Fit bits
Dietary salt promotes cognitive impairment through tau phosphorylation
Giuseppe Faraco et al.
Nature, 31 October 2019, Pages 686-690
Abstract:
Dietary habits and vascular risk factors promote both Alzheimer's disease and cognitive impairment caused by vascular factors. Furthermore, accumulation of hyperphosphorylated tau, a microtubule-associated protein and a hallmark of Alzheimer's pathology, is also linked to vascular cognitive impairment. In mice, a salt-rich diet leads to cognitive dysfunction associated with a nitric oxide deficit in cerebral endothelial cells and cerebral hypoperfusion. Here we report that dietary salt induces hyperphosphorylation of tau followed by cognitive dysfunction in mice, and that these effects are prevented by restoring endothelial nitric oxide production. The nitric oxide deficiency reduces neuronal calpain nitrosylation and results in enzyme activation, which, in turn, leads to tau phosphorylation by activating cyclin-dependent kinase 5. Salt-induced cognitive impairment is not observed in tau-null mice or in mice treated with anti-tau antibodies, despite persistent cerebral hypoperfusion and neurovascular dysfunction. These findings identify a causal link between dietary salt, endothelial dysfunction and tau pathology, independent of haemodynamic insufficiency. Avoidance of excessive salt intake and maintenance of vascular health may help to stave off the vascular and neurodegenerative pathologies that underlie dementia in the elderly.
The Effects of Prenatal Exposure to Seasonal Influenza on Life Course Outcomes in the United States
Julia Dennett
Harvard Working Paper, November 2019
Abstract:
Seasonal influenza is a common infectious disease that jeopardizes the health of pregnant women. Prenatal exposure to the flu likely disturbs fetal development and harms health at birth, but long run effects have been difficult to identify. I investigate the impact of in utero exposure to seasonal influenza over the life course in the U.S. by exploiting state and time variation in influenza-related mortality, a proxy for disease severity in the local environment. I first show adverse effects on birth weight and an increased risk of heart malformations, and then evaluate impacts on long term outcomes. Exposure to seasonal influenza while in utero increases disability and decreases childhood school attendance, adult high school completion, and labor force participation. I examine implications for influenza vaccination as a policy intervention and find that historical vaccine uptake accounted for economically meaningful improvements in life course outcomes. Furthermore, my estimates suggest substantial returns to future reductions in flu exposure due to vaccination expansions, including 10,000 fewer infants born each year with low birth weight, 54,000 more workers in the labor force, and 34,000 more adults without a disability.
Measles virus infection diminishes preexisting antibodies that offer protection from other pathogens
Michael Mina et al.
Science, 1 November 2019, Pages 599-606
Abstract:
Measles virus is directly responsible for more than 100,000 deaths yearly. Epidemiological studies have associated measles with increased morbidity and mortality for years after infection, but the reasons why are poorly understood. Measles virus infects immune cells, causing acute immune suppression. To identify and quantify long-term effects of measles on the immune system, we used VirScan, an assay that tracks antibodies to thousands of pathogen epitopes in blood. We studied 77 unvaccinated children before and 2 months after natural measles virus infection. Measles caused elimination of 11 to 73% of the antibody repertoire across individuals. Recovery of antibodies was detected after natural reexposure to pathogens. Notably, these immune system effects were not observed in infants vaccinated against MMR (measles, mumps, and rubella), but were confirmed in measles-infected macaques. The reduction in humoral immune memory after measles infection generates potential vulnerability to future infections, underscoring the need for widespread vaccination.
Analgesic use at ovulation and implantation and human fertility
Anne Marie Jukic et al.
American Journal of Obstetrics and Gynecology, forthcoming
Study Design: We analyzed data from a prospective cohort study of women between 30 to 44 years of age who were trying to conceive naturally from 2008-2015. Using daily diaries, medication usage was classified as acetaminophen, aspirin, or non-aspirin nonsteroidal anti-inflammatory drug (NSAID), during four time periods of interest - pre-ovulatory, peri-ovulatory and implantation - as well as the overall non-menstrual bleeding days of the cycle. Menstrual cycles during the prospective attempt to become pregnant were enumerated using daily diary menstrual bleeding information. Conception was defined as a positive home pregnancy test. Discrete time fecundability models were used to estimate the fecundability ratio (FR) and 95% confidence interval (CI) in each of the four time windows of interest and for each pain reliever (aspirin use, non-aspirin NSAID use, acetaminophen) compared with no medication use, after adjustment for several covariates including age, race, education, body mass index, alcohol and caffeine use, frequency of intercourse, and a history of migraines or uterine fibroids.
Results: Medication use was infrequent in the 858 women and 2366 cycles in this analysis. Use of non-aspirin NSAIDs or acetaminophen were not associated with fecundability in any of the time windows of interest. Although the sample size was small, aspirin use during the implantation window was associated with increased fecundability (adjusted FR(CI): 2.05 (1.23, 3.41). This association remained when limiting the analysis to cycles with minimal missing data or when adjusting for gravidity. None of the other medications were associated with fecundability.
Screening Human Embryos for Polygenic Traits Has Limited Utility
Ehud Karavani et al.
Cell, forthcoming
Abstract:
The increasing proportion of variance in human complex traits explained by polygenic scores, along with progress in preimplantation genetic diagnosis, suggests the possibility of screening embryos for traits such as height or cognitive ability. However, the expected outcomes of embryo screening are unclear, which undermines discussion of associated ethical concerns. Here, we use theory, simulations, and real data to evaluate the potential gain of embryo screening, defined as the difference in trait value between the top-scoring embryo and the average embryo. The gain increases very slowly with the number of embryos but more rapidly with the variance explained by the score. Given current technology, the average gain due to screening would be ?2.5 cm for height and ?2.5 IQ points for cognitive ability. These mean values are accompanied by wide prediction intervals, and indeed, in large nuclear families, the majority of children top-scoring for height are not the tallest.
Adolescents' and Parents' Genomic Testing Decisions: Associations With Age, Race, and Sex
Melanie Myer, Lisa Martin & Cynthia Prows
Journal of Adolescent Health, forthcoming
Methods: Adolescents aged between 13 and 17 years and a parent (dyads) were recruited through flyers, social media, employee emails, and clinic visits at a pediatric hospital. Dyads used a decision tool to independently choose the categories of conditions they wanted to learn about the adolescent. They then came together to discuss their independent decisions and make final joint decisions. Conditions were categorized by preventability, treatability, adult-onset conditions, and carrier status. Participants could make granular choices by including or excluding conditions in each category. Categorical choices were collapsed into the "aggregate choice" to learn all or not all results.
Results: Study visits were completed by 163 dyads. Adolescents were less likely than their parents to independently choose to learn all results (64.4% vs. 76.1%; p = .0056). Parents were less likely to independently choose to learn all results for their daughters than their sons (odds ratio = .41, 95% confidence interval .18-.96; p = .032). Black adolescents were less likely to independently choose to learn all results than white adolescents (odds ratio = .22; 95% confidence interval .08-.55; p = .0015). After making joint decisions, 70.6% of dyads chose to learn all results.