A novel nonsense mutation in cathepsin C gene in an Egyptian patient presenting with Papillon–Lefe`vre syndrome

Background: Cathepsin C gene (CTSC) (MIM#602365) is a lysosomal cysteine proteinase coding gene which encodes for CTSC protein that plays a major role in the activation of granule serine proteases, particularly leukocyte elastase and granzymes A and B. This activity was proposed to play a role in epithelial differentiation and desquamation. Mutations that cause Disruption in the CTSC expression or function will result in loss of immunological response such as defects of phagocytic function and deregulation of localized polymorphonuclears response with subsequent clinical manifestation.Aim: The aim of this study is to detect the mutation in CTSC gene expected to be the cause of Papillon Lefe`vre syndrome (PLS) in an Egyptian patient clinically diagnosed as PLS and to characterize the clinical features.Patient and methods: A 5 year and 3 month old girl from the outpatient’s Oro-Dental Genetics clinic – National Research Center presented with the typical clinical findings of Papillon Lefevre syndrome. Genomic DNA was extracted from peripheral blood samples of the patient, her parents and 20 healthy Egyptian controls using standard procedures. All exons of the CTSC gene were amplified by PCR. Sequence analysis of the patient, her parents and controls was performed for mutation detection.Results: Mutation analysis of the CTSC gene in our patient revealed a novel homozygous nonsense mutation in exon 5 (W237X). Her parents revealed the presence of the same mutation in a heterozygous state. The 20 controls showed only the wild type sequence of all exons (no mutation).Conclusion: This study reported a novel nonsense mutation in the CTSC gene in an Egyptian patient. This novel nonsense mutation is predicted to produce truncated dipeptidyl-peptidase1 causing PLS phenotype in this patient

Predicting progression of Alzheimer’s disease using new survival analysis approach

It is critical to determine the risk of Alzheimer’s disease (AD) in people with mild cognitive impairment (MCI) to begin treatment early. Its development is affected by many things, but how each effect and how the disease worsens is unclear. Nevertheless, an in-depth examination of these factors may provide a reasonable estimate of how long it will take for patients at various stages of the disease to develop Alzheimer’s. Alzheimer’s disease neuroimaging initiative (ADNI) database had 900 people with 63 features from magnetic resonance imaging (MRI), genetic, cognitive, demographic, and cerebrospinal fluid data. These characteristics are used to track AD progression. A hybrid approach for dynamic prediction in clinical survival analysis has been developed to track progression to AD. The method uses a random forest cox regression approach to figure out how long it will take for MCI to turn into AD. In order to evaluate the result concordance index is used. The concordance index measures the rank correlation between predicted risk scores and observed time points. The concordance index was statistically considerably higher in the suggested work than in previous approaches with a score of 95.3%, which is higher than others

Modulatory role of chelating agents in diet-induced hypercholesterolemia in rats

AbstractIntroductionHypercholesterolemia is a major risk factor for the development of atherosclerosis and endothelial dysfunction. Chelating agents may play a modulatory role in atherosclerosis by removal of calcium from atherosclerotic plaques.AimThe present study aimed to explore the effects of calcium disodium ethylenediaminetetraacetic acid (CaNa2EDTA) and meso-2,3-dimercaptosuccinic acid (DMSA) on diet-induced hypercholesterolemia in rats using simvastatin as a reference standard.MethodsHypercholesterolemia was induced by feeding rats with cholesterol-rich diet for six weeks. Rats were divided into five groups (n=8): normal control, hypercholesterolemic control, simvastatin (20mg/kg; p.o.), CaNa2EDTA (100mg/kg; i.p.) and DMSA (100mg/kg; i.p.). Treatments continued daily for the six weeks of diet feeding.ResultsDiet-induced hypercholesterolemia resulted in alterations in the lipid profile markers and a state of oxidative stress coupled by compensatory increase in serum nitric oxide (NO) level and decreased aortic endothelial nitric oxide synthase (eNOS) activity parallel to increased inducible nitric oxide synthase (iNOS) activity, aortic calcium content and aortic wall thickness. Treatment with simvastatin, CaNa2EDTA and DMSA improved lipid profile and oxidative stress markers. In addition, they attenuated hypercholesterolemia-induced changes in serum NO level, aortic eNOS and iNOS activities, calcium content and aortic wall thickness.ConclusionPretreatment of hypercholesterolemic rats with simvastatin, CaNa2EDTA or DMSA attenuated most of the changes induced by feeding rats with cholesterol-rich diet owing to their observed anti-hyperlipidemic and antioxidant properties

Comparison Of In Vitro Models Of Diabetic Nephropathy Using Renal Tubular Cells

Background: Diabetic nephropathy (DN) is a chronic and serious complication associated with diabetes. The standardization of an in vitro model to best represent DN is very challenging due to the chronic nature of the condition. Therefore, two different renal tubule cell lines - Madin-Darby canine kidney cells (MDCK) and Normal rat kidney cells (NRK-52E) - were used to investigate the effects of high glucose on kidney cells. Objective: To determine the effects of high glucose concentrations on cell viability (using MTT assay), oxidative stress (using dichlorofluorescein (DCF) staining), and expression of proteins activated in DN such as aldose reductase and glucose-regulated protein-78 (GRP78), an endoplasmic reticulum chaperone (using western blotting). Results: MDCK cells showed a subtle decrease in viability when exposed to high glucose concentrations (30 mM and 1% FBS) for 48 h. Furthermore, there was a slight increase in aldose reductase expression after 48 h of high glucose exposure, however; the GRP78 levels remained unchanged. NRK-52E cells showed more consistent decrease in viability after 48 and 72 h of high glucose exposure (30 mM and 1% FBS). In addition, the DCF staining also demonstrated an increase in oxidative stress after 24 h of high glucose exposure. Furthermore, a 30% increase in aldose reductase expression has been observed after 48 h of high glucose exposure. Conclusion: Although the 48 h high glucose exposure in MDCK cells can be used as a model for in vitro DN, the results are less reproducible, whereas NRK-52E cells seem to be a better and more reliable cell line to mimic the features of DN in vitro. Key words: Diabetic nephropathy; In vitro; Kidney; Oxidative Stress; ER Stress.qscienc

Population-based rapid assessment of avoidable blindness survey in Sohag governorate in Egypt.

OBJECTIVES: To determine the prevalence and causes of blindness and vision impairment, and the coverage and quality of cataract surgical services, among population aged 50 years and older in Sohag governorate in Egypt. DESIGN: A population-based cross-sectional survey using two-stage cluster random sampling following the rapid assessment of avoidable blindness methodology. SETTING: A community-based survey conducted by six teams of ophthalmologists, assistants and local guides. Enrolment and examination were door-to-door in selected clusters. PARTICIPANTS: Using 2016 census data, 68 population units were randomly selected as clusters (of 60 people) with probability proportionate to population size. Anyone aged 50 years and older, residing in a non-institutional setting in a cluster for at least 6 months, was eligible to participate. PRIMARY AND SECONDARY OUTCOME MEASURES: The prevalence and causes of blindness and vision impairment. Secondary outcomes were CSC and effectiveness and participant-reported barriers to cataract surgery. RESULTS: Of 4078 participants enrolled, 4033 (98.9%) were examined. The age-adjusted and sex-adjusted prevalence of blindness, severe vision impairment and moderate vision impairment were 5.9% (95% CI 4.8% to 6.9%), 4.7% (95% CI 3.8% to 5.7%) and 18.9% (95% CI 16.8% to 21.0%), respectively. Cataract caused most of blindness (41.6%), followed by non-trachomatous corneal opacity (15.7%) and posterior segment diseases (14.5%). Cataract surgical coverage (CSC) for persons for visual acuity <3/60 was 86.8%, the proportion of cataract surgeries with poor visual outcome was 29.5% and effective CSC (eCSC) was 44.9%. eCSC was lower in women than men. The most frequently reported barrier to surgery was cost (51.5%). CONCLUSIONS: The prevalence of blindness in Sohag governorate is higher than districts in other middle-income countries in the region. CSC was high; however, women suffer worse quality-corrected CSC than men. The quality of cataract surgery needs to be addressed, while health system strengthening across government and private settings could alleviate financial barriers

Treatment of Bronchiolitis Using Nebulized Hypertonic Saline in Asthma-Prone and Non-Asthma-Prone Patients

Background: In bronchiolitis, children under the age of two experience cough, dyspnea and wheezing, following a viral upper respiratory infection. Frequently recurrent bronchiolitis in infants with atopic background is the best example of asthma-prone viral-induced wheeze. In bronchiolitis management, inhaled hypertonic saline is the subject of debate among pediatricians and researchers. Nebulized hypertonic saline acts by increasing fluidity of airway surface liquid. Bronchospasm is a theoretical risk for inhaled hypertonic saline when used without adjunctive bronchodilators. Objective: To compare the response to nebulized hypertonic saline plus B 2 agonists, with nebulized isotonic saline plus B 2 agonists, in asthma-prone and non-asthma-prone bronchiolitis patients. Patients and methods: This study was a randomized double blind controlled trial, which was carried out at Pulmonology Unit, Pediatric Department, Zagazig University Children Hospital. The study was conducted on 104 infants with acute viral bronchiolitis of mild to moderate severity. They were divided into two groups 52 in each group. Group 1: Asthma-prone patients and group 2, which included non-asthma-prone patients. Patients were randomly assigned to receive inhalation of 0.3 mg/kg salbutamol added to 5 ml of either normal saline 0.9% or hypertonic saline 3%. Within each group the number of patients receiving hypertonic or isotonic saline inhalation was equal to 26. Results: Nebulized hypertonic saline salbutamol mixture resulted in better improvement of the studied asthmaprone and non-asthma prone bronchiolitis patients. Hypertonic saline decreased case severity and days of hospital stay. Conclusion: Nebulized hypertonic saline shortened the days of hospital admission and improved the respiratory distress in mild to moderate bronchiolitis. Nebulized hypertonic saline is equally effective in asthmaprone and non-asthma-prone patients and its beneficial effect outweighs its theoretical broncho-constrictive effect

Relation Between Intimate Partner Violence During Pregnancy and Postpartum Mother Psychological Wellbeing

Background: Intimate partner violence (IPV) may be physical violence, psychological or sexual abuse by a current or former intimate partner. It is an avoidable global public health problem. IPV in pregnancy, despite being a common problem but remains a neglected condition (1). The severity of violence from a partner during pregnancy was reported to be greater than violence before pregnancy due to possibly change in a couple’s relationship and lifestyle accompanying pregnancy (2).Numerous studies revealed that experiencing IPV during pregnancy negatively affects both mothers and infants during the post- partum period(3).Objectives:&nbsp; to assess prevalence of&nbsp; postpartum depression and anxiety and assess possible relation between partner violence during pregnancy and postpartum psychological health. Design: prospective cohort study Method: This study was carried out on 176 pregnant women attending antenatal care to explore the possible relation between intimate partner violence and postpartum depression and anxiety. The assessment was done during the second trimester by screening the sociodemographic factors, screening of intimate partner violence was done using the Arabic version of the Composite Abuse Scale. Postpartum assessment by screening of maternal depression was done by the Arabic version of the Edinburgh post-partum depression scale, and screening of anxiety using the Arabic version of Perinatal Anxiety Screening Scale. Results: the prevalence of intimate partner violence during pregnancy was 19.3%. Near half of participants suffered from postpartum depressive illness and around one quarter suffered from possible depression. More than half of participants suffered from mild to moderate postpartum anxiety. Partner violence had also significant relation with depression during pregnancy and post-partum with p-value &lt;0.001 for both. Conclusions: intimate partner violence may be a risk factor for postpartum depression and anxiety.so, we should screen for it and learn how to deal with this problem

Renoprotective Effects of Aldose Reductase Inhibitor Epalrestat against High Glucose-Induced Cellular Injury

Diabetic nephropathy (DN) is the leading cause of end stage renal disease worldwide. Increased glucose flux into the aldose reductase (AR) pathway during diabetes was reported to exert deleterious effects on the kidney. The objective of this study was to investigate the renoprotective effects of AR inhibition in high glucose milieu in vitro. Rat renal tubular (NRK-52E) cells were exposed to high glucose (30 mM) or normal glucose (5 mM) media for 24 to 48 hours with or without the AR inhibitor epalrestat (1 M) and assessed for changes in Akt and ERK1/2 signaling, AR expression (using western blotting), and alterations in mitochondrial membrane potential (using JC-1 staining), cell viability (using MTT assay), and cell cycle. Exposure of NRK-52E cells to high glucose media caused acute activation of Akt and ERK pathways and depolarization of mitochondrial membrane at 24 hours. Prolonged high glucose exposure (for 48 hours) induced AR expression and G1 cell cycle arrest and decreased cell viability (84% compared to control) in NRK-52E cells. Coincubation of cells with epalrestat prevented the signaling changes and renal cell injury induced by high glucose. Thus, AR inhibition represents a potential therapeutic strategy to prevent DN

PREVALENCE OF PAROTID TUMORS AMONG YEMENI PATIENTS IN SANA'A CITY, YEMEN

Background and aims: Parotid gland tumors (PGT) are a moderately scarce group of tumors with a broad range of histopathological manifestations and clinical characteristics. To date, most epidemiological studies on salivary gland tumors including PGT are limited in Yemen and this is one of the first studies, so the aim of the study was to determine the prevalence of different tumors affecting the parotid glands and the effect of age and sex on their distribution. Methods: Epidemiological information as well as demographic data, anatomical site, and histological analysis of PGT were analyzed. The data analyzed included age, sex, site, and histological diagnosis. Data were collected from all histopathological centers covering the majority of Sana'a city between 2019 and 2023. Results: A total of 284 cases- 69% benign and 31% malignant tumors were examined. Both benign and malignant tumors showed a little male inclination (52.5%) and a peak occurrence between the third and fifth decade. Mucoepidermoid carcinoma (36.4%) and adenoid cystic carcinoma (11.4%) are two common malignant tumor types. Benign parotid tumors include pleomorphic adenoma (71.4%) and Warthin tumors (11.2%) of benigns. Other malignants and benigns are less frequent. Conclusions: This study presents the first retrospective study to date to analyze PGT data from health centers spread across Sana'a city. These results should serve the same as the basis for prospect studies assessing the epidemiological geography of these tumors in Sana'a in particular and Yemen in general.                   Peer Review History: Received 18 May 2024;   Reviewed 12 July 2024; Accepted 23 August; Available online 15 September 2024 Academic Editor: Dr. Nuray Arı, Ankara University, Turkiye, [email protected] Average Peer review marks at initial stage: 6.5/10 Average Peer review marks at publication stage: 7.5/10 Reviewers: Asmaa Ahmed Mohamed Ahmed Khalifa, Pharos University, Alexandria, Egypt, [email protected] Dr. George Zhu, Tehran University of Medical Sciences, Tehran, Iran, [email protected]