Pharmaco-Epidemiological Studies on Antidepressant Use in Older Adults

__Abstract__ With the increasing number of patients using antidepressants, the number of patients at risk to develop antidepressant-associated adverse drug reactions is also increasing. However, there were not much studies conducted on antidepressant safety in older adults, although older adults are of special interest due to there more frequent use of multiple concomitant drugs and more comorbidities. In this thesis, we describe that, also in Dutch primary care, antidepressants are more often prescribed between 1996 and 2012. However, antidepressants were less frequently prescribed for depression and more for other indications, such as neuropathic pain and anxiety complaints. In the Rotterdam Study, a population cohort study, we described that the use of Selective Serotonin Reuptake Inhi

Multi-ancestry sleep-by-SNP interaction analysis in 126,926 individuals reveals lipid loci stratified by sleep duration

Both short and long sleep are associated with an adverse lipid profile, likely through different biological pathways. To elucidate the biology of sleep-associated adverse lipid profile, we conduct multi-ancestry genome-wide sleep-SNP interaction analyses on three lipid traits (HDL-c, LDL-c and triglycerides). In the total study sample (discovery + replication) of 126,926 individuals from 5 different ancestry groups, when considering either long or short total sleep time interactions in joint analyses, we identify 49 previously unreported lipid loci, and 10 additional previously unreported lipid loci in a restricted sample of European-ancestry cohorts. In addition, we identify new gene-sleep interactions for known lipid loci such as LPL and PCSK9. The previously unreported lipid loci have a modest explained variance in lipid levels: most notable, gene-short-sleep interactions explain 4.25% of the variance in triglyceride level. Collectively, these findings contribute to our understanding of the biological mechanisms involved in sleep-associated adverse lipid profiles

Aktivitas Anti Obesitas Ekstrak Daun Tin (Ficus carica Linn) pada Tikus yang diberi Diet Lemak Tinggi

Obesity is a health problem in the community because it can cause a risk of degenerative diseases such as type 2 diabetes mellitus, high blood pressure, heart disease, cancer, and atherosclerosis. Unhealthy lifestyles such as lack of physical activity by exercising, a diet high in carbohydrates and fats, can cause fat deposits in the body, especially in the abdomen. The use of chemical drugs such as Orlistat as a weight loss or to help reduce the risk of regaining lost weight, is less effective because it requires a long consumption time and the presence of side effects. Tin leaf content (Ficus carica Linn) is flavonoids, alkaloids, tannins and steroids, tin leaf extract has IC50 150mg/L antioxidant activity. This study was to determine the anti-obesity activity of tin leaf extract in male Sprague-Dawley rats given a high fat diet. 30 Sprague-Dawley rats were classified into 6 groups. The results obtained, in the group dose of 100 mg / kg obtained an average body weight of 381.8 grams, the test group 200 mg / kg obtained an average body weight of 414.5 grams, in the test group 400 mg / kg obtained 387 grams. The conclusion of this study is that the activity of Tin leaf extract (Ficus carica Linn) can be used as an anti-obesity.Kegemukan merupakan masalah kesehatan di masyarakat karena dapat menyebabkan resiko penyakit degeneratif seperti diabetes militus tipe 2, tekanan darah tinggi, jantung, kanker, dan aterosklerosis. Gaya hidup yang tidak sehat seperti kurangnya aktivitas fisik dengan berolahraga, diet tinggi karbohidrat dan lemak, dapat menimbulkan timbunan lemak didalam tubuh terutama pada abdomen. Penggunaan obat kimia seperti Orlistat sebagai penurun berat badan atau untuk membantu mengurangi risiko mendapatkan kembali berat badan yang sudah hilang, kurang efektif karena memerlukan waktu konsumsi yang lama dan adanya efek samping. Kandungan daun Tin (Ficus carica Linn) adalah flavonoid, alkaloid, tanin dan steroid, ekstrak daun timah memiliki aktivitas antioksidan IC50 150mg/L. Penelitian ini untuk mengetahui aktivitas anti obesitas ekstrak daun tin pada tikus Sprague-Dawley jantan yang diberikan diet lemak tinggi. 30 tikus Sprague-Dawley diklasifikasikan ke dalam 6 kelompok. Hasil yang diperoleh, pada kelompok dosis 100 mg / kg diperoleh berat badan rata-rata 381,8 gram, kelompok uji 200 mg / kg diperoleh berat badan rata-rata 414,5 gram, pada kelompok uji 400 mg / kg diperoleh 387 gram. Kesimpulan dari penelitian ini adalah aktivitas ekstrak daun Tin (Ficus carica Linn) dapat digunakan sebagai anti-obesitas

Antioxidant Supplementation in Oxidative Stress-Related Diseases: What Have We Learned from Studies on Alpha-Tocopherol?

Oxidative stress has been proposed as a key contributor to lifestyle- and age-related diseases. Because free radicals play an important role in various processes such as immune responses and cellular signaling, the body possesses an arsenal of different enzymatic and non-enzymatic antioxidant defense mechanisms. Oxidative stress is, among others, the result of an imbalance between the production of various reactive oxygen species (ROS) and antioxidant defense mechanisms including vitamin E (α-tocopherol) as a non-enzymatic antioxidant. Dietary vitamins, such as vitamin C and E, can also be taken in as supplements. It has been postulated that increasing antioxidant levels through supplementation may delay and/or ameliorate outcomes of lifestyle- and age-related diseases that have been linked to oxidative stress. Although supported by many animal experiments and observational studies, randomized clinical trials in humans have failed to demonstrate any clinical benefit from antioxidant supplementation. Nevertheless, possible explanations for this discrepancy remain underreported. This review aims to provide an overview of recent developments and novel research techniques used to clarify the existing controversy on the benefits of antioxidant supplementation in health and disease, focusing on α-tocopherol as antioxidant. Based on the currently available literature, we propose that examining the difference between antioxidant activity and capacity, by considering the catabolism of antioxidants, will provide crucial knowledge on the preventative and therapeutical use of antioxidant supplementation in oxidative stress-related diseases

Telomere length and metabolic syndrome traits: a Mendelian randomisation study

Observational studies have revealed associations between short leucocyte telomere length (LTL), a TL marker in somatic tissues and multiple Metabolic Syndrome (MetS) traits. Animal studies have supported these findings by showing that increased telomere attrition leads to adipose tissue dysfunction and insulin resistance. We investigated the associations between genetically instrumented LTL and MetS traits using Mendelian Randomisation (MR). Fifty-two independent variants identified at FDR<0.05 from a genome-wide association study (GWAS) including 78,592 Europeans and collectively accounting for 2.93% of LTL variance were selected as genetic instruments for LTL. Summary-level data for MetS traits and for the MetS as a binary phenotype were obtained from the largest publicly available GWAS and two-sample MR analyses were used to estimate the associations of LTL with these traits. The combined effect of the genetic instruments was modelled using inverse variance weighted regression and sensitivity analyses with MR-Egger, weighted-median and MR-PRESSO were performed to test for and correct horizonal pleiotropy. Genetically instrumented longer LTL was associated with higher waist-to-hip ratio adjusted for body mass index (beta = 0.045 SD, SE = 0.018, p = 0.01), raised systolic (beta = 1.529 mmHg, SE = 0.332, p = 4x10(-6)) and diastolic (beta = 0.633 mmHg, SE = 0.222, p = 0.004) blood pressure, and increased MetS risk (OR = 1.133, 95% CI 1.057-1.215). Consistent results were obtained in sensitivity analyses, which provided no evidence of unbalanced horizontal pleiotropy. Telomere shortening might not be a major driver of cellular senescence and dysfunction in human adipose tissue. Future experimental studies should examine the mechanistic bases for the links between longer LTL and increased upper-body fat distribution and raised blood pressure.Pathophysiology, epidemiology and therapy of agein

Subtraction of Bright Point Sources from Synthesis Images of the Epoch of Reionization

Bright point sources associated with extragalactic AGN and radio galaxies are an important foreground for low frequency radio experiments aimed at detecting the redshifted 21cm emission from neutral hydrogen during the epoch of reionization. The frequency dependence of the synthesized beam implies that the sidelobes of these sources will move across the field of view as a function of observing frequency, hence frustrating line-of-sight foreground subtraction techniques. We describe a method for subtracting these point sources from dirty maps produced by an instrument such as the MWA. This technique combines matched filters with an iterative centroiding scheme to locate and characterize point sources in the presence of a diffuse background. Simulations show that this technique can improve the dynamic range of EOR maps by 2-3 orders of magnitude.Comment: 11 pages, 8 figures, 1 table, submitted to PAS

Both low circulating insulin-like growth factor-1 and high-density lipoprotein cholesterol are associated with hair loss in middle-aged women.

YesBackground: Multiple biomarkers have been associated with hair loss in women, but studies showed inconsistent results. Objective: We investigated the association between markers of cardiovascular disease risk (e.g., serum lipid levels and hypertension) and aging (e.g., 25-hydroxyvitamin D and insulin-like growth factor) with hair loss in a population of middle-aged women. Methods: In a random subgroup of 323 middle-aged women (mean age: 61.5 years) from the Leiden Longevity Study, hair loss was graded by three assessors using the Sinclair scale; women with a mean score higher than 1.5 were classified as cases with hair loss. Results: Every standard deviation increase in HDL cholesterol was associated with a 0.65 times lower risk (95% confidence interval [CI]: 0.46–0.91) of hair loss; for IGF-1 the risk was 0.68 times lower (95% CI: 0.48–0.97) per standard deviation increase, independent of the other studied variables. Women with both IGF-1 and HDL cholesterol levels below the median of the study population had a 3.47 times higher risk (95% CI: 1.30–9.25) of having hair loss. Limitations: The observational setting limits causal inference of the findings. Conclusion: Low HDL cholesterol and IGF-1 were associated with a higher risk of hair loss in women.This study was funded by the Innovation Oriented Research Program on Genomics (SenterNovem; IGE01014 and IGE5007), the Centre for Medical Systems Biology (CMSB), the Netherlands Genomics Initiative/Netherlands Organization for Scientific Research (05040202 and 050-060-810, NCHA), Unilever PLC and the European Union-funded Network of Excellence Lifespan (FP6 036894)

Use of antidepressants and the risk of myocardial infarction in middle-aged and older adults: A matched case-control study

Purpose: Antidepressants, specifically selective serotonin reuptake-inhibiting antidepressants (SSRIs), decrease platelet activation and aggregation in in vitro experiments and could therefore decrease the risk of myocardial infarction (MI). However, prior studies addressing this hypothesis showed contradictory results. Our purpose was to investigate the association between the use of any antidepressant drug and incident MI among middle-aged and older adults. Methods: We embedded a case-control study in the prospective Rotterdam Study (1991-2011). Controls were matched to MI cases based on sex and age at the same calendar date, and confounding factors were taken into account as time-varying covariates. The relative risk of MI during current and past use of an antidepressant was analyzed with conditional logistic regression with never use of antidepressant dr

Single-collision scattering of keV-energy Kr ions off a polycrystalline Cu surface

In the keV-energy regime, the scattering of krypton ions off a copper sample has been studied. In addition to the broad energy spectrum arising from multiple-collision scattering, the energy distributions of the backscattered ions exhibit prominent peaks at energies where single-collision (SC) scattering peaks are expected. Such SC peaks were shown to be absent in Sn – Mo/Ru scattering, systems of similar mass ratio and thus similar kinetics. The present Kr on Cu results allow for a comparison to a simulation package as SRIM. An important difference found between the present experiment and the predictions of SRIM is that the SC contribution is observed to decrease with scattering angle, whereas SRIM predicts this contribution to be constant. The intensity of the experimental SC peaks, though much weaker than in the SRIM simulations, may be used as markers to improve SRIM in its description of low-energy heavy particle scattering off surfaces

Diet-derived circulating antioxidants and risk of coronary heart disease a Mendelian randomization study

BACKGROUND Previously, observational studies have identified associations between higher levels of dietary-derived antioxidants and lower risk of coronary heart disease (CHD), whereas randomized clinical trials showed no reduction in CHD risk following antioxidant supplementation.OBJECTIVES The purpose of this study was to investigate possible causal associations between dietary-derived circulating antioxidants and primary CHD risk using 2-sample Mendelian randomization (MR).METHODS Single-nucleotide polymorphisms for circulating antioxidants (vitamins E and C, retinol, 13-carotene, and lycopene), assessed as absolute levels and metabolites, were retrieved from the published data and were used as genetic instrumental variables. Summary statistics for gene-CHD associations were obtained from 3 databases: the CARDIoGRAMplusC4D consortium (60,801 cases; 123,504 control subjects), UK Biobank (25,306 cases; 462,011 control subjects), and FinnGen study (7,123 cases; 89,376 control subjects). For each exposure, MR analyses were performed per outcome database and were subsequently meta-analyzed.RESULTS Among an analytic sample of 768,121 individuals (93,230 cases), genetically predicted circulating antioxidants were not causally associated with CHD risk. For absolute antioxidants, the odds ratio for CHD ranged between 0.94 (95% confidence interval [CI]: 0.63 to 1.41) for retinol and 1.03 (95% CI: 0.97 to 1.10) for 13-carotene per unit increase in ln-transformed antioxidant values. For metabolites, the odds ratio ranged between 0.93 (95% CI: 0.82 to 1.06) for g-tocopherol and 1.01 (95% CI: 0.95 to 1.08) for ascorbate per 10-fold increase in metabolite levels.CONCLUSIONS Evidence from our study did not support a protective effect of genetic predisposition to high dietaryderived antioxidant levels on CHD risk. Therefore, it is unlikely that taking antioxidants to increase blood antioxidants levels will have a clinical benefit for the prevention of primary CHD. (C) 2021 by the American College of Cardiology Foundation.Clinical epidemiolog