Physicians' attitudes towards using elective oocyte cryopreservation to accommodate the demands of their career.

PURPOSE: Among medical professionals, there appears to be a significant lack of knowledge about oocyte cryopreservation. Medical professionals may be potential candidates for elective oocyte cryopreservation due to the demands and commitments of medical training. There is a paucity of data on this topic among medical professionals. The aim of this study was to assess knowledge, understanding, and beliefs towards elective egg freezing among medical professionals to assess whether they are potential candidates for elective egg freezing. METHODS: This is a cross-sectional descriptive study in a university-based training program. All medical students, residents, fellows, and faculty were included. An online survey was emailed to potential participants. It included demographic questions regarding childbearing decision-making factors, fertility knowledge, and attitudes towards using elective oocyte cryopreservation. RESULTS: A total of 1000 emails were sent. Of those, 350 completed surveys were received. On average, 33% of responders provided a correct answer to each fertility knowledge question. The duration of training and the heavy workload with long duty hours were the most common influencing factors when deciding the timing of childbearing. Overall, 65% of the male and female responders were concerned about their future fertility. Among those women who had future fertility concerns, 8% were not aware of egg freezing as a fertility option and wished they had had an opportunity to freeze their eggs at an earlier time. CONCLUSIONS: Physicians' childbearing decisions can be affected by the demands of their careers. Elective oocyte cryopreservation could be considered an option for family planning. Educational sessions and awareness programs are needed to provide information about available fertility preservation options, which can potentially decrease the rate of regret.

Long-term PM2.5 pollution over China: Identification of PM2.5 pollution hotspots and source contributions.

Fine particulate matter, with an aerodynamic diameter ≤ 2.5 µm (PM2.5), is a severe problem in China. The lack of ground-based measurements and its sparse distribution obstruct long-term air pollution impact studies over China. Therefore, the present study used newly updated Global Estimates (V5. GL.02) of monthly PM2.5 data from 2001 to 2020 based on Geographically Weighted Regression (GWR) by Washington University. The GWR PM2.5 data were validated against ground-based measurements from 2014 to 2020, and the validation results demonstrated a good agreement between GWR and ground-based PM2.5 with a higher correlation (r = 0.95), lower error (8.14), and lower bias (-3.10 %). The long-term (2001-2020) PM2.5 data were used to identify pollution hotspots and sources across China using the potential source contribution function (PSCF). The results showed highly significant PM2.5 pollution hotspots in central (Henan, Hubei), North China Plain (NCP), northwest (Taklimakan), and Sichuan Basin (Chongqing, Sichuan) in China, with the most severe pollution occurring in winter compared to other seasons. During the winter, PM2.5 was in the range from 6.08 to 93.05 µg/m3 in 33 provinces, which is 1.22 to 18.61 times higher than the World Health Organization (WHO) Air Quality Guidelines (AQG-2021; annual mean: 5 µg/m3). In 26 provinces, the reported PM2.5 was 1.07 to 2.66 times higher than the Chinese Ambient Air Quality Standard (AAQS; annual mean: 35 µg/m3). Furthermore, provincial-level trend analysis shows that in most Chinese provinces, PM2.5 increased significantly (3-43 %) from 2001 to 2012, whereas it decreased by 12-94 % from 2013 to 2020 due to the implementation of air pollution control policies. Finally, the PSCF analysis demonstrates that China's air quality is mainly affected by local PM2.5 sources rather than by pollutants imported from outside China.

Misdiagnosis of cervical ectopic pregnancy.

PURPOSE: To determine the presenting symptoms as well as the frequency and reasons for the delayed diagnosis of cervical ectopic pregnancy (CEP) in order to increase detection and prevent treatment delay. METHODS: Retrospective case series of 15 women treated for CEP from January 1997 through December 2008 at a university teaching hospital. RESULTS: Fifteen patients were treated for CEP during the study period. Eight patients presented to the emergency department, of which 6 (75%) were initially misdiagnosed. The most common misdiagnosis was threatened miscarriage (n = 5). All patients with accurately diagnosed CEP presented with heavy vaginal bleeding; those misdiagnosed reported mild to moderate vaginal bleeding. Three of six patients misdiagnosed did not have an ultrasound performed upon presentation, and three patients had an ultrasound report not suggestive of CEP. CEP was diagnosed on follow-up ultrasound, delaying treatment 1-4 days. CONCLUSIONS: Misdiagnosis of CEP upon initial presentation is a common occurrence. Transvaginal ultrasound performed by a qualified practitioner may increase detection and prevent treatment delay.

Hepatoprotective effect of combination of L-carnitine and magnesium-hydroxide in nonalcoholic fatty liver disease patients: a double-blinded randomized controlled pilot study.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) still has no accepted pharmacological therapy. Even though monotherapy of L-carnitine or magnesium supplementation exhibits an essential beneficial role in NAFLD treatment, and despite that new NAFLD treatment strategies focus on combination therapies, the combination of L-carnitine with magnesium has not yet been examined in NAFLD patients. We aimed to assess the efficacy of L-carnitine in combination with magnesium in NAFLD patients. PATIENTS AND METHODS: Double-blinded, randomized controlled trial with 22 NAFLD participants who were randomized to either control group receiving placebo for the first 8 weeks and an additional 8 weeks with CIRRHOS product (2 gr L-carnitine and 150 mg magnesium) or treatment group receiving CIRRHOS product for 16 weeks. Weight, serum aspartate aminotransferase (AST), alanine transaminase (ALT) and C-reactive protein (CRP) levels were measured monthly. Lipid profile and serum insulin levels were monitored at baseline and at week 16 of treatment. Shear-wave elastography was used to evaluate liver stiffness (LS). RESULTS: While AST and ALT levels decreased progressively over 16 weeks of treatment in the treatment group, AST and ALT levels of the control group were increased modestly or unaffected. AST and ALT levels of the treatment group decreased by 25% (p=0.9) and 20% (p=0.1) respectively, compared to AST and ALT levels at baseline. However, serum CRP levels, insulin levels, lipid profile and LS were not affected by treatment. CONCLUSIONS: Our findings suggest that L-carnitine with magnesium supplementation could be a potential therapy for NAFLD. However, further studies with a larger population and high-sensitivity diagnostic parameters for early stages of NAFLD are needed to elucidate L-carnitine and magnesium efficacy in NAFLD.

Advanced diffuse gastric adenocarcinoma in young Syrian woman. A case report.

Introduction: Gastric cancer is a deadly disease with vague early symptoms. Its occurrence and prognosis in young patients have demonstrated significant variation and delay in detection, which is the most critical variable in disease prognosis. Case presentation: We report a rare case of a 27-year-old Syrian female with metastasis diffuse gastric cancer with delayed diagnosis and poor prognosis without relevant history. She presented with two years of fatigue, loss of appetite, and postprandial abdominal pain, which has worsened over the past two months, vomiting, weight loss, and ascites. Gastroduodenoscopy showed superficial ulcers, with a positive Helicobacter Pylori infection. The computerized tomography (CT) scan revealed extensive thickening of the stomach, ascites, and Sister Mary Joseph nodule. The nodule tissue morphology coupled with immunostaining showed a poorly differentiated adenocarcinoma metastatic from the stomach. She was referred to a specialized oncology hospital for follow-up and palliative treatment. Clinical discussion: Gastric adenocarcinoma affects people in their fifties and sixties, and rarely in their twenties. Risk factors include diet, smoking, alcoholism, long-term use of proton pump inhibitors, Helicobacter pylori infection, pernicious anemia, and a genetic and family history of malignancies. Diagnosis at an early stage is essential in predicting prognosis. The diffuse gastric cancer spreads along the wall rather than into the lumen. The challenge is to detect tumors. Conclusion: Gastric diffuse cancer screening and surveillance programs have yet to be defined. It is still unclear who should be screened when the screening should begin, and how the screening should take place.

Solving transparency in drought forecasting using attention models.

Droughts are one of the most devastating and recurring natural disaster due to a multitude of reasons. Among the different drought studies, drought forecasting is one of the key aspects of effective drought management. The occurrence of droughts is related to a multitude of factors which is a combination of hydro-meteorological and climatic factors. These variables are non-linear in nature, and neural networks have been found to effectively forecast drought. However, classical neural nets often succumb to over-fitting due to various lag components among the variables and therefore, the emergence of new deep learning and explainable models can effectively solve this problem. The present study uses an Attention-based model to forecast meteorological droughts (Standard Precipitation Index) at short-term forecast range (1-3 months) for five sites situated in Eastern Australia. The main aim of the work is to interpret the model outcomes and examine how a deep neural network achieves the forecasting results. The plots show the importance of the variables along with its short-term and long-term dependencies at different lead times. The results indicate the importance of large-scale climatic indices at different sequence dependencies specific to the study site, thus providing an example of the necessity to build a spatio-temporal explainable AI model for drought forecasting. The use of such interpretable models would help the decision-makers and planners to use data-driven models as an effective measure to forecast droughts as they provide transparency and trust while using these models.

Cellular functions of the ClpP protease impacting bacterial virulence.

Proteostasis mechanisms significantly contribute to the sculpting of the proteomes of all living organisms. ClpXP is a central AAA+ chaperone-protease complex present in both prokaryotes and eukaryotes that facilitates the unfolding and subsequent degradation of target substrates. ClpX is a hexameric unfoldase ATPase, while ClpP is a tetradecameric serine protease. Substrates of ClpXP belong to many cellular pathways such as DNA damage response, metabolism, and transcriptional regulation. Crucially, disruption of this proteolytic complex in microbes has been shown to impact the virulence and infectivity of various human pathogenic bacteria. Loss of ClpXP impacts stress responses, biofilm formation, and virulence effector protein production, leading to decreased pathogenicity in cell and animal infection models. Here, we provide an overview of the multiple critical functions of ClpXP and its substrates that modulate bacterial virulence with examples from several important human pathogens.

Benzo(a)pyrene causes PRKAA1/2-dependent ID2 loss in trophoblast stem cells.

Benzo(a)pyrene (BaP), a cigarette smoke component, is metabolized to diol esters (BPDE) that bind to DNA and form mutagenic BPDE-DNA adducts. BaP activates stress enzymes including stress-activated protein kinase/jun kinase (MAPK8/9) in embryos, AMP-activated protein kinase alpha1/2 subunits (PRKAA1/2) in somatic cells, and inhibits the proliferation of trophoblast cell lineages. The loss of transcription factor inhibitor of differentiation (ID)2 is required for the initial differentiation of mouse trophoblast stem cells (TSC) in implanting mouse embryo to produce the first placental hormone, chorionic sommatomammotropin (CSH)1. Here we demonstrate that BaP activates PRKAA1/2 and causes ID2 protein loss in TSC in a time- and dose-dependent manner. Although PRKAA1/2 was activated at low BaP doses, PRKAA1/2-dependent ID2 protein loss occurred at a dose that was similar to the threshold that results in a significant decrease in TSC accumulation and decreased fraction of proliferating TSC. This suggests a possible relationship between stress-induced declines in cell accumulation and stem cell differentiation when BaP levels are high. The threshold BaP dose that induces significant ID2 loss is in the range of a 2-3 pack/day habit, suggesting that this mechanism may be involved with implantation failure in smoking women.

The role of hysteroscopic biopsy in obtaining specimens for cytogenetic evaluation in missed abortion prior to suction dilatation and curettage.

AIM: To estimate whether hysteroscopic-guided biopsy of gestational sac(s) in first trimester missed abortion increases the sensitivity of detecting aneuploidy compared to washing and careful specimen collection after suction dilatation and curettage (D&C). MATERIALS AND METHODS: Thirty-five patients with first trimester missed abortion of which 25 underwent 29 suction D&Cs and 10 underwent hysteroscopic-guided biopsy of 12 gestational sacs prior to suction D&C. The karyotype of products of conception specimens were analyzed by G-banding techniques. RESULTS: The percentage of specimens with 46,XX, 46,XY and aneuploidy were not significantly different in the hysteroscopic group [4/12 (33.3%), 3/12 (25.0%) and 5/12 (41.7%)] compared with the D&C group [8/29 (27.6%), 5/29 (17.2%) and 16/29 (55.2%)]. Although parity differed significantly between groups, it did not hold in a multivariable logistic regression model built to estimate whether the parity, gestational age and specimen collection method predict the likelihood of detecting a 46,XX chromosomal complement. CONCLUSIONS: Direct hysteroscopic-guided biopsies of gestational sac(s) do not increase the sensitivity of conventional cytogenetics for detecting aneuploidy when compared to specimens obtained by washing and microscopic identification of villi or fetal tissue after suction D&C.

Elective egg freezing: what is the vision of women around the globe?

AIM: The interest in oocyte cryopreservation (OC) for nonmedically indicated reasons is increasing. Knowing women's beliefs and knowledge from various geographic regions could help providers to understand the similarities and differences that could facilitate proper counseling. MATERIALS & METHODS: Articles about social egg freezing published over the past 18 years were extracted from the literature. RESULTS: We demonstrated that there are common rationales toward OC among women in the USA and other countries. The ultimate goal was to prolong fertility. The most commonly reported reasons were aging, lack of partner, career and financial status. CONCLUSION: The beliefs and rationales toward elective OC among women in the USA and other countries are consistent.