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Background Coronavirus (COVID-19) pandemic has affected the training and wellbeing of obstetrics and gynaecology (O&G) trainees. The aim of this review is to offer a worldwide overview on its’ impact on the mental health of O&G trainees, so that measures can be put into place to better support trainees during the transition back to the ‘new normal’.Methods Key search terms used on PubMed and Google Scholar databases include: mental health, COVID-19, O&G, trainees, residents.Results Fifteen articles (cumulative number of respondents = 3230) were identified, of which eight employed validated questionnaires (n = 1807 respondents), while non-validated questionnaires were used in seven (n = 1423 respondents). Studies showed that COVID-19 appeared to exert more of a negative impact on females and on senior trainees’ mental health, while protective factors included marriage/partner and having had children. Validated and non-validated questionnaires suggested that trainees were exposed to high levels of anxiety and depression. Their mental health was also affected by insomnia, stress, burnout and fear of passing on the virus.Discussion This review analyses the global impact of COVID-19 on O&G trainees’ mental health, showing a pervasive negative effect linked to fear of the virus. Limited psychological support has led to prolonged issues, hindering patient safety and increasing sick leave. The study underscores the urgency of comprehensive support, particularly in female-dominated fields. Addressing these challenges is crucial for future pandemics, highlighting the need to learn from past mistakes and prioritise mental health resources for trainee well-being during and beyond pandemics.

Abstract Background The ROLO Study (Randomised cOntrol trial of a Low glycaemic index diet in pregnancy to prevent macrosomia) was a randomised control trial conducted between 2007 and 2011 to examine if a low glycaemic index (GI) diet could reduce the incidence of macrosomia. The ROLO Family Advisory Committee is a self-selected group of parents who are involved in the longitudinal follow-up of the ROLO Study. The committee was established in 2017 and the goal is to achieve a partnership between ROLO families and researchers, leading to improved research quality, relevance, and outcomes. This research method is termed “Public and patient involvement (PPI)” and describes how researchers collaborate and engage with the public in order to make research more relevant to them. Methods The ROLO study mothers and children have been prospectively followed-up at multiple time points post-pregnancy. In October 2017, all women were invited to join the ROLO Family Advisory Committee via email or via advertisement on the ROLO Study Facebook page. Fathers and other guardians of the study children were also invited to join. Two annual meetings with the research team and parents were held in 2018 and 2019. The meetings were recorded, transcribed verbatim by researchers, and thematically analysed. Results Parents provided opinions on the areas they felt should be explored within the ROLO study using information that was collected up to the current follow-up point. They also shared views on research interests which were of importance to them. These topics included; child mental health, fussy eating in childhood and healthy eating policies in schools. Mothers were much more concerned about factors which influenced their child’s health rather than their own. Incorporating an element of PPI to this study was found to be a positive learning experience for participants and researchers. Conclusion The involvement of parents has enriched the research agenda at the UCD Perinatal Research Centre. We will continue to engage with the parents of the ROLO Study and plan to involve the children to explore their opinions at the next opportunity.

Ice-nucleating particles (INPs) have been found to influence the amount, phase and efficiency of precipitation from winter storms, including atmospheric rivers. Warm INPs, those that initiate freezing at temperatures warmer than −10 ∘C, are thought to be particularly impactful because they can create primary ice in mixed-phase clouds, enhancing precipitation efficiency. The dominant sources of warm INPs during atmospheric rivers, the role of meteorology in modulating transport and injection of warm INPs into atmospheric river clouds, and the impact of warm INPs on mixed-phase cloud properties are not well-understood. In this case study, time-resolved precipitation samples were collected during an atmospheric river in northern California, USA, during winter 2016. Precipitation samples were collected at two sites, one coastal and one inland, which are separated by about 35 km. The sites are sufficiently close that air mass sources during this storm were almost identical, but the inland site was exposed to terrestrial sources of warm INPs while the coastal site was not. Warm INPs were more numerous in precipitation at the inland site by an order of magnitude. Using FLEXPART (FLEXible PARTicle dispersion model) dispersion modeling and radar-derived cloud vertical structure, we detected influence from terrestrial INP sources at the inland site but did not find clear evidence of marine warm INPs at either site. We episodically detected warm INPs from long-range-transported sources at both sites. By extending the FLEXPART modeling using a meteorological reanalysis, we demonstrate that long-range-transported warm INPs were observed only when the upper tropospheric jet provided transport to cloud tops. Using radar-derived hydrometeor classifications, we demonstrate that hydrometeors over the terrestrially influenced inland site were more likely to be in the ice phase for cloud temperatures between 0 and −10 ∘C. We thus conclude that terrestrial and long-range-transported aerosol were important sources of warm INPs during this atmospheric river. Meteorological details such as transport mechanism and cloud structure were important in determining (i) warm INP source and injection temperature and (ii) ultimately the impact of warm INPs on mixed-phase cloud properties.

Objective: To investigate the impact of chemotherapy on the uterus., Design: Cross-sectional pilot study., Setting: Single university fertility clinic., Patients: Twelve patients with a history of alkylating agent chemotherapy exposure after Hodgkin lymphoma (cancer) vs. 12 normally menstruating women (controls)., Interventions: The inclusion criteria were age of 18-45 years and consent for endometrial biopsy. The exclusion criteria were the absence of the uterus, completed pelvic radiation, uterine or cervical cancer, and metastatic cancer. Each participant underwent endometrial biopsy and pelvic ultrasound. All study visits were conducted in the late proliferative phase of the menstrual cycle., Main Outcome Measures: Uterine volume, blood flow, endometrial thickness, histology, deoxyribonucleic acid methylation pattern, and relative ribonucleic acid (RNA) expression level during the same phase of the menstrual cycle., Results: In the study group, visits were conducted at a median of 31.5 (13.5-42.5) months after chemotherapy. The median uterine volume among cancer survivors was 36 (11.3-67) cm 3 , and that of the general population controls was 39 (13-54) cm 3 . On histologic examination, there were no cytologic or architectural atypia. The RNA-sequencing analysis revealed poor clustering of both control and treatment samples. However, we identified 3 differentially expressed genes on RNA-sequencing, but there was no concordance found among the differentially expressed genes and deoxyribonucleic acid methylation changes suggesting most likely false-positive results., Conclusions: Approximately 2.5 years after chemotherapy, a time at which several survivors of Hodgkin lymphoma may resume family-building, endometrial thickness and endometrial histology were not significantly affected by a history of alkylating agent chemotherapy exposure., (© 2022 The Authors.)

A diagnosis of perineural invasion (PNI) is widely accepted as an unfavorable prognostic factor in various solid malignancies. Although PNI has been described as a high-risk parameter in oral squamous cell carcinoma (OSCC), its role in the current staging manuals of the American Joint Committee on Cancer (AJCC) is rather subordinate. We analysed the prognostic value of PNI on survival and recurrence in a large, multicenter OSCC cohort and a population-based approach. A total of 493 OSCC patients with primary tumor resection to negative margins and concomitant neck dissection between 2010 and 2017 were enrolled. PNI was evaluated in relation to overall survival (OAS) and recurrence-free survival (RFS) using uni- and multi-variable Cox regression. The median follow-up time was 5.0 years and PNI was diagnosed in 48 patients (9.7%). A pathohistological verification of PNI correlated significantly with a deteriorated OAS in uni- (HR 2.312; 95% CI 2.312-3.493, p = 0.001) and multivariable Cox regression (HR 1.820; 95% CI 1.164-2.847, p = 0.009). Additionally, a diagnosis of PNI correlated with increased cumulative, as well as distant, metastasis 5-year-recurrence rates ( p = 0.027 and p = 0.011, respectively). The application of adjuvant radiotherapy (RT) or radiochemotherapy (RCT) in patients with PNI did not alter OAS or RFS in survival analysis when compared to patients without PNI. The results underline the adverse impact of PNI on the survival and recurrence of surgically treated OSCC patients. Based on our findings, we highly recommend an emphasis on PNI in the TNM staging concept.

Microsatellite instability (MSI) is caused by defective mismatch repair in 15-20% of colorectal cancers (CRCs). Higher mutation loads in tumors with mismatch repair deficiency can predict response to pembrolizumab, an anti-programmed death 1 (PD-1) immune checkpoint inhibitor. We analyzed the mutations in 113 CRCs without MSI (MSS) and 29 CRCs with MSI-High (MSI-H) using the 50-gene AmpliSeq cancer panel. Overall, MSI-H CRCs showed significantly higher mutations than MSS CRCs, including insertion/deletion mutations at repeat regions. MSI-H CRCs showed higher incidences of mutations in the BRAF, PIK3CA, and PTEN genes as well as mutations in the receptor tyrosine kinase families. While the increased mutations in BRAF and PTEN in MSI-H CRCs are well accepted, we also support findings of mutations in the mTOR pathway and receptor tyrosine kinase family genes. MSS CRCs showed higher incidences of mutations in the APC, KRAS and TP53 genes, confirming previous findings. NGS assays may be designed to detect driver mutations for targeted therapeutics and to identify tumors with high mutation loads for potential treatment with immune checkpoint blockade therapies. Further studies may be warranted to elucidate potential targeted therapeutics against mutations in the mTOR pathway and the receptor tyrosine kinase family in MSI-H CRCs as well as the benefit of anti-PD-1 immunotherapy in hypermutated MSS CRCs or other cancers.

Single mouse cardiomyocytes were exposed to defined ischemia. We designed chambers on glass chips with a volume of 192 pL (picochambers). After a picochamber was loaded with a single cardiomyocyte, P(O2) in the picochamber was equilibrated with that in the headspace, where it was controlled in the critical range between <0.2 and 10 mm Hg. Because the extracellular fluid volume in a picochamber was restricted, these conditions are close to tissue ischemia. Responses of the sarcolemmal K(ATP)-channel current (I(KATP)), the production of reactive oxygen species (ROS), and the mitochondrial membrane potential (delta psi) of single cardiomyocytes to graded ischemia and, in particular, to rapid changes of the ischemic grade by defined oxygen steps were studied. The results show that I(KATP) is readily activated during ischemia and that the grade of ischemia tightly controls the amplitude of I(KATP). Furthermore, maximal ischemia-induced I(KATP) was similar when it followed either reoxygenation or reperfusion, suggesting that there is no major autocrine modulation of maximal I(KATP) during ischemia. A P(O2) staircase from <0.2 to 10 mm Hg increased the ROS signal, starting already at a P(O2) of approximately 0.3 mm Hg. With a similar P(O2) staircase, delta psi first hyperpolarized and then, above 1 mm Hg, depolarized. The depolarizing response of delta psi at a P(O2) of >1 mm Hg could be blocked by increasing the antioxidant defense with glutathione-monoethyl ester. It is concluded that in an ischemic cardiomyocyte I(KATP) is essentially controlled by Po(2) and that at low P(O2) delta psi is balanced by oxygen-induced hyperpolarization and ROS-induced depolarization.

We determined the concentration and effusion/serum ratio of mucin-like carcinoma-associated antigen (MCA) in comparison to carcinoembryonic antigen, carbohydrate antigen 19-9, cancer antigen 125, and cancer antigen 15-3 in 80 sera and 99 effusions from 64 patients with histologically confirmed malignancies (4 patients out of this group showed various effusions simultaneously, which were analyzed separately) and 31 patients with various nonneoplastic diseases. Tumor cells were detected by cytological examination in 41 effusions (60.3%) from patients with neoplastic diseases, while in another 27 cases this method failed to demonstrate the malignant origin of the effusion. Of the cytological "positive" malignant effusions 90% were also correctly identified by an elevated MCA concentration at a cutoff level of 10 U/ml, whereas only one effusion of benign origin (3%) showed a slightly elevated MCA concentration of 10.5 U/ml. In 33% of cytologically "negative" effusions of patients with neoplastic diseases, the MCA concentration was also elevated, with a maximum of 453 U/ml. Increased MCA levels in cytologically confirmed malignant effusions were not restricted to metastatic breast cancer. All 17 cytologically "positive" "non-breast cancer" effusions were correctly identified by their MCA concentrations. None of the other tumor markers reached this high sensitivity at the same level of specificity. The ratio of effusion/serum concentration of all tumor markers as well as the concentration of cancer antigen 125 in effusions was of little diagnostic value. Our results indicate that the MCA concentration in an effusion correlates very closely with its malignant origin and is superior to all the other antigens tested.(ABSTRACT TRUNCATED AT 250 WORDS)