Parental refusal of prenatal screening for aneuploidies.

OBJECTIVES: To analyze the reasons for refusal of aneuploidy screening in a multicultural Middle Eastern population. METHODS: The study included patients delivering in a university hospital, who had refused aneuploidy screening during their pregnancy. We evaluated through a questionnaire submitted during the postpartum period the sociodemographic characteristics, beliefs, attitudes, and the main reason underpinning their choice. Religious, ethical, and financial factors, personal beliefs, medical information, perceived media information, and familial input were assessed through a Likert scale. RESULTS: Our pilot study included 70 patients. The main reason (33 %) was the refusal to terminate pregnancy if the screening tests ultimately led to a diagnosis of aneuploidy. Lack of adequate information on the availability and benefits of this screening method (28 %), religious beliefs (17 %), in addition to other minor reasons such as financial considerations, familial recommendations, late pregnancy follow-ups, and media influence were also identified as contributing factors. CONCLUSIONS: Aneuploidy screening is routinely offered to couples, with varying uptake rates observed worldwide. Sufficient information on prenatal screening and diagnosis should be provided to all pregnant women, presenting all available options, thus enabling them to make a free and informed choice during their pregnancy.

Diagnosis and Management of Polyorchidism: A Case Report and Literature Review.

Polyorchidism, or supernumerary testis, is a rare congenital abnormality of the genitourinary system. In this paper, we present the case of triorchidism in a seven-year-old asymptomatic child with a suspect left scrotal mass detected on routine physical examination. Imaging studies revealed a third testicle in the left hemiscrotum, with comparable dimensions, signal intensity on MRI, and Doppler flow on ultrasound with the ipsilateral testis. We also discuss the clinical presentations, classifications, and current diagnostic and therapeutic strategies of this condition.

HPV Vaccination Prevalence among Lebanese Female University Students: A Cross-Sectional Study.

Background: Cervical cancer is the fourth most common cancer in women, worldwide. Most often, cervical cancer is caused by a human papillomavirus (HPV) infection. A lack of studies concerning HPV knowledge and vaccination among the Lebanese population is noticed. We aim to assess the prevalence of HPV vaccine administration among female university students in Lebanon alongside determining the predictors influencing vaccine uptake. Lastly, knowledge scores concerning HPV and HPV vaccination are also computed. Methods: This is a cross-sectional analytical study. It is an anonymous, online-based, close-ended questions survey conducted between the 24th of February 2021 and the 30th of March 2021. Our questionnaire was addressed to females aged between 17 and 30 years and enrolled in a Lebanese university. The collected data were analyzed using Statistical Package for Social Sciences (SPSS) v.26. We used bivariate analysis to compare the rate of vaccination with different variables. We used the chi-square test for categorical variables and Student's t-test for continuous variables. Logistic linear regression was conducted between the state of vaccination and other statistically significant variables from the bivariate analysis. Results: We have received a total of 454 questionnaires. Among the respondents, only 18.9% had received a minimum of one dose of the HPV vaccine. The mean age of up taking the first dose of the vaccine was 17.5 years. In addition, 48% of the respondents were not willing to take the HPV vaccine during the upcoming year. Barriers to not taking the HPV vaccine were mainly the low levels of knowledge concerning HPV and its vaccine. In the multivariate analysis, three predictors were found to affect the rate of HPV vaccination: university type, paternal educational level, and HPV vaccine knowledge score. In detail, a student enrolled in a public university had 77% likelihood of not being vaccinated. Furthermore, female students with a paternal educational level higher than a university degree had 88% probability of being vaccinated. Finally, every increase in the HPV vaccination knowledge of one point increased the likelihood of being vaccinated by 37%. Conclusion: A low vaccination rate among female university students in Lebanon was noticed in our study. In addition, a lack of HPV and HPV vaccine knowledge was found in our population. An awareness campaign alongside public vaccination programs is recommended in order to accomplish higher rates of HPV immunization.

A Potential Protective Effect of Alcohol Consumption in Male Genital Lichen Sclerosus: A Case-Control Study.

Materials and Methods: A nested case-control study design was chosen. Subjects enrolled were adult male patients who had a circumcision between January 2010 and December 2020 at our university hospital, with a confirmed LSc diagnosis on pathology. Cases were matched with controls by age with a ratio of 1 : 1, all of whom were circumcised and had a negative pathology report. Data collection consisted of sociodemographic, behavioral, and past medical and familial history characteristics. Results: A total of 94 patients were enrolled. The mean age was 49.81 (±22.92) in the group of men with LSc. No significant differences in sociodemographic characteristics (age and BMI) were found between the two compared groups. Smoking cannot predict LSc as opposed to alcohol consumption, which we found to be a protective factor against the appearance of LSc (p=0.027). Men with LSc had significantly higher rates of diabetes (p=0.021) and hypertension (p=0.004). No associations were found between LSc and the presenting chief complaints, family history of LSc, and past penile trauma. Conclusion: In this study, we were able to compare multiple variables between 47 circumcised patients diagnosed with LSc and a control group. We found that LSc patients showed higher rates of diabetes and hypertension. A potential protective effect of alcohol consumption is to be explored in future projects with bigger sample sizes and higher statistical powers.

Spatial regulation of amacrine cell genesis by Semaphorin 3f.

PURPOSE: The axonal projections of retinal ganglion cells (RGCs) of the eye are topographically organized so that spatial information from visual images is preserved. This retinotopic organization is established during development by secreted morphogens that pattern domains of transcription factor expression within naso-temporal and dorso-ventral quadrants of the embryonic eye. Poorly understood are the downstream signaling molecules that generate the topographically organized retinal cells and circuits. The secreted signaling molecule Semaphorin 3fa (Sema3fa) belongs to the Sema family of molecules that provide positional information to developing cells. Here, we test a role for Sema3fa in cell genesis of the temporal zebrafish retina. METHODS: We compare retinal cell genesis in wild type and sema3fa CRISPR zebrafish mutants by in situ hybridization and immunohistochemistry. RESULTS: We find that mRNAs for sema3fa and known receptors, neuropilin2b (nrp2b) and plexina1a (plxna1a), are expressed by progenitors of the temporal, but not nasal zebrafish embryonic retina. In the sema3faca304/ca304 embryo, initially the domains of expression for atoh7 and neurod4, transcription factors necessary for the specification of RGCs and amacrine cells, respectively, are disrupted. Yet, post-embryonically only amacrine cells of the temporal retina are reduced in numbers, with both GABAergic and glycinergic subtypes affected. CONCLUSIONS: These data suggest that Sema3fa acts early on embryonic temporal progenitors to control in a spatially-dependent manner the production of amacrine cells, possibly to allow the establishment of neural circuits with domain-specific functions. We propose that spatially restricted extrinsic signals in the neural retina control cell genesis in a domain-dependent manner.

Semaphorin3f as a cardiomyocyte derived regulator of heart chamber development.

BACKGROUND: During development a pool of precursors form a heart with atrial and ventricular chambers that exhibit distinct transcriptional and electrophysiological properties. Normal development of these chambers is essential for full term survival of the fetus, and deviations result in congenital heart defects. The large number of genes that may cause congenital heart defects when mutated, and the genetic variability and penetrance of the ensuing phenotypes, reveals a need to understand the molecular mechanisms that allow for the formation of chamber-specific cardiomyocyte differentiation. METHODS: We used in situ hybridization, immunohistochemistry and functional analyses to identify the consequences of the loss of the secreted semaphorin, Sema3fb, in the development of the zebrafish heart by using two sema3fb CRISPR mutant alleles. RESULTS: We find that in the developing zebrafish heart sema3fb mRNA is expressed by all cardiomyocytes, whereas mRNA for a known receptor Plexina3 (Plxna3) is expressed preferentially by ventricular cardiomyocytes. In sema3fb CRISPR zebrafish mutants, heart chamber development is impaired; the atria and ventricles of mutants are smaller in size than their wild type siblings, apparently because of differences in cell size and not cell numbers. Analysis of chamber differentiation indicates defects in chamber specific gene expression at the border between the ventricular and atrial chambers, with spillage of ventricular chamber genes into the atrium, and vice versa, and a failure to restrict specialized cardiomyocyte markers to the atrioventricular canal (AVC). The hypoplastic heart chambers are associated with decreased cardiac output and heart edema. CONCLUSIONS: Based on our data we propose a model whereby cardiomyocytes secrete a Sema cue that, because of spatially restricted expression of the receptor, signals in a ventricular chamber-specific manner to establish a distinct border between atrial and ventricular chambers that is important to produce a fully functional heart. Video abstract.

Prostate Cancer awareness in the Lebanese population: a cross sectional national survey.

BACKGROUND: Prostate cancer (Pca) is the second most common cause of cancer among Lebanese men. Screening is an effective method to reduce prostate cancer mortality. This study assessed the knowledge, awareness, and screening practices among Lebanese population regarding Pca. METHODS: A cross-sectional national study over all the Lebanese governorates on 1558 persons was undergone. Information on Pca knowledge and attitudes towards screening was obtained using a semi structured questionnaire. Bivariate and binary logistic regression were used to assess relations between Pca knowledge and socio-demographic characteristics. RESULTS: The sample consisted of 1088 (69.8%) males and 470 (30.2%) females, with a mean age of 40 Y.O. Concerning early detection methods of Pca, its frequency, the ideal screening age, symptoms and curability of Pca, a significant difference (p < 0.05) was found when studying the following variables: the educational level (university level group having the highest percentage of correct answers), the individual monthly income (more correct answers were found with higher monthly income) and the age groups (most correct answers in the younger age groups). CONCLUSION: Our study points to the need of developing Pca prevention and education programs that should especially target older men, and people of low socioeconomic status and education in Lebanon. Such programs would increase awareness to Pca and screening, ultimately reducing the burden of advanced cancer through its early diagnosis.

Endothelial Semaphorin 3fb regulates Vegf pathway-mediated angiogenic sprouting.

Vessel growth integrates diverse extrinsic signals with intrinsic signaling cascades to coordinate cell migration and sprouting morphogenesis. The pro-angiogenic effects of Vascular Endothelial Growth Factor (VEGF) are carefully controlled during sprouting to generate an efficiently patterned vascular network. We identify crosstalk between VEGF signaling and that of the secreted ligand Semaphorin 3fb (Sema3fb), one of two zebrafish paralogs of mammalian Sema3F. The sema3fb gene is expressed by endothelial cells in actively sprouting vessels. Loss of sema3fb results in abnormally wide and stunted intersegmental vessel artery sprouts. Although the sprouts initiate at the correct developmental time, they have a reduced migration speed. These sprouts have persistent filopodia and abnormally spaced nuclei suggesting dysregulated control of actin assembly. sema3fb mutants show simultaneously higher expression of pro-angiogenic (VEGF receptor 2 (vegfr2) and delta-like 4 (dll4)) and anti-angiogenic (soluble VEGF receptor 1 (svegfr1)/ soluble Fms Related Receptor Tyrosine Kinase 1 (sflt1)) pathway components. We show increased phospho-ERK staining in migrating angioblasts, consistent with enhanced Vegf activity. Reducing Vegfr2 kinase activity in sema3fb mutants rescues angiogenic sprouting. Our data suggest that Sema3fb plays a critical role in promoting endothelial sprouting through modulating the VEGF signaling pathway, acting as an autocrine cue that modulates intrinsic growth factor signaling.

Semaphorin 3fa Controls Ocular Vascularization From the Embryo Through to the Adult.

Purpose: Pathological blood vessel growth in the eye is implicated in several diseases that result in vision loss, including age-related macular degeneration and diabetic retinopathy. The limits of current disease therapies have created the need to identify and characterize new antiangiogenic drugs. Here, we identify the secreted chemorepellent semaphorin-3fa (Sema3fa) as an endogenous anti-angiogenic in the eye. Methods: We generated a CRISPR/Cas9 sema3fa zebrafish mutant line, sema3faca304/304. We assessed the retinal and choroidal vasculature in both larval and adult wild-type and sema3fa mutant zebrafish. Results: We find sema3fa mRNA is expressed by the ciliary marginal zone, neural retina, and retinal pigment epithelium of zebrafish larvae as choroidal vascularization emerges and the hyaloid/retinal vasculature is remodeled. The hyaloid vessels of sema3fa mutants develop appropriately but fail to remodel during the larval period, with adult mutants exhibiting a denser network of capillaries in the retinal periphery than seen in wild-type. The choroid vasculature is also defective in that it develops precociously, and aberrant, leaky sprouts are present in the normally avascular outer retina of both sema3faca304/304 larvae and adult fish. Conclusions: Sema3fa is a key endogenous signal for maintaining an avascular retina and preventing pathologic vascularization. Furthermore, we provide a new experimentally accessible model for studying choroid neovascularization (CNV) resulting from primary changes in the retinal environment that lead to downstream vessel infiltration.

Large Cell Neuroendocrine Carcinoma of the Bladder with Adenocarcinomatous Component.

Large cell neuroendocrine carcinoma (LCNC) is one of the rarest types of bladder cancer occurring in <1%. Either pure or mixed with another component, it remains one of the most aggressive types of bladder cancer. We report a case of LCNC of the bladder with an adenocarcinomatous component. The patient was a 64-year-old smoker male, who presented for the first time with dysuria and hematuria. A bladder tumor invading the anterior and right lateral bladder walls was discovered, without any secondary localizations. Tumor biopsy showed an LCNC with adenocarcinomatous components. The patient was treated by recurrent tumor resections, chemotherapy, and radiotherapy. No improvement was noted despite close follow-up and adequate treatment. Neuroendocrine bladder tumor is known to have an aggressive, rapid, and disadvantageous evolution. Multiple case reports were published so far, and a recent review was conducted in March 2020 by Sanguedolce et al. (2020). More cases are needed to establish the best management plan for this type of tumor.

Bilateral Laparoscopic Transperitoneal Pyelolithomy: Dare You Do This?

Introduction: The aim of this article is to describe our technique of bilateral laparoscopic pyelolithotomy (LP) in a 54-year-old patient with bilateral large stones of which one is a staghorn stone (SS). Case Presentation: The patient's legs were extended and spaced from each other; the table was tilted to the right and to the left in a way to use only five trocars for both sides. The calculi were delivered intact at the end of the procedure. Operating time was 208 minutes. Blood loss was 250 mL. Hospital stay was 3 days. Double-J stents were removed 4 weeks later. The patient was stone free with a stable serum creatinine. Conclusion: This case report is the first to describe a bilateral LP for large and SS. This procedure can minimize the postoperative morbidity and is associated with high stone-free rates. It is safe when done by expert surgeons, but further investigations are required to assess its reproducibility.

Bellini Duct Carcinoma Misdiagnosed with Urothelial Papillary Carcinoma.

BACKGROUND: Collecting (Bellini) duct carcinoma (CDC) or Bellini duct carcinoma (BDC) is a rare subtype of kidney tumors, accounting for less than 3% and known to have the worst prognosis. It is known to have multiple clinical presentations; this is why it can be easily misdiagnosed. The aim of this article is to present a case of CDC that was initially misdiagnosed with urothelial papillary carcinoma (UPC) in a 41-year-old male. Case Presentation. Our patient presented with a left flank pain evolving for one month and one episode of gross macroscopic hematuria. Upon presentation, he had left costovertebral angle tenderness. Initial lab tests were normal. Computed tomography revealed a 5 cm solid mass of the left renal pelvis and multiple infracentimetric perihilar lymph nodes. Subsequently, the patient had left nephroureterectomy. Microscopic examination showed the presence of a high-grade urothelial papillary carcinoma of the renal pelvis' lumen. All four of the dissected lymph nodes showed disease metastasis. Three years after establishing the diagnosis, the patient presented again for chronic abdominal pain, with a recent history of weight loss. CT scan showed a left paraaortic mass infiltrating the left psoas muscle over a length of 12 cm. Immunohistochemical profiling of this mass confirmed the diagnosis of Bellini duct carcinoma, rejecting the initial diagnosis of UPC. Therefore, the patient required a cisplatin-gemcitabine-based chemotherapy regimen. CONCLUSION: BDC remains one of the rare aggressive subtypes of RCC, having a multitude of initial clinical presentations and an unfavorable prognosis. In this patient, CDC was masquerading as a transitional cell carcinoma that should always be kept in mind as a possible presentation. Corresponding early imaging and histopathology exams are primordial for a correct diagnosis and thus a better prognosis.

Endourologic treatment for a fibroepithelial ureteral polyp protruding from the urethra.

Fibroepithelial polyps (FP) of the ureter are rare and benign mesodermal tumors frequently mistaken for transitional cell carcinoma. We hereby report a rare case of a 19-year-old patient with two FPs, originating from the distal left ureter that were successfully treated with ureteroscopy. One of these polyps was completely protruding outside the bladder through the urethra, which makes this case unique in the literature. Ureteroscopy is currently the best method available for identification, histologic diagnosis and treatment of these polyps.

Polarity and morphogenesis of the eye epithelium requires the adhesion junction associated adaptor protein Traf4.

During development, neuroepithelial progenitors acquire apico-basal polarity and adhere to one another via apically located tight and adherens junction complexes. This polarized neuroepithelium must continue to integrate cells arising through cell divisions and intercalation, and allow for cell movements, at the same time as undergoing morphogenesis. Cell proliferation, migration and intercalation all occur in the morphing embryonic eye. To understand how eye development might depend on dynamic epithelial adhesion, we investigated the function of a known regulator of junctional plasticity, Tumour necrosis factor receptor-associated factor 4 (Traf4). traf4a mRNA is expressed in the developing eye vesicle over the period of optic cup morphogenesis, and Traf4a loss leads to disrupted evagination and elongation of the eye vesicles, and aberrant organization and apico-basal polarity of the eye epithelium. We propose a model whereby Traf4a regulates apical junction plasticity in nascent eye epithelium, allowing for its polarization and morphogenesis. Symbols and Abbreviations: AB: apico-basal; aPKC: atypical protein kinase-C; CRISPR: clustered regularly-interspaced short palindromic repeats; GFP: green fluorescent protein; hpf: hours post-fertilization; MO: antisense morpholino oligonucleotide; pHH3: phospho histone H3; ss: somite stage; Traf4: Tumour necrosis factor receptor-associated factor 4; ZO-1: zona occludens-1.

Developmental Origins for Kidney Disease Due to Shroom3 Deficiency.

CKD is a significant health concern with an underlying genetic component. Multiple genome-wide association studies (GWASs) strongly associated CKD with the shroom family member 3 (SHROOM3) gene, which encodes an actin-associated protein important in epithelial morphogenesis. However, the role of SHROOM3 in kidney development and function is virtually unknown. Studies in zebrafish and rat showed that alterations in Shroom3 can result in glomerular dysfunction. Furthermore, human SHROOM3 variants can induce impaired kidney function in animal models. Here, we examined the temporal and spatial expression of Shroom3 in the mammalian kidney. We detected Shroom3 expression in the condensing mesenchyme, Bowman's capsule, and developing and mature podocytes in mice. Shroom3 null (Shroom3Gt/Gt) mice showed marked glomerular abnormalities, including cystic and collapsing/degenerating glomeruli, and marked disruptions in podocyte arrangement and morphology. These podocyte-specific abnormalities are associated with altered Rho-kinase/myosin II signaling and loss of apically distributed actin. Additionally, Shroom3 heterozygous (Shroom3Gt/+) mice showed developmental irregularities that manifested as adult-onset glomerulosclerosis and proteinuria. Taken together, our results establish the significance of Shroom3 in mammalian kidney development and progression of kidney disease. Specifically, Shroom3 maintains normal podocyte architecture in mice via modulation of the actomyosin network, which is essential for podocyte function. Furthermore, our findings strongly support the GWASs that suggest a role for SHROOM3 in human kidney disease.

Understanding early organogenesis using a simplified in situ hybridization protocol in Xenopus.

Organogenesis is the study of how organs are specified and then acquire their specific shape and functions during development. The Xenopuslaevis embryo is very useful for studying organogenesis because their large size makes them very suitable for identifying organs at the earliest steps in organogenesis. At this time, the primary method used for identifying a specific organ or primordium is whole mount in situ hybridization with labeled antisense RNA probes specific to a gene that is expressed in the organ of interest. In addition, it is relatively easy to manipulate genes or signaling pathways in Xenopus and in situ hybridization allows one to then assay for changes in the presence or morphology of a target organ. Whole mount in situ hybridization is a multi-day protocol with many steps involved. Here we provide a simplified protocol with reduced numbers of steps and reagents used that works well for routine assays. In situ hybridization robots have greatly facilitated the process and we detail how and when we utilize that technology in the process. Once an in situ hybridization is complete, capturing the best image of the result can be frustrating. We provide advice on how to optimize imaging of in situ hybridization results. Although the protocol describes assessing organogenesis in Xenopus laevis, the same basic protocol can almost certainly be adapted to Xenopus tropicalis and other model systems.