Renal medulla in hypertension

Abstract: Studies have found that blood flow to the renal medulla is an important determinant of pressure-natriuresis and the long-term regulation of arterial pressure. First, a brief review of methods developed enabling the study of the medullary circulation is presented. Second, studies performed in rats are presented showing medullary blood flow plays a vital role in the pressure-natriuresis relationship and thereby in hypertension. Third, it is shown that chronic reduction of medullary blood flow results in hypertension and that enhancement of medullary blood flow reduces hypertension hereditary models of both salt-sensitive rats and salt-resistant forms of hypertension. The key role that medullary nitric oxide production plays in protecting this region from ischemic injury associated with circulating vasoconstrictor agents and reactive oxygen species is presented. The studies cited are largely the work of my students, research fellows, and colleagues with whom I have performed these studies dating from the late 1980s to more recent years.

Equine intraocular melanocytic neoplasia.

Objective: To describe the clinical appearance, histopathology, and treatment of equine intraocular melanocytic neoplasia in adult horses. Animals and procedure: A retrospective review of medical records was conducted. Data recorded included signalment, ocular examination findings, physical examination findings, therapeutic interventions, and case outcomes. Histopathologic characteristics of enucleated globes were evaluated. A Student's t-test was used to evaluate differences in the interval from diagnosis to last known outcome between horses receiving therapeutic interventions and horses undergoing monitoring alone. Results: Of the 55 horses included, Arabian was the most common breed (15/55, 27%). Gray was the most common coat color (85%). Physical examination was completed for 75% of horses at time of diagnosis, and of those, 67% had cutaneous melanoma. The interval from diagnosis to last known outcome was not different (P = 0.312) between horses that underwent monitoring alone (median: 2.0 y) and those that received treatment (mean: 2.25 y). Conclusion: Equine intraocular melanocytic neoplasms are highly associated with cutaneous melanoma and gray coat color, and they are more prevalent than previously published reports suggest. Clinical relevance: A complete ophthalmic examination is indicated for all horses with cutaneous melanoma. Additional research into the timing and rationale for treatment of intraocular melanocytic neoplasia is necessary.

Néoplasie mélanocytaire intraoculaire équine. Objectif: Décrire l'aspect clinique, l'histopathologie et le traitement de la néoplasie mélanocytaire intraoculaire équine chez le cheval adulte. Animaux et procédure: Une étude rétrospective des dossiers médicaux a été réalisée. Les données enregistrées comprenaient le signalement, les résultats de l'examen oculaire, les résultats de l'examen physique, les interventions thérapeutiques et les résultats des cas. Les caractéristiques histopathologiques des globes énucléés ont été évaluées. Un test t de Student a été utilisé pour évaluer les différences dans l'intervalle entre le diagnostic et le dernier résultat connu entre les chevaux recevant des interventions thérapeutiques et les chevaux soumis à une surveillance seule. Résultats: Sur les 55 chevaux inclus, l'Arabe était la race la plus répandue (15/55, 27 %). Le gris était la couleur de robe la plus courante (85 %). L'examen physique a été réalisé pour 75 % des chevaux au moment du diagnostic, et parmi eux, 67 % présentaient un mélanome cutané. L'intervalle entre le diagnostic et le dernier résultat connu n'était pas différent (P = 0,312) entre les chevaux ayant subi une surveillance seule (médiane : 2,0 ans) et ceux ayant reçu un traitement (moyenne : 2,25 ans). Conclusion: Les néoplasmes mélanocytaires intraoculaires équins sont fortement associés au mélanome cutané et à la couleur du pelage gris, et ils sont plus fréquents que ne le suggèrent les rapports publiés précédemment. Pertinence clinique: Un examen ophtalmologique complet est indiqué pour tous les chevaux atteints de mélanome cutané. Des recherches supplémentaires sur la planification et la justification du traitement de la néoplasie mélanocytaire intraoculaire sont nécessaires.(Traduit par Dr Serge Messier).

Bovine papillomavirus gene expression and inflammatory pathway activation vary between equine sarcoid tumour subtypes.

Equine sarcoids are common non-metastasising skin tumours in horses, associated with bovine papillomavirus (BPV) infection. Six subtypes are recognised (occult, verrucose, nodular, fibroblastic, mixed and malevolent lesions), with variable clinical behaviour. The pathophysiology underlying varying tumour phenotype is poorly understood, and previous data on associations with viral load have been conflicting. To better understand this clinical variation, we investigated associations between tumour subtype and viral load, viral early protein gene expression, and expression of 10 host genes by quantitative polymerase chain reaction in 27 sarcoids and 5 normal skin samples. Viral DNA copy number did not differ between subtypes but was significantly higher in animals with fewer tumours. Expression of BPV E2 and E6 was higher in occult lesions compared to fibroblastic or nodular lesions, while E5 expression was higher in previously-treated lesions. Of the host genes, only IL6 and IL1B differed between subtypes, with higher expression in fibroblastic lesions, while IL10 and CCL5 were elevated compared to skin in all lesion types, and elevations in TNF and TGFB1 were significant for occult lesions only. Expression of TLR9, ATR, VEGFA and PTGS2 in sarcoids was not significantly different from normal skin, suggesting differences between BPV and human papillomavirus tumorigenesis. Results for BPV viral load and gene expression differed from previous reports and are insufficient to explain the spectrum of tumour phenotypes. Activation of both pro-inflammatory and anti-inflammatory immune pathways in sarcoids could influence tumour growth and effective immune responses, and the contribution of specific infiltrating immune cells requires further investigation.

Simultaneous viscoelasticity and sprayability in antimicrobial acetic acid-alginate fluid gels.

Acetic acid is a promising alternative to antibiotics for topical applications, particularly burn wounds, however its site specificity and retention are impaired by poor material properties. In this study, acetic acid was investigated as both the gelling agent and antimicrobial active in alginate fluid gels. The formed microstructure was found to be directly dependent on acetic acid concentration, leading to highly tuneable material properties. At clinically relevant concentrations of 2.5-5 % acetic acid, the fluid gels were elastically dominated at rest, with viscosities up to 7 orders of magnitude greater than acetic acid alone. These material properties imparted long term surface retention and microparticle barrier function, not seen with either acetic acid or alginate solutions. Most notably, sprayability was enhanced simultaneously with the increased viscosity and elasticity due to the introduction of a discretised microstructure, leading to a remarkable tenfold increase in spray coverage. Formulation was found not to inhibit antimicrobial activity, despite the less acidic pH, with common burn wound pathogens Staphylococcus aureus and Pseudomonas aeruginosa being equally susceptible to the fluid gels as to acetic acid solutions.

The role of PINK1-Parkin in mitochondrial quality control.

Mitophagy mediated by the recessive Parkinson's disease genes PINK1 and Parkin responds to mitochondrial damage to preserve mitochondrial function. In the pathway, PINK1 is the damage sensor, probing the integrity of the mitochondrial import pathway, and activating Parkin when import is blocked. Parkin is the effector, selectively marking damaged mitochondria with ubiquitin for mitophagy and other quality-control processes. This selective mitochondrial quality-control pathway may be especially critical for dopamine neurons affected in Parkinson's disease, in which the mitochondrial network is widely distributed throughout a highly branched axonal arbor. Here we review the current understanding of the role of PINK1-Parkin in the quality control of mitophagy, including sensing of mitochondrial distress by PINK1, activation of Parkin by PINK1 to induce mitophagy, and the physiological relevance of the PINK1-Parkin pathway.

The glutamate receptor antagonist ifenprodil inhibits hepatitis E virus infection.

Infection with hepatitis E virus (HEV) represents a global problem, with over 20 million people infected annually. No specific antiviral drugs are available for treating HEV infection, necessitating the development of novel targeted therapeutics. Here, we report that the N-methyl-D-aspartate receptor (NMDAR) antagonist ifenprodil, a clinically approved drug used to treat idiopathic pulmonary fibrosis (IPF), is an HEV inhibitor in liver-derived cells. In vitro investigation demonstrates that ifenprodil suppresses viral protein expression in a dose-dependent manner in human hepatoma cells by inhibiting early stages of viral infection. We also found that ifenprodil modulates host cell intrinsic biological processes distinct from virus-induced innate immunity, inhibiting HEV RNA accumulation in primary human hepatocytes. Finally, the inhibitory effect of ifenprodil in vivo was also tested in rabbits challenged with the HEV-3ra CHN-BJ-R14 strain. Fecal virus shedding was below the limit of detection in two animals for both ribavirin-treated and ifenprodil-treated rabbits compared to vehicle-treated control animals. Our data demonstrate that ifenprodil is an effective anti-HEV compound with potential as a therapeutic candidate for the treatment of HEV infection.

1-year health outcomes associated with systemic corticosteroids for COVID-19: a longitudinal cohort study.

Background: In patients with coronavirus disease 2019 (COVID-19) requiring supplemental oxygen, dexamethasone reduces acute severity and improves survival, but longer-term effects are unknown. We hypothesised that systemic corticosteroid administration during acute COVID-19 would be associated with improved health-related quality of life (HRQoL) 1 year after discharge. Methods: Adults admitted to hospital between February 2020 and March 2021 for COVID-19 and meeting current guideline recommendations for dexamethasone treatment were included using two prospective UK cohort studies (Post-hospitalisation COVID-19 and the International Severe Acute Respiratory and emerging Infection Consortium). HRQoL, assessed by the EuroQol-Five Dimensions-Five Levels utility index (EQ-5D-5L UI), pre-hospital and 1 year after discharge were compared between those receiving corticosteroids or not after propensity weighting for treatment. Secondary outcomes included patient-reported recovery, physical and mental health status, and measures of organ impairment. Sensitivity analyses were undertaken to account for survival and selection bias. Findings: Of the 1888 participants included in the primary analysis, 1149 received corticosteroids. There was no between-group difference in EQ-5D-5L UI at 1 year (mean difference 0.004, 95% CI -0.026-0.034). A similar reduction in EQ-5D-5L UI was seen at 1 year between corticosteroid exposed and nonexposed groups (mean±sd change -0.12±0.22 versus -0.11±0.22). Overall, there were no differences in secondary outcome measures. After sensitivity analyses modelled using a cohort of 109 318 patients admitted to hospital with COVID-19, EQ-5D-5L UI at 1 year remained similar between the two groups. Interpretation: Systemic corticosteroids for acute COVID-19 have no impact on the large reduction in HRQoL 1 year after hospital discharge. Treatments to address the persistent reduction in HRQoL are urgently needed.

Detection of carbon dioxide and hydrogen peroxide on the stratified surface of Charon with JWST.

Charon, Pluto's largest moon, has been extensively studied, with research focusing on its primitive composition and changes due to radiation and photolysis. However, spectral data have so far been limited to wavelengths below 2.5 µm, leaving key aspects unresolved. Here we present the detection of carbon dioxide (CO2) and hydrogen peroxide (H2O2) on the surface of Charon's northern hemisphere, using JWST data. These detections add to the known chemical inventory that includes crystalline water ice, ammonia-bearing species, and tholin-like darkening constituents previously revealed by ground- and space-based observations. The H2O2 presence indicates active radiolytic/photolytic processing of the water ice-rich surface by solar ultraviolet and interplanetary medium Lyman-α photons, solar wind, and galactic cosmic rays. Through spectral modeling of the surface, we show that the CO2 is present in pure crystalline form and, possibly, in intimately mixed states on the surface. Endogenically sourced subsurface CO2 exposed on the surface is likely the primary source of this component, with possible contributions from irradiation of hydrocarbons mixed with water ice, interfacial radiolysis between carbon deposits and water ice, and the implantation of energetic carbon ions from the solar wind and solar energetic particles.

Endonasal Thermal Imaging Before and After Nasal Airway Surgery.

OBJECTIVE: Nasal airway surgery is often applied when treatment fails to relieve nasal obstruction. However, surgery that improves airflow does not always alleviate the symptoms of nasal obstruction. The perception of nasal breathing is likely more related to changes in mucosal temperature than the mechanical sensation of flow or pressure. This study aims to measure intranasal mucosal temperature pre-and post-surgery using endonasal thermal imaging, exploring its correlation with subjective nasal breathing and objective airflow measurements. METHODS: A prospective study of adult patients with nasal obstruction managed with nasal airway surgery was performed. Intranasal mucosal temperatures were determined using the thermal endonasal image of the nasal passage produced by the infrared radiometric thermal camera (FILR VS290). A comparison was made between the mean values of mid-expiration (ExT) and mid-inspiration (InT) temperature data (internal nasal valve, nasal cavity, inferior turbinate, and overall airway [mean value]) and visual analog scale (VAS), Nasal Obstruction Symptom Evaluation (NOSE) scale and nasal airway resistance (NAR) before and after surgery. RESULTS: Seven patients (35.14 ± 16.45 years, 57.14% female) were included. All NOSE, VAS, and NAR improved after surgery (59.29 ± 10.89 vs 17.14 ± 14.64; P < .001, 64.50 ± 26.79 vs 18.57 ± 19.99; P < .001, 0.82 ± 0.48 vs 0.34 ± 0.11 Pa/cm3/s; P = .002, respectively). ExT, InT, and the difference between ExT and InT of three areas and overall airway were similar between pre-and post-surgery. No statistically significant correlations were found between intranasal mucosal temperature, VAS, NOSE, and NAR at pre-and post-surgery except for the difference between ExT and InT of overall airway and NOSE pre-operative (Pearson r = 0.57; 95% CI 0.06-1.09; P = .03). CONCLUSION: Endonasal thermal imaging can assess the intranasal mucosal temperature of a patient. However, more precise imaging of the nasal passages and data acquisition are required to establish mucosal temperature as an objective measure of nasal obstruction before and after nasal airway surgery in a clinical setting.

The Alzheimer's Disease Neuroimaging Initiative Neuropathology Core: An update.

INTRODUCTION: Biomarkers for Alzheimer's disease neuropathologic change (ADNC) have been instrumental in developing effective disease-modifying therapeutics. However, to prevent/treat dementia effectively, we require biomarkers for non-AD neuropathologies; for this, neuropathologic examinations and annotated tissue samples are essential. METHODS: We conducted clinicopathologic correlation for the first 100 Alzheimer's Disease Neuroimaging Initiative (ADNI) Neuropathology Core (NPC) cases. RESULTS: Clinical syndromes in this cohort showed 95% sensitivity and 79% specificity for predicting high/intermediate ADNC, a 21% false positive rate, and a ∼44% false negative rate. In addition, 60% with high/intermediate ADNC harbored additional potentially dementing co-pathologies. DISCUSSION: These results suggest that clinical presentation imperfectly predicts ADNC and that accurate prediction of high/intermediate ADNC does not exclude co-pathology that may modify presentation, biomarkers, and therapeutic responses. Therefore, new biomarkers are needed for non-AD neuropathologies. The ADNI NPC supports this mission with well-characterized tissue samples (available through ADNI and the National Institute on Aging) and "gold-standard" diagnostic information (soon to include digital histology). HIGHLIGHTS: The Alzheimer's Disease Neuroimaging Initiative (ADNI) Neuropathology Core (NPC) brain donation cohort now exceeds 200 cases. ADNI NPC data in National Alzheimer's Coordinating Center format are available through the Laboratory of Neuro Imaging. Digitized slide files from the ADNI NPC will be available in 2025. Requests for ADNI brain tissue samples can be submitted online for ADNI/National Institute on Aging evaluation. Clinical diagnoses of Alzheimer's disease (AD)/AD and related dementias (ADRD) do not always predict post mortem neuropathology. Neuropathology is essential for the development of novel AD/ADRD biomarkers.

A randomized, placebo-controlled, dose-escalation phase I/II multicenter trial of low-dose cidofovir for BK polyomavirus nephropathy.

BACKGROUND: BK polyomavirus-associated nephropathy (BKPyVAN) is an important cause of allograft dysfunction and failure in kidney transplant recipients (KTRs) and there are no proven effective treatments. Case reports and in vitro data support the potential activity of cidofovir against BK polyomavirus (BKPyV). METHODS: We report the results of a phase I/II, double-blind, placebo-controlled randomized dose-escalation trial of cidofovir in KTRs with biopsy-confirmed BKPyVAN and estimated glomerular filtration rate ≥30 mL/min. Intravenous cidofovir (0.25 mg/kg/dose or 0.5 mg/kg/dose) or placebo was administered on days 0, 7, 21, and 35, with final follow-up through day 49. RESULTS: The trial was prematurely discontinued due to slow accrual after 22 KTRs had completed the study. Cidofovir was safe and tolerated at the doses and duration studied. The proportion of subjects with any adverse event (AE) was similar between groups (9/14 [64%] in the combined cidofovir dose groups and 6/8 [75%] in the placebo group); 84% of AEs were mild. BKPyV DNAemia reduction by day 49 was similar between groups (>1 log10 reduction in (2/9 [22.2%] of 0.25 mg/kg group, 1/5 [20%] of 0.5 mg/kg group, and 2/8 [25%] of placebo group). CONCLUSIONS: These preliminary results indicate that low-dose cidofovir was safe and tolerated but had no significant BKPyV-specific antiviral effect in KTRs with BKPyVAN.

Clinical Implications of Basic Research: Exploring the Transformative Potential of Spatial 'Omics in Uro-oncology.

New spatial molecular technologies are poised to transform our understanding and treatment of urological cancers. By mapping the spatial molecular architecture of tumours, these platforms uncover the complex heterogeneity within and around individual malignancies, offering novel insights into disease development, progression, diagnosis, and treatment. They enable tracking of clonal phylogenetics in situ and immune-cell interactions in the tumour microenvironment. A whole transcriptome/genome/proteome-level spatial analysis is hypothesis generating, particularly in the areas of risk stratification and precision medicine. Current challenges include reagent costs, harmonisation of protocols, and computational demands. Nonetheless, the evolving landscape of the technology and evolving machine learning applications have the potential to overcome these barriers, pushing towards a future of personalised cancer therapy, leveraging detailed spatial cellular and molecular data. PATIENT SUMMARY: Tumours are complex and contain many different components. Although we have been able to observe some of these differences visually under the microscope, until recently, we have not been able to observe the genetic changes that underpin cancer development. Scientists are now able to explore molecular/genetic differences using approaches such as "spatial transcriptomics" and "spatial proteomics", which allow them to see genetic and cellular variation across a region of normal and cancerous tissue without destroying the tissue architecture. Currently, these technologies are limited by high associated costs, and a need for powerful and complex computational analysis workflows. Future advancements and results through these new technologies may assist patients and their doctors as they make decisions about treating their cancer.

Flavored electronic nicotine delivery system product use among adults in New York State post-statewide restriction implementation.

In May 2020, New York State restricted the sale of flavored e-liquids, excluding tobacco flavor. We conducted a Web-based survey to assess support and changes in use behavior between July and October 2020 (n = 946), with a follow-up between April and June 2021 (n = 542). Most electronic nicotine delivery system (ENDS) users (n = 82/55) continued to use, with 39%/33% reporting continuing to purchase flavored e-liquids, 20%/32% reporting using tobacco flavor, 5%/6% reporting quitting ENDS and smoking cigarettes, and 8%/3% reporting quitting ENDS and not smoking cigarettes. In 2020, 65% of non-users, 53% of cigarette users, 34% of cigarette/ENDS users, and 18% of ENDS users supported this policy restriction on e-liquids. Similar results were observed in 2021. Many ENDS users continued purchasing flavored e-liquids, suggesting that compliance with the policy can be improved. Cigarette smoking did not appear to increase. Continued evaluation of how restrictions on sales of products influence use is critical to understanding the long-term impact on behavior.

Make It or Break It? Injury Impacts More Than Half of Deselected Athletes Who Dropped Out of the High-Performance Pathway System. A 4-Year Retrospective Cohort Study.

To investigate: (1) the injury epidemiology in an Australian academy; (2) how athletes transition through the high-performance sport (HPS) pathway; and (3) why athletes leave this HPS program. This retrospective cohort study was conducted at an Australian HPS academy over a 4-year period. Medical attention injuries were prospectively recorded. Injury incidence rates (IIR) and burden were calculated per 365 athlete-days, according to sport, sex, and pathway level. Athlete pathway levels were mapped to the Foundations, Talent, Elite, and Mastery (FTEM) framework. Reasons for athletes transitioning out were reported. Four hundred and eighty-one injuries were reported across 124 athletes at an IIR of 2.09 injuries per 365 athlete-days (95% CI = 1.91-2.29). Most athletes (103, 83.1%) were injured at least once over the 4-year period. IIRs increased (IRR = 1.17, 95% CI = 1.06-1.29, p = 0.001) as athletes progressed through the pathway. The most common reason for athlete attrition was deselection due to performance (n = 18), with 55.6% of these athletes sustaining an injury in the season prior to deselection. Injury burden was highest at E2 (119.5 days absence per 365 athlete-days (95% CI = 62.18-229.67)) and lowest at T4 (30.47 days absence per 365 athlete-days (95% CI = 21.98-42.24)). Injury occurrence is common across HPS, with IIRs increasing as athletes progressed to higher talent levels. Deselection due to poor performance was the main attrition factor, with more than half the deselected athletes impacted by injury prior to deselection. This study highlights an increased risk of deselection, following injury, and indicates the need for further development of prevention strategies targeting pathway athletes.

An IL-17-DUOX2 axis controls gastrointestinal colonization by Candida albicans.

Candida albicans is a ubiquitous fungus in the human gut microbiome as well as a prevalent cause of opportunistic mucosal and systemic disease. There is currently little understanding, however, as to how crosstalk between C. albicans and the host regulates colonization of this key niche. Here, we performed expression profiling on ileal and colonic tissues in germ-free mice colonized with C. albicans to define the global response to this fungus. We reveal that Duox2 and Duoxa2 , encoding dual NADPH oxidase activity, are upregulated in both the ileum and colon, and that induction requires the C. albicans yeast-hyphal transition and the hyphal-specific toxin candidalysin. Hosts lacking the IL-17 receptor failed to upregulate Duox2/Duoxa2 in response to C. albicans , while addition of IL-17A to colonoids induced these genes together with the concomitant production of hydrogen peroxide. To directly define the role of Duox2/Duoxa2 in fungal colonization, antibiotic-treated mice lacking intestinal DUOX2 activity were evaluated for C. albicans colonization and host responses. Surprisingly, loss of DUOX2 function reduced fungal colonization at extended time points (>17 days colonization) and increased the proportion of hyphal cells in the gut. IL-17A levels were also elevated in C. albicans -colonized mice lacking functional DUOX2 highlighting cross-regulation between this cytokine and DUOX2. Together, these experiments reveal novel links between fungal cells, candidalysin toxin and the host IL-17-DUOX2 axis, and that a complex interplay between these factors regulates C. albicans filamentation and colonization in the gut.

The Relationship Between Physical Activity and Non-Modifiable Risk Factors on Alzheimer's Disease and Brain Health Markers: A UK Biobank Study.

Background: Modifiable (physical activity) and non-modifiable (sex and genotype) risk factors interact to affect Alzheimer's disease (AD) risk. Further investigation is necessary to understand if these factors influence brain volume and cognition. Objective: The study aimed to assess the effect of physical activity, APOE genotype, and sex on AD risk, brain volume, and cognition. Methods: UK Biobank data from 2006 to 2023 was accessed. Physical activity was measured by accelerometers, and International Physical Activity Questionnaire. Outcomes were AD incidence; brain volume (ventricular cerebrospinal fluid and total brain); and cognition (executive function, memory, visuospatial ability, processing speed, and reaction time). Logistic and linear regression models were conducted. Results: 69,060 participants met inclusion criteria (mean age: 62.28 years, SD: 7.84; 54.64% female). Higher self-reported (OR = 0.63, 95% CI [0.40, 1.00], p = 0.047) and accelerometer-assessed (OR = 0.96 [0.93, 0.98], p = 0.002) physical activity was associated with lower disease incidence. Smaller ventricular cerebrospinal fluid volume (ß= - 65.43 [- 109.68, - 17.40], p = 0.007), and larger total brain volume (ß= 4398.46 [165.11, 8631.82], p <  0.001) was associated with increased accelerometer-assessed and self-reported physical activity respectively. Both brain volume analyses were moderated by sex. Increased accelerometer-assessed physical activity levels were associated with faster reaction time (ß= - 0.43 [- 0.68, - 0.18], p = 0.001); though poorer visuospatial ability (ß= - 0.06 [- 0.09, - 0.03], p <  0.001), and executive function (ß= 0.49 [0.31, 0.66], p <  0.001; ß= 0.27 [0.10, 0.45], p = 0.002) was related to self-reported physical activity levels. Conclusions: Higher levels of physical activity reduce AD risk independently of non-modifiable risk factors. Moderation of sex on brain volume highlighted the importance of incorporating non-modifiable risk factors in analysis.

A Validated Calculator to Estimate Risk of Chorioamnionitis in Laboring and Induced Patients at Term.

OBJECTIVE: Chorioamnionitis is associated with neonatal morbidity and infection-related mortality, but our ability to predict intrapartum infection is limited. We sought to derive and validate a prediction model for chorioamnionitis among patients presenting to labor and delivery at term. STUDY DESIGN: This was a planned secondary analysis of a large cohort study from 2014 through 2018 at an academic tertiary care center. To derive a prediction model for chorioamnionitis, we limited our analysis to full-term (≥37 weeks) patients with a singleton gestation undergoing labor induction and presenting in labor. Both nulliparous and multiparous patients were included. Patients with a planned cesarean delivery, fever on admission, or missing data were excluded. The model was derived using multivariable logistic regression. Refinement of the prediction model with internal calibration was performed. External validation was performed utilizing a publicly available database (Consortium on Safe Labor) and applying the same inclusion and exclusion criteria. The discriminative power of each model was assessed using a bootstrap, bias-corrected area under the curve. RESULTS: The chorioamnionitis rates in the derivation and external validation groups were: 5% (1,005/19,966) and 5.8% (n = 3,005/52,171), respectively. In multivariable modeling, maternal age, nulliparity, gestational age, smoking status, group B streptococcus colonization, hours ruptured, number of cervical exams, length of labor, epidural use, internal monitoring, and meconium were significantly associated with infection. A calculator was created and externally validated with an area under the curve of 0.82 (95% confidence interval, 0.81-0.82). External validity was further confirmed with a calibration intercept of 0.81. CONCLUSION: This is the first infection calculator created and validated for the prediction of developing chorioamnionitis in patients undergoing induction of labor at term. This calculator can be used to augment patient counseling and guide intrapartum infection surveillance in laboring patients.

Group Comparisons of the Sexual Interests and Behaviors of Assigned Males and Their Association with Genital Ablation Fantasies.

We describe here the sexual histories and characteristics of 338 individuals with interests in castration (orchiectomy) and, more broadly, genital ablation (i.e., orchiectomy, penectomy, and/or nullification), recruited from the Eunuch Archive. We compared four groups: those who only fantasize about castration (Fantasy, n = 66), those who wish to be castrated in the future (Aspiring, n = 166), and those who have been castrated (Eunuchs) both with (n = 42) or without (n = 64) androgen replacement therapy (ART). In our sample, 35.6-53.8% had sexual fantasies of castrating someone, 83.3-90.8% had fantasies of being castrated, 20.6-33.3% had fantasies of removing someone's penis, and 45.3-61.9% had fantasies of having a penectomy. The four groups had similar arousal by high-risk sex behaviors, anal sex play, attraction to people under 18, common sex behaviors, and fetishistic behaviors. Fantasy of being castrated by someone was associated with elevated high-risk sexual behaviors and attraction to individuals aged 18 to 49 after controlling for age, groups, and sexual attraction. In addition, after adjusting for age, groups, and sexual attraction, fantasy of castrating someone was associated with more attraction to individuals under the age of 18 and being aroused by interaction with a stranger, whereas fantasy of cutting off someone's penis was associated with less tendency for common sexual behaviors and digital sex communication. Fantasy of being penectomized was associated with high risk and fetishistic sexual behaviors. These results support screening for high-risk behaviors in individuals who endorse an interest in genital ablation, with treatments focused on harm reduction.