Canadian women in otolaryngology: head and neck surgery part 2-challenges in family planning, fertility, and lactation.

BACKGROUND: Previous literature demonstrates that female surgeons face difficulties in family planning, meeting breastfeeding goals, leadership and advancement opportunities. These issues have received limited attention in Canadian surgeons despite different maternity leave patterns compared to the general Canadian population. We sought to describe the experience of otolaryngologist-head and neck surgeons in family planning, fertility, and lactation and to identify the role of gender and career stage in these experiences. METHODS: A RedCAP® survey was disseminated to Canadian otolaryngology-head and neck surgeons and residents from March to May of 2021 through social media and the national listserv. This survey examined fertility, pregnancy losses, and infant feeding. Major independent variables include gender and career stage (faculty and resident). Dependent variables include respondent experiences with fertility, number of children, and length of parental leave. Responses were tabulated and presented descriptively to communicate the experience of Canadian otolaryngologists. Further, statistical comparisons such as chi-square and t-tests were employed to identify relationships between these variables. Thematic analysis was conducted for narrative comments. RESULTS: We received 183 completed surveys (22% response rate). 54% of females versus 13% of males agreed that career influenced their ability to have children (p = 0.002). 74% of female respondents without children have concerns about future fertility compared to 4% of men (p < 0.001). Furthermore, 80% of women versus 20% of men have concerns about future family planning (p < 0.001). The average maternity leave was 11.5 weeks for residents, and 22.2 weeks for staff. Additionally, significantly more women than men stated that maternity leave impacted advancement opportunities (32% vs. 7%) and salary/remuneration (71% vs. 24%) (p < 0.001). Over 60% of those choosing to pump breastmilk at work reported having inadequate time, space, and breastmilk storage. In total, 62% of breastfed infants were receiving breastmilk at 1 year. CONCLUSION: Canadian female otolaryngologists-head and neck surgeons face challenges in family planning, ability to conceive, and breastfeeding. Focused effort is required to provide an inclusive environment that helps all otolaryngologists-head and neck surgeons achieve both their career and family goals, regardless of gender or career stage.

Canadian Women in Otolaryngology-Head and Neck Surgery part 1: the relationship of gender identity to career trajectory and experiences of harassment.

INTRODUCTION: Women in surgical specialties face different challenges than their male peers. However, there is a paucity of literature exploring these challenges and their effects on a Canadian surgeon's career. METHODS: A REDCap® survey was distributed to Canadian Otolaryngology-Head and Neck Surgery (OHNS) staff and residents in March 2021 using the national society listserv and social media. Questions examined practice patterns, leadership positions, advancement, and experiences of harassment. Gender differences in survey responses were explored. RESULTS: 183 completed surveys were obtained, representing 21.8% of the Canadian society membership [838 members with 205 (24.4%) women]. 83 respondents self-identified as female (40% response rate) and 100 as male (16% response rate). Female respondents reported significantly fewer residency peers and colleagues identifying as their gender (p < .001). Female respondents were significantly less likely to agree with the statement "My department had the same expectations of residents regardless of gender" (p < .001). Similar results were observed in questions about fair evaluation, equal treatment, and leadership opportunities (all p < .001). Male respondents held the majority of department chair (p = .028), site chief (p = .011), and division chief positions (p = .005). Women reported experiencing significantly more verbal sexual harassment during residency (p < .001), and more verbal non-sexual harassment as staff (p = .03) than their male colleagues. In both female residents and staff, this was more likely to originate from patients or family members (p < .03). DISCUSSION: There is a gender difference in the experience and treatment of OHNS residents and staff. By shedding light on this topic, as a specialty we can and must move towards greater diversity and equality.

Here and there a trophoblast, a transcriptional evaluation of trophoblast cell models.

A recent explosion of methods to produce human trophoblast and stem cells (hTSCs) is fuelling a renewed interest in this tissue. The trophoblast is critical to reproduction by facilitating implantation, maternal physiological adaptations to pregnancy and the growth of the fetus through transport of nutrients between the mother and fetus. More broadly, the trophoblast has phenotypic properties that make it of interest to other fields. Its angiogenic and invasive properties are similar to tumours and could identify novel drug targets, and its ability to regulate immunological tolerance of the allogenic fetus could lead to improvements in transplantations. Within this review, we integrate and assess transcriptomic data of cell-based models of hTSC alongside in vivo samples to identify the utility and applicability of these models. We also integrate single-cell RNA sequencing data sets of human blastoids, stem cells and embryos to identify how these models may recapitulate early trophoblast development.

A Rare Case of Factor VII Inhibitor in a Patient Presenting with Primary Splenic Marginal Zone Lymphoma.

BACKGROUND Here, we report the novel presentation of a factor VII inhibitor in association with a new diagnosis of splenic marginal zone lymphoma in a previously healthy 38-year-old woman. There are only 4 reported cases of factor VII inhibitors, none of which are secondary to a splenic marginal zone lymphoma. CASE REPORT Our patient, a 38-year-old woman, presented reporting increased abdominal swelling and early satiety. She was found to have pancytopenia, an elevated international normalized ratio (INR), normal partial thromboplastin time (PTT), and massive splenomegaly. Further investigation revealed a morphology and immunophenotype most consistent with splenic marginal zone lymphoma. A mixing study was unable to bring the INR into normal range after 60 min, confirming a factor VII inhibition. Therefore, the final diagnosis was primary splenic marginal zone lymphoma and secondary factor VII inhibitors. Owing to the elevated INR, both chemotherapy and splenectomy were avoided and we began a 4-week course of weekly rituximab infusions. After a second course of 4 treatments, there was a resolution of both the coagulopathy and the splenomegaly. At this point, the splenectomy was safely performed. Maintenance rituximab continued for 2 years. Our patient has now been in remission 12 years. CONCLUSIONS We successfully treated a rare factor VII inhibitor and its underlying splenic marginal zone lymphoma with rituximab immunotherapy. A complete response was documented by splenectomy. The patient's 12-year remission of both the lymphoma and the inhibitor helps to support the causative relationship between the lymphoma and the factor VII inhibitor.

Human placental gene sets improve analysis of placental pathologies and link trophoblast and cancer invasion genes.

INTRODUCTION: Interpretation of gene expression uses set enrichment or overrepresentation methods that depend on sets of annotated genes, such as the popular Gene Ontology. The placenta is understudied relative to other major organs creating a deficit of molecular and functional knowledge about this organ. The lack of placental and trophoblast research significantly impacts our ability to interpret the results of high throughput experiments. METHODS: Gene sets were generated by a semi-automated re-analysis of 330 microarray and 91 RNA sequencing experiments involving placental and trophoblast samples, excluding those related to pathology. Microarray data was obtained from the Gene Expression Omnibus and processed using the R package limma. RNA-sequencing data was extracted from the short read archive and processed using Kallisto and limma. The workflow consisted of quality control for experimental design and data. Sets were generated by pairwise differential expression with a maximum of 200 genes per set. RESULTS: We created 235 human placenta and trophoblast specific gene sets and found unique subnetworks relative to Gene Ontology. We applied these new placental gene sets to the investigation of preeclampsia and fetal growth restriction as well as invasive tumors and cell models finding matching terms related to cell types and oxygen tension (hypoxia). DISCUSSION: The human placental gene sets provide an improved context for interpretation of high throughput gene expression studies on placental pathologies beyond the Gene Ontology. Significant enrichment of placental gene sets to cancer samples and cell models indicates a utility beyond applications to placental and trophoblast cells.

Circadian GLP-1 Secretion in Mice Is Dependent on the Intestinal Microbiome for Maintenance of Diurnal Metabolic Homeostasis.

The incretin glucagon-like peptide 1 (GLP-1) is secreted by the intestinal L cell upon nutrient ingestion. GLP-1 also exhibits a circadian rhythm, with highest release at the onset of the feeding period. Similarly, microbial composition and function exhibit circadian rhythmicity with fasting-feeding. The circadian pattern of GLP-1 release was found to be dependent on the oral route of glucose administration and was necessary for the rhythmic release of insulin and diurnal glycemic control in normal male and female mice. In mice fed a Western (high-fat/high-sucrose) diet for 16 weeks, GLP-1 secretion was markedly increased but arrhythmic over the 24-h day, whereas levels of the other incretin, glucose-dependent insulinotropic polypeptide, were not as profoundly affected. Furthermore, the changes in GLP-1 secretion were shown to be essential for the maintenance of normoglycemia in this obesogenic environment. Analysis of the primary L-cell transcriptome, as well as of the intestinal microbiome, also demonstrated time-of-day- and diet-dependent changes paralleling GLP-1 secretion. Finally, studies in antibiotic-induced microbial depleted and in germ-free mice with and without fecal microbial transfer, provided evidence for a role of the microbiome in diurnal GLP-1 release. In combination, these findings establish a key role for microbiome-dependent circadian GLP-1 secretion in the maintenance of 24-h metabolic homeostasis.