A vertebrate Vangl2 translational variant required for planar cell polarity.

First described in the milkweed bug Oncopeltus fasciatus, planar cell polarity (PCP) is a developmental process essential for embryogenesis and development of polarized structures in Metazoans. This signaling pathway involves a set of evolutionarily conserved genes encoding transmembrane (Vangl, Frizzled, Celsr) and cytoplasmic (Prickle, Dishevelled) molecules. Vangl2 is of major importance in embryonic development as illustrated by its pivotal role during neural tube closure in human, mouse, Xenopus, and zebrafish embryos. Here, we report on the molecular and functional characterization of a Vangl2 isoform, Vangl2-Long, containing an N-terminal extension of about 50 aa, which arises from an alternative near-cognate AUA translation initiation site, lying upstream of the conventional start codon. While missing in Vangl1 paralogs and in all invertebrates, including Drosophila, this N-terminal extension is conserved in all vertebrate Vangl2 sequences. We show that Vangl2-Long belongs to a multimeric complex with Vangl1 and Vangl2. Using morpholino oligonucleotides to specifically knockdown Vangl2-Long in Xenopus, we found that this isoform is functional and required for embryo extension and neural tube closure. Furthermore, both Vangl2 and Vangl2-Long must be correctly expressed for the polarized distribution of the PCP molecules Pk2 and Dvl1 and for centriole rotational polarity in ciliated epidermal cells. Altogether, our study suggests that Vangl2-Long significantly contributes to the pool of Vangl2 molecules present at the plasma membrane to maintain PCP in vertebrate tissues.

The planar cell polarity Vangl2 protein: From genetics to cellular and molecular functions.

Planar cell polarity (PCP) refers to the capacity of a tissue, typically, but not exclusively, an epithelium, to transmit directional information across the tissue plane such that its cellular constituents can differentiate, divide or move in a coordinated manner and along a common axis, generally orthogonal to the apical-basal axis. PCP relies on a core module of highly conserved proteins originally identified in Drosophila which can act intra- and extracellularly. In this review, we focus on the vertebrate ortholog of one of these core PCP components, namely the Vangl2 protein. After a brief historical perspective, we discuss novel cellular settings for which a cellular Vangl2 requirement has been recently documented, with a particular emphasis on adult tissues that rely on Vangl2 for the maintenance of their regenerative capacity or their physiological functions. Finally we compile the most recent data about Vangl2 interacting proteins.

The Tumor Suppressor SCRIB is a Negative Modulator of the Wnt/ß-Catenin Signaling Pathway.

SCRIB is a scaffold protein containing leucine-rich repeats (LRR) and PSD-95/Dlg-A/ZO-1 domains (PDZ) that localizes at the basolateral membranes of polarized epithelial cells. Deregulation of its expression or localization leads to epithelial defects and tumorigenesis in part as a consequence of its repressive role on several signaling pathways including AKT, ERK, and HIPPO. In the present work, a proteomic approach is used to characterize the protein complexes associated to SCRIB and its paralogue LANO. Common and specific sets of proteins associated to SCRIB and LANO by MS are identified and an extensive landscape of their associated networks and the first comparative analysis of their respective interactomes are provided. Under proteasome inhibition, it is further found that SCRIB is associated to the ß-catenin destruction complex that is central in Wnt/ß-catenin signaling, a conserved pathway regulating embryonic development and cancer progression. It is shown that the SCRIB/ß-catenin interaction is potentiated upon Wnt3a stimulation and that SCRIB plays a repressing role on Wnt signaling. The data thus provide evidence for the importance of SCRIB in the regulation of the Wnt/ß-catenin pathway.

The maternal childbirth experience more than a decade after delivery.

BACKGROUND: Maternal satisfaction with the birth experience is multidimensional and influenced by many factors, including mode of delivery. To date, few studies have investigated maternal satisfaction outside of the immediate postpartum period. OBJECTIVE: This study investigated whether differences in satisfaction based on mode of delivery are observed more than a decade after delivery. STUDY DESIGN: This was a planned, supplementary analysis of data collected for the Mothers' Outcomes after Delivery study, a longitudinal cohort study of pelvic floor disorders in parous women and their association with mode of delivery. Obstetric and demographic data were obtained through patient surveys and obstetrical chart review. Maternal satisfaction with childbirth experience was assessed via the Salmon questionnaire, administered to Mothers' Outcomes after Delivery study participants >10 years from their first delivery. This validated questionnaire yields 3 scores: fulfillment, distress, and difficulty. These 3 scores were compared by mode of delivery (cesarean prior to labor, cesarean during labor, spontaneous vaginal delivery, and operative vaginal delivery). In addition, the impact of race, age, education level, parity, episiotomy, labor induction, and duration of second stage of labor on maternal satisfaction were examined. RESULTS: Among 576 women, 10.1-17.5 years from delivery, significant differences in satisfaction scores were noted by delivery mode. Salmon scale scores differed between women delivering by cesarean and those delivering vaginally: women delivering vaginally reported greater fulfillment (0.40 [-0.37 to 0.92] vs 0.15 [-0.88 to 0.66], P < .001) and less distress (-0.34 [-0.88 to 0.38] vs 0.20 [-0.70 to 0.93], P < .001) than those who delivered by cesarean. Women who delivered by cesarean prior to labor reported the greatest median fulfillment scores and the lowest median difficulty scores. Median distress scores were lowest among those who delivered by spontaneous vaginal birth. Among women who underwent cesarean delivery, labor induction and prolonged second stage were associated with higher difficulty scores. These factors did not affect satisfaction scores among women who delivered vaginally. Among women who delivered vaginally, operative vaginal delivery was associated with less favorable scores across all 3 scores. CONCLUSION: Maternal satisfaction with childbirth is influenced by mode of delivery. The birth experience leaves an impression on women more than a decade after delivery.

Peritoneal inclusion cysts in a young male: A case report.

INTRODUCTION AND IMPORTANCE: Peritoneal inclusion cyst is a rare benign condition with low potential for malignant transformation but high recurrence rates. Debulking surgery is the recommended first line management for these patients, however, recurrence rates are up to 50 % (Padmanabhan et al., 2020; Chapel and Husain, 2021). CASE PRESENTATION: A 26-year-old male being worked up for non-specific abdominal pain with cross-sectional imaging showing multiple multicystic lesions in the abdomen and pelvis. There was a pre-operative suspicion of Pseudomyxoma Peritonei and decision was made for diagnostic laparoscopy and biopsy. Mucin and an abnormal small bowel mesentery was found intraoperatively and sampled leading to the diagnosis of peritoneal inclusion cyst. CLINICAL DISCUSSION: Treatment of peritoneal inclusion cyst range from surveillance to aggressive treatment with complete cytoreductive surgery with involved field peritonectomy and hyperthermic intra-peritoneal chemotherapy. CONCLUSION: First line management of peritoneal inclusion cysts is for debulking surgery. Arguments for less invasive and more aggressive management has been proposed, however, further data needs to be collected to determine gold standard of treatment.

Predicting breast cancer-specific survival in metaplastic breast cancer patients using machine learning algorithms.

Metaplastic breast cancer (MpBC) is a rare and aggressive subtype of breast cancer, with data emerging on prognostic factors and survival prediction. This study aimed to develop machine learning models to predict breast cancer-specific survival (BCSS) in MpBC patients, utilizing a dataset of 160 patients with clinical, pathological, and biological variables. An in-depth variable selection process was carried out using gain ratio and correlation-based methods, resulting in 10 variables for model estimation. Five models (decision tree with bagging; logistic regression; multilayer perceptron; naïve Bayes; and, random forest algorithms) were evaluated using 10-fold cross-validation. Despite the constraints posed by the absence of therapeutic information, the random forest model exhibited the highest performance in predicting BCSS, with an ROC area of 0.808. This study emphasizes the potential of machine learning algorithms in predicting prognosis for complex and heterogeneous cancer subtypes using clinical datasets, and their potential to contribute to patient management. Further research that incorporates additional variables, such as treatment response, and more advanced machine learning techniques will likely enhance the predictive power of MpBC prognostic models.

Tobacco Smoking and Use of Smokeless Tobacco and Their Association with Psychological Distress and Other Factors in a Rural District in Bangladesh: A Cross-Sectional Study.

Background: Tobacco smoking and use of smokeless tobacco are the most preventable cause of death in Bangladesh. The prevalence of psychological distress is increasing globally. This paper reports the smoking status and their association with psychological distress and other factors in a rural district, Narail, of Bangladesh. Materials and Methods: Data were collected from 2425 adults of age 18-90 years. Smoking status along with sociodemographic characteristics and measures of psychological distress using the Kessler 10-item questionnaire were collected using a face-to-face data collection method. Results: The crude (age-standardized) prevalence of ever smoking was 27.1 (24.3)% that includes current 25.6 (23.7) and smoker 1.5 (0.6)%, and the prevalence of smokeless tobacco (SLT) was 23.5 (13.4)%. The prevalence of ever smoking was the highest in daily labourers (62.9%) and SLT use was the highest in widowed people (47.2%). After adjustment for covariates, no education (odds ratio (OR): 3.78, 95% confidence interval (CI): 1.57-9.07 for females and OR: 2.69, 95% CI: 1.87-3.87 for males) compared to at least secondary level of education and daily labours (OR: 6.66, 95% CI: 1.67-26.6 for females and OR: 5.12, 95% CI: 1.30-20.19 for males) compared to housework were associated with higher prevalence of ever smoking. Any level of psychological distress, such as mild psychological distress, was associated with at least double the prevalence of tobacco smoking in females (OR: 2.12, 95% CI: 1.67-3.83) but not in males (OR: 1.12, 95% CI: 0.80-1.56). Psychological distress was not associated with SLT use. Conclusions: Prevalence of both smoking and SLT use was high, particularly in daily labourers, people with no education, and females with psychological distress in rural Bangladesh. Appropriate intervention programs should especially target those of low levels of education and laborious occupations for increasing awareness for the cessation of smoking in rural Bangladesh.