Trait variation and performance across varying levels of drought stress in cultivated sunflower (Helianthus annuus L.).

Drought is a major agricultural challenge that is expected to worsen with climate change. A better understanding of drought responses has the potential to inform efforts to breed more tolerant plants. We assessed leaf trait variation and covariation in cultivated sunflower (Helianthus annuus L.) in response to water limitation. Plants were grown under four levels of water availability and assessed for environmentally induced plasticity in leaf stomatal and vein traits as well as biomass (performance indicator), mass fractions, leaf area, leaf mass per area, and chlorophyll content. Overall, biomass declined in response to stress; these changes were accompanied by responses in leaf-level traits including decreased leaf area and stomatal size, and increased stomatal and vein density. The magnitude of trait responses increased with stress severity and relative plasticity of smaller-scale leaf anatomical traits was less than that of larger-scale traits related to construction and growth. Across treatments, where phenotypic plasticity was observed, stomatal density was negatively correlated with stomatal size and positively correlated with minor vein density, but the correlations did not hold up within treatments. Four leaf traits previously shown to reflect major axes of variation in a large sunflower diversity panel under well-watered conditions (i.e. stomatal density, stomatal pore length, vein density, and leaf mass per area) predicted a surprisingly large amount of the variation in biomass across treatments, but trait associations with biomass differed within treatments. Additionally, the importance of these traits in predicting variation in biomass is mediated, at least in part, through leaf size. Our results demonstrate the importance of leaf anatomical traits in mediating drought responses in sunflower, and highlight the role that phenotypic plasticity and multi-trait phenotypes can play in predicting productivity under complex abiotic stresses like drought.

Adult attachment assessed via the ASA and AAI: Empirical convergence and links with autonomic physiological responding during attachment assessments.

This study examined the empirical convergence of Attachment Script Assessment (ASA) deactivation, hyperactivation, and anomalous scripts with conceptually corresponding attachment patterns assessed via the Adult Attachment Interview (AAI), and the significance of ASA dimensions for autonomic physiological reactivity during adult attachment assessments. Young adults' (50% male; Mage = 19 years; 80% White/European American) ASA deactivation, hyperactivation, and anomalous content were significantly associated with AAI dismissing (r = .26-.38), preoccupied (r = .31-.35), and unresolved (r = .37) states of mind, respectively. ASA hyperactivation and anomalous content were associated with heightened RSA reactivity to the AAI and ASA, aligning with expectations that these attachment patterns capture the tendency to heighten expressions of negative, traumatic experiences. ASA deactivation was associated with smaller increases in electrodermal activity to the ASA-indicative of less sympathetic arousal-converging with the tendency of individuals higher in deactivation to avoid discussing attachment themes in the ASA.

Deactivation, hyperactivation, and anomalous content in the attachment script assessment: stability over time and significance for parenting behavior and physiology.

This study examined the stability of Attachment Script Assessment (ASA) deactivation, hyperactivation, and anomalous content and their significance for parenting outcomes in mothers (Mage = 31 years; 78% White/European American) and 6-month-old infants. Comparable to ASA secure base script knowledge (SBSK), mothers' ASA deactivation, hyperactivation, and anomalous content were significantly, moderately stable over two years (r's = .40 - .43). Mothers' ASA hyperactivation and anomalous content were associated with greater maternal intrusiveness, whereas ASA deactivation was associated with greater detachment and less intrusiveness. Only ASA anomalous content was associated with lower maternal sensitivity. Mothers' ASA deactivation was associated with less dynamic change in respiratory sinus arrhythmia during the Still-Face Procedure-reflective of limited mobilization of physiological resources to support responding to infants. Findings support the validity of ASA deactivation, hyperactivation, and anomalous content scripts, and demonstrate their utility in examining adult attachment stability and predictive significance for parent-child outcomes.

The predictive significance of attachment script assessment hyperactivation and deactivation: evidence of associations with romantic relationship functioning.

This study examined the significance of a novel coding system for evaluating hyperactivation, deactivation, and anomalous content in the Attachment Script Assessment for romantic relationship functioning. In a sample of 208 couples (69% White, Mage 28.7 years), we tested whether ASA hyperactivation and deactivation were associated with theoretically relevant correlates, including observed behavior, parasympathetic reactivity, self-reported affective reactivity to conflict, and relationship satisfaction. Exploratory analyses examined associations of secure base script knowledge (SBSK) and anomalous content with these outcomes. ASA hyperactivation and deactivation were associated with behavioral, physiological, and self-reported functioning in theory-consistent ways. Anomalous content was not associated with romantic functioning. SBSK was associated with satisfaction, but this was not robust to covariates. Findings support the predictive validity of the hyperactivation and deactivation dimensions and suggest that these scales complement SBSK, enabling researchers to assess a wider range of behavioral and physiological indicators associated with distinctive forms of attachment insecurity.

The Attachment Script Assessment: Introduction of a coding system to evaluate deactivation, hyperactivation, and anomalous content.

Although research on adult attachment has yielded insight into the legacy of attachment for functioning in adulthood, methodological challenges persist in the assessment of adult attachment. The Adult Attachment Interview (AAI) offers a rich assessment of secure, insecure, and unresolved states of mind. However, it is resource intensive to administer and code. Attachment Script Assessment (ASA) offers a resource-effective alternative to the AAI. However, the ASA coding system only yields a single, security-like dimension: secure base script knowledge. Here, we introduce a complementary coding system for the ASA to assess attachment deactivation (i.e. script characterized by limited interpersonal connection and minimization of attachment problems/emotions), hyperactivation (i.e. script in which attachment-relevant problems and negative emotions are heightened), and anomalous content (i.e. script in which attachment problems contain elements of fear and/or disorientation); and we discuss the conceptual convergence of these scripts with corresponding patterns of attachment insecurity and disorganization.

Barriers to therapy adherence in narcolepsy.

BACKGROUND: Treatment adherence (TA) in narcolepsy is a complex phenomenon influenced by various factors beyond patient-related aspects. The management of narcolepsy involves non-pharmacological and symptomatic pharmacological treatment. Factors such as chronic daytime sleepiness, cognitive deficits, psychiatric comorbidities and adverse effects of pharmacological treatment are aspects of narcolepsy that could undermine TA, impacting patients' ability or willingness to consistently follow treatment plans. The aim of this study was to identify the factors influencing TA in narcolepsy and to determine the most significant barriers to adherence. METHODS: An online survey was conducted during the pandemic, assessing demographic and clinical data, medication usage, and adverse effects of treatment. Various questionnaires, such as the Adherence Barriers Questionnaire (ABQ) and Epworth Sleepiness Scale (ESS), were utilized. The ABQ identified patient-specific barriers to medication adherence, while the Patient Health Questionnaire (PHQ-9) assessed depressive symptoms. RESULTS: We analyzed 243 narcolepsy patients (77 % female, mean age 35.7 ± 12.3 years) with 71 % having narcolepsy type 1 (NT1). The average ESS score was 16.4 (SD ± 3.7). Adherence barriers (AB) were identified in 89 % of patients (216/243) based on ABQ score. The most common barriers reported were "Forgetfulness" (77 %), "Depression" (57 %), and "Side effect-driven medication reduction/stopping behavior" (49 %). Approximately 72 % of patients reported side effects from their narcolepsy medication, leading to discontinuation in 78 % of cases. A moderate correlation was found between the severity of adherence barriers (ABQ score) and levels of depression (PHQ-9 score; rs = 0.412, p = 00.000), as well as ESS score (p = . 048). The results of this study may have been influenced by the pandemic situation. CONCLUSION: Adherence barriers are common (89 %) and diverse among people with narcolepsy. Many barriers are related to excessive daytime sleepiness (EDS), cognitive deficits or depressive symptoms, highlighting the importance of recognizing and addressing them for optimal TA. Medication side effects, especially occurring when polypharmacology is utilized, also significantly contribute to adherence challenges. Effective communication regarding therapy adherence and improved detection and management of EDS and depression are crucial for enhancing TA in narcolepsy patients.

An Exploration of Contraceptive Choice Pathways in Adolescents and Young Adults.

PURPOSE: To visualize contraceptive choice pathways among adolescent and young adults (AYA) designated female at birth (DFAB) as a means of exploring the relationships between current contraceptive use, desired contraceptive, and ultimately, chosen contraceptive method. METHODS: A retrospective cross-sectional study was conducted of AYA DFAB (N=2369), aged 14-24 years, presenting for initial visit at a contraceptive clinic with standardized efficacy-based counseling. Sankey diagrams were utilized to visualize patient flow through the contraceptive decision-making process. Outcomes of interest were current contraceptive method, desired contraceptive prior to contraceptive counseling, and then chosen contraception. Chi-Square tests were conducted to quantify the strength of the relationships identified by the Sankey diagrams. RESULTS: Sankey diagrams demonstrated a fair amount of change from current contraceptive to desired contraceptive and from current contraceptive to chosen contraceptive. A stronger relationship was evident between desired contraceptive method and chosen method; most patients did not change their desired contraceptive after receiving counseling except AYA who were undecided about their desired contraceptive who flowed variably into all available methods. Chi-Square test assessing the association between desired and chosen contraceptive method was significant at p-value <0.001, validating the patterns identified with the Sankey diagrams. DISCUSSION: We identified distinct contraceptive decision-making pathways among AYA which could inform the framework for a more tailored counseling approach. These findings are aligned with national medical organizations' recommendations for provision of non-coercive, patient-centered contraceptive counseling to promote adolescent reproductive autonomy.

Interdisciplinary Implementation of a Synoptic Reporting Template for Melanoma Nodal Surveillance Ultrasound.

BACKGROUND: With nodal surveillance increasingly used for sentinel lymph node-positive (SLN+) melanoma following the Second Multicenter Selective Lymphadenectomy Trial (MSLT-II), high-quality nodal ultrasonography (U/S) has become a critical need. Previous work has demonstrated low utilization of MSLT-II U/S criteria to define abnormal lymph nodes requiring intervention or biopsy. To address this gap, an evidence-based synoptic template was designed and implemented in this single-center study. METHODS: Sentinel lymph node-positive patients undergoing nodal surveillance at a tertiary cancer center from July 2017 to June 2023 were identified retrospectively. Ultrasound reporting language was analyzed for MSLT-II criteria reported and clinically actionable recommendations (e.g., normal, abnormal with recommendation for biopsy). Following a multidisciplinary design process, the synoptic template was implemented in January 2023. Postimplementation outcomes were evaluated by using U/S reports and provider surveys. RESULTS: A total of 337 U/S studies were performed on 94 SLN+ patients, with a median of 3 U/S per patient (range 1-12). Among 42 synoptic-eligible U/S performed postimplementation, 32 U/S (76.0%) were reported synoptically. Significant increases were seen in the number of MSLT-II criteria reported (Pre 0.5 ± 0.8 vs. Post 2.5 ± 1.0, p < 0.001), and clinically actionable recommendations for abnormal findings (Pre 64.0% vs. Post 93.0%, p = 0.04). Nearly all surgeon and radiologist survey respondents were "very" or "completely" satisfied with the clinical utility of the synoptic template (90.0%). CONCLUSIONS: Following implementation of a synoptic template, U/S reports were significantly more likely to document MSLT-II criteria and provide an actionable recommendation, increasing usefulness to providers. Efforts to disseminate this synoptic template to other centers are ongoing.

Rapid simultaneous estimation of relaxation rates using multi-echo, multi-contrast MRI.

PURPOSE: Multi-echo, multi-contrast methods are increasingly used in dynamic imaging studies to simultaneously quantify R2∗ and R2. To overcome the computational challenges associated with nonlinear least squares (NLSQ) fitting, we propose a generalized linear least squares (LLSQ) solution to rapidly fit R2∗ and R2. METHODS: Spin- and gradient-echo (SAGE) data were simulated across T2∗ and T2 values at high (200) and low (20) SNR. Full (four-parameter) and reduced (three-parameter) parameter fits were implemented and compared with both LLSQ and NLSQ fitting. Fit data were compared to ground truth using concordance correlation coefficient (CCC) and coefficient of variation (CV). In vivo SAGE perfusion data were acquired in 20 subjects with relapsing-remitting multiple sclerosis. LLSQ R2∗ and R2, as well as cerebral blood volume (CBV), were compared with the standard NLSQ approach. RESULTS: Across all fitting methods, T2∗ was well-fit at high (CCC = 1, CV = 0) and low (CCC ≥ 0.87, CV ≤ 0.08) SNR. Except for short T2∗ values (5-15 ms), T2 was well-fit at high (CCC = 1, CV = 0) and low (CCC ≥ 0.99, CV ≤ 0.03) SNR. In vivo, LLSQ R2∗ and R2 estimates were similar to NLSQ, and there were no differences in R2∗ across fitting methods at high SNR. However, there were some differences at low SNR and for R2 at high and low SNR. In vivo NLSQ and LLSQ three parameter fits performed similarly, as did NLSQ and LLSQ four-parameter fits. LLSQ CBV nearly matched the standard NLSQ method for R2∗- (0.97 ratio) and R2-CBV (0.98 ratio). Voxel-wise whole-brain fitting was faster for LLSQ (3-4 min) than NLSQ (16-18 h). CONCLUSIONS: LLSQ reliably fit for R2∗ and R2 in simulated and in vivo data. Use of LLSQ methods reduced the computational demand, enabling rapid estimation of R2∗ and R2.

Cancer-related cognitive impairment as a key contributor to psychopathology in cancer survivors: implications for prevention, treatment and supportive care.

A significant proportion of cancer survivors will experience some form of mental health compromise across domains including mood, anxiety, psychosis, eating disorders, and substance use. This psychopathology within cancer survivors is related to a range of negative outcomes and can also have a substantial negative impact on quality of life. Along with psychopathology, cognitive impairments are also commonly experienced, resulting in deficits in memory, reasoning, decision-making, speed of processing, and concentration, collectively referred to as cancer-related cognitive impairment (CRCI). Within the non-oncology literature, cognitive deficits are consistently demonstrated to be a key transdiagnostic aetiological feature of psychopathology, functionally contributing to the development and perpetuation of symptoms. Whilst there is an acknowledgement of the role mental health concerns might play in the development of and perception of CRCI, there has been limited acknowledgement and research exploring the potential for CRCI to functionally contribute toward the development of transdiagnostic psychopathology in cancer survivors beyond simply psychosocial distress. Given the theoretical and empirical evidence suggesting cognitive deficits to be an aetiological factor in psychopathology, we provide a rationale for the potential for CRCI to be a factor in the development and perpetuation of transdiagnostic psychopathology in cancer survivors. This potential functional association has significant implications for risk identification, prevention, treatment, and supportive cancer care approaches regarding psychopathology in cancer survivorship. We conclude by providing directions for future research in this area.

Potential effects of traffic noise on anuran call characteristics in Louisiana, USA during winter.

Urban environments expose wildlife to levels of anthropogenic noise they would not experience in rural areas (e.g., traffic noise), and research suggests that many species adjust their acoustic signals for optimal transmission in urban soundscapes. However, our understanding of anuran (order Anura) responses to noise pollution in urban environments of the southeastern United States is limited, particularly for species that can breed during winter. Our goal was to examine how vocal anuran advertisement call characteristics during winter varied with increasing distance from roadways in bottomland hardwoods of Louisiana, USA. We deployed acoustic recording units at two sites (i.e., rural and urban) perpendicular to Interstate 10 at 200-, 400-, and 600-m intervals (i.e., close, middle, and far) from November 2019 to January 2020. We detected Cajun Chorus Frogs (Pseudacris fouquettei) and Cricket Frogs (Acris spp.) at our rural site, and only detected Cricket Frogs at our urban site. At the rural site, Cajun Chorus Frogs produced longer duration notes at the far location compared to the middle location. At the urban site, Cricket Frogs produced higher dominant frequency calls at the close location compared to the far and middle locations and longer duration notes at the far location compared to the close location. We were unable to account for additional factors in our models (e.g., temperature, noise levels), but our results generally align with previous research. Our study provides baseline data for future research to examine the potential effects of traffic noise on winter advertisement calls in locations with similar environmental conditions and species.

Pigmented Villonodular Synovitis: A Metastatic Melanoma Imitator.

ABSTRACT: A 45-year-old woman with a history of previously treated left plantar foot melanoma presented with a left thigh mass. Fine needle aspiration findings were concerning for metastatic melanoma (MM). Imaging was remarkable for PET-avidity of both the biopsied thigh mass and of a left posterior knee nodule. The knee nodule was also enhancing on MRI, concerning for a site of metastasis. Resection of the thigh mass and intra-articular nodule was performed. The thigh lesion was positive for MM. The specimen obtained from the knee demonstrated a proliferation of spindle and epithelioid cells associated with focal fibrosis and scattered giant cells with brown pigment, raising the possibility of melanoma metastasis with treatment effect. Additional immunohistochemical studies with anti-SOX10 failed to demonstrate melanoma cells in the lesion. The final diagnosis for the knee nodule was pigmented villonodular synovitis. This case highlights the potential for pigmented villonodular synovitis to mimic MM, requiring additional pathologic analysis to yield an accurate diagnosis.

Clinician characteristics associated with fluoride varnish applications during well-child visits.

OBJECTIVES: To identify factors associated with clinicians' likelihood and intensity of applying fluoride varnish (FV) overall and for visits paid by Medicaid and private insurers. STUDY DESIGN: Observational study using claims data. METHODS: Using the Massachusetts All-Payer Claims Database (2016-2018), we conducted a repeated cross-sectional study of 2911 clinicians (7277 clinician-year observations) providing well-child visits to children aged 1 to 5 years. Zero-inflated negative binomial models estimated the probability of a clinician applying FV and the number of visits with FV applications, overall and separately for visits paid by Medicaid and private insurers. RESULTS: A total of 30.9% of clinician-years applied FV at least once, and overall, an average of 8.4% of a clinician's well-child visits included FV annually. Controlling for all covariates, having a higher percentage of patients insured by Medicaid was associated with applying FV (OR, 1.35; 95% CI, 1.23-1.45) and a higher expected number of applications (OR, 1.05; 95% CI, 1.02-1.09). Additionally, having a higher percentage of patients aged 1 to 5 years was associated with applying FV (OR, 1.20; 95% CI, 1.01-1.43), but not the number of applications. Similar associations were observed among visits paid by private insurers. CONCLUSIONS: Despite clinical recommendations and mandated insurance reimbursements, the likelihood and intensity of FV applications was low for most pediatric primary care clinicians. Clinician behavior was associated with patient-panel characteristics, suggesting the need for interventions that account for these differences.

Diagnosis of Graves' Disease and Methimazole-Induced Lupus Erythematosus in an Adolescent Male During the COVID-19 Era: A Case Report.

Graves' disease is the most common form of hyperthyroidism in the pediatric population. Methimazole is the recommended regimen that is well-tolerated in most patients. Treatment with methimazole leading to drug-induced lupus erythematosus (DILE) is not well reported in the pediatric population, especially in the COVID-19 era. We present a case of a 14-year-old Caucasian male who presented with concerns of long COVID due to shortness of breath, hypertension, and fatigue. He was not noted to have significant weight loss, exophthalmos, or sleeping difficulties. He was followed by his general pediatrician, pediatric endocrinologist, cardiologist, and rheumatologist. Laboratory tests confirmed the diagnosis of Graves' disease, and treatment was initiated with methimazole and atenolol. One month into treatment, the patient developed polyarthritis, urticarial rash, and difficulty with gait. Based on clinical suspicion and antibody panels, he was diagnosed with DILE secondary to treatment with methimazole. The patient was then started on a potassium iodide (Lugol) solution to promote the euthyroid state and proceed with total thyroidectomy. Post surgery, the patient developed hypothyroidism, which was managed with oral levothyroxine, to which the patient responded well. By discussing the clinical presentation and treatment of this patient, the goal is to raise awareness and increase clinical suspicion in diagnosing Graves' and DILE in adolescents with upper respiratory presentations.

Cocoa and Polyphenol-Rich Cocoa Fractions Fail to Improve Acute Colonic Inflammation in Dextran Sulfate Sodium-Treated Mice.

SCOPE: A study is conducted to determine the anti-inflammatory effects of cocoa and polyphenol-rich cocoa fractions in the dextran sulfate sodium (DSS)-induced mouse model of acute colonic inflammation. METHODS AND RESULTS: Male C57BL/6J mice are treated with dietary cocoa powder, an extractable cocoa polyphenol fraction, or a non-extractable cocoa polyphenol fraction for 2 weeks prior to treatment with 2.5% DSS in the drinking water for 7 days to induce colonic inflammation. Cocoa treatment continues during the DSS period. Cocoa and/or cocoa fractions exacerbate DSS-induced weight loss and fail to mitigate DSS-induced colon shortening but do improve splenomegaly. Cocoa/cocoa fraction treatment fails to mitigate DSS-induced mRNA and protein markers of inflammation. Principal component analysis shows overlap between cocoa or cocoa fraction-treated mice and DSS-induced controls, but separation from mice not treated with DSS. CONCLUSION: The results suggest cocoa and cocoa polyphenols may not be useful in mitigating acute colonic inflammation.

Ambulatory Surgery Centers Reduce Patient Out-of-Pocket Expenditures for Isolated Arthroscopic Rotator Cuff Repair, but Patient Out-of-Pocket Expenditures Are Increasing at a Faster Rate Than Total Healthcare Utilization Reimbursement From Payers.

PURPOSE: To categorize and trend annual out-of-pocket expenditures for arthroscopic rotator cuff repair (RCR) patients relative to total healthcare utilization (THU) reimbursement and compare drivers of patient out-of-pocket expenditures (POPE) in a granular fashion via analyses by insurance type and surgical setting. METHODS: Patients who underwent outpatient arthroscopic RCR in the United States from 2013 to 2018 were identified from the IBM MarketScan Database. Primary outcome variables were total POPE and THU reimbursement, which were calculated for all claims in the 9-month perioperative period. Trends in outcome variables over time and differences across insurance types were analyzed. Multivariable analysis was performed to investigate drivers of POPE. RESULTS: A total of 52,330 arthroscopic RCR patients were identified. Between 2013 and 2018, median POPE increased by 47.5% ($917 to $1,353), and median THU increased by 9.3% ($11,964 to $13,076). Patients with high deductible insurance plans paid $1,910 toward their THU, 52.5% more than patients with preferred provider plans ($1,253, P = .001) and 280.5% more than patients with managed care plans ($502, P = .001). All components of POPE increased over the study period, with the largest observed increase being POPE for the immediate procedure (P = .001). On multivariable analysis, out-of-network facility, out-of-network surgeon, and high-deductible insurance most significantly increased POPE. CONCLUSIONS: POPE for arthroscopic RCR increased at a higher rate than THU over the study period, demonstrating that patients are paying an increasing proportion of RCR costs. A large percentage of this increase comes from increasing POPE for the immediate procedure. Out-of-network facility status increased POPE 3 times more than out-of-network surgeon status, and future cost-optimization strategies should focus on facility-specific reimbursements in particular. Last, ambulatory surgery centers (ASCs) significantly reduced POPE, so performing arthroscopic RCRs at ASCs is beneficial to cost-minimization efforts. CLINICAL RELEVANCE: This study highlights that although payers have increased reimbursement for RCR, patient out-of-pocket expenditures have increased at a much higher rate. Furthermore, this study elucidates trends in and drivers of patient out-of-pocket payments for RCR, providing evidence for development of cost-optimization strategies and counseling of patients undergoing RCR.

Collagen modification remodels the sarcoma tumor microenvironment and promotes resistance to immune checkpoint inhibition.

Molecular mechanisms underlying immune checkpoint inhibitor (ICI) response heterogeneity in solid tumors, including soft tissue sarcomas (STS), remain poorly understood. Herein, we demonstrate that the collagen-modifying enzyme, procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (Plod2), which is over-expressed in many tumors relative to normal tissues, promotes immune evasion in undifferentiated pleomorphic sarcoma (UPS), a relatively common and aggressive STS subtype. This finding is consistent with our earlier observation that Plod2 promotes tumor metastasis in UPS, and its enzymatic target, collagen type VI (ColVI), enhances CD8+ T cell dysfunction. We determined that genetic and pharmacologic inhibition of Plod2 with the pan-Plod transcriptional inhibitor minoxidil, reduces UPS growth in an immune competent syngeneic transplant system and enhances the efficacy of anti-Pd1 therapy. These findings suggest that PLOD2 is an actionable cancer target and its modulation could augment immunotherapy responses in patients with UPS, and potentially other sarcomas and carcinomas.

Innate immune response to Candida auris.

Candida auris, a newly emergent fungal species, has been spreading in health care systems and causing life-threatening infections. Intact innate immunity is essential for protection against many invasive fungal infections, including candidiasis. Here, we highlight recent studies exploring immune interactions with C. auris, including investigations using animal models and ex vivo immune cells. We summarize innate immune studies comparing C. auris and the common fungal pathogen Candida albicans. We also discuss how structures of the C. auris cell wall influence immune recognition, the role of soluble host factors in immune recognition, and areas of future study.

Influenza A virus during pregnancy disrupts maternal intestinal immunity and fetal cortical development in a dose- and time-dependent manner.

Epidemiological studies link exposure to viral infection during pregnancy, including influenza A virus (IAV) infection, with increased incidence of neurodevelopmental disorders (NDDs) in offspring. Models of maternal immune activation (MIA) using viral mimetics demonstrate that activation of maternal intestinal T helper 17 (TH17) cells, which produce effector cytokine interleukin (IL)-17, leads to aberrant fetal brain development, such as neocortical malformations. Fetal microglia and border-associated macrophages (BAMs) also serve as potential cellular mediators of MIA-induced cortical abnormalities. However, neither the inflammation-induced TH17 cell pathway nor fetal brain-resident macrophages have been thoroughly examined in models of live viral infection during pregnancy. Here, we inoculated pregnant mice with two infectious doses of IAV and evaluated peak innate and adaptive immune responses in the dam and fetus. While respiratory IAV infection led to dose-dependent maternal colonic shortening and microbial dysregulation, there was no elevation in intestinal TH17 cells nor IL-17. Systemically, IAV resulted in consistent dose- and time-dependent increases in IL-6 and IFN-γ. Fetal cortical abnormalities and global changes in fetal brain transcripts were observable in the high-but not the moderate-dose IAV group. Profiling of fetal microglia and BAMs revealed dose- and time-dependent differences in the numbers of meningeal but not choroid plexus BAMs, while microglial numbers and proliferative capacity of Iba1+ cells remained constant. Fetal brain-resident macrophages increased phagocytic CD68 expression, also in a dose- and time-dependent fashion. Taken together, our findings indicate that certain features of MIA are conserved between mimetic and live virus models, while others are not. Overall, we provide consistent evidence of an infection severity threshold for downstream maternal inflammation and fetal cortical abnormalities, which recapitulates a key feature of the epidemiological data and further underscores the importance of using live pathogens in NDD modeling to better evaluate the complete immune response and to improve translation to the clinic.