SARS-CoV-2 antibodies detected in human breast milk postvaccination

Importance The SARS-CoV-2 pandemic has infected over a hundred million people worldwide, with almost 2.5 million deaths at the date of this publication. In the United States, Pfizer-BioNTech and Moderna vaccines were first administered to the public starting in December 2020, and no lactating women were included in the initial trials of safety/efficacy. Research on SARS-CoV-2 vaccination in lactating women and the potential transmission of passive immunity to the infant through breast milk is needed to guide patients, clinicians and policy makers during the worldwide effort to curb the spread of this virus. Objective To determine whether SARS-CoV-2 specific immunoglobins are found in breast milk post-vaccination, and to characterize the time course and types of immunoglobulins present. Design Prospective cohort study Setting Providence Portland Medical Center, Oregon, USA Participants Six lactating women who planned to receive both doses of the Pfizer-BioNTech or Moderna vaccine between December 2020 and January 2021. Breast milk samples were collected pre-vaccination and at 11 additional timepoints, with last sample at 14 days post 2nd dose of vaccine. Exposure Two doses of Pfizer-BioNTech or Moderna SARS-CoV-2 vaccine. Main Outcome(s) and Measure(s) Levels of SARS-CoV-2 specific IgA and IgG immunoglobulins in breast milk. Results In this cohort of 6 lactating women who received 2 doses of SARS-CoV-2 vaccine, we observed significantly elevated levels of SARS-CoV-2 specific IgG and IgA antibodies in breast milk beginning at Day 7 after the initial vaccine dose, with an IgG-dominant response. Conclusions and Relevance We are the first to show that maternal vaccination results in SARS-CoV-2 specific immunoglobulins in breast milk that may be protective for infants. Competing Interest Statement The authors have declared no competing interest. Funding Statement This work was supported by generous grants from Nancy Lematta (BAF) and the Chiles Foundation (BAF)

Timing of PD-1 Blockade Is Critical to Effective Combination Immunotherapy with Anti-OX40.

Purpose: Antibodies specific for inhibitory checkpoints PD-1 and CTLA-4 have shown impressive results against solid tumors. This has fueled interest in novel immunotherapy combinations to affect patients who remain refractory to checkpoint blockade monotherapy. However, how to optimally combine checkpoint blockade with agents targeting T-cell costimulatory receptors, such as OX40, remains a critical question.Experimental Design: We utilized an anti-PD-1-refractory, orthotopically transplanted MMTV-PyMT mammary cancer model to investigate the antitumor effect of an agonist anti-OX40 antibody combined with anti-PD-1. As PD-1 naturally aids in immune contraction after T-cell activation, we treated mice with concurrent combination treatment versus sequentially administering anti-OX40 followed by anti-PD-1.Results: The concurrent addition of anti-PD-1 significantly attenuated the therapeutic effect of anti-OX40 alone. Combination-treated mice had considerable increases in type I and type II serum cytokines and significantly augmented expression of inhibitory receptors or exhaustion markers CTLA-4 and TIM-3 on T cells. Combination treatment increased intratumoral CD4+ T-cell proliferation at day 13, but at day 19, both CD4+ and CD8+ T-cell proliferation was significantly reduced compared with untreated mice. In two tumor models, sequential combination of anti-OX40 followed by anti-PD-1 (but not the reverse order) resulted in significant increases in therapeutic efficacy. Against MMTV-PyMT tumors, sequential combination was dependent on both CD4+ and CD8+ T cells and completely regressed tumors in approximately 30% of treated animals.Conclusions: These results highlight the importance of timing for optimized therapeutic effect with combination immunotherapies and suggest the testing of sequencing in combination immunotherapy clinical trials. Clin Cancer Res; 23(20); 6165-77. ©2017 AACRSee related commentary by Colombo, p. 5999

Heterodimeric IL-15 delays tumor growth and promotes intratumoral CTL and dendritic cell accumulation by a cytokine network involving XCL1, IFN-γ, CXCL9 and CXCL10.

BACKGROUND: Interleukin-15 (IL-15) promotes growth and activation of cytotoxic CD8 METHODS: The antitumor activity of hetIL-15 produced from mammalian cells was tested in mouse tumor models (MC38 colon carcinoma and TC-1 epithelial carcinoma). The functional diversity of the immune infiltrate and the cytokine/chemokine network within the tumor was evaluated by flow cytometry, multicolor immunohistochemistry (IHC), gene expression profiling by Nanostring Technologies, and protein analysis by electrochemiluminescence and ELISA assays. RESULTS: hetIL-15 treatment resulted in delayed primary tumor growth. Increased NK and CD8 CONCLUSIONS: Our results show that hetIL-15 administration enhances T cell entry into tumors, increasing the success rate of immunotherapy interventions. Our study further supports the incorporation of hetIL-15 in tumor immunotherapy approaches to promote the development of antitumor responses by favoring effector over regulatory cells and by promoting lymphocyte and DC localization into tumors through the modification of the tumor chemokine and cytokine milieu

Seed systems smallholder farmers use

Seed can be an important entry point for promoting productivity, nutrition and resilience among smallholder farmers. While investments have primarily focused on strengthening the formal sector, this article documents the degree to which the informal sector remains the core for seed acquisition, especially in Africa. Conclusions drawn from a uniquely comprehensive data set, 9660 observations across six countries and covering 40 crops, show that farmers access 90.2 % of their seed from informal systems with 50.9 % of that deriving from local markets. Further, 55 % of seed is paid for by cash, indicating that smallholders are already making important investments in this arena. Targeted interventions are proposed for rendering formal and informal seed sector more smallholder-responsive and for scaling up positive impacts

Mitigation of Cognitive Bias with a Serious Game: Two Experiments Testing Feedback Timing and Source

One of the benefits of using digital games for education is that games can provide feedback for learners to assess their situation and correct their mistakes. We conducted two studies to examine the effectiveness of different feedback design (timing, duration, repeats, and feedback source) in a serious game designed to teach learners about cognitive biases. We also compared the digital game-based learning condition to a professional training video. Overall, the digital game was significantly more effective than the video condition. Longer durations and repeats improve the effects on bias-mitigation. Surprisingly, there was no significant difference between just-in-time feedback and delayed feedback, and computer-generated feedback was more effective than feedback from other players

Depressive symptoms and cortisol variability prior to surgery for suspected endometrial cancer

Endometrial cancer (EC) is the most common type of gynecologic cancer affecting women; however, very little research has examined relationships between psychological factors and hypothalamic-pituitary-adrenal (HPA) axis dysregulation in this population. The current study examined relations between depressive/anxious symptoms and salivary cortisol diurnal rhythm and variability in women undergoing surgery for suspected endometrial cancer. Depressive and anxious symptoms were measured prior to surgery using the Structured Interview Guide for the Hamilton Depression Inventory (SIGH-AD). Saliva was collected four times a day for the three days prior to surgery and then assayed by ELISA to obtain cortisol concentrations. Cortisol slopes and intraindividual variability were then calculated across subjects. Relations between depressive/anxious symptoms and cortisol indices were examined using multilevel modeling and linear regression analyses. Participants were 82 women with nonmetastatic endometrial cancer. Anxious symptoms were not associated with either cortisol slope or intraindividual variability, and depressive symptoms were unrelated to cortisol slope. However, after controlling for presence of poorer prognosis cancer subtypes, greater depressive symptoms (excluding symptoms possibly/definitely due to health/treatment factors) in the week preceding surgery were significantly related to greater cortisol intraindividual variability (β=.214; p<.05). These results suggest that depressive symptoms prior to surgery for suspected endometrial cancer are related to greater cortisol intraindividual variability, which is suggestive of more erratic HPA axis arousal. Future research should examine whether mood symptoms may be associated with compromised health outcomes via erratic HPA axis arousal in this population

Exoplanet Diversity in the Era of Space-based Direct Imaging Missions

This whitepaper discusses the diversity of exoplanets that could be detected by future observations, so that comparative exoplanetology can be performed in the upcoming era of large space-based flagship missions. The primary focus will be on characterizing Earth-like worlds around Sun-like stars. However, we will also be able to characterize companion planets in the system simultaneously. This will not only provide a contextual picture with regards to our Solar system, but also presents a unique opportunity to observe size dependent planetary atmospheres at different orbital distances. We propose a preliminary scheme based on chemical behavior of gases and condensates in a planet's atmosphere that classifies them with respect to planetary radius and incident stellar flux.Comment: A white paper submitted to the National Academy of Sciences Exoplanet Science Strateg

The Need for Laboratory Measurements and Ab Initio Studies to Aid Understanding of Exoplanetary Atmospheres

We are now on a clear trajectory for improvements in exoplanet observations that will revolutionize our ability to characterize their atmospheric structure, composition, and circulation, from gas giants to rocky planets. However, exoplanet atmospheric models capable of interpreting the upcoming observations are often limited by insufficiencies in the laboratory and theoretical data that serve as critical inputs to atmospheric physical and chemical tools. Here we provide an up-to-date and condensed description of areas where laboratory and/or ab initio investigations could fill critical gaps in our ability to model exoplanet atmospheric opacities, clouds, and chemistry, building off a larger 2016 white paper, and endorsed by the NAS Exoplanet Science Strategy report. Now is the ideal time for progress in these areas, but this progress requires better access to, understanding of, and training in the production of spectroscopic data as well as a better insight into chemical reaction kinetics both thermal and radiation-induced at a broad range of temperatures. Given that most published efforts have emphasized relatively Earth-like conditions, we can expect significant and enlightening discoveries as emphasis moves to the exotic atmospheres of exoplanets.Comment: Submitted as an Astro2020 Science White Pape

Ammonium-Acetate Is Sensed by Gustatory and Olfactory Neurons in Caenorhabditis elegans

Background: Caenorhabditis elegans chemosensation has been successfully studied using behavioral assays that treat detection of volatile and water soluble chemicals as separate senses, analogous to smell and taste. However, considerable ambiguity has been associated with the attractive properties of the compound ammonium-acetate (NH 4Ac). NH 4Ac has been used in behavioral assays both as a chemosensory neutral compound and as an attractant. Methodology/Main Findings: Here we show that over a range of concentrations NH4Ac can be detected both as a water soluble attractant and as an odorant, and that ammonia and acetic acid individually act as olfactory attractants. We use genetic analysis to show that NaCl and NH4Ac sensation are mediated by separate pathways and that ammonium sensation depends on the cyclic nucleotide gated ion channel TAX-2/TAX-4, but acetate sensation does not. Furthermore we show that sodium-acetate (NaAc) and ammonium-chloride (NH4Cl) are not detected as Na + and Cl 2 specific stimuli, respectively. Conclusions/Significance: These findings clarify the behavioral response of C. elegans to NH4Ac. The results should have an impact on the design and interpretation of chemosensory experiments studying detection and adaptation to soluble compounds in the nematode Caenorhabditis elegans