Chromosomal changes in uroepithelial carcinomas

This article reviews and summarizes chromosomal changes responsible for the initiation and progression of uroepithelial carcinomas. Characterization of these alterations may lead to a better understanding of the genetic mechanisms and open the door for molecular markers that can be used for better diagnosis and prognosis of the disease. Such information might even help in designing new therapeutic strategies geared towards prevention of tumor recurrences and more aggressive approach in progression-prone cases. The revision of 205 cases of uroepithelial carcinomas reported with abnormal karyotypes showed karyotypic profile characterized by nonrandom chromosomal aberrations varying from one or few changes in low-grade and early stage tumors to massively rearranged karyotypes in muscle invasive ones. In general, the karyotypic profile was dominated by losses of chromosomal material seen as loss of entire chromosome and/or deletions of genetic materials. Rearrangements of chromosome 9 resulting in loss of material from 9p, 9q, or of the entire chromosome were the most frequent cytogenetic alterations, seen in 45% of the cases. Whereas loss of material from chromosome arms 1p, 8p, and 11p, and gains of chromosome 7, and chromosome arm 1q, and 8q seem to be an early, but secondary, changes appearing in superficial and well differentiated tumors, the formation of an isochromosome for 5p and loss of material from 17p are associated with more aggressive tumor phenotypes. Upper urinary tract TCCs have identical karyotypic profile to that of bladder TCCs, indicating the same pathogenetic mechanisms are at work in both locales. Intratumor cytogenetic heterogeneity was not seen except in a few post-radiation uroepithelial carcinomas in which distinct karyotypic and clonal pattern were characterized by massive intratumor heterogeneity (cytogenetic polyclonality) with near-diploid clones and simple balanced and/or unbalanced translocations. In the vast majority of cases strong correlation between the tumors grade/stage and karyotypic complexity was seen, indicating that progressive accumulation of acquired genetic alterations is the driving force behind multistep bladder TCC carcinogenesis. Although most of these cytogenetic alterations have been identified for many years, the molecular consequences and relevant cancer genes of these alterations have not yet been identified. However, loss of TSG(s) from chromosome 9 seems to be the primary and important event(s) in uroepithelial carcinogenesi

Editorial: Diagnosis of COVID-19 in Countries with Limited Health Resources – Blood Markers versus rRT–PCR

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The Necessity of Continuing Professional Development for EFL Teachers

      The teaching profession involves renewed work in the ever-changing and rapidly changing world of knowledge and technology. Which requires teachers to maintain the highest standards of professional practice to perform well with this innovation and rapid change. This study aimed to investigate the process through which EFL teachers become capable of engaging in, sharing control of, influencing events and in situations that affect their work as teachers. The study also aimed at investigating EFL teachers perceptions of Continuing professional development and identifying the main characteristics of existing practices, besides offering some suggestions to improve EFL teachers Continuing professional development. The study adopted the descriptive analytical method. The data was collected with a questionnaire. The sample consist of (60) EFL teachers from EL-Hasaheisa Locality. The data were analyzed with (SPSS) programme. As the  result of the analysis it is found that: Effective Continuing professional development requires time and  space, support from the Ministry of Education. Successful Continuing professional development is often grounded in teacher collaboration . The Ministry of Education does not have a budget for EFL teacher Continuing professional development. This study recommends that: The Ministry of Education should establish Continuing teachers training centres. Opportunities should be provided to teachers to participate in more activities and Continuing training. Finally the process of Continuing professional development of EFL teachers should be monitored continually

Overview on the first human cytogenetic research in Sudan

Introduction: The present study is the first human cytogenetic project in Sudan which was titled: Cytogenetic and FISH analyses in Sudanese patients with dysmorphic features, ambiguous genitalia, and infertility. The aim of the present study was not only to characterize the genetic alterations in patients with dysmorphic features, ambiguous genitalia and/or infertility among Sudanese population, but also to attract the medical community attention to the importance of human cytogenetics in clinical genetics practice, and also to facilitate the introduction and clinical application of such valuable service in Sudan. Materials and Methods: In this study chromosomal G–banding and fluorescence in situ hybridisation (FISH) analysis were performed on 44 Sudanese patients, 29 females, 14 males, and one patient with unassigned sex. Patients age ranging between 17 days-39 years (mean 18 years), Of the 44 patients, 20 had ambiguous genitalia, 8 dysmorphic features, 11 have puberty and/or fertility complains, and 5 were healthy individual (parents of 3 patients with dysmorphic features). Results: Cytogenetic analysis of 20 patients complaining of ambiguous genitalia (13 females and 6 males, and one case with unassigned sex) showed that 8 has karyotypes different from their assigned sex and the other cases showed karyotypes consistent with Edward syndrome (47,XX,+18) (case 7), and a case with 45,Xdel(X)(p11) (case 11) respectively, when using FISH the 45,Xdel(X)(p11) case showed translocation of the SRY (sex-determining region Y), gene to the active X chromosome. For the 8 patients of dysmorphic features; five showed karyotypes consistent with Down syndrome, of which one showed Robertsonian translocation, with both FISH and ordinary G-banding, and the other three showed normal karyotypes. All the parents showed normal karyotypes. Among the infertility cases all showed normal karyotypes, except for two which showed karyotypes consistent with Turner syndrome and one which showed a male karyotype although the case was raised as a female; ultrasound showed a mass in the position of prostate. Discussion: The study, the ever first one in Sudan, assured the importance, the possibility, and the need for cytogenetic and FISH analysis in diagnosis, management and genetic counseling of genetic diseases caused by constitutional chromosomal changes among Sudanese patients. Sudan Journal of Medical Sciences Vol. 1(1) 2006: 25-3

Unexpected Diagnosis of Complete Androgen Insensitivity Syndrome (CAIS) During Inguinal Hernia Repair in 11-year-old-girl

Complete Androgen Insensitivity Syndrome (CAIS) is an X-link recessive genetic mutation of androgen receptor (AR) gene leading to complete inability of cell to respond to the androgens. CAIS occurs in 1 out of 20,400 XY live-birth babies, and affects about 1–2% of prepubertal girls that present with an inguinal hernia. Although individuals with CAIS have XY, those with grades 6 and 7 on the Quigley scale are born phenotypically female, without any signs of genital masculinization. Thus, individuals affected by CAIS develop a normal external female phenotype with normal female external genitalia, well-developed breast, absent uterus, and bilateral undescended testicles. The question of CAIS diagnosis does not come forward until the absent menses at the puberty is noted or accidentally during an inguinal hernia repair in a premenarchal girl. The present study reports a case of inguinal hernia repair on 11-year-old girl, which led to unexpected intraoperative notion of CAIS. The diagnostic work-up, genetic counseling, sex assignment, and the need for preoperative CAIS screening in girls with bilateral inguinal hernia are described and discussed. Keywords: DSD, CAIS, bilateral inguinal hernia, gonadectom

Rare Suprasellar Chordoid Meningioma with INI1 Gene Mutation

Background: Chordoid Meningioma is a rare brain tumour characterized genetically by loss of genetic material from chromosome 22q at cytogenetic level resulting in mutation of NF2 gene. Objectives and case report: In the present report, we described a rare case of suprasellar chordoid meningioma, which presented in a 32-year-old-woman. Her only complain was throbbing headache. Neurological examination showed left temporal hemianopia, decreased visual acuity (3/6), and no physical abnormalities related to Castleman syndrome were noted. Cranial magnetic resonance (MR) images demonstrated a 28x15 mm mass in the sellar region, which showed iso-to low intensity that enhanced vividly after gadolinium with upwards displacement of the Optic chiasm. Total surgical excision of the tumour was performed and subsequent histological examination of the tumour showed typical histology pattern of chordoid meningioma grade II according to the WHO classification system of meningiomas. Genomic DNA was extracted and mutation analysis for INI1 gene using primer of exon 4, 5, 7, and 9 showed mutation involving exon 9. DNA sequencing showedheterozygosity C­­­­­­­­­­­­­­­­­­-T mutation in exon 9 of INI1 gene leading to change of amino acid serine to phenylalanine at (codon 63). The details of this case are presented with a review of the literature

Blood pressure response to renal denervation is correlated with baseline blood pressure variability: a patient-level meta-analysis

Background: Sympathetic tone is one of the main determinants of blood pressure (BP) variability and treatment-resistant hypertension. The aim of our study was to assess changes in BP variability after renal denervation (RDN). In addition, on an exploratory basis, we investigated whether baseline BP variability predicted the BP changes after RDN. Methods: We analyzed 24-h BP recordings obtained at baseline and 6 months after RDN in 167 treatmentresistant hypertension patients (40% women; age, 56.7 years; mean 24-h BP, 152/90 mmHg) recruited at 11 expert centers. BP variability was assessed by weighted SD [SD over time weighted for the time interval between consecutive readings (SDiw)], average real variability (ARV), coefficient of variation, and variability independent of the mean (VIM). Results: Mean office and 24-h BP fell by 15.4/6.6 and 5.5/ 3.7 mmHg, respectively (P < 0.001). In multivariable-adjusted analyses, systolic/diastolic SDiw and VIM for 24-h SBP/DBP decreased by 1.18/0.63 mmHg (P 0.01) and 0.86/0.42 mmHg (P 0.05), respectively, whereas no significant changes in ARV or coefficient of variation occurred. Furthermore, baseline SDiw (P ¼ 0.0006), ARV (P ¼ 0.01), and VIM (P ¼ 0.04) predicted the decrease in 24-h DBP but not 24-h SBP after RDN. Conclusion: RDN was associated with a decrease in BP variability independent of the BP level, suggesting that responders may derive benefits from the reduction in BP variability as well. Furthermore, baseline DBP variability estimates significantly correlated with mean DBP decrease after RDN. If confirmed in younger patients with less arterial damage, in the absence of the confounding effect of drugs and drug adherence, baseline BP variability may prove a good predictor of BP response to RDN

Accuracy of non-invasive cuffless blood pressure in the intensive care unit: Promises and challenges

ObjectiveContinuous non-invasive cuffless blood pressure (BP) monitoring may reduce adverse outcomes in hospitalized patients if accuracy is approved. We aimed to investigate accuracy of two different BP prediction models in critically ill intensive care unit (ICU) patients, using a prototype cuffless BP device based on electrocardiogram and photoplethysmography signals. We compared a pulse arrival time (PAT)-based BP model (generalized PAT-based model) derived from a general population cohort to more complex and individualized models (complex individualized models) utilizing other features of the BP sensor signals.MethodsPatients admitted to an ICU with indication of invasive BP monitoring were included. The first half of each patient’s data was used to train a subject-specific machine learning model (complex individualized models). The second half was used to estimate BP and test accuracy of both the generalized PAT-based model and the complex individualized models. A total of 7,327 measurements of 15 s epochs were included in pairwise comparisons across 25 patients.ResultsThe generalized PAT-based model achieved a mean absolute error (SD of errors) of 7.6 (7.2) mmHg, 3.3 (3.1) mmHg and 4.6 (4.4) mmHg for systolic BP, diastolic BP and mean arterial pressure (MAP) respectively. Corresponding results for the complex individualized model were 6.5 (6.7) mmHg, 3.1 (3.0) mmHg and 4.0 (4.0) mmHg. Percentage of absolute errors within 10 mmHg for the generalized model were 77.6, 96.2, and 89.6% for systolic BP, diastolic BP and MAP, respectively. Corresponding results for the individualized model were 83.8, 96.2, and 94.2%. Accuracy was significantly improved when comparing the complex individualized models to the generalized PAT-based model in systolic BP and MAP, but not diastolic BP.ConclusionA generalized PAT-based model, developed from a different population was not able to accurately track BP changes in critically ill ICU patients. Individually fitted models utilizing other cuffless BP sensor signals significantly improved accuracy, indicating that cuffless BP can be measured non-invasively, but the challenge toward generalizable models remains for future research to resolve

Detection of Nonadherence to Antihypertensive Treatment by Measurements of Serum Drug Concentrations

Nonadherence to drugs is a challenge in hypertension treatment. We aimed to assess the prevalence of nonadherence by serum drug concentrations compared with 2 indirect methods and relate to the prescribed drug regimens in a nationwide multicenter study. Five hundred fifty patients with hypertension using ≥2 antihypertensive agents participated. We measured concentrations of 23 antihypertensive drugs using ultra high performance liquid chromatography tandem mass-spectrometry and compared with patients’ self-reports and investigators’ assessment based on structured interview. We identified 40 nonadherent patients (7.3%) using serum drug concentrations. They had higher office diastolic blood pressure (90 versus 83 mm Hg, P<0.01) and daytime diastolic blood pressure (85 versus 80 mm Hg, P<0.01) though systolic blood pressures did not differ significantly. They had more prescribed daily antihypertensive pills (2.5 versus 2.1 pills, P<0.01) and total daily pills (5.5 versus 4.4 pills, P=0.03). Prescription of fixed-dose combination pills were lower among the nonadherent patients identified by serum concentrations (45.0 versus 67.1%, P<0.01). Fifty-three patients self-reported nonadherence, while the investigators suspected 69 nonadherent patients. These groups showed no or few differences in drug regimens, respectively. In summary, we detected 7.3% prevalence of nonadherence by serum drug measurements in patients using ≥2 antihypertensive agents in a nationwide study; they had higher office and ambulatory diastolic blood pressures, higher number of prescribed daily pills, more daily antihypertensive pills, and less frequent prescriptions of fixed-dose combination pills. Indirect methods showed poor overlap with serum drugs concentrations and no or minimal medication differences. Thus, serum measurements of drugs were useful in detection and characterization of nonadherence to antihypertensive treatment.acceptedVersio

Production of insulin producing cells from cord blood mesenchymal stem cells and their potential in cell therapy

Introduction: Mesenchymal stem cells (MSCs) were described as adherent cells with a fibroblast-like appearance, have a great capacity for self-renewal while maintaining their multipotency and differentiation into multiple tissues in vivo and in vitro. Methods: MSCs were isolated from cord blood of Sudanese donors using Ficoll-Hypaque gradient density protocol, and differentiate into β- like cells using 3-step protocol. STZ induced diabetic rats were injected intraperitoneally with the differentiated islet β- like cells and blood glucose levels were monitored for seven days. Results: The adherent cell appeared round and sphere after one-week of incubation, and the fibroblast-like colony was strongly attached after three weeks of seeding. The phenotyping of cells showed positivity for CD13, and negativity for CD34, CD45 and HLADR. MSCs were induced into islet-like cells using a 3-step (15-days) protocol. The differentiated cells showed positive diathizone stain and positive imuno-reactivity to anti-human insulin antibody. Secretion of insulin by insulin-producing cells showed positive result with &gt;3.4 u/ml scale reading in high glucose concentration medium. After one-week of transplantation the level of blood glucose was reduced from 410 to 225 mg/dl in the experimental rat. Conclusion: Human UCB-MSCs can be differentiated into insulin-secreting cells invitro, and are able to produce and secrete insulin in response to high glucose concentration in vivo and in vitro. Keywords: Cord blood, Mesenchymal stem cell, islets β-like cell