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BACKGROUND: Cancer bladder is the most common malignant tumor affecting the urinary tract. Genetic alterations are tightly associated with the development of cancer bladder. MicroRNAs (miRNA) are small, noncoding single-stranded RNA molecules that have been linked to bladder cancer. miR-124-3pa exhibits altered expression in various types of human malignancies. DNA methyltransferase 3B (DNMT3B) is responsible for de novo DNA methylation which is a fundamental epigenetic process in carcinogenesis. This work was performed to study the expression of DNMT3B and miR 124-3pa in bladder cancer tissues, and investigate their significance in the diagnosis and prognosis of the disease. SUBJECTS & METHODS: This case-control study included one hundred and six tissue samples of patients with primary urothelial bladder cancer. The tissues were separated into two parts. The first part was immediately frozen and kept at - 80 °C for total RNA extraction with subsequent detection of miR 124-3pa and DNMT3B expressions. The other part was preserved in formalin solution for histopathological examination. RESULTS: There was a highly statistically significant difference between the cancerous and the normal tissues as regarding miRNA-124-3pa and DNMT3B expression (P < 0.001) for each. Also, there was a highly statistically significant strong negative correlation between miRNA-124-3pa and DNMT3B expression (r=-0.750, P < 0.001). The combined performance of miR-124-3pa and DNMT3B revealed that the cutoff point of ≥ 3.3 can be used as a predictor of the presence of cancer bladder with sensitivity of 98.1% and specificity of 80%. CONCLUSION: miR-124-3pa and DNMT3B can be used as predictors of the presence of cancer bladder.
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MicroRNAs , Neoplasias da Bexiga Urinária , Humanos , Estudos de Casos e Controles , MicroRNAs/genética , MicroRNAs/metabolismo , DNA (Citosina-5-)-Metiltransferases/genética , DNA (Citosina-5-)-Metiltransferases/metabolismo , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Metilação de DNA/genética , Regulação Neoplásica da Expressão Gênica/genética , Linhagem Celular Tumoral , DNA Metiltransferase 3BRESUMO
We report the results of clinical exome sequencing (CES) on >2,200 previously unpublished Saudi families as a first-tier test. The predominance of autosomal-recessive causes allowed us to make several key observations. We highlight 155 genes that we propose to be recessive, disease-related candidates. We report additional mutational events in 64 previously reported candidates (40 recessive), and these events support their candidacy. We report recessive forms of genes that were previously associated only with dominant disorders and that have phenotypes ranging from consistent with to conspicuously distinct from the known dominant phenotypes. We also report homozygous loss-of-function events that can inform the genetics of complex diseases. We were also able to deduce the likely causal variant in most couples who presented after the loss of one or more children, but we lack samples from those children. Although a similar pattern of mostly recessive causes was observed in the prenatal setting, the higher proportion of loss-of-function events in these cases was notable. The allelic series presented by the wealth of recessive variants greatly expanded the phenotypic expression of the respective genes. We also make important observations about dominant disorders; these observations include the pattern of de novo variants, the identification of 74 candidate dominant, disease-related genes, and the potential confirmation of 21 previously reported candidates. Finally, we describe the influence of a predominantly autosomal-recessive landscape on the clinical utility of rapid sequencing (Flash Exome). Our cohort's genotypic and phenotypic data represent a unique resource that can contribute to improved variant interpretation through data sharing.
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Consanguinidade , Sequenciamento do Exoma/métodos , Genes Recessivos , Doenças Genéticas Ligadas ao Cromossomo X/epidemiologia , Doenças Genéticas Ligadas ao Cromossomo X/genética , Predisposição Genética para Doença , Mutação , Criança , Estudos de Coortes , Feminino , Homozigoto , Humanos , Masculino , Fenótipo , Gravidez , Arábia Saudita/epidemiologiaRESUMO
BACKGROUND: Tumor boards are part of standard care of patients with complex cancers, but appropriate multidisciplinary expertise and infrastructure are often not available in low- and middle-income countries (LMIC) for pediatric cancers, such as neuroblastoma. Our goal was to review results of a Global Neuroblastoma Network (GNN) tumor board accessible to LMIC. METHODS: De-identified clinical cases presented via internet conference during a weekly GNN virtual tumor board from 2010 through 2020 were evaluated in a standardized format, including diagnostic imaging, pathology, therapy information, resource limitations, and questions for discussion. Information summarized included the presentations, a survey of the impact on care, and a resource questionnaire. RESULTS: Registered GNN participants included 575 individuals from 77 countries, with a median of 39 participants per session. Total 412 cases were presented from 32 countries, including 351 unique neuroblastoma patients, 52 follow-up cases, and nine non-neuroblastoma diagnoses. Twenty-eight educational sessions were presented. Limited critical resources for diagnostics and staging of cases included MYCN analysis (54.7%), metaiodobenzylguanidine (MIBG) scans (38.7%), and International Neuroblastoma Pathology Classification (49%). Therapies were also limited, with markedly decreased use of radiation and autologous stem cell transplant for high-risk cases, and no availability of anti-GD2 antibody in LMIC. Limited sampling with a post-presentation survey showed that 100% found the GNN helpful, and 70% altered the care plan based on the discussion. CONCLUSION: This report shows the utility of an international tumor board for LMIC focused on a challenging solid tumor where local expertise may be limited, with international multidisciplinary expert participation and educational sessions.
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Transplante de Células-Tronco Hematopoéticas , Neuroblastoma , 3-Iodobenzilguanidina , Criança , Humanos , Neuroblastoma/patologia , Cintilografia , Transplante AutólogoRESUMO
AIM OF THE WORK: Preoperative hormone stimulation (PHS) is used to increase the glans size and may improve the cosmetic appearance after hypospadias surgery. The exact effect of PHS on different penile tissues remains unclear and controversial. Previous studies showed that PHS increased vessel density in the foreskin. However, the effect of PHS on the urethral has never been studied before. In this study we examine the PHS effects on the urethral plate. MATERIALS AND METHODS: Specimens of the urethral plate and the underlying tissue were excised to correct severe chordee in 16 children with proximal and perineal hypospadias with severe chordee in 2 groups. Group A consisted of 8 children received PHS prior to surgery. Group B included 8 children with proximal and perineal hypospadias with severe chordee who did not receive PHS and served as a control group. Specimens were examined blindly using hematoxylin-eosin and elastic van-Gieson stain as well as factor 8 and SMA antibodies. RESULTS: The median age of Group A was 13 (range 10-20) months. The median age of Group B (without prior PHS) was 17 (range 14-29) months (p = 0,03). The median vessel-density in group A (82 vessels per mm2) was significantly higher than in Group B (65 per mm2), (p < 0.05). The median vessel diameter was also significantly higher in Group A (13 µm) than in Group B (11 µm), (p < 0.05). The median epithelial layer thickness in Group A was 110 µm and in Group B 98 µm, but showed no statistical significance (p = 0,16). There was no significant change in dartos fascia layer thickness or androgen receptor expression. There was no visual change in the organization of elastic fibers. CONCLUSION: This study is the first study to document the effect of PHS on the urethral plate in hypospadias with severe chordee. PHS significantly increased the median vessel-density as well as median vessel diameter as compared to a matching control group. The findings of the study may justify PHS administration before the first operation to improve the vascularity and may reduce the severity of chordee.
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The COVID-19 pandemic has significantly affected nursing, as nurses are crucial in providing healthcare services. Understanding the factors influencing nurse retention is essential for maintaining a strong and long-lasting workforce because nurse retention is becoming increasingly complex. This study aimed to investigate the influence of professional identity and job satisfaction on the intention to remain employed while also evaluating the levels of professional identity, job satisfaction, and intention to stay among paediatric nurses amidst the COVID-19 pandemic. This correlational and descriptive study included a stratified sample of 257 paediatric nurses and was guided by the STROBE checklist. Data were collected through valid and reliable questionnaires, which included a nurses' professional identity scale, job satisfaction survey, intention to stay scale, and a demographic questionnaire. Data collection was conducted from January to April 2022. The study was approved by the ethical research committee at the Nursing Faculty - Mansoura University, ensuring adherence to the Helsinki Declaration. The paediatric nurses reported elevated professional identity, moderate job satisfaction, and moderate intention to stay employed with mean scores of 80.35 ± 13.22, 113.70 ± 19.58, and 8.40 ± 3.55, respectively. Multiple regression explained 13.0% of the variation in paediatric nurses' intention to remain employed (F = 18.50, p < 0.001). Professional identity positively correlated with the intention to stay (ß = 2.69, p = 0.008). Job satisfaction also had a positive relationship with the intention to stay (ß = 3.49, p < 0.001). Healthcare managers should focus on professional identity strategies such as supportive work environments, growth opportunities, and valuing paediatric nurses' contributions. Implementing interventions such as fair compensation, support, and rewards can enhance paediatric nurses' retention and quality of patient care.
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Atitude do Pessoal de Saúde , COVID-19 , Criança , Humanos , Satisfação no Emprego , Intenção , Pandemias , Estudos Transversais , Reorganização de Recursos HumanosRESUMO
INTRODUCTION: Sex hormone imbalance in utero is hypothesized to play an important role in the pathogenesis of hypospadias. Due to its easy accessibility, foreskin samples have been used to describe hormone receptor expression in rodents, and both adult and pediatric patients. In this study we conducted a systematic approach to assess hormone receptor expression in pediatric patients with hypospadias compared to healthy controls with a focus on age-matching and differences in severity and degree of hypospadias. METHODS: Foreskin samples were collected from 35 children during hypospadias operations (18 distal and 17 proximal hypospadias) and compared with ventral foreskin samples of a control group of 32 children during circumcision (15 age-matched and 17 older boys). The samples were stained with H/E, androgen (AR), estrogen (ER) and progesterone receptors (PR). The receptor stainings were blindly evaluated. An Allred score was used to evaluate receptor expression in both the epithelium as well as stroma. RESULTS: AR was detected in all cases. AR expression in the stroma was more evident than in the epithelium. AR expression in the hypospadias groups was significantly less than the age matched controls (p < 0.05). There was no significant difference between the two hypospadias groups nor between the two control groups. Older control group showed significantly elevated levels of AR expression compared to the hypospadias group (p < 0.05). ER was also detected in all cases. The stroma showed more ER than in epithelium. PR was minimal or negative in all samples. CONCLUSION: Boys with hypospadias showed significantly weaker expression of androgen receptors than age matched controls. The severity of hypospadias did not influence hormone receptor distribution. AR expression is better observed in the stroma than in the epithelium. There was no difference in ER expression between the hypospadias group (distal or proximal) and age matched normal controls. ER was expressed in larger numbers in normal older preputial tissue. The foreskin of prepubertal boys shows little to no expression of PR.
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Hipospadia , Masculino , Humanos , Criança , Hipospadia/patologia , Prepúcio do Pênis/cirurgia , Expressão Gênica , Receptores Androgênicos , AndrogêniosRESUMO
OBJECTIVE: To examine the urethral plate and the underlying tissues in children with proximal hypospadias associated with severe chordee. MATERIALS AND METHODS: The urethral plate and the underlying tissue specimens were excised to correct severe chordee in 17 children with proximal and perineal hypospadias with severe chordee. The median age was 20 months (range 8-36). Sections samples were marked and examined from proximal to distal. Specimens were examined histologically using hematoxylin-eosin (H/E) and Elastic van Gieson (EvG) stain. Histochemical examination was also performed using smooth muscle actin (SMA) and factor 8 antibodies. For control, samples from four patients with hypoplastic urethra proximal to the meatus including the hypoplastic segments until the normal urethra were taken. In addition, the urethra of an adult patient with penile tumor was used as control. RESULTS: The average size of the 17 tissue samples was 0.5 cm × 0.5 cm x 0.3 cm in depth. There was a common pattern that was seen in all the 17 specimens with a variable degree of expression. H/E staining showed that the epithelial lining changed from pseudostratified epithelium at the proximal intact urethra to non-keratinized stratified squamous epithelium at the urethral meatus to keratinized stratified squamous epithelium distally at the urethral plate level. EvG staining showed overall very few elastic fibres that increased slightly in the distal urethral plate. SMA staining showed a circular pattern of smooth muscle cells in the proximal intact urethra that changed to a U-shaped pattern at the level of the meatus, to a triangle shaped pattern just distal to the meatus. The distal urethral plate showed an irregular, disorganized rather flat pattern of the smooth muscles. Factor 8 antibodies staining the blood spaces revealed dysplastic unorganized large blood sinusoids underneath the urethral plate that were different from normal capillaries surrounding the proximal urethra. CONCLUSION: The urethral plate and the underlying tissues in patients with severe chordee have different structure from normal urethra as compared to available literature and the adult control patient. The lack of elastic fibres may help to explain the rigidity of the ventral penis causing chordee. The disorganized irregular distribution of the smooth muscle fibres is suggestive of the hypoplastic corpus spongiosum. The abnormal large blood sinusoids may explain the poor healing quality of the ventral penis in patients with perineal and proximal patients associated with severe chordee. This may explain persistent/recurrent chordee observed later in those patients with severe chordee when dorsal plication is used. The study also supports the recent trend of 2 stage procedure as a plan of management for patients with proximal and perineal hypospadias with severe chordee and excision of all the dysplastic tissues during the first operation.
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Carcinoma de Células Escamosas , Hipospadia , Doenças do Pênis , Carcinoma de Células Escamosas/cirurgia , Criança , Pré-Escolar , Fator VIII , Humanos , Hipospadia/patologia , Hipospadia/cirurgia , Lactente , Masculino , Doenças do Pênis/cirurgia , Pênis/patologia , Pênis/cirurgia , Uretra/patologia , Uretra/cirurgia , Procedimentos Cirúrgicos Urológicos Masculinos/métodosRESUMO
Background: Rheumatic heart disease affects primarily cardiac valves, it could involve the myocardium either primarily or secondary to heart valve affection. The influence of balloon mitral valvuloplasty (BMV) on left ventricular function has not been sufficiently studied. Aim: To determine the influence of balloon mitral valvuloplasty (BMV) on both global and regional left ventricular (LV) function. Methods: Thirty patients with isolated rheumatic mitral stenosis (MS) were studied. All patients had cardiac magnetic resonance imaging (CMR) before, 6 months and 1 year after successful BMV. LV volumes, ejection fraction (EF), regional and global LV deformation, and LV late gadolinium enhancement were evaluated. Results: At baseline, patients had median EF of 57 (range: 45-69) %, LVEDVI of 74 (44-111) ml/m2 and LVESVI of 31 (14-57) ml/m2 with absence of late gadolinium enhancement in all myocardial segments. Six months following BMV, there was a significant increase in LV peak systolic global longitudinal strain (GLS) (-16.4 vs. -13.8, p < 0.001) and global circumferential strain (GCS) (-17.8 vs. -15.6, p = 0.002). At 1 year, there was a trend towards decrease in LVESVI (29 ml/m2, p = 0.079) with a significant increase in LV EF (62%, p < 0.001). A further significant increase, compared to 6 months follow up studies, was noticed in GLS (-17.9 vs. -16.4, p = 0.008) and GCS (-19.4 vs. -17.8 p = 0.03). Conclusions: Successful BMV is associated with improvement in global and regional LV systolic strain which continues for up to 1 year after the procedure.
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BACKGROUND: Breast cancer (BC) is a commonly reported cancer that is widely prevalent among women. Its early detection improves patient survival and results in better outcomes. For diagnosis and follow-up care, tumor markers are one of the feasible investigations to be ordered. 8-Iso-prostaglandin F2α (8-iso-PGF2α) serves as a serum marker reflecting oxidative stress and subsequent damaging of DNA. In the present study, we aimed to evaluate both diagnostic and predictive values of 8-iso-PGF2α in BC patients. MATERIALS AND METHODS: Serum levels of 8-iso-PGF2α were assessed for 66 women with benign breast tumors and 65 women who had malignant BC. To compare the patients who had breast tumors with healthy individuals, 63 women free of breast diseases were selected as controls. RESULTS: The serum level of 8-iso-PGF2α in the BC patients (57.92 pg/mL) was significantly higher compared to those with benign tumors (18.89 pg/mL) (p < 0.001). In addition, individuals with no breast diseases had less 8-iso-PGF2α (4.02 pg/mL) compared to those who had developed a tumor (p < 0.001). Serum 8-iso-PGF2α was found to be positively correlated with both carcinoembryonic antigen (r = 0.74, p < 0.001) and cancer antigen 15-3 (r = 0.80, p < 0.001). Furthermore, serum 8-iso-PGF2α showed high diagnostic performance in BC (AUC = 0.999, sensitivity = 100%, specificity = 99.2% at a cutoff value of 36.18 pg/mL). CONCLUSIONS: Our study found that the high level of serum 8-iso-PGF2α helps to provide a non-invasive indicator to detect BC. Future work with a larger sample size and various phases of BC can confirm the current results which provide insights into the early detection of cancer.
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Neoplasias da Mama/sangue , Neoplasias da Mama/diagnóstico , Dinoprosta/análogos & derivados , Adulto , Idoso , Biomarcadores Tumorais/sangue , Antígeno Carcinoembrionário/sangue , Dinoprosta/sangue , Feminino , Humanos , Peroxidação de Lipídeos , Pessoa de Meia-Idade , Mucina-1/sangue , Estresse Oxidativo , PrognósticoRESUMO
OBJECTIVE: To examine the safety and efficacy of quartz head laser ablation of the prostate (QLAP) in the treatment of large and huge prostates as compared with small- and medium-sized ones. MATERIALS AND METHODS: Two hundred forty-two patients with lower urinary tract symptoms secondary to benign prostatic hypertrophy (BPH) were included in the study, of which 210 patients were evaluable. Patients were divided into 2 groups: group A: patients with BPH volume of <80 mL (120 patients) and group B patients with gland size ≥80 mL. All patients were subjected to QLAP procedure. They were evaluated perioperatively and 1 week; 1, 3, and 6 months; and every 6 months thereafter postoperatively. RESULTS: Patients' demographics and preoperative data were similar except for the gland size (group A, 54.96 ± 15.49 mL [20-79 mL] and group B, 124.68 ± 40.88 mL [80-233 mL]). Operative time corrected to gland volume was shorter in group B. Only 10% of all patients needed 2 fibers. There was no significant electrolyte change in both groups. Hemoglobin has minimally decreased in both groups but was statistically significant. Group B outcome was significantly better regarding International Prostate Symptom Score, International Prostate Symptom Score quality of life, and uroflowmetry. Prostate size decreased by 47 ± 2% and 62.7 ± 2% at 6 months post operatively for groups A and B, respectively. CONCLUSION: QLAP demonstrated good efficacy and safety in treating large and huge BPH. It possessed no added risk as compared with small prostates. It can be a good alternative to open prostatectomy especially in patients with significant comorbidities.