Good Health
Cumulative Effect of Retirement on Mortality
Shiro Furuya
Demography, October 2025, Pages 1523-1552
Abstract:
Prior research on the mortality effects of retirement has rarely been informative in the sense of finding a statistically significant effect. However, this does not necessarily indicate the absence of a mortality effect of retirement. While earlier studies assumed an instantaneous change in mortality risk upon retirement, the mortality effect of retirement may cumulatively evolve upon retirement. Using the Health and Retirement Study and fuzzy regression discontinuity and kink designs, I estimate mortality effects of retirement and retirement duration. Consistent with prior work, I find no evidence for a sudden jump in mortality risk at retirement. By contrast, I find that each additional year of retirement duration increases mortality risk by 0.9 percentage points, suggesting growing inequalities in mortality risk between retirees and counterfactual nonretirees. The positive, cumulative mortality effect of retirement at the Social Security eligibility age has important implications for an increase in the eligibility age, population health, and welfare programs to support older people in the United States.
SARS-CoV-2 mRNA vaccines sensitize tumours to immune checkpoint blockade
Adam Grippin et al.
Nature, forthcoming
Abstract:
Immune checkpoint inhibitors (ICIs) extend survival in many patients with cancer but are ineffective in patients without pre-existing immunity. Although personalized mRNA cancer vaccines sensitize tumours to ICIs by directing immune attacks against preselected antigens, personalized vaccines are limited by complex and time-intensive manufacturing processes. Here we show that mRNA vaccines targeting SARS-CoV-2 also sensitize tumours to ICIs. In preclinical models, SARS-CoV-2 mRNA vaccines led to a substantial increase in type I interferon, enabling innate immune cells to prime CD8+ T cells that target tumour-associated antigens. Concomitant ICI treatment is required for maximal efficacy in immunologically cold tumours, which respond by increasing PD-L1 expression. Similar correlates of vaccination response are found in humans, including increases in type I interferon, myeloid–lymphoid activation in healthy volunteers and PD-L1 expression on tumours. Moreover, receipt of SARS-CoV-2 mRNA vaccines within 100 days of initiating ICI is associated with significantly improved median and three-year overall survival in multiple large retrospective cohorts. This benefit is similar among patients with immunologically cold tumours. Together, these results demonstrate that clinically available mRNA vaccines targeting non-tumour-related antigens are potent immune modulators capable of sensitizing tumours to ICIs.
Heart Rate Variability Biofeedback for Substance Use Disorder: A Randomized Clinical Trial
David Eddie et al.
JAMA Psychiatry, forthcoming
Design, Setting, and Participants: This phase 2 randomized clinical trial included 8 weeks of outpatient treatment. Recruitment was conducted virtually across the US from February 2023 to June 2024. Treatment-seeking adults with SUD [substance use disorder] were randomized to receive HRVB [heart rate variability biofeedback] + treatment as usual (TAU) or TAU only.
Results: Of 260 individuals assessed for eligibility, 120 were randomized to receive HRVB + TAU or TAU only. Among study participants (69 female participants of 115 [60.0%]; mean [SD] age, 46.18 [11.59] years), HRVB was associated with significant reductions in negative affect (b, –0.01; z, –3.21; P = .001) and craving (b, –0.01; z, –4.60; P < .001) over 8 weeks. In contrast, the control group experienced increases in both negative affect and craving. No differences were observed for positive affect. HRVB was also associated with a significantly lower proportion of AOD [alcohol and other drug] use days (odds ratio [OR], 0.36; 95% credible interval [CrI], 0.25-0.54), representing a 64% reduction in AOD use compared to controls. Treatment condition moderated the within-person relationship between craving and later AOD use (OR, 0.84; 95% CrI, 0.73-0.97), such that those receiving HRVB were less likely to use AOD following craving (b, –0.18; 95% CrI, –0.32 to –0.03).
Federal Calorie Menu Labeling Policy and Calories Purchased in Restaurants in a National Fast Food Chain: A Quasi-Experimental Study
Pasquale Rummo et al.
American Journal of Preventive Medicine, January 2026
Methods: Using synthetic control methods, Taco Bell restaurants that implemented menu labels after nationwide labeling (n=5,060 restaurants) were matched to restaurants that added calorie labels to menus after local labeling legislation (and prior to nationwide labeling). The effect of menu labeling on calories purchased per transaction after nationwide labeling between groups (i.e., “later-treated” and “early-treated” restaurants) was estimated using a two-way fixed effects regression model, with time modeled as relative month from implementation and fixed effects for calendar month and restaurant.
Results: In the baseline period, average calories per transaction was 1,242 (SD=178) in the national menu labeling group and 1,245 (SD=183.9) in the comparison group, with parallel trends between groups. Difference-in-differences model results indicated that transactions from restaurants in the national menu labeling group included 7.4 (95% CI: 7.3, 7.5) more calories than was predicted based on the trend in the comparison group. Average number of total transactions per month decreased ∼2% more in the national menu labeling group relative to the comparison group.
Seasonal Allergies and Mental Health: Do Small Health Shocks Affect Suicidality?
Joelle Abramowitz, Shooshan Danagoulian & Owen Fleming
Journal of Health Economics, December 2025
Abstract:
Suicide rates increased 37% in the US from 2000 to 2018; while structural factors are extensively studied, short-term triggers remain less understood. We examine the impact of small exogenous shocks -- allergies triggered by seasonal pollen -- on suicides. Pollen allergies diminish cognitive function and disrupt sleep -- predictors of suicidality. Combining disparate datasets across 34 localities in the United States from 2006 to 2018, we use a specification with granular fixed effects to identify the effect of pollen on suicides from daily variation in each. We find that as pollen levels rise, the count of suicides in a county increases -- up to 7.4% more suicides when pollen levels at their highest levels. We find that individuals with a known mental health condition or treatment have 8.6% higher incidence of suicides on days with highest pollen. We also show that this effect is not spurious -- Google searches for allergy and depression symptoms increase substantively as pollen levels rise. These estimates are robust to multiple specifications. As climate change extends and intensifies the pollen season, we expect its impact to more than double the number of suicides by the end of the century. These results point toward the importance of relatively small exogenous shocks on suicidality and the potential for relatively inexpensive and routine health care measures such as allergy testing and treatment to improve mental health.
Paracetamol (N-acetyl-para-aminophenol) [acetaminophen/Tylenol] disrupts early embryogenesis by cell cycle inhibition
Brian Nielsen et al.
Human Reproduction, October 2025, Pages 1860-1876
Study Design, Size, Duration: To address the challenges in determining the mechanism of action and the effects of APAP [N-acetyl-para-aminophenol] during PID [pre-implantation development], we utilized a range of approaches, including in vitro, ex vivo, and in vivo methods across various models ranging from yeasts to human embryos and women of fertile age.
Participants/Materials, Setting, Methods: A total of 90 human embryos were exposed in vitro (22 cleavage stage and 68 blastocyst-stage embryos). Endometrial tissue and uterine fluid were collected from seven women as part of an endometrial scratching procedure. Follicular fluid was collected from 26 women during transvaginal ultrasound guided aspiration of the pre-ovulatory follicles. All human material was sampled in accordance with relevant guidelines and regulations with consent from the regional scientific ethical committee of the Capital Region of Denmark and signed informed patient consent given prior to donation. All mouse experiments were approved by the Danish Animal Experiments Inspectorate and under EU directive 2010/63/EU on the protection of animals used for scientific purposes. The cultivation of the human embryonic stem cell lines H1 and HUES4 was conducted in compliance with relevant guidelines and regulations, following approval from the regional scientific ethical committee of the Capital Region of Denmark.
Main Results and the Role of Chance: After exposure to APAP, we found an unequivocal repression of cell division across all used model systems. APAP exposure hindered cell cycle progression, likely by inhibiting ribonucleotide reductase, leading to reduced DNA synthesis and accumulation in the S-phase. At concentrations found in the reproductive system of women after standard dosing, APAP exposure decreased cell numbers in mouse and human cleavage-stage embryos or caused direct embryonic death. Similar exposure to mouse and human blastocyst-stage embryos resulted in a reduced inner cell mass and decreased DNA synthesis, respectively.
The Cook County Tax on Sweetened Beverages: The Impact on Purchases of its Announcement, Implementation, and Repeal
Felipe Lozano Rojas, John Cawley & David Frisvold
NBER Working Paper, October 2025
Abstract:
Taxes on sweetened beverages have been widely adopted in response to increases in diet-related chronic disease. An episode of particular interest occurred in Cook County, Illinois, where a beverage tax was announced, implemented, and then repealed. This paper is the first to estimate the effects of this tax using household-level data on purchases. We estimate difference-in-differences models that compare the change in beverage purchases over time in Cook County to that in comparison areas. The results indicate that consumer purchases did not detectably respond to the announcement of the tax. Implementation of the tax reduced purchases by 22.5% for all taxed beverages, 16.5% for high-calorie taxed beverages and a 33% for low-calorie (e.g. diet) taxed beverages. This implies a price elasticity of demand of -0.66 for all taxed beverages, -0.48 for high-calorie taxed beverages and -0.97 for low-calorie taxed beverages. The impact of the tax did not vary by household income, and there is no detectable impact of the tax on purchases of possible substitutes (bottled water, fruit juice, milk). After repeal of the tax, purchases of taxed beverages returned to their baseline quantities; there was no evidence of habit formation.
Evidence for improved DNA repair in long-lived bowhead whale
Denis Firsanov et al.
Nature, forthcoming
Abstract:
At more than 200 years, the maximum lifespan of the bowhead whale exceeds that of all other mammals. The bowhead is also the second-largest animal on Earth, reaching over 80,000 kg. Despite its very large number of cells and long lifespan, the bowhead is not highly cancer-prone, an incongruity termed Peto’s paradox. Here, to understand the mechanisms that underlie the cancer resistance of the bowhead whale, we examined the number of oncogenic hits required for malignant transformation of whale primary fibroblasts. Unexpectedly, bowhead whale fibroblasts required fewer oncogenic hits to undergo malignant transformation than human fibroblasts. However, bowhead whale cells exhibited enhanced DNA double-strand break repair capacity and fidelity, and lower mutation rates than cells of other mammals. We found the cold-inducible RNA-binding protein CIRBP to be highly expressed in bowhead fibroblasts and tissues. Bowhead whale CIRBP enhanced both non-homologous end joining and homologous recombination repair in human cells, reduced micronuclei formation, promoted DNA end protection, and stimulated end joining in vitro. CIRBP overexpression in Drosophila extended lifespan and improved resistance to irradiation. These findings provide evidence supporting the hypothesis that, rather than relying on additional tumour suppressor genes to prevent oncogenesis, the bowhead whale maintains genome integrity through enhanced DNA repair. This strategy, which does not eliminate damaged cells but faithfully repairs them, may be contributing to the exceptional longevity and low cancer incidence in the bowhead whale.
Genetic and Environmental Influences on Sweet Taste Liking and Related Traits: New Insights from Twin Cohorts
Rhiannon Armitage et al.
Behavior Genetics, September 2025, Pages 407-421
Abstract:
Reducing sugar intake is a key component of global health policies and dietary guidelines. However, individuals vary substantially in sweet-liking, commonly characterized by sweet-liking status (extreme sweet-likers, moderate sweet-likers, and sweet-dislikers), yet the heritability of these categories remains unexplored. Monozygotic and dizygotic twins from Finland (FinnTwin12; n = 468; 60% female, aged 21–24) and the UK (TwinsUK; n = 967; 90% female, aged 18–81) rated their liking and perceived intensity of a 20% (w/v) sucrose solution, reported their liking and consumption-frequency of food and beverages and completed additional behavioral, eating and personality measures. We estimated the contribution of additive genetic (A), nonadditive genetic (D), shared (C), and unshared environmental factors (E) in the variance and covariance of sweet-liking (defined ordinally through sweet-liking status and continuously) with related traits to see if they share similar proportions of genetic and environmental factors. Model-fitting indicated 30–48% of the variability in sweet-liking was attributed to (A) additive genetic factors and 52–70% to (E) environmental exposures not shared by siblings. Importantly, such AE models consistently fit best, regardless of sex, cohort, or sweet-liking assessment method. Broadly, correlations between sweet-liking and behavioral, eating, and personality measures were modest (–0.19 to 0.21), mostly positive and largely driven by shared genetic rather than environmental factors, with the strongest relationship seen for reported liking, consumption-frequency and craving for sweet foods. We demonstrate that unshared environment modulates individual differences in sweet-liking alongside a substantial genetic component that is partly shared with reported liking, consumption-frequency and craving for sweet foods.
Floss-based vaccination targets the gingival sulcus for mucosal and systemic immunization
Rohan Ingrole et al.
Nature Biomedical Engineering, forthcoming
Abstract:
The oral cavity is an accessible site for vaccination, but its sublingual and buccal sites have limited vaccine uptake. Here we show that flat tape dental floss can deliver vaccines through the junctional epithelium of the gingival sulcus, exploiting its naturally leaky properties. Floss-based vaccination delivered protein, inactivated virus, peptide-presenting immunogenic nanoparticles and messenger RNA. In mice, gold nanoparticles functionalized with a peptide derived from the ectodomain of the transmembrane matrix 2 protein of human influenza virus stimulated local lymph nodes, increased CD4+T cells in lymph nodes, lungs and spleen, and boosted antibody-secreting cells in the bone marrow. Floss-based immunization induced strong and sustained immune activation across multiple organs, robust systemic and mucosal antibody responses, and durable protection against lethal influenza infection, independent of age, food and liquid consumption. Floss-based vaccination was superior to sublingual and comparable with intranasal vaccination. In human participants, fluorescent dye delivered via floss picks effectively reached gingival sulcus, supporting clinical feasibility. These findings establish floss-based vaccination as a simple, needle-free strategy that enhances vaccine delivery and immune activation compared with existing mucosal immunization methods.