAS mutations in any human cancer. Concentrations of trace elements differed markedly between PDAC cases with and without mutations in codon 12 of the KRAS oncogene, thus suggesting a role for trace elements in pancreatic and perhaps other cancers with such mutations. Environ. Mol. Mutagen., 60:693-703, 2019. © 2019 Wiley Periodicals, Inc.
PMCID:6786909
PMID: 31066938
ISSN: 1098-2280
CID: 4214332
Multiple sessions of transcranial direct current stimulation (tDCS) combined with aerobic physical activity improves walking speed [Meeting Abstract]
Background: Walking impairments are one of the most impactful consequences of multiple sclerosis (MS). Recently, physical rehabilitation research has focused on developing synergistic protocols to enhance clinical benefit. Recent studies have shown that transcranial direct current stimulation (tDCS) and aerobic physical activity (PA) have converging activation pathways and when completed simultaneously, they may promote cortical neuroplasticity.
Objective(s): To harness cortical plasticity to improve gait for individuals with MS.
Aim(s): To investigate the effects of multiple sessions of PA with simultaneously administered tDCS on walking abilities.
Method(s): MS participants (EDSS: 1-6.5, Relapsing-Remitting or Secondary-Progressive subtype) with clinically significant gait deviations were recruited for a randomized controlled trial of 10 sessions of either active or sham tDCS paired with unloaded cycling for 20 minutes. Stimulation was administered over the primary motor cortex (2.5 mA-2.0 mA; anode over C3/cathode over FP2). Walking speed was assessed quantitatively by using a single inertial sensor placed on the lower back and perceived walking abilities were evaluated using the 12-Item MS Walking Scale (MSWS-12), a self-report questionnaire. Measurements were collected at baseline, the end of tDCS intervention, and 4-weeks post-intervention. Two-way repeated measures-ANOVA (Time, Treatment) was performed to investigate differences between active and sham conditions.
Result(s): Thirty-two participants were enrolled in the study, 22 underwent active treatment. No demographic differences were detected between active and sham groups (active:EDSS 4.3+/-1.2, age 55.5+/-10.3; sham:EDSS 4.5+/-1.5, age 49.7+/-13.9). Statistical analysis showed significant Treatment by Time interactions for gait speed and MSWS-12 score. Post-hoc analysis revealed that gait speed increased significantly after active treatment (Baseline vs. End Treatment, 0.98 vs. 1.16 m/s, p< 0.001; Baseline vs. Follow-up, 0.98 vs. 1.20 m/s, p< 0.001). Active group further reported significant improvement in self-report measure (Baseline vs. End Treatment, 58.04 vs. 49.73, p< 0.05). No significant difference was detected after sham stimulation.
Conclusion(s): Our results indicate that multiple sessions of tDCS administered simultaneously with PA induce cumulative and selfreport improvement in walking and benefits persisted until 4-week post-intervention
Objective(s): To harness cortical plasticity to improve gait for individuals with MS.
Aim(s): To investigate the effects of multiple sessions of PA with simultaneously administered tDCS on walking abilities.
Method(s): MS participants (EDSS: 1-6.5, Relapsing-Remitting or Secondary-Progressive subtype) with clinically significant gait deviations were recruited for a randomized controlled trial of 10 sessions of either active or sham tDCS paired with unloaded cycling for 20 minutes. Stimulation was administered over the primary motor cortex (2.5 mA-2.0 mA; anode over C3/cathode over FP2). Walking speed was assessed quantitatively by using a single inertial sensor placed on the lower back and perceived walking abilities were evaluated using the 12-Item MS Walking Scale (MSWS-12), a self-report questionnaire. Measurements were collected at baseline, the end of tDCS intervention, and 4-weeks post-intervention. Two-way repeated measures-ANOVA (Time, Treatment) was performed to investigate differences between active and sham conditions.
Result(s): Thirty-two participants were enrolled in the study, 22 underwent active treatment. No demographic differences were detected between active and sham groups (active:EDSS 4.3+/-1.2, age 55.5+/-10.3; sham:EDSS 4.5+/-1.5, age 49.7+/-13.9). Statistical analysis showed significant Treatment by Time interactions for gait speed and MSWS-12 score. Post-hoc analysis revealed that gait speed increased significantly after active treatment (Baseline vs. End Treatment, 0.98 vs. 1.16 m/s, p< 0.001; Baseline vs. Follow-up, 0.98 vs. 1.20 m/s, p< 0.001). Active group further reported significant improvement in self-report measure (Baseline vs. End Treatment, 58.04 vs. 49.73, p< 0.05). No significant difference was detected after sham stimulation.
Conclusion(s): Our results indicate that multiple sessions of tDCS administered simultaneously with PA induce cumulative and selfreport improvement in walking and benefits persisted until 4-week post-intervention
EMBASE:631450545
ISSN: 1352-4585
CID: 4385732
There are good clinical, scientific, and social reasons to strengthen links between biomedical and environmental research
Clinical epidemiology rarely addresses biological, clinical, epidemiological, environmental, economic, and other social and scientific issues posed by environmental chemical contaminants such as endocrine-disrupting chemicals. There is a considerable gap between research and practice in clinical medicine and in environmental health. Organizations often fail to appreciate the human and economic costs of the diseases that environmental chemical contaminants contribute to cause. Also, the relative lack of attention to environmental causes of disease by researchers in medicine and clinical epidemiology cannot be explained just on scientific grounds. Many scientists have shown the virtues of integrative research. Knowledge on the causes of disease is often secondary in clinical practice, but in other instances, to help patients, clinicians tackle causes of diseases. We can better address how environmental contaminants influence negatively not just the occurrence of disease but its course. To do so, we can generate better evidence and strengthen the social conversation on environmental influences on all dimensions of health and disease.
PMCID:6664300
PMID: 30905697
ISSN: 1878-5921
CID: 4214312
Agnostic Pathway/Gene Set Analysis of Genome-Wide Association Data Identifies Associations for Pancreatic Cancer
Background/UNASSIGNED:Genome-wide association studies (GWAS) identify associations of individual single-nucleotide polymorphisms (SNPs) with cancer risk but usually only explain a fraction of the inherited variability. Pathway analysis of genetic variants is a powerful tool to identify networks of susceptibility genes. Methods/UNASSIGNED:We conducted a large agnostic pathway-based meta-analysis of GWAS data using the summary-based adaptive rank truncated product method to identify gene sets and pathways associated with pancreatic ductal adenocarcinoma (PDAC) in 9040 cases and 12 496 controls. We performed expression quantitative trait loci (eQTL) analysis and functional annotation of the top SNPs in genes contributing to the top associated pathways and gene sets. All statistical tests were two-sided. Results/UNASSIGNED:We identified 14 pathways and gene sets associated with PDAC at a false discovery rate of less than 0.05. After Bonferroni correction (P ≤ 1.3 × 10-5), the strongest associations were detected in five pathways and gene sets, including maturity-onset diabetes of the young, regulation of beta-cell development, role of epidermal growth factor (EGF) receptor transactivation by G protein-coupled receptors in cardiac hypertrophy pathways, and the Nikolsky breast cancer chr17q11-q21 amplicon and Pujana ATM Pearson correlation coefficient (PCC) network gene sets. We identified and validated rs876493 and three correlating SNPs (PGAP3) and rs3124737 (CASP7) from the Pujana ATM PCC gene set as eQTLs in two normal derived pancreas tissue datasets. Conclusion/UNASSIGNED:Our agnostic pathway and gene set analysis integrated with functional annotation and eQTL analysis provides insight into genes and pathways that may be biologically relevant for risk of PDAC, including those not previously identified.
PMID: 30541042
ISSN: 1460-2105
CID: 3563572
Toenail concentrations of trace elements and occupational history in pancreatic cancer
BACKGROUND:Some occupations potentially entailing exposure to cadmium, arsenic, lead, selenium, nickel, and chromium have been associated with an increased risk of exocrine pancreatic cancer (EPC), but no studies have assessed whether body concentrations of such compounds differed among subjects occupationally exposed and unexposed. No studies which found that exposure to such metals increased the risk of EPC assessed whether past occupations were the source of exposure. OBJECTIVE:The aim was to analyse the relationship between toenail concentrations of trace elements and occupational history in EPC patients. METHODS:The study included 114 EPC cases personally interviewed on occupational history and lifestyle factors. Occupations were coded according to the International Standard Classification of Occupations 1988. Selected occupational exposures were assessed by two industrial hygienists and with the Finnish job-exposure matrix (Finjem). Concentrations of 12 trace elements were determined in toenail samples by inductively coupled plasma mass spectrometry. Adjusted geometric means (aGMs) and 95% confidence intervals (95% CI) were calculated. RESULTS:Patients occupationally exposed to aromatic hydrocarbon solvents (AHs) had higher concentrations of cadmium, manganese, lead, iron and vanadium. The aGM of cadmium concentrations for cases exposed to any pesticide was 0.056 μg/g [95% CI: 0.029-0.108], and, for unexposed cases, 0.023 μg/g [0.017-0.031]. Patients occupationally exposed to pesticides had higher concentrations of cadmium and manganese. Higher concentrations of vanadium, lead and arsenic were related to exposure to formaldehyde. Vanadium and lead were also associated with exposure to chlorinated hydrocarbon solvents, and arsenic was related to exposure to polycyclic aromatic hydrocarbons (PAHs). CONCLUSIONS:Patients occupationally exposed to AHs, pesticides, chlorinated hydrocarbon solvents, formaldehyde, volatile sulphur compounds and PAHs had higher concentrations of several metals. These elements may account for some of the occupational risks previously reported for pancreatic cancer.
PMID: 30928845
ISSN: 1873-6750
CID: 4214322
Organochlorine pesticides and polychlorinated biphenyls (PCBs) in early adulthood and blood lipids over a 23-year follow-up
BACKGROUND:Some evidence in humans suggests that persistent organic pollutants (POPs), including organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs), may alter the blood lipid composition. This study analyzed associations between serum POPs concentrations in young adulthood with blood lipid levels up to 23 years later. METHODS:Serum POPs were measured in year 2 of follow-up (n = 180 men and women, ages: 20-32y), and plasma lipids in follow-up years 2, 7, 10, 15, 20 and 25. 32 POPs were detectable in ≥75% of participants (23 PCBs, 8 OCPs and PBB-153). We created summary scores for PCBs and OCPs for both wet-weight, and lipid standardized (LP) concentrations. We used repeated measures regression adjusting for demographic factors, BMI, smoking, diabetes status, among others. RESULTS:[95%CI]: 5.0 mg/dL [0.7, 9.2]), triglycerides (7.8 mg/dL [-0.9, 16.5]), LDL (4.2 mg/dL [0.2, 8.2]), oxidized LDL 3.4 U/L (-0.05, 6.8), and cholesterol/HDL ratio (0.2 [0.02, 0.3]). The associations for triglycerides (14.7 mg/dL [0.4, 20.1]), cholesterol/HDL (0.33 [0.09, 0.56]) and, to some extent, LDL (4.7 md/dL [-1.6, 10.9]) were only observed among participants in the upper 50th percentile of BMI. Non-dioxin-like PCBs had stronger associations that dioxin-like PCBs. OCPs and PBB-s had positive associations with most outcomes. CONCLUSIONS:PCBs and PBB-153 measured in young adulthood were positively associated with prospective alterations in most blood lipid components, with evidence of effect modification by BMI. Further longitudinal studies with multiple measures of POPs overtime are needed.
PMID: 30594847
ISSN: 1872-7077
CID: 4214302
Methodological issues in a prospective study on plasma concentrations of persistent organic pollutants and pancreatic cancer risk within the EPIC cohort
BACKGROUND:The use of biomarkers of environmental exposure to explore new risk factors for pancreatic cancer presents clinical, logistic, and methodological challenges that are also relevant in research on other complex diseases. OBJECTIVES/OBJECTIVE:First, to summarize the main design features of a prospective case-control study -nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort- on plasma concentrations of persistent organic pollutants (POPs) and pancreatic cancer risk. And second, to assess the main methodological challenges posed by associations among characteristics and habits of study participants, fasting status, time from blood draw to cancer diagnosis, disease progression bias, basis of cancer diagnosis, and plasma concentrations of lipids and POPs. Results from etiologic analyses on POPs and pancreatic cancer risk, and other analyses, will be reported in future articles. METHODS:Study subjects were 1533 participants (513 cases and 1020 controls matched by study centre, sex, age at blood collection, date and time of blood collection, and fasting status) enrolled between 1992 and 2000. Plasma concentrations of 22 POPs were measured by gas chromatography - triple quadrupole mass spectrometry (GC-MS/MS). To estimate the magnitude of the associations we calculated multivariate-adjusted odds ratios by unconditional logistic regression, and adjusted geometric means by General Linear Regression Models. RESULTS:There were differences among countries in subjects' characteristics (as age, gender, smoking, lipid and POP concentrations), and in study characteristics (as time from blood collection to index date, year of last follow-up, length of follow-up, basis of cancer diagnosis, and fasting status). Adjusting for centre and time of blood collection, no factors were significantly associated with fasting status. Plasma concentrations of lipids were related to age, body mass index, fasting, country, and smoking. We detected and quantified 16 of the 22 POPs in more than 90% of individuals. All 22 POPs were detected in some participants, and the smallest number of POPs detected in one person was 15 (median, 19) with few differences by country. The highest concentrations were found for p,p'-DDE, PCBs 153 and 180 (median concentration: 3371, 1023, and 810 pg/mL, respectively). We assessed the possible occurrence of disease progression bias (DPB) in eight situations defined by lipid and POP measurements, on one hand, and by four factors: interval from blood draw to index date, tumour subsite, tumour stage, and grade of differentiation, on the other. In seven of the eight situations results supported the absence of DPB. CONCLUSIONS:The coexistence of differences across study centres in some design features and participant characteristics is of relevance to other multicentre studies. Relationships among subjects' characteristics and among such characteristics and design features may play important roles in the forthcoming analyses on the association between plasma concentrations of POPs and pancreatic cancer risk.
PMID: 30529143
ISSN: 1096-0953
CID: 3678782
Scientists' opinions and attitudes towards citizens' understanding of science and their role in public engagement activities
The increasing perception that public communication in science and technology is an important tool to create a knowledge society is encouraging numerous public engagement activities. However, too little is known about scientists' opinions of and attitudes towards the public with whom they interact during these activities, especially in southern European countries such as Spain. If we want to establish an effective dialogue between science and society, we need to be aware of the opinions and perceptions that both parties have of each other. In this study, we address this issue by focusing on 1022 responses to a survey conducted among scientists in Spain to discover their views of the public, and we then compare these responses with data from other national surveys on the public's understanding of science. The results show that approximately 75% of Spanish scientists think that the general public has a serious lack of knowledge and understanding of scientific reasoning, although scientists do recognize that science interests the public (73%). Scientists believe that the public values the scientific profession to a lesser extent than suggested by public surveys: on a scale of 1-5, survey respondents rate their valuation of the scientific profession at 4.22, whereas scientists rate the public's valuation of the profession at 3.12, on average. Significant differences were detected between scientists' perceptions of how citizens are informed about science and what citizens report in surveys. The challenge for the future is to narrow this gap in order to help scientists gain a better understanding of the public and their interests and to make public engagement activities more effective.
PMCID:6853295
PMID: 31721768
ISSN: 1932-6203
CID: 4214342
