Cohort Profile: Better Health in Late Life.

Purpose: Humans are living longer and may develop multiple chronic diseases in later life. The Better Health in Late Life cohort study aims to improve our understanding of the risks and outcomes of multimorbidity in the Danish population. Methods: A randomly-selected sample of Danish residents who were 50-65 years of age received a questionnaire and an invitation to participate in this study. Respondents completed an online survey between October 2021 and January 2022 which addressed topics that included self-assessed health, mental health, sleep, specific medical conditions, use of painkillers, diet, alcohol consumption, smoking, physical activity, and body composition. This information was linked to the Danish health and social registries (some established in 1943 and onwards) that maintain data on filled prescriptions, hospital records, socioeconomic status, and health care utilization. Results: Responses were received from 115,431 of the 301,244 residents invited to participate (38%). We excluded respondents who answered none of the questions as well as those who provided no information on sex or indicated an age other than 50-65 years. Of the 114,283 eligible respondents, 54.8% were female, 30.3% were overweight, and 16.7% were obese. Most participants reported a weekly alcohol consumption of less than seven units and 13.3% were current smokers; 5.2% had a history of hospitalization for solid cancer, and 3.0%, 2.3%, 2.0%, and 0.9% reported chronic pulmonary disease, diabetes, stroke, and myocardial infarction, respectively. The most frequently filled prescriptions were for medications used to treat the nervous system and cardiovascular diseases (38.1% and 37.4%, respectively).

Feasibility of salivary DNA collection in a population-based case-control study: a pilot study of pediatric Crohn's disease.

BACKGROUND: Epidemiologic studies combining exposure and outcome data with the collection of biosamples are needed to study gene-environment interactions that might contribute to the etiology of complex diseases such as pediatric Crohn's disease (CD). Nationwide registries, including those in Denmark and other Scandinavian countries, provide efficient and reliable sources of data for epidemiological studies evaluating the environmental determinants of disease. We performed a pilot study to test the feasibility of collecting salivary DNA to augment registry data in established cases of pediatric CD and randomly selected, population-based controls. SUBJECTS AND METHODS: Cases of CD born after 1995 and residing in the central region of Denmark were identified through the Danish National Patient Registry and confirmed by using standard diagnostic criteria. Age- and gender-matched controls were selected at random through the civil registration system. Cases and controls were contacted by mail and telephone and invited to submit a saliva sample. DNA was extracted and genotyped for six CD-associated single-nucleotide polymorphisms (SNPs). RESULTS: A total of 53 cases of pediatric CD were invited, and 40 contributed a saliva sample (75% response rate). A total of 126 controls were invited, and 54 contributed a saliva sample (44% response rate). As expected, demographic characteristics did not differ between cases and controls. DNA was successfully isolated from 93 of 94 samples. Genotyping was performed with only 2% undetermined genotypes. For five of six SNPs known to be associated with CD, risk allele frequencies were higher in cases than controls. CONCLUSION: This pilot study strongly supports the feasibility of augmenting traditional epidemiological data from Danish population-based registries with the de novo collection of genetic information from population-based cases and controls. This will facilitate rigorous studies of gene-environment interactions in complex chronic conditions such as CD.

Costs and Efficiency of Online and Offline Recruitment Methods: A Web-Based Cohort Study.

BACKGROUND: The Internet is widely used to conduct research studies on health issues. Many different methods are used to recruit participants for such studies, but little is known about how various recruitment methods compare in terms of efficiency and costs. OBJECTIVE: The aim of our study was to compare online and offline recruitment methods for Internet-based studies in terms of efficiency (number of recruited participants) and costs per participant. METHODS: We employed several online and offline recruitment methods to enroll 18- to 45-year-old women in an Internet-based Danish prospective cohort study on fertility. Offline methods included press releases, posters, and flyers. Online methods comprised advertisements placed on five different websites, including Facebook and Netdoktor.dk. We defined seven categories of mutually exclusive recruitment methods and used electronic tracking via unique Uniform Resource Locator (URL) and self-reported data to identify the recruitment method for each participant. For each method, we calculated the average cost per participant and efficiency, that is, the total number of recruited participants. RESULTS: We recruited 8252 study participants. Of these, 534 were excluded as they could not be assigned to a specific recruitment method. The final study population included 7724 participants, of whom 803 (10.4%) were recruited by offline methods, 3985 (51.6%) by online methods, 2382 (30.8%) by online methods not initiated by us, and 554 (7.2%) by other methods. Overall, the average cost per participant was €6.22 for online methods initiated by us versus €9.06 for offline methods. Costs per participant ranged from €2.74 to €105.53 for online methods and from €0 to €67.50 for offline methods. Lowest average costs per participant were for those recruited from Netdoktor.dk (€2.99) and from Facebook (€3.44). CONCLUSIONS: In our Internet-based cohort study, online recruitment methods were superior to offline methods in terms of efficiency (total number of participants enrolled). The average cost per recruited participant was also lower for online than for offline methods, although costs varied greatly among both online and offline recruitment methods. We observed a decrease in the efficiency of some online recruitment methods over time, suggesting that it may be optimal to adopt multiple online methods.

In vitro toxicity of cationic micelles and liposomes in cultured human hepatocyte (HepG2) and lung epithelial (A549) cell lines.

The aim of this study was to compare the effects of cationic micelle and liposome drug delivery systems on liver and lung cells in a toxicological in vitro screening model, with observations on cytotoxicity and genotoxicity. A screening battery was established for assessment of a broad range of parameters related to adverse effects. Clear concentration response effects were observed related to impairment of mitochondrial function, membrane integrity and oxidative stress markers, but no effect was observed on genotoxicity. The adverse effects were highest for the liposomes. The High Content Screening seems optimal for initial screening of adverse effects, and combined with standard cytotoxicity measurements initial screening can be performed for predictive toxicological screening.

Using a physics experiment in a lecture setting to engage biology students with the concepts of Poiseuille's law.

Biology students enrolled in a typical undergraduate physiology course encounter Poiseuille's law, a physics equation that describes the properties governing the flow of blood through the circulation. According to the equation, a small change in vessel radius has an exponential effect on resistance, resulting in a larger than expected change in blood flow. To help engage students in this important concept, we performed a physics experiment as a lecture demonstration to mimic the original research by the 19th-century French scientist. We tested its impact as a research project and found that students who viewed the demonstration reacted very positively and showed an immediate increase in test performance, while the control group was able to independently "catch up" at the fourth week posttest. We further examined whether students' math skills mapped to learning gains. The students with lower math scores who viewed the demonstration had slightly more improvement in test performance than those students who did not view the demonstration. Our data suggest that watching a lecture demonstration may be of even greater benefit to biology students with lower math achievement.

Transient activation of mTOR following forced treadmill exercise in rats.

The beneficial effect of exercise on hippocampal plasticity is possibly mediated by increased angiogenesis and neurogenesis. In angiogenesis, insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), and hypoxia-inducible factor 1, alpha subunit (HIF1α) are important factors, while the induction of neurogenesis requires signaling through the VEGF receptor, Flk-1 (VEGFR-2). VEGF expression is believed to be regulated by two distinct mTOR (mammalian target of Rapamycin)-containing multiprotein complexes mTORC1 and mTORC2, respectively. This study was initiated to investigate the effect of exercise on the expression of VEGF, cognate receptors, HIF1α, mTORC1, and mTORC2 in hippocampus and frontal cortex. To this end, we measured messenger RNA (mRNA) levels in rat brain using quantitative real-time polymerase chain reaction (real-time qPCR) after forced treadmill exercise for 1 day, 2 weeks, and 8 weeks. Rats were euthanized either immediately (0 h) or 24 h after last exercise session. Here, we show that exercise affected mRNA levels of VEGF, VEGFR2, and the coreceptor neuropilin 2 (NRP2) when the rats were euthanized immediately, whereas at 24 h only the expression of mTOR was regulated after a single bout of exercise. In conclusion, the effect of treadmill exercise on the VEGF system is acute rather than chronic and there is a transient activation of mTOR. More studies are needed to understand whether this could be beneficial in the treatment of neuropsychiatric disorders.

Caffeinated beverage and soda consumption and time to pregnancy.

BACKGROUND: Many epidemiologic studies have evaluated the association between caffeine and fertility, with inconsistent results. Some studies suggest that various caffeine-containing beverages may affect fertility differently. METHODS: We evaluated the relation of caffeine, coffee, tea, and sodas with time to pregnancy in a prospective cohort study of 3628 women planning a pregnancy, in Denmark (2007-2010). Women reported beverage intake at baseline and every 8 weeks during follow-up until they became pregnant or for up to 12 cycles. We used discrete-time Cox proportional hazards regression to estimate fecundability ratios (FRs) and 95% confidence intervals (CIs), controlling for potential confounders. RESULTS: There was little relation between fecundability and caffeine intake of 300+ mg/day compared with < 100 mg/day (FR = 1.04 [95% CI = 0.90-1.21]) or coffee intake of 3+ servings/day compared with none (1.05 [0.85-1.33]). Soda consumption was associated with reduced fecundability: for all types of sodas combined, the adjusted FRs were 0.89 (0.80-0.98), 0.85 (0.71-1.02), 0.84 (0.57-1.25), and 0.48 (0.21-1.13) for < 1, 1, 2, and 3+ servings per day, respectively, compared with none. Tea drinking was associated with a slight increase in fecundability, with FR = 1.27 (0.98-1.64) for 2+ servings/day versus none. CONCLUSION: In this prospective study of time to pregnancy, the association between caffeine intake and fertility differed by beverage type. Although we controlled for many confounders, our findings of reduced fecundability among soda drinkers and increased fecundability among tea drinkers could have resulted from confounding by unmeasured lifestyle characteristics.

A successful implementation of e-epidemiology: the Danish pregnancy planning study 'Snart-Gravid'.

The attraction of being able to use the internet for the recruitment of an epidemiologic cohort stems mainly from cost efficiency and convenience. The pregnancy planning study ('Snart-Gravid')-a prospective cohort study of Danish women planning a pregnancy-was conducted to evaluate the feasibility and cost efficiency of using internet-based recruitment and follow-up. Feasibility was assessed by examining patient accrual data over time, questionnaire-specific response rates and losses to follow-up. The relative cost efficiency was examined by comparing the study costs with those of an alternative non internet-based study approach. The target recruitment of 2,500 participants over 6 months was achieved using advertisements on a health-related website, supported by a coordinated media strategy at study initiation. Questionnaire cycle-specific response rates ranged from 87 to 90% over the 12-month follow-up. At 6 months, 87% of women had a known outcome or were still under follow-up; at 12 months the figure was 82%. The study cost of $400,000 ($160 per enrolled subject) compared favorably with the estimated cost to conduct the same study using a conventional non-internet based approach ($322 per subject). The gain in efficiency with the internet-based approach appeared to be even more substantial with longer follow-up and larger study sizes. The successful conduct of this pilot study suggests that the internet may be a useful tool to recruit and follow subjects in prospective cohort studies.

Environmental correlates of population differentiation in Atlantic herring.

The marine environment is characterized by few physical barriers, and pelagic fishes commonly show high migratory potential and low, albeit in some cases statistically significant, levels of genetic divergence in neutral genetic marker analyses. However, it is not clear whether low levels of differentiation reflect spatially separated populations experiencing gene flow or shallow population histories coupled with limited random genetic drift in large, demographically isolated populations undergoing independent evolutionary processes. Using information for nine microsatellite loci in a total of 1951 fish, we analyzed genetic differentiation among Atlantic herring from eleven spawning locations distributed along a longitudinal gradient from the North Sea to the Western Baltic. Overall genetic differentiation was low (theta = 0.008) but statistically significant. The area is characterized by a dramatic shift in hydrography from the highly saline and temperature stable North Sea to the brackish Baltic Sea, where temperatures show high annual variation. We used two different methods, a novel computational geometric approach and partial Mantel correlation analysis coupled with detailed environmental information from spawning locations to show that patterns of reproductive isolation covaried with salinity differences among spawning locations, independent of their geographical distance. We show that reproductive isolation can be maintained in marine fish populations exhibiting substantial mixing during larval and adult life stages. Analyses incorporating genetic, spatial, and environmental parameters indicated that isolating mechanisms are associated with the specific salinity conditions on spawning locations.