Well-being in healthy Icelandic women varies with extreme seasonality in ambient light.

Seasonal variation in photoperiod may affect psychosocial and physical well-being in healthy persons. We tested this hypothesis in healthy pre-menopausal women, without a history of mood disorders, living year-round in Reykjavik, Iceland (64.1°N). Participants reported daily self-assessments of well-being throughout a complete ovulatory menstrual cycle in summer and/or winter (70% participated in both seasons). Scores for mood, cognitive acuity, social support, physical health and a composite of these four indicators were each significantly higher in summer than in winter (linear mixed effects models: p < .001 for each model); tiredness did not differ by season. The effect of season was not significantly changed by inclusion of body mass index and/or age as covariates. Some prior studies have been hampered by sparse time sampling, inattention to covariates and/or relying on recalled data. This is to our knowledge the first investigation to test the study hypothesis with daily real-time data spanning complete ovulatory menstrual cycles in each of two seasons. This dense sampling has revealed modest seasonal variation in well-being in healthy women. Daylength (sunlight exposure) is likely a major, but not necessarily sole, factor in these seasonal differences in well-being; temperature is likely less important given Iceland's relatively moderate (for its high latitude) seasonal temperature swings.

Menstrual Cycle Characteristics of U. S. Adolescents According to Gynecologic Age and Age at Menarche.

STUDY OBJECTIVE: To characterize typical menstrual cycle characteristics in adolescents and determine how these differ with age at menarche or years since menarche (gynecologic age). METHODS: We surveyed 13 to 18-year-old U.S. users of the Clue app (N = 6,486) and linked their responses to app-recorded cycle data (N=38,916 cycles). We analyzed cycle characteristics including cycle length, cycle variability, period length, experience of heavy flow, and dysmenorrhea in relation to gynecologic age and menarcheal age using mixed effects models. RESULTS: With increasing gynecologic age, we observed dose-dependent associations of lower odds of cycle irregularity (defined as cycles that were highly variable, short, or long) and higher odds of reporting ≥1 day of heavy flow. Individuals <1 year post-menarche had lower odds of heavy flow (Odds Ratio (OR) = 0.3; 95% confidence interval (CI): 0.1, 0.6), and increased odds of having a highly variable cycle (OR = 2.6; 95% CI: 1.3, 5.2) or short cycles (OR = 5.0; 95% CI: 2.3, 11.0) compared to those who were 6+ years post-menarche. We also found associations with early and late age at menarche. Compared to menarcheal age of 14+ years, menarcheal age ≤10 years was associated with shorter cycle length (ß = -1.63 days; 95% CI: -2.51, -0.75), increased odds of dysmenorrhea (OR = 3.2; 95% CI: 2.3, 4.6), and decreased odds of high cycle variability (OR = 0.8; 95% CI: 0.6, 1.0). CONCLUSION: Cycle characteristics in adolescence are associated with menarcheal age and gynecologic age. Notably, highly variable cycles are common, especially among those with younger gynecologic age or older menarcheal age.

The association of COVID-19 vaccination and menstrual health: A period-tracking app-based cohort study.

Background: In initial COVID-19 clinical trials, menstrual health was not formally monitored, yet anecdotal reports of menstruation changes surfaced on social media. This study aims to assess the association between COVID-19 vaccines and menstruation using Clue, a period-tracking application. Study design: A survey assessing demographics, menstrual health, stress levels, and COVID-19 vaccination was sent to Clue users between 12/7/2021 and 2/9/2022. Inclusion criteria were (1) 18 years or older (2) currently menstruating (3) not pregnant or breastfeeding since 1/2020. Menstrual data was collected for each participant. Users with cycle lengths more than 90 days were excluded. Cycle lengths were calculated for the 6-month average pre-vaccination (PRIOR), the cycle during which vaccination was administered (DURING), the cycle following DURING (AFTER1), and the cycle following AFTER1 (AFTER2). For periods, individuals were stratified based on whether vaccination was received during their menstrual period (DURING). Period lengths were additionally calculated for the 6-month average pre-vaccination (PRIOR), the first period following vaccination (AFTER1), and the period following AFTER1 (AFTER2). For unvaccinated participants, an index date (4/1/2022) was used to similarly designate menstrual cycles and periods. For each participant, cycle length changes for DURING, AFTER1, and AFTER2 compared to PRIOR were determined. Student's t-test compared the mean of these changes between vaccinated and unvaccinated groups. Results: Of 7,559 participants, 6,897 (91 %) were vaccinated. Compared to PRIOR, individuals vaccinated during their menstrual period demonstrated a statistically significant increase in the DURING period length, but not AFTER1 (p = 0.463) and AFTER2 (p = 0.692). No statistically significant changes were observed in period lengths of those vaccinated in between periods or in cycle lengths overall. Conclusion: A small but statistically significant change in period length was observed only in individuals vaccinated for COVID-19 during their menstrual period. Providers can better counsel menstruating individuals to reduce vaccine misinformation.

Associations Among Menstrual Cycle Length, Coronavirus Disease 2019 (COVID-19), and Vaccination.

OBJECTIVE: To assess whether coronavirus disease 2019 (COVID-19) is associated with menstrual cycle length changes and, if so, how that compares with those undergoing vaccination or no event (control). METHODS: We conducted a retrospective cohort analysis in which we analyzed prospectively tracked cycle-length data from users of a period tracker application who also responded to a survey regarding COVID-19 symptoms and vaccination. We restricted our sample to users aged 16-45 years, with normal cycle lengths (24-38 days) and regular tracking behavior during the five cycles around COVID-19 symptoms or vaccination or a similar time period for those experiencing no event (control group). We calculated the within-user change in cycle length (days) from the three consecutive cycles preevent average (either vaccination, disease, or neither; cycles 1-3) to the event (cycle 4) and postevent (cycle 5) cycles. We used mixed-effects models to estimate the age- and country-adjusted difference in change in cycle length across the groups. RESULTS: We included 6,514 users from 110 countries representing 32,570 cycles (COVID-19 symptoms: 1,450; COVID-19 vaccination: 4,643; control: 421). The COVID-19 cohort experienced a 1.45-day adjusted increase in cycle length during cycle 4 (COVID-19) compared with their three preevent cycles (95% CI 0.86-2.04). The vaccinated group experienced a 1.14-day adjusted increase in cycle length during cycle 4 (COVID-19 vaccine) compared with their preevent average (95% CI 0.60-1.69). The control group (neither vaccine nor disease) experienced a 0.68-day decrease (95% CI -1.18 to -0.19) in a similar time period. Post hoc tests showed no significant differences in the magnitude of changes between the COVID-19 and vaccination cohorts. In both cohorts, cycle length changes disappeared in the postevent cycle. CONCLUSION: Experiencing COVID-19 is associated with a small change in cycle length similar to COVID-19 vaccination. These changes resolve quickly within the next cycle.

Effects of clinically relevant radionuclides on the activation of a type I interferon response by radiopharmaceuticals in syngeneic murine tumor models.

Radiopharmaceutical therapies (RPT) activate a type I interferon (IFN1) response in tumor cells. We hypothesized that the timing and amplitude of this response varies by isotope. We compared equal doses delivered by 90 Y, 177 Lu, and 225 Ac in vitro as unbound radionuclides and in vivo when chelated to NM600, a tumor-selective alkylphosphocholine. Response in murine MOC2 head and neck carcinoma and B78 melanoma was evaluated by qPCR and flow cytometry. Therapeutic response to 225 Ac-NM600+anti-CTLA4+anti-PD-L1 immune checkpoint inhibition (ICI) was evaluated in wild-type and stimulator of interferon genes knockout (STING KO) B78. The timing and magnitude of IFN1 response correlated with radionuclide half-life and linear energy transfer. CD8 + /Treg ratios increased in tumors 7 days after 90 Y- and 177 Lu-NM600 and day 21 after 225 Ac-NM600. 225 Ac-NM600+ICI improved survival in mice with WT but not with STING KO tumors, relative to monotherapies. Immunomodulatory effects of RPT vary with radioisotope and promote STING-dependent enhanced response to ICIs in murine models. Teaser: This study describes the time course and nature of tumor immunomodulation by radiopharmaceuticals with differing physical properties.

Obesity modulates the cellular and molecular microenvironment in the peritoneal cavity: implication for ovarian cancer risk.

Introduction: Abdominal obesity increases the risk of developing ovarian cancer but the molecular mechanisms of how obesity supports ovarian cancer development remain unknown. Here we investigated the impact of obesity on the immune cell and gene expression profiles of distinct abdominal tissues, focusing on the peritoneal serous fluid (PSF) and the omental fat band (OFB) as critical determinants for the dissemination of ovarian metastases and early metastatic events within the peritoneal cavity. Methods: Female C57BL/6 mice were fed a low-fat (LFD) or a high-fat diet (HFD) for 12 weeks until the body weights in the HFD group were significantly higher and the mice displayed an impaired glucose tolerance. Then the mice were injected with the murine ovarian cancer cells (MOSE-LTICv) while remaining on their diets. After 21 days, the mice were sacrificed, tumor burden was evaluated and tissues were harvested. The immune cell composition of abdominal tissues and changes in gene expression in the PSF and OFB were evaluated by flow cytometry and qPCR RT2-profiler PCR arrays and confirmed by qRT-PCR, respectively. Other peritoneal adipose tissues including parametrial and retroperitoneal white adipose tissues as well as blood were also investigated. Results: While limited effects were observed in the other peritoneal adipose tissues, feeding mice the HFD led to distinct changes in the immune cell composition in the PSF and the OFB: a depletion of B cells but an increase in myeloid-derived suppressor cells (MDSC) and mono/granulocytes, generating pro-inflammatory environments with increased expression of cyto- and chemokines, and genes supporting adhesion, survival, and growth, as well as suppression of apoptosis. This was associated with a higher peritoneal tumor burden compared to mice fed a LFD. Changes in cellular and genetic profiles were often exacerbated by the HFD. There was a large overlap in genes that were modulated by both the HFD and the cancer cells, suggesting that this 'genetic fingerprint' is important for ovarian metastases to the OFB. Discussion: In accordance with the 'seed and soil' theory, our studies show that obesity contributes to the generation of a pro-inflammatory peritoneal environment that supports the survival of disseminating ovarian cancer cells in the PSF and the OFB and enhances the early metastatic adhesion events in the OFB through an increase in extracellular matrix proteins and modulators such as fibronectin 1 and collagen I expression as well as in genes supporting growth and invasion such as Tenacin C. The identified genes could potentially be used as targets for prevention strategies to lower the ovarian cancer risk in women with obesity.

Comparative Study of the Effect of Radiation Delivered by Lutetium-177 or Actinium-225 on Anti-GD2 Chimeric Antigen Receptor T Cell Viability and Functions.

BACKGROUND AND PURPOSE: Chimeric antigen receptor (CAR) T cells have been relatively ineffective against solid tumors. Low-dose radiation which can be delivered to multiple sites of metastases by targeted radionuclide therapy (TRT) can elicit immunostimulatory effects. However, TRT has never been combined with CAR T cells against solid tumors in a clinical setting. This study investigated the effects of radiation delivered by Lutetium-177 (177Lu) and Actinium-225 (225Ac) on the viability and effector function of CAR T cells in vitro to evaluate the feasibility of such therapeutic combinations. After the irradiation of anti-GD2 CAR T cells with various doses of radiation delivered by 177Lu or 225Ac, their viability and cytotoxic activity against GD2-expressing human CHLA-20 neuroblastoma and melanoma M21 cells were determined by flow cytometry. The expression of the exhaustion marker PD-1, activation marker CD69 and the activating receptor NKG2D was measured on the irradiated anti-GD2 CAR T cells. Both 177Lu and 225Ac displayed a dose-dependent toxicity on anti-GD2 CAR T cells. However, radiation enhanced the cytotoxic activity of these CAR T cells against CHLA-20 and M21 irrespective of the dose tested and the type of radionuclide. No significant changes in the expression of PD-1, CD69 and NKG2D was noted on the CAR T cells following irradiation. Given a lower CAR T cell viability at equal doses and an enhancement of cytotoxic activity irrespective of the radionuclide type, 177Lu-based TRT may be preferred over 225Ac-based TRT when evaluating a potential synergism between these therapies in vivo against solid tumors.