Gender differences in pharmacokinetics and tissue distribution of 3 perfluoroalkyl and polyfluoroalkyl substances in rats

The aim of this study was to confirm and investigate the gender differences in pharmacokinetic (PK) characteristics and tissue distribution of 3 perfluoroalkyl and polyfluoroalkyl substances (PFASs) consisted of perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), and perfluorohexane sulfonic acid (PFHxS) in both male and female rats. For this study, a simultaneous determination method of the 3 PFASs in rat plasma and tissues was developed and validated using a UPLC-MS/MS system. The PK parameters after a single oral or intravenous administration of the 3 PFASs in both rats were calculated using WinNonlin^® software. The mean half-life of the 3 PFASs in female and male rats was in the range of 0.15–0.19 and 1.6–1.8 days for PFOA, 23.5–24.8 and 26.4–28.7 days for PFOS, and 0.9–1.7 and 20.7–26.9 days for PFHxS, respectively. The 3 PFASs were highly distributed in the liver and kidney. These results suggest that there are gender differences in the PKs for PFOA and PFHxS in rats, whereas the PFOS represented no significant gender differences except the Kp value of liver. The validated simultaneous determination method of the 3 PFASs was also within the accepted criteria of the international guidance.     

Sex-discrete role of depressive symptomatology on 10-year first and recurrent cardiovascular disease incidence: results from ATTICA and GREECS prospective studies

ObjectiveThe sex-specific effect of depressive symptomatology on 10-year first and recurrent cardiovascular disease (CVD) events was evaluated.MethodsThe Greek samples from ATTICA (2002-2012, n = 845 free-of-CVD subjects) and GREECS (2004-2014, n = 2,172 subjects with acute coronary syndrome (ACS)) prospective epidemiological studies with baseline psychological assessments were used for the first and the recurrent event, respectively. Depressive symptomatology was assessed at baseline, through Zung Self-Rating Depression Scale in the ATTICA study, and through the Center for Epidemiological Studies-Depression scale in the GREECS study.ResultsACS as well as free-of-CVD women scored significantly higher for depressive symptomatology. Men scored higher than women against first (19.7% vs. 11.7%) and subsequent CVD events (38.8% vs. 32.9%). In participants with depressive symptoms man-to-woman first and recurrent CVD event rate ratio was below 1, confirming that depressive women were more likely to have a CVD event than depressive men. Multiadjusted analysis revealed that depressive symptomatology had an independent aggravating effect on the first (hazard ratio (HR) = 2.72, 95% confidence interval (95% CI) 1.50, 9.12) and recurrent (HR = 1.31, 95% CI 1.01, 1.69) CVD events only in women. Mediation analysis in women revealed that 35% (23%, 44%) of excess first-CVD-event risk of depressive symptoms was attributed to conventional risk factors. The respective number for recurrent CVD events was 46% (23%, 53%); different patterns of ranking regarding the mediating effect corresponding to each adjustment factor were observed.ConclusionsThe present work augments prior evidence that psychological stressors possess important drivers of CVD onset and progression mainly in women, while it gives rise to research toward unidentified paths behind this claim.     

Differentiating autoimmune pancreatitis from pancreatic ductal adenocarcinoma with CT radiomics features

PurposeThe purpose of this study was to determine whether computed tomography (CT)-based machine learning of radiomics features could help distinguish autoimmune pancreatitis (AIP) from pancreatic ductal adenocarcinoma (PDAC).Materials and MethodsEighty-nine patients with AIP (65 men, 24 women; mean age, 59.7 ± 13.9 [SD] years; range: 21–83 years) and 93 patients with PDAC (68 men, 25 women; mean age, 60.1 ± 12.3 [SD] years; range: 36–86 years) were retrospectively included. All patients had dedicated dual-phase pancreatic protocol CT between 2004 and 2018. Thin-slice images (0.75/0.5 mm thickness/increment) were compared with thick-slices images (3 or 5 mm thickness/increment). Pancreatic regions involved by PDAC or AIP (areas of enlargement, altered enhancement, effacement of pancreatic duct) as well as uninvolved parenchyma were segmented as three-dimensional volumes. Four hundred and thirty-one radiomics features were extracted and a random forest was used to distinguish AIP from PDAC. CT data of 60 AIP and 60 PDAC patients were used for training and those of 29 AIP and 33 PDAC independent patients were used for testing.ResultsThe pancreas was diffusely involved in 37 (37/89; 41.6%) patients with AIP and not diffusely in 52 (52/89; 58.4%) patients. Using machine learning, 95.2% (59/62; 95% confidence interval [CI]: 89.8–100%), 83.9% (52:67; 95% CI: 74.7–93.0%) and 77.4% (48/62; 95% CI: 67.0–87.8%) of the 62 test patients were correctly classified as either having PDAC or AIP with thin-slice venous phase, thin-slice arterial phase, and thick-slice venous phase CT, respectively. Three of the 29 patients with AIP (3/29; 10.3%) were incorrectly classified as having PDAC but all 33 patients with PDAC (33/33; 100%) were correctly classified with thin-slice venous phase with 89.7% sensitivity (26/29; 95% CI: 78.6–100%) and 100% specificity (33/33; 95% CI: 93–100%) for the diagnosis of AIP, 95.2% accuracy (59/62; 95% CI: 89.8–100%) and area under the curve of 0.975 (95% CI: 0.936–1.0).ConclusionsRadiomic features help differentiate AIP from PDAC with an overall accuracy of 95.2%.     

Validation and confirmatory factor analysis of the pediatric Adherence Barriers to Continuous Positive Airway Pressure Questionnaire

ObjectiveTo evaluate and refine a newly proposed factor structure for the Adherence Barriers to Continuous Positive Airway Pressure Questionnaire (ABCQ) and to present psychometric data from a large, geographically diverse sample of children and young adults with sleep disordered breathing (SDB) treated with positive airway pressure (PAP).MethodsA sample of 181 patients prescribed PAP for treatment of SDB, ages 8–21 years, and caregivers (n = 234) of patients ages 2–21 years, completed the ABCQ during routine sleep medicine clinic visits. Adherence data from participants' PAP machines were obtained via electronic download, providing objective data on PAP adherence immediately preceding the clinic visit during which the ABCQ was completed.ResultsA three-factor structure (1. Behavior, Beliefs, Environment, 2. Emotional Barriers, & 3. Physical Barriers) exhibited good model fit in confirmatory factor analysis. Results indicate that the ABCQ has strong psychometric properties, including good internal consistency among subscales and strong convergent validity with objectively measured PAP adherence. Analysis of the Receiver Operator Characteristic Curve (ROC) yielded an ABCQ total cut-off score of 46.5 for patient report and 53.5 for caregiver report. Scores above the cutpoint predicted nonadherence to PAP, defined as failure to use PAP for ≥4 h on 70% of nights.ConclusionsThe three-factor ABCQ appears to be a useful patient- and caregiver-report instrument to measure barriers to PAP treatment in children and young adults with sleep disordered breathing.     

Gender differences in NIH grant funding in neurological surgery

Research productivity is a vital component to an academic neurosurgeon’s career. We sought to evaluate gender differences in NIH funding among faculty in neurological surgery departments. NIH funding awarded to PIs of neurological surgery departments from 2014 to 2019 were obtained and analyzed for gender differences in funding trends, with attention to terminal degree and academic rank, as well as publication range in length of years and h-index. 79.4% of all NIH grants were awarded to male PIs, with the remaining 20.5% given to their female counterparts. Mean of the total NIH grants awarded to men was significantly higher at $1,796,684 (± Standard Error of Mean (SEM) $155,849, IQR: $1,759,250) compared to women at $1,151,968 (± SEM $137,914, IQR: $1,388,538) (P = 0.022). Mean NIH funding per grant for men was $365,760 (± SEM: $39,592, IQR: $189,692) and for women was $292,912 (± SEM: 28,239, IQR: $283,177). Differences in mean NIH funding per grant approached but did not reach statistical significance between men and women (P = 0.122). When stratified for academic rank, there was a significant difference in mean NIH funding per grant between men and women on the associate professor level (p < 0.005), with women exceeding men in funding at this academic level, with other academic ranks remaining non-significant. Overall, male neurosurgeons receive significantly more total NIH grant funding than their female counterparts, except at the level of associate professor where women were found to surpass men.     

Transidentités et réassignation de sexe : le rôle des psychologues au sein d’une équipe pluridisciplinaire spécialisée

This interview is the continuation and supplement of the article “Transidentity and sex change: The sociologist's point of view, the psychiatrist's role”. Psychologists Sandrine Coussinoux, Eirini Rari and psychiatrist Thierry Gallarda discuss the issue of sex reassignment for transidentitarian people as well as the role of psychologists who work on this subject in the Parisian multidisciplinary team specialized in “Gender dysphoria and mental health”.