Social disparities in delivery choice among patients with history of cesarean.

OBJECTIVE: Given the call to reduce rates of non-medically indicated cesarean deliveries (CDs) by encouraging trials of labor after cesarean (TOLAC), this study looks at social characteristics of patients choosing a TOLAC versus a scheduled repeat cesarean delivery (SRCD) to determine disparities regarding delivery method choice. METHODS: This was a retrospective cohort study of patients with a history of one CD between April 29, 2015-April 29, 2020. Patients were divided based on type of delivery chosen at admission. Chi-squared tests examined proportional differences between groups and logistic regression models examined odd ratios of choosing TOLAC versus SRCD according to socially dependent categories including race/ethnicity, health insurance, pre-pregnancy body mass index, and Social Vulnerability Index (SVI). RESULTS: 1,983 patients were included. Multivariable logistic regression models revealed that patients with a high SVI (reference: low/medium SVI) (AOR 2.0, CI: 1.5, 2.5), self-identified as Black/ African American (AOR: 2.4, CI: 1.6, 3.6) or Hispanic/Latina (AOR: 2.0, CI: 1.4, 2.8) (reference: White), had public insurance (reference: private insurance) (AOR: 3.7, CI: 2.8, 5.0), and who had an obese BMI (reference: non-obese BMI) were more likely to opt for a TOLAC rather than SRCD. CONCLUSION: These findings demonstrate differences in delivery method preferences. Specifically, more disadvantaged patients are more likely to choose TOLAC, suggesting that social and economic factors may play a role in delivery preferences. These findings have implications for improving individualized counselling and engaging in shared decision-making around mode of delivery.

Sustained fentanyl exposure inhibits neuronal activity in dissociated striatal neuronal-glial co-cultures through actions independent of opioid receptors.

Besides having high potency and efficacy at the µ- (MOR) and other opioid receptor types, fentanyl has some affinity for some adrenergic receptor types, which may underlie its unique pathophysiological differences from typical opioids. To better understand the unique actions of fentanyl, we assessed the extent to which fentanyl alters striatal medium spiny neuronal (MSNs) activity via opioid or α1 adrenoceptors in dopamine type 1 or type 2 receptor- (D1 or D2) -expressing MSNs. In neuronal and mixed-glial co-cultures from the striatum, acute fentanyl (100 nM) exposure decreased the frequency of spontaneous action potentials. Overnight exposure of co-cultures to 100 nM fentanyl severely reduced the proportion of MSNs with spontaneous action potentials, which was unaffected by co-exposure to the opioid receptor antagonist naloxone (10 µM), but fully negated by co-administering the pan-α1 adrenoceptor inverse agonist prazosin (100 nM) and partially reversed by the selective α1A/C adrenoceptor antagonist RS 100329 (300 nM). Acute fentanyl (100 nM) exposure modestly reduced the frequency of action potentials and caused firing rate adaptations in D2, but not D1, MSNs. Prolonged (2-5 h) fentanyl (100 nM) application dramatically attenuated firing rates in both D1 and D2 MSNs. To identify possible cellular sites of α1 adrenoceptor action, α1 adrenoceptors were localized in subpopulations of striatal astroglia and neurons by immunocytochemistry, and Adra1a mRNA by in situ hybridization in astrocytes. Thus, sustained fentanyl exposure can inhibit striatal MSN activity via a non-opioid receptor-dependent pathway, that may be modulated via complex actions in α1 adrenoceptor-expressing striatal neurons and/or glia.

Enhancing radiotherapy response via intratumoral injection of a TLR9 agonist in autochthonous murine sarcomas.

Radiation therapy (RT) is frequently used to treat cancers, including soft-tissue sarcomas. Prior studies established that the toll-like receptor 9 (TLR9) agonist cytosine-phosphate-guanine oligodeoxynucleotide (CpG) enhances the response to RT in transplanted tumors, but the mechanisms of this enhancement remain unclear. Here, we used CRISPR/Cas9 and the chemical carcinogen 3-methylcholanthrene (MCA) to generate autochthonous soft-tissue sarcomas with high tumor mutation burden. Treatment with a single fraction of 20 Gy RT and 2 doses of CpG significantly enhanced tumor response, which was abrogated by genetic or immunodepletion of CD8+ T cells. To characterize the immune response to CpG+RT, we performed bulk RNA-Seq, single-cell RNA-Seq, and mass cytometry. Sarcomas treated with 20 Gy and CpG demonstrated increased CD8 T cells expressing markers associated with activation and proliferation, such as Granzyme B, Ki-67, and IFN-γ. CpG+RT also upregulated antigen presentation pathways on myeloid cells. Furthermore, in sarcomas treated with CpG+RT, TCR clonality analysis suggests an increase in clonal T cell dominance. Collectively, these findings demonstrate that CpG+RT significantly delays tumor growth in a CD8 T cell-dependent manner. These results provide a strong rationale for clinical trials evaluating CpG or other TLR9 agonists with RT in patients with soft-tissue sarcoma.

Modulation of aryl hydrocarbon receptor activity by tyrosine kinase inhibitors (ponatinib and tofacitinib).

Ponatinib and tofacitinib, established kinase inhibitors and FDA-approved for chronic myeloid leukemia and rheumatoid arthritis, are recently undergoing investigation in diverse clinical trials for potential repurposing. The aryl hydrocarbon receptor (AhR), a transcription factor influencing a spectrum of physiological and pathophysiological activities, stands as a therapeutic target for numerous diseases. This study employs molecular modelling tools and in vitro assays to identify ponatinib and tofacitinib as AhR ligands, elucidating their binding and molecular interactions in the AhR PAS-B domain. Molecular docking analyses revealed that ponatinib and tofacitinib occupy the central pocket within the primary cavity, similar to AhR agonists 2,3,7,8-tetrachlorodibenzodioxin (TCDD) and (benzo[a]pyrene) B[a]P. Our simulations also showed that these compounds exhibit good stability, stabilizing many hot spots within the PAS-B domain, including the Dα-Eα loop, which serves as a regulatory element for the binding pocket. Binding energy calculations highlighted ponatinib's superior predicted affinity, revealing F295 as a crucial residue in maintaining strong interaction with the two compounds. Our in vitro data suggest that ponatinib functions as an AhR antagonist, blocking the downstream signaling of AhR pathway induced by TCDD and B[a]P. Additionally, both tofacitinib and ponatinib cause impairment in AhR-regulated CYP1A1 enzyme activity induced by potent AhR agonists. This study unveils ponatinib and tofacitinib as potential modulators of AhR, providing valuable insights into their therapeutic roles in AhR-associated diseases and enhancing our understanding of the intricate relationship between kinase inhibitors and AhR.

RNA-sequencing reveals differential fibroblast responses to bleomycin and pneumonectomy.

Pulmonary fibrosis is characterized by pathological accumulation of scar tissue in the lung parenchyma. Many of the processes that are implicated in fibrosis, including increased extracellular matrix synthesis, also occur following pneumonectomy (PNX), but PNX instead results in regenerative compensatory growth of the lung. As fibroblasts are the major cell type responsible for extracellular matrix production, we hypothesized that comparing fibroblast responses to PNX and bleomycin (BLM) would unveil key differences in the role they play during regenerative versus fibrotic lung responses. RNA-sequencing was performed on flow-sorted fibroblasts freshly isolated from mouse lungs 14 days after BLM, PNX, or sham controls. RNA-sequencing analysis revealed highly similar biological processes to be involved in fibroblast responses to both BLM and PNX, including TGF-ß1 and TNF-α. Interestingly, we observed smaller changes in gene expression after PNX than BLM at Day 14, suggesting that the fibroblast response to PNX may be muted by expression of transcripts that moderate pro-fibrotic pathways. Itpkc, encoding inositol triphosphate kinase C, was a gene uniquely up-regulated by PNX and not BLM. ITPKC overexpression in lung fibroblasts antagonized the pro-fibrotic effect of TGF-ß1. RNA-sequencing analysis has identified considerable overlap in transcriptional changes between fibroblasts following PNX and those overexpressing ITPKC.

Prenatal Cannabis Use and Maternal Pregnancy Outcomes.

Importance: Many studies have evaluated whether in utero cannabis exposure is associated with fetal and neonatal outcomes, yet little is known about whether prenatal cannabis use is associated with maternal health outcomes during pregnancy. Objective: To evaluate whether prenatal cannabis use is associated with maternal health outcomes during pregnancy. Design, Setting, and Participants: This population-based retrospective cohort study included pregnancies in Northern California from January 2011 to December 2019 that lasted 20 weeks or longer and were screened for prenatal cannabis use. Exposures: Prenatal cannabis use was defined as any self-reported use during early pregnancy or a positive toxicology test result based on universal screening at entrance to prenatal care (approximately 8-10 weeks' gestation). Self-reported frequency of use (daily, weekly, monthly or less, never, unknown), use defined only by self-report, and use defined only by toxicology test results were examined. Main Outcomes and Measures: Electronic health record data were used to define the following outcomes: gestational hypertension, preeclampsia, eclampsia, gestational diabetes, gestational weight gain greater and less than guidelines, placenta previa, placental abruption, placenta accreta, and severe maternal morbidity. Adjusted risk ratios (aRRs) were calculated using a modified Poisson regression. Results: The sample (n = 316 722 pregnancies; 250 221 unique individuals) included 84 039 (26.5%) Asian/Pacific Islander, 20 053 (6.3%) Black, 83 145 (26.3%) Hispanic, and 118 333 (37.4%) White individuals; the mean (SD) age was 30.6 (5.4) years. Overall, 20 053 (6.3%) screened positive for prenatal cannabis use; 2.9% were positive by self-report, 5.3% by toxicology testing, and 1.8% by both. The frequency of cannabis use was 1930 (0.6%) daily, 2345 (0.7%) weekly, 4892 (1.5%) monthly or less, and 10 886 (3.4%) unknown. Prenatal cannabis use was associated with greater risk of gestational hypertension (aRR, 1.17; 95% CI, 1.13-1.21), preeclampsia (aRR, 1.08; 95% CI, 1.01-1.15), weight gain less than (aRR, 1.05; 95% CI, 1.01-1.08) and greater than (aRR, 1.09; 95% CI, 1.08-1.10) guidelines, and placental abruption (aRR, 1.19; 95% CI, 1.05-1.36). The pattern of results was similar when defining prenatal cannabis use only by self-report or only by toxicology testing, and associations between the frequency of prenatal cannabis use and outcomes varied with outcome. Conclusions and Relevance: The results of this cohort study suggest that prenatal cannabis use was associated with several adverse maternal health outcomes during pregnancy. Continued research is needed to understand whether characteristics of prenatal cannabis use (eg, dose, mode, and timing) moderate these associations.

Severe Spaceflight-Associated Neuro-Ocular Syndrome in an Astronaut With 2 Predisposing Factors.

Importance: Understanding potential predisposing factors associated with spaceflight-associated neuro-ocular syndrome (SANS) may influence its management. Objective: To describe a severe case of SANS associated with 2 potentially predisposing factors. Design, Setting, and Participants: Ocular testing of and blood collections from a female astronaut were completed preflight, inflight, and postflight in the setting of the International Space Station (ISS). Exposure: Weightlessness throughout an approximately 6-month ISS mission. Mean carbon dioxide (CO2) partial pressure decreased from 2.6 to 1.3 mm Hg weeks before the astronaut's flight day (FD) 154 optical coherence tomography (OCT) session. In response to SANS, 4 B-vitamin supplements (vitamin B6, 100 mg; L-methylfolate, 5 mg; vitamin B12, 1000 µg; and riboflavin, 400 mg) were deployed, unpacked on FD153, consumed daily through FD169, and then discontinued due to gastrointestinal discomfort. Main Outcomes and Measures: Refraction, distance visual acuity (DVA), optic nerve, and macular assessment on OCT. Results: Cycloplegic refraction was -1.00 diopter in both eyes preflight and +0.50 - 0.25 × 015 in the right eye and +1.00 diopter in the left eye 3 days postflight. Uncorrected DVA was 20/30 OU preflight, 20/16 or better by FD90, and 20/15 OU 3 days postflight. Inflight peripapillary total retinal thickness (TRT) peaked between FD84 and FD126 (right eye, 401 µm preflight, 613 µm on FD84; left eye, 404 µm preflight, 636 µm on FD126), then decreased. Peripapillary choroidal folds, quantified by surface roughness, peaked at 12.7 µm in the right eye on FD154 and 15.0 µm in the left eye on FD126, then decreased. Mean choroidal thickness increased throughout the mission. Genetic analyses revealed 2 minor alleles for MTRR 66 and 2 major alleles for SHMT1 1420 (ie, 4 of 4 SANS risk alleles). One-week postflight, lumbar puncture opening pressure was normal, at 19.4 cm H2O. Conclusions and Relevance: To the authors' knowledge, no other report of SANS documented as large of a change in peripapillary TRT or hyperopic shift during a mission as in this astronaut, and this was only 1 of 4 astronauts to experience chorioretinal folds approaching the fovea. This case showed substantial inflight improvement greater than the sensitivity of the measure, possibly associated with B-vitamin supplementation and/or reduction in cabin CO2. However, as a single report, such improvement could be coincidental to these interventions, warranting further evaluation.

A crucial nexus: Phylogenetic versus ecological support of the life-cycle of Ixodes ricinus (Ixodoidea: Ixodidae) and Borrelia spp. amplification.

The tick Ixodes ricinus parasitizes a wide range of vertebrates. These hosts vary in the relative contribution to the feeding of the different tick life stages, and their interplay is pivotal in the transmission dynamics of tick-borne pathogens. We aimed to know if there is a phylogenetic signal in the feeding and propagation hosts of I. ricinus, independently of other traits, as well as in the amplification of Borrelia burgdorferi (s.l.) in feeding larvae. We used a compilation of 1127 published field surveys in Europe, providing data for 96,586 hosts, resulting in 265,124 larvae, 72,080 nymphs and 37,726 adults. The load of immature ticks on hosts showed a significant phylogenetic signal towards the genera Psammodromus, Podarcis, and Lacerta (nymphs only). We hypothesize that such signal is the background hallmark of the primitive hosts associations of I. ricinus, probably in the glaciation refugia. A secondary phylogenetic signal for tick immatures appeared for some genera of Rodentia and Eulipotyphla. Results suggest the notion that the tick gained these hosts after spread from glaciation refugia. Analyses support a phylogenetic signal in the tick adults, firmly linked to Cetartiodactyla, but not to Carnivora or Aves. This study provides the first demonstration of host preferences in the generalist tick I. ricinus. We further demonstrate that combinations of vertebrates contribute in different proportions supporting the tick life-cycle in biogeographical regions of the Western Palaearctic as each region has unique combinations of dominant hosts. Analysis of the amplification of B. burgdorferi (s.l.) demonstrated that each genospecies is better amplified by competent reservoirs with which a strong phylogenetic signal exists. These vertebrates are the same along the spatial range: environmental traits do not change the reservoirs along the large territory studied. The transmission of B. burgdorferi (s.l.) is amplified by a few species of vertebrates, that share biogeographical regions with the tick vector in variable proportions.

Prioritizing research needs and opportunities at the intersection of implementation science and engagement science.

BACKGROUND: There has been increased attention to the need for, and the positive impact of, engaged or participatory science in recent years. Implementation scientists have an opportunity to leverage and contribute to engagement science (ES) through the systematic integration of engagement into implementation science (IS). The purpose of this study was to gather information from researchers and others to develop a prioritized list of research needs and opportunities at the intersection of IS and ES. METHODS: We conducted three Zoom-based focus groups with 20 researchers to generate a list of unmet needs, barriers, and to describe normative themes about use of ES and IS. Then a panel of nine experts in IS and/or engagement ranked the needs and barriers using a survey and met via a Zoom meeting to discuss and generate research opportunities and questions, with reference to the focus group outputs. RESULTS: Respondents and experts concurred on the importance of engagement in IS. Focus group participants reported 28 needs and barriers under the themes of 1) need for best practice guidance related to engagement processes and outcomes and 2) structural barriers to integrating ES in IS. The expert panel prioritized six structural barriers and four barriers related to generating best practice guidance, with corresponding recommendations on research opportunities. Example research opportunities related to engagement processes included: define "successful" engagement in IS contexts; adapt engagement tools and best practices from other disciplines into IS. Example research opportunities related to outcomes included: assess the impact of engagement on IS outcomes; examine engagement practices that lead to optimal engaged research. Example research opportunities related to structural barriers included: leverage research evidence to create structural changes needed to expand support for engaged IS; examine factors that influence institutional buy-in of engagement in IS. CONCLUSIONS: Research needs exist that relate to engagement processes, outcomes, and structural barriers, even for scientists who value engaged research. Expert panelists recommended sequential and reinforcing research opportunities that implementation and engagement scientists can tackle together to advance both fields and health equity. Future work should assess insights from broader invested parties, particularly patients and community members.

Targeting CEBPA to restore cellular identity and tissue homeostasis in pulmonary fibrosis.

Fibrosis in the lung is thought to be driven by epithelial cell dysfunction and aberrant cell-cell interactions. Unveiling the molecular mechanisms of cellular plasticity and cell-cell interactions is imperative to elucidate lung regenerative capacity and aberrant repair in pulmonary fibrosis. By mining publicly available RNA-seq datasets, we identified loss of CCAAT enhancer-binding protein alpha (CEBPA) as a candidate contributor to idiopathic pulmonary fibrosis (IPF). We used conditional knockout mice, scRNA-seq, lung organoids, small-molecule inhibition and novel gene manipulation methods to investigate the role of CEBPA in lung fibrosis and repair. Long term (6 month+) of Cebpa loss in AT2 cells caused spontaneous fibrosis and increased susceptibility to bleomycin-induced fibrosis. Cebpa knockout in these mice significantly decreased AT2 cell numbers in the lung and reduced expression of surfactant homeostasis genes, while increasing inflammatory cell recruitment as well as upregulating S100a8/a9 in AT2 cells. In vivo treatment with an S100A8/A9 inhibitor alleviated experimental lung fibrosis. Restoring CEBPA expression in lung organoids ex vivo and during experimental lung fibrosis in vivo rescued CEBPA deficiency-mediated phenotypes. Our study establishes a direct mechanistic link between CEBPA repression, impaired AT2 cell identity, disrupted tissue homeostasis, and lung fibrosis.

Caseload factors predictive of family abuse and neglect treatment outcomes.

BACKGROUND: In child welfare, caseloads are frequently far higher than optimal. Not all cases are created equal; however, little is known about which combination and interaction of factors make caseloads more challenging and impact child and family outcomes. OBJECTIVE: This study aims to identify which case, provider, and organizational factors most strongly differentiate between families with favorable and less-than-positive treatment outcomes. PARTICIPANTS AND SETTING: Participants were 25 family advocacy program providers and 17 supervisors at 11 Department of the Air Force installations. METHODS: Following informed consent, participants completed demographic and caseload questionnaires, and we collected information about organizational factors. Providers were sent a weekly case update and burnout questionnaire for seven months. We used linear mixed-effects model tree (LMM tree) algorithms to determine the provider, client, and organizational characteristics that best distinguish between favorable vs. unfavorable outcomes. RESULTS: The LMM tree predicting provider-rated treatment success yielded three significant partitioning variables: (a) commander involvement, (b) case complexity, and (c) % of clients in a high-risk field. The LMM predicting client-rated treatment progress yielded seven significant partitioning variables: (a) command involvement; (b) ease of reaching tenant unit command; (c) # of high-risk cases; (d) % of clients receiving Alcohol and Drug Abuse Prevention and Treatment services; (e) ease of reaching command; (f) % of clients with legal involvement; (g) provider age. CONCLUSIONS: This study is a first step toward developing a dynamic caseload management tool. An intelligent, algorithm-informed approach to case assignment could help child welfare agencies operate in their typically resource-scarce contexts in a manner that improves outcomes.

The effect of corticosterone on the acquisition of Pavlovian conditioned approach behavior in rats is dependent on sex and vendor.

Cues in the environment become predictors of biologically relevant stimuli, such as food, through associative learning. These cues can not only act as predictors but can also be attributed with incentive motivational value and gain control over behavior. When a cue is imbued with incentive salience, it attains the ability to elicit maladaptive behaviors characteristic of psychopathology. We can capture the propensity to attribute incentive salience to a reward cue in rats using a Pavlovian conditioned approach paradigm, in which the presentation of a discrete lever-cue is followed by the delivery of a food reward. Upon learning the cue-reward relationship, some rats, termed sign-trackers, develop a conditioned response directed towards the lever-cue; whereas others, termed goal-trackers, approach the food cup upon lever-cue presentation. Here, we assessed the effects of systemic corticosterone (CORT) on the acquisition and expression of sign- and goal-tracking behaviors in male and female rats, while examining the role of the vendor (Charles River or Taconic) from which the rats originated in these effects. Treatment naïve male and female rats from Charles River had a greater tendency to sign-track than those from Taconic. Administration of CORT enhanced the acquisition of sign-tracking behavior in males from Charles River and females from both vendors. Conversely, administration of CORT had no effect on the expression of the conditioned response. These findings demonstrate a role for CORT in cue-reward learning and suggest that inherent tendencies towards sign- or goal-tracking may interact with this physiological mediator of motivated behavior.

Beyond attachment theory: Indigenous perspectives on the child-caregiver bond from a northwest tribal community.

Healthy Indigenous child development is grounded in Indigenous ways of knowing and being. Attachment theory has been influential in understanding the significance of parenting for infant development in Western science but has focused on child-caregiver bonds predominantly within the parent-child dyad. To bring forth Indigenous perspectives regarding understandings of parenting, the attachment bond, and the well-being of Indigenous children, we conducted semi-structured interviews with 28 members of a Northwest tribal community (21 female) in spring and summer 2020. Themes included Community caregiving, Family value systems, Bonding, Traditional teachings, and Historical trauma. The need to expand the lens of attachment theory beyond the dyad is clear. Implications for improving the child welfare system and prevention programs within Indigenous communities are discussed.

DNA typing of cyanoacrylate fumed latent fingerprints using GlobalFiler™ and ForenSeq™ Signature Prep kits.

DNA typing of latent fingerprints is highly desirable to increase chances of individualization. We recovered DNA from Cyanoacrylate (CA) fumed fingerprints and used both GlobalFiler™ and ForenSeq™ DNA Signature Prep kits for DNA typing. For GlobalFiler™, samples were processed using a protocol modified for Low Template (LT)-DNA samples (half-volume reactions, 30 cycles) while for ForenSeq™ DNA Signature Prep, samples were processed using a standard protocol and fluorometer-based library quantitation. We evaluated genotyping success and quality of profiles in terms of completeness, Peak Height Ratio/Allele Coverage Ratio, presence of PCR artifacts and drop-in alleles. With GlobalFiler™, average autosomal STR (aSTR) profile completeness was 44.4% with 2-20 pg, 54.3% with 22-60 pg, and 95% with 64-250 pg DNA input. CODIS uploadable profiles were obtained in 2/10, 3/11, and 11/12 samples in these ranges. With ForenSeq™ DNA Signature Prep, average aSTR profile completeness was 19.7% with 1-20 pg and 45.2% with 22-47 pg but increased to 78.3% with 68-122 pg and 86.7% with 618-1000 pg DNA input. Uploadable profiles were obtained in 0/12, 4/11, 4/7, and 3/3 samples for these ranges. Results show very high sensitivity using both kits. Half-volume reactions and 30 cycles had minimal negative effect on Globalfiler™ profile quality, providing support for wider use after validation experiments to routinely improve results from LT samples. A standard protocol for the ForenSeq™ DNA Signature Prep kit was also highly successful with LT DNA obtained from CA-fumed fingerprints with additional information from isometric STR alleles and other markers.

Nasal cathelicidin is expressed in early life and is increased during mild, but not severe respiratory syncytial virus infection.

Respiratory syncytial virus is the major cause of acute lower respiratory tract infections in young children, causing extensive mortality and morbidity globally, with limited therapeutic or preventative options. Cathelicidins are innate immune antimicrobial host defence peptides and have antiviral activity against RSV. However, upper respiratory tract cathelicidin expression and the relationship with host and environment factors in early life, are unknown. Infant cohorts were analysed to characterise early life nasal cathelicidin levels, revealing low expression levels in the first week of life, with increased levels at 9 months which are comparable to 2-year-olds and healthy adults. No impact of prematurity on nasal cathelicidin expression was observed, nor were there effects of sex or birth mode, however, nasal cathelicidin expression was lower in the first week-of-life in winter births. Nasal cathelicidin levels were positively associated with specific inflammatory markers and demonstrated to be associated with microbial community composition. Importantly, levels of nasal cathelicidin expression were elevated in infants with mild RSV infection, but, in contrast, were not upregulated in infants hospitalised with severe RSV infection. These data suggest important relationships between nasal cathelicidin, upper airway microbiota, inflammation, and immunity against RSV infection, with interventional potential.

Transcriptomics analysis reveals molecular alterations underpinning spaceflight dermatology.

BACKGROUND: Spaceflight poses a unique set of challenges to humans and the hostile spaceflight environment can induce a wide range of increased health risks, including dermatological issues. The biology driving the frequency of skin issues in astronauts is currently not well understood. METHODS: To address this issue, we used a systems biology approach utilizing NASA's Open Science Data Repository (OSDR) on space flown murine transcriptomic datasets focused on the skin, biochemical profiles of 50 NASA astronauts and human transcriptomic datasets generated from blood and hair samples of JAXA astronauts, as well as blood samples obtained from the NASA Twins Study, and skin and blood samples from the first civilian commercial mission, Inspiration4. RESULTS: Key biological changes related to skin health, DNA damage & repair, and mitochondrial dysregulation are identified as potential drivers for skin health risks during spaceflight. Additionally, a machine learning model is utilized to determine gene pairings associated with spaceflight response in the skin. While we identified spaceflight-induced dysregulation, such as alterations in genes associated with skin barrier function and collagen formation, our results also highlight the remarkable ability for organisms to re-adapt back to Earth via post-flight re-tuning of gene expression. CONCLUSION: Our findings can guide future research on developing countermeasures for mitigating spaceflight-associated skin damage.

Spaceflight is a hostile environment which can lead to health problems in astronauts, including in the skin. It is not currently well understood why these skin problems occur. Here, we analyzed data from the skin of space flown mice and astronauts to try and identify possible explanations for these skin problems. It appears that changes in the activation of genes related to damage to DNA, skin barrier health, and mitochondria (the energy-producing parts of cells) may play a role in these skin problems. Further research will be needed to confirm exactly how these changes influence skin health, which could lead to solutions for preventing and managing such issues in astronauts.

Single-cell multi-ome and immune profiles of the Inspiration4 crew reveal conserved, cell-type, and sex-specific responses to spaceflight.

Spaceflight induces an immune response in astronauts. To better characterize this effect, we generated single-cell, multi-ome, cell-free RNA (cfRNA), biochemical, and hematology data for the SpaceX Inspiration4 (I4) mission crew. We found that 18 cytokines/chemokines related to inflammation, aging, and muscle homeostasis changed after spaceflight. In I4 single-cell multi-omics data, we identified a "spaceflight signature" of gene expression characterized by enrichment in oxidative phosphorylation, UV response, immune function, and TCF21 pathways. We confirmed the presence of this signature in independent datasets, including the NASA Twins Study, the I4 skin spatial transcriptomics, and 817 NASA GeneLab mouse transcriptomes. Finally, we observed that (1) T cells showed an up-regulation of FOXP3, (2) MHC class I genes exhibited long-term suppression, and (3) infection-related immune pathways were associated with microbiome shifts. In summary, this study reveals conserved and distinct immune disruptions occurring and details a roadmap for potential countermeasures to preserve astronaut health.

WILDbase: towards a common database to improve wildlife disease surveillance in Europe.

BackgroundTo be better prepared for emerging wildlife-borne zoonoses, we need to strengthen wildlife disease surveillance.AimThe aim of this study was to create a topical overview of zoonotic pathogens in wildlife species to identify knowledge gaps and opportunities for improvement of wildlife disease surveillance.MethodsWe created a database, which is based on a systematic literature review in Embase focused on zoonotic pathogens in 10 common urban wildlife mammals in Europe, namely brown rats, house mice, wood mice, common voles, red squirrels, European rabbits, European hedgehogs, European moles, stone martens and red foxes. In total, we retrieved 6,305 unique articles of which 882 were included.ResultsIn total, 186 zoonotic pathogen species were described, including 90 bacteria, 42 helminths, 19 protozoa, 22 viruses and 15 fungi. Most of these pathogens were only studied in one single animal species. Even considering that some pathogens are relatively species-specific, many European countries have no (accessible) data on zoonotic pathogens in these relevant animal species. We used the Netherlands as an example to show how this database can be used by other countries to identify wildlife disease surveillance gaps on a national level. Only 4% of all potential host-pathogen combinations have been studied in the Netherlands.ConclusionsThis database comprises a comprehensive overview that can guide future research on wildlife-borne zoonotic diseases both on a European and national scale. Sharing and expanding this database provides a solid starting point for future European-wide collaborations to improve wildlife disease surveillance.

Spatiotemporal expression and control of haemoglobin in space.

It is now widely recognised that the environment in space activates a diverse set of genes involved in regulating fundamental cellular pathways. This includes the activation of genes associated with blood homoeostasis and erythropoiesis, with a particular emphasis on those involved in globin chain production. Haemoglobin biology provides an intriguing model for studying space omics, as it has been extensively explored at multiple -omic levels, spanning DNA, RNA, and protein analyses, in both experimental and clinical contexts. In this study, we examined the developmental expression of haemoglobin over time and space using a unique suite of multi-omic datasets available on NASA GeneLab, from the NASA Twins Study, the JAXA CFE study, and the Inspiration4 mission. Our findings reveal significant variations in globin gene expression corresponding to the distinct spatiotemporal characteristics of the collected samples. This study sheds light on the dynamic nature of globin gene regulation in response to the space environment and provides valuable insights into the broader implications of space omics research.