Evaluation of Sleep Difficulties in Egyptian Children with Down Syndrome: A Case-Control Study.

Sleep is a major concern in Down syndrome children. Obstructive sleep apnea, delayed sleep onset, night-time and early awakenings have been reported contributing to the cognitive and behavioral outcomes. The aim is to evaluate sleep related difficulties in Down syndrome young children. A questionnaire of sleep related difficulties was translated and validated into Arabic language then was filled in by caregivers of 45 Down syndrome and 48 normal children. The questionnaire consisted of sections related to snoring, breathing difficulties, mouth breathing, upper respiratory tract infections, sleep position, restless sleep and frequent awakening, and daytime behavior. The results show highly significant differences between the total and subtotal questionnaire scores with higher scores in the control group. The questionnaire has a good reliability. Test-retest reliability of the questionnaire revealed a significant positive correlation in the total questionnaire and all the subitems except for the 7th subitem of the daytime behavior which showed no significant correlation. The questionnaire showed 100% sensitivity and 70.8% Specificity with at cut-off value of 8.5. The sleep related difficulties questionnaire has good psychometric properties and could detect significant sleep problems in Down syndrome children. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-023-04090-9.

Systematic review of epidemiological and toxicological evidence on health effects of fluoride in drinking water.

INTRODUCTION: Fluoride is a naturally occurring substance that is also added to drinking water, dental hygiene products, and food supplements for preventing dental caries. Concerns have been raised about several other potential health risks of fluoride. OBJECTIVE: To conduct a robust synthesis of evidence regarding human health risks due to exposure to fluoride in drinking water, and to develop a point of departure (POD) for setting a health-based value (HBV) for fluoride in drinking water. METHODS: A systematic review of evidence published since recent reviews of human, animal, and in vitro data was carried out. Bradford Hill considerations were used to weigh the evidence for causality. Several key studies were considered for deriving PODs. RESULTS: The current review identified 89 human studies, 199 animal studies, and 10 major in vitro reviews. The weight of evidence on 39 health endpoints was presented. In addition to dental fluorosis, evidence was considered strong for reduction in IQ scores in children, moderate for thyroid dysfunction, weak for kidney dysfunction, and limited for sex hormone disruptions. CONCLUSION: The current review identified moderate dental fluorosis and reduction in IQ scores in children as the most relevant endpoints for establishing an HBV for fluoride in drinking water. PODs were derived for these two endpoints, although there is still some uncertainty in the causal weight of evidence for causality for reducing IQ scores in children and considerable uncertainty in the derivation of its POD. Given our evaluation of the overall weight of evidence, moderate dental fluorosis is suggested as the key endpoint until more evidence is accumulated on possible reduction of IQ scores effects. A POD of 1.56 mg fluoride/L for moderate dental fluorosis may be preferred as a starting point for setting an HBV for fluoride in drinking water to protect against moderate and severe dental fluorosis. Although outside the scope of the current review, precautionary concerns for potential neurodevelopmental cognitive effects may warrant special consideration in the derivation of the HBV for fluoride in drinking water.

Predictive Value of Serum CYFRA 21-1 and CK19-2G2 for Tumor Aggressiveness and Overall Survival in Hepatitis C-Related Hepatocellular Carcinoma Among Egyptians: A Prospective Study.

PURPOSE: Cytokeratin 19 fragment 21-1 (CYFRA 21-1) and cytokeratin 19 fragment 2G2 (CK 19-2G2) are two soluble fragments of cytokeratin 19 (CK 19) that can be detected in serum. CK 19-positive hepatocellular carcinoma (HCC) is characterized by an aggressive behavior and a poor outcome. This study aimed to assess the prognostic value of serum CYFRA 21-1 and CK 19-2G2 in predicting tumor aggressiveness and overall survival (OS) in patients with hepatic C virus (HCV)-related HCC. METHODS: The current study included 138 patients with HCV-related HCC recruited from the Hepatobiliary and Interventional Radiology Units at Alexandria's main university hospitals and 40 healthy individuals as controls. Patients were assessed for clinical, radiological tumor characteristics, and aggressiveness index. Baseline serum CYFRA 21-1 and CK 19-2G2 levels were measured by enzyme-linked immunosorbent assay. RESULTS: Elevated CYFRA 21-1 levels were associated with tumors size ≥ 5 cm (p < 0.001), malignant portal vein thrombosis (mPVT) (p < 0.001), distant metastasis (p = 0.030), ill-defined/infiltrative pattern (p = 0.010), and aggressiveness index > 4 (p = 0.045). Elevated CK19-2G2 levels were not associated with any clinical or radiological characteristics. Either or both elevated serum CYFRA 21-1 and CK 19-2G2 in combination with alpha-feto protein (AFP) ≥ 400 ng/ml have a better predictability for mPVT and ill-defined/infiltrative patterns (sensitivity (10-25%) and specificity (96-100%)). Elevated levels of CYFRA 21-1, CK 19-2G2, or AFP ≥ 400 ng/ml were associated with decreased 1-year OS. CONCLUSIONS: Either or both elevated serum CYFRA 21-1 and CK 19-2G2 levels when added to AFP ≥ 400 ng/ml are specific but less sensitive biomarkers for predicting tumor aggressiveness. These biomarkers can be used independently to predict reduced 1-year OS in Egyptian patients with HCV-related HCC.

Should we screen aging physicians for cognitive decline?

OBJECTIVES: To synthesize evidence relevant for informed decisions concerning cognitive testing of older physicians. METHODS: Relevant literature was systematically searched in Medline, EMBASE, PsycInfo, and ERIC, with key findings abstracted and synthesized. RESULTS: Cognitive abilities of physicians may decline in an age range where they are still practicing. Physician competence and clinical performance may also decline with age. Cognitive scores are lower in physicians referred for assessment because of competency or performance concerns. Many physicians do not accurately self-assess and continue to practice despite declining quality of care; however, perceived cognitive decline, although not an accurate indicator of ability, may accelerate physicians' decision to retire. Physicians are reluctant to report colleagues' cognitive problems. Several issues should be considered in implementing cognitive screening. Most cognitive assessment tools lack normative data for physicians. Scientific evidence linking cognitive test results with physician performance is limited. There is no known level of cognitive decline at which a doctor is no longer fit to practice. Finally, relevant domains of cognitive ability vary across medical specialties. CONCLUSION: Physician cognitive decline may impact clinical performance. If cognitive assessment of older physicians is to be implemented, it should consider challenges of cognitive test result interpretation.

Effects of using collagen and aloe vera grafted fibroin scaffolds on osteogenic differentiation of rat bone marrow mesenchymal stem cells in SBF-enriched cell culture medium.

In the study, collagen and aloe vera were grafted onto silk fibroin with two different methods, and 3D-microporous scaffolds (1F5C4A1 and 2F5C4A1) were formed by lyophilization. Three osteogenic cultures were started by seeding rat bone marrow mesenchymal stem cells (MSCs) and pre-induced MSC (osteoblast (OB)) on biopolymeric scaffolds. The osteogenic medium was enriched with 10% (v/v) simulated body fluid (SBF) to promote mineralization and osteogenic differentiation in one of the MSC cultures and the OB culture. X-ray diffraction (XRD), scanning electron microscopy (SEM), scanning electron microscopy- energy dispersive spectrum (SEM-EDS) analyses on cellular samples and histochemical (alizarin red, safranin-O, alcian blue) and immunohistochemical (anti-collagen-1, anti-osteocalcin, anti-osteopontin) staining showed that bone-like mineralization was occurred by both chemically and cellular activity. In addition, pre-osteogenic induction of MSCs in 2D-cultured was found to promote osteogenesis more rapidly when started 3D-cultured. These results indicated that enrichment of the cell culture medium with SBF is sufficient forin vitromineralization rather than using high concentrations of SBF. The findings showed that OB cells on the 2F5C4A1 scaffold obtained the best osteogenic activity. Still, other culture media with 10% SBF content could be used for bone tissue engineering under osteogenic induction.

Studying the pathogenicity of 26 variants characterized in the first molecular analyses of Egyptian aplastic anemia patients.

BACKGROUND: Aplastic anemia (AA) is a bone marrow disorder characterized by peripheral pancytopenia and marrow hypoplasia which can lead to life-threatening complications. Our objective was to study the telomerase genes (TERT and TERC) variants, explore their relationship to telomere shortening and TERT gene expression, and to identify variants in the MPL gene within Egyptian AA patients. METHODS: Forty AA patients and 40 sex- and age-matched healthy individuals as the control group were studied through sequencing of TERT, TERC, and MPL genes. Quantitative real-time PCR (qRT-PCR) was used for measuring TERT gene expression. Telomere length (TL) was measured using the Quantitative Fluorescence In Situ Hybridization (Q-FISH) technique. In silico analysis was performed for the prediction of the pathogenicity of resultant variants. RESULTS: Sequencing of MPL, TERT, and TERC genes identified 26 variants. Eleven variants were identified in the MPL gene. Three of them are pathogenic: two missense [c.305 G>A, c.1589 C>T] and one splice site [g.9130T>G]. TERT gene sequencing showed thirteen variants, among them, four novel [c.484G>A, c.499G>A, c.512G>A, c.3164C>G] and two previously reported [c.835G>A, c.2031C>T] were predicted to be pathogenic. Two variants were characterized within the TERC gene; n.514A>G and n.463 C>T. TERT gene expression was downregulated in 70% of studied patients and the Q-FISH technique detected telomere shortening in 82.5% of patients. CONCLUSIONS: Twenty-six pathogenic and benign variants within the TERC, TERT, and MPL genes were identified among the studied AA patients that were in several cases associated with shortened telomeres and/or lower TERT gene expression. Genotype/phenotype correlation in AA patients is of great importance in explaining the disease severity and guiding therapeutic decisions.

Importance of TREC and KREC as molecular markers for immunological evaluation of down syndrome children.

Recurrent and severe infections occurred in children with Down Syndrome (DS) due to immunological parameter defects have been reported. The aim of the study is to evaluate the importance of using T-cell receptor excision circle (TREC) and kappa-deleting recombination excision circle (KREC) as molecular markers for immunological investigation of children with DS. The study included 40 non-disjunction trisomy 21 confirmed DS children, and 25 healthy controls. Peripheral blood (PB) was analyzed for lymphocyte subpopulations by flow cytometry, serum immunoglobulin levels, and TREC and KREC copy numbers using quantitative real-time PCR. DS patients showed significantly lower absolute counts of PB T lymphocytes, T helper lymphocytes, T cytotoxic lymphocytes, B lymphocytes, and Natural killer cells, and lower serum IgA, IgG, and IgM levels compared to healthy controls. Copy number of TREC and KREC showed no significant differences between DS patients and healthy controls. There is a significant positive correlation between TREC copy number with a percentage and absolute count of helper T lymphocytes in patients. Also, the KREC copy number was significantly negatively correlated with the age of patients. These findings suggest that copy numbers of TREC and KREC could be useful as molecular markers for immunological evaluation of patients with DS.

Detecting Cyber Attacks In-Vehicle Diagnostics Using an Intelligent Multistage Framework.

The advanced technology of vehicles makes them vulnerable to external exploitation. The current trend of research is to impose security measures to protect vehicles from different aspects. One of the main problems that counter Intrusion Detection Systems (IDSs) is the necessity to have a low false acceptance rate (FA) with high detection accuracy without major changes in the vehicle network infrastructure. Furthermore, the location of IDSs can be controversial due to the limitations and concerns of Electronic Control Units (ECUs). Thus, we propose a novel framework of multistage to detect abnormality in vehicle diagnostic data based on specifications of diagnostics and stacking ensemble for various machine learning models. The proposed framework is verified against the KIA SOUL and Seat Leon 2018 datasets. Our IDS is evaluated against point anomaly attacks and period anomaly attacks that have not been used in its training. The results show the superiority of the framework and its robustness with high accuracy of 99.21%, a low false acceptance rate of 0.003%, and a good detection rate (DR) of 99.63% for Seat Leon 2018, and an accuracy of 99.22%, a low false acceptance rate of 0.005%, and good detection rate of 98.59% for KIA SOUL.

Expanding the phenotypic spectrum and clinical severity associated with WLS gene.

WLS (Wnt ligand secretion mediator or Wntless) orchestrates the secretion of all Wnt proteins, a family of evolutionary conserved proteins, involved in Wnt signaling pathway that has many essential biological functions including the regulation of development, cell proliferation, migration and apoptosis. Biallelic variants in WLS have recently been described in 10 patients with pleiotropic multiple congenital anomalies (MCA) known as Zaki syndrome. We identified a likely disease-causing variant in WLS (c.1579G>A, p.Gly527Arg) in a boy presented with a broad range of MCA including microcephaly, facial dysmorphism, alopecia, ophthalmologic anomalies, and complete soft tissue syndactyly. These features were reminiscent of Zaki syndrome although variable clinical severity was observed. In a detailed clinical assessment, our patient also displayed microphthalmia, dental anomalies, skeletal dysplasia with spontaneous fractures and Dandy-Walker malformation. As such, we extend the phenotype linked to Zaki syndrome. This study further highlights the importance of a thorough clinical evaluation to delineate the phenotypic spectrum associated with WLS variants and suggests that genotype-phenotype correlations due to variant localization seems likely. However, future work on additional patients and more functional studies may give further insights into genotype-phenotype correlations and the complex function of WLS.

Outlining the Clinical Profile of TCIRG1 14 Variants including 5 Novels with Overview of ARO Phenotype and Ethnic Impact in 20 Egyptian Families.

TCIRG1 gene mutations underlie osteopetrosis, a rare genetic disorder impacting osteoclast function with consequent brittle bones prone to fracture, in spite of being characterized by increased bone density. The disorder is known to exhibit marked genetic heterogeneity, has no treatment, and is lethal in most instances. There are reports of ethnic variations affecting bone mineral density and variants' expression as diverse phenotypes even within individuals descending from the same pedigree. We herein focus on one of osteopetrosis's three types: the autosomal recessive malignant form (MIM 259700) (ARO) that is almost always associated with severe clinical symptoms. We reviewed the results of about 1800 Egyptian exomes and we did not detect similar variants within our Egyptian dataset and secondary neurological deficit. We studied twenty Egyptian families: sixteen ARO patients, ten carrier parents with at least one ARO affected sib, and two fetuses. They were all subjected to thorough evaluation and TCIRG1 gene sequencing. Our results of twenty-eight individuals descending from twenty Egyptian pedigrees with at least one ARO patient, expand the phenotype as well as genotype spectrum of recessive mutations in the TCIRG1 gene by five novel pathogenic variants. Identifying TCIRG1 gene mutations in Egyptian patients with ARO allowed the provision of proper genetic counseling, carrier detection, and prenatal diagnosis starting with two families included herein. It also could pave the way to modern genomic therapeutic approaches.

Impact of Isonicotinic Acid Blending in Chitosan/Polyvinyl Alcohol on Ripening-Dependent Changes of Green Stage Tomato.

The effect of isonicotinic acid (INA) in a chitosan (CS)/polyvinyl alcohol (PVA) blend on ripening-dependent changes of preserved green tomatoes (Solanum lycopersicum L.) was examined at room temperature. The results showed that CS/PVA/INA 0.5 mM and CS/PVA/INA 1.0 mM formulations retarded firmness loss and delayed the pigmentation parameters i.e., lycopene (LYP), total carotenes (TCs), and titratable acidity (TA). The CS/PVA/INA 0.5 mM and CS/PVA/INA 1.0 mM formulations were able to delay the increase in malondialdehyde (MDA) and total polyphenol (TP) contents. Furthermore, the peroxidase (POD), polyphenoloxidase (PPO), and phenylalanine ammonia-lyase (PAL) activities of tomatoes coated with CS/PVA/INA 0.5 mM and CS/PVA/INA 1.0 mM formulations were lower than those in other treatments. Meanwhile, the CS/PVA blend had the highest TP content, as well as the highest PPO and PAL activities, at the late stage of maturation. The UV analysis showed that the CS/PVA/INA blend film is a promising UV-protective food packaging material. The pure CS, PVA, and INA formulations, as well as the CS/PVA, CS/PVA/INA 0.5 mM, and CS/PVA/INA 1.0 mM formulations, were characterized by infrared (FTIR). The three polymer formulations showed strong antifungal activity against Alternaria alternata and Botrytis cinerea.

In Vitro Antidiabetic, Antioxidant, and Prebiotic Activities of the Chemical Compounds Isolated from Guizotia abyssinica.

India and Ethiopia employ Guizotia abyssinica (niger plant) as a source of edible vegetable oil. Previous studies have documented the niger plant's antioxidant properties and dietary benefits. Here, G. abyssinica extract was obtained and ten known bioactive components (1-10) were isolated. The antioxidant, antidiabetic, and prebiotic properties of whole extract and isolated components of niger and the plant's ability to cooperate symbiotically with probiotic strains were examined. Compound 10, myricetin-3-O-L-rhamnoside, had the highest antioxidant capacity measured in the 2,2-diphenylpicrylhydrazyl (DPPH, 4629.76 ± 6.02 µmol Trolox equivalent/g compound) and ferric-reducing antioxidant power (FRAP, 2667.62 ± 7.5 mol Trolox equivalent/g compound) assays. The lowest α-amylase and glycogen phosphorylase activities and glucose diffusion were obtained with whole G. abyssinica extracts, whereas compounds 8-10 had moderate inhibitory effects. G. abyssinica extract also induced the highest glucose absorption by yeast cells in the presence of 5 mM of glucose. Moreover, Lactobacillus plantarum and L. rhamnosus incubated with ß-sitosterol 3-O-D-glucoside (compound 7) showed the highest prebiotic activity score. The levels of L-(+)-lactic acid isomer in the probiotic strains were the highest in presence of the whole extract and decreased progressively in the presence of flavonoid glycosides (compounds 8-10) and ß-sitosterol 3-O-D-glucoside. The enzymatic profile of the probiotic strains was unaffected by the niger extract and compounds 7-10. The findings revealed that the biological activities of G. abyssinica extract are mediated by the compounds 1-10, and it may be considered as a promising plant for the treatment of diabetes mellitus.

Phytosynthesis of Co3O4 Nanoparticles as the High Energy Storage Material of an Activated Carbon/Co3O4 Symmetric Supercapacitor Device with Excellent Cyclic Stability Based on a Na2SO4 Aqueous Electrolyte.

The benign preparation of cobalt oxide nanoparticles (Co3O4-NPs) was performed using marine red algae extract (Grateloupia sparsa) as a simple, cost-effective, scalable, and one-pot hydrothermal technique. The nominated extract was employed as an environmental reductant and stabilizing agent. The resultant product showed the typical peak of Co3O4-NPs around 400 nm wavelength as ascertained by UV-vis spectroscopy. Size and morphological techniques combined with X-ray diffraction (XRD) showed the small size of Co3O4-NPs deformed in a spherical shape. The activated carbon (AC) electrode and Co3O4-NP electrode delivered a specific capacitance (C sp) of 125 and 182 F g-1 at 1 A g-1, respectively. The energy density of the AC and AC/Co3O4 electrodes with a power density of 543.44 and 585 W kg-1 was equal to 17.36 and 25.27 Wh kg-1, respectively. The capacitance retention of designed electrodes was 99.2 and 99.5% after 3000 cycles. Additionally, a symmetric AC/Co3O4//AC/Co3O4 supercapacitor device had a specific capacitance (C sp) of 125 F g-1 and a high energy density of 55 Wh kg-1 at a power density of 650 W kg-1. Meanwhile, the symmetric device exhibited superior cyclic stability after 8000 cycles, with a capacitance retention of 93.75%. Overall, the adopted circular criteria, employed to use green technology to avoid noxious chemicals, make the AC/Co3O4 nanocomposite an easily accessible electrode for energy storage applications.

Soluble CD163 for Prediction of High-Risk Esophageal Varices and Variceal Hemorrhage in Patients with Liver Cirrhosis.

Introduction: Activation of hepatic macrophages in liver disease is pathogenically related to portal hypertension (PH). Soluble CD163 (sCD163) is shed in blood by activated macrophages and may predict PH progression noninvasively. This study was designed to investigate the relation of serum sCD163 to the grade and bleeding risk of esophageal varices (EV) and its role for prediction of variceal hemorrhage (VH). Methods: The study included cirrhotic patients divided into 3 groups: patients who presented with acute upper gastrointestinal bleeding (UGIB) proved to originate from EV on endoscopy, patients without any history of UGIB but who revealed EV on surveillance endoscopy, and patients without endoscopic evidence of varices. Variceal grade and risk signs and bleeding stigmata were noted simultaneously with measurement of serum sCD163 concentration. Results: Serum sCD163 concentration showed a significant increase in cirrhotic patients compared to healthy subjects (p < 0.001) with a stepwise increase among the group without varices, nonbleeder group, and bleeder group sequentially. Serum sCD163 levels correlated positively with the variceal grade and risk signs in both the bleeder and nonbleeder groups (p = 0.002, p < 0.001 and p = 0.004, p < 0.001, respectively). Serum sCD163 at a cutoff value of 3.6 mg/L performed significantly for prediction of EV presence (AUC = 0.888). Serum sCD163 at a cutoff value >4 mg/L significantly predicted large-size and high-risk EV (AUC = 0.910 and AUC = 0.939, respectively) and the index bleed risk (AUC = 0.977). Serum sCD163 at a cutoff value >4.05 mg/L modestly discriminated bleeding EV from those that had never bled (AUC = 0.811). Conclusions: Serum sCD163 levels accurately predicted high-grade and high-risk EV and could help plan for primary prophylaxis. However, it modestly identified VH occurrence, and endoscopy would be required to make a definitive diagnosis.

Introdução: A ativação dos macrófagos hepáticos na doença hepática está patogenicamente relacionada com a hipertensão portal (HP). O CD163 solúvel (sCD163) é libertado no sangue por macrófagos ativados e pode predizer a progressão da HP de forma não invasiva. Este estudo foi desenhado para investigar a relação do sCD163 ao grau e risco hemorrágico por varizes esofágicas (VE) e o seu papel da predição na hemorragia varicosa (HV). Métodos: Estudo incluiu doentes cirróticos divididos em três grupos: doentes com hemorragia digestiva alta aguda (HDA) por VE, doentes sem história de HDA mas com VE comprovadas endoscopicamente e doentes sem evidência de VE. O grau, sinais de risco e estigmas hemorrágicos das varizes foram avaliados simultaneamente com a medição sérica da concentração de sCD163. Resultados: A concentração sérica de sCD163 apresentou um aumento significativo nos doentes cirróticos comparados com os indivíduos saudáveis (>4 mg/L) previu de forma significativa VE grandes e de alto-risco (AUC = 0.910 e AUC = 0.939 respectivamente) e o risco index-hemorrágico (AUC = 0.977). O valor cut-off de sCD163 sérico >4.05 mg/L discriminou de forma modesta VE sangrantes daquelas que nunca sangraram (AUC = 0.811). Conclusões: Os níveis de sCD163 sérico predizem com acuidade VE grandes e de alto-risco e podem ajudar a planear a profilaxia primária. Contudo, apenas modestamente identificaram a ocorrência de HV, sendo a endoscopia necessária para fazer um diagnóstico definitivo.

Impacts of Gum Arabic and Polyvinylpyrrolidone (PVP) with Salicylic Acid on Peach Fruit (Prunus persica) Shelf Life.

Peaches are grown in many Egyptian orchards for local and global fresh market sales. The interior fruit tissue breakdown (IFTB), often resulting in decayed peaches, is a severe problem during marketing. Therefore, to minimize FTB of peaches, in this study, gum arabic (GA) and polyvinylpyrrolidone (PVP) were mixed with different concentrations of salicylic acid (SA) (0, 1, and 2 mM) and were applied as edible coating to extend the shelf life of peach fruits. Mature peaches were selected and harvested when peaches reached total soluble solid content (SSC: 8.5%) and fruit firmness of about 47 N. Fruits were coated and stored at room temperature (26 ± 1 °C and air humidity 51 ± 1%) for 10 days during two seasons: 2020 and 2021. Fruit coated with GA/PVP-SA 2 mM showed a significant (p < 0.05) inhibition in degrading enzyme activities (CWDEs), such as lipoxygenase (LOX), cellulase (CEL), and pectinase (PT), compared to uncoated and coated fruits during the shelf-life period. Hence, cell wall compartments were maintained. Consequently, there was a reduction in browning symptoms in fruits by inhibiting polyphenol oxidase (PPO) and phenylalanine ammonia-lyase (PAL) activities. Thus, the fruit skin browning index showed almost no symptoms. The lipid peroxidation process and ionic permeability declined as well. The result suggests that, by applying GA/PVP-SA 2 mM as an edible coating, fruit tissue breakdown can be minimized, and the shelf life of peach can be extended up to 10 days without symptoms of tissue breakdown.

Systemic quinolones and risk of retinal detachment III: a nested case-control study using a US electronic health records database.

BACKGROUND: Quinolones are popular antibiotics that are known for their potency, broad coverage, and reasonable safety. Concerns have been raised about a possible association between quinolones and retinal detachment (RD). METHODS: We conducted a nested case-control study using electronic health records (EHR) from the Health Facts® Database. The initial cohort included all patients who were admitted between 2000 and 2016, with no history of eye disease, and had a minimum medical history of one year. Eligible cases comprised inpatients who were first admitted with a primary diagnosis of RD between 2010 and 2015. Each eligible case was matched without replacement to five unique controls by sex, race, age, and period-at-risk. We used conditional logistic regression to calculate RD risk, adjusting for exposure to other medications, and major risk factors. RESULTS: We identified 772 cases and 3860 controls. Whereas our primary analysis of all subjects revealed no quinolone-associated RD risk, elevated but non-significant risks were noted in African Americans (ciprofloxacin and levofloxacin), those aged 56-70 years old (moxifloxacin), and women (ciprofloxacin). CONCLUSION: Our study did not identify an elevated RD risk within 30 days following systemic administration of quinolone antibiotics. Suggestions of increased risk observed in some population subgroups warrant further investigation.

Three waves changes, new variant strains, and vaccination effect against COVID-19 pandemic.

It has been more than one year since the first case of the coronaviruses was infected by COVID-19 in China. The world witnessed three waves of the corona virus till now, and more upcoming is expected, whereas several challenges are presented. Empirical data displayed that the features of the virus effects do vary between the three periods. The severity of the disease, differences in symptoms, attitudes of the people have been reported, although the comparative characteristics of the three waves still keep essentially indefinite. In contrast, the sense of danger toward the cries gradually decreases in most countries. This may be due to some factors, including the approved vaccines, introducing alternative plans from politicians to control and deal with the epidemic, and decreasing the mortality rates. However, the alarm voice started to rise again with the appearance of new variant strains with several mutations in the virus. Several more questions began to be asked without sufficient answers. Mutations in COVID-19 have introduced an extreme challenge in preventing and treating SARS-COV-2. The essential feature for mutations is producing new variants known by high tensmibility, disturbing the viral fitness, and enhancing the virus replication. One of the variants that has emerged recently is the Delta variant (B.1.617.2), which was firstly detected in India. In November 2021, a more ferocious mutant appeared in South Africa, also called omicron (B.1.1.529). These mutants grabbed world attention because of their higher transmissibility than the progenitor variants and spread rapidly. Several information about the virus are still confusing and remains secret. There are eight approved vaccines in the market; however, the investigation race about their effect against reinfection and their role against the new variants is still under investigation. Furthermore, this is the first time vaccinating against COVID-19, so the question remains: Will we need an annual dose of the corona vaccines, and the side effects don't been observed till now?

Genetic Implications in High-Risk Pregnancy and Its Outcome: A 2-Year Study.

OBJECTIVE: The aim of this study is to evaluate high-risk pregnant females' offspring as regard the presence of any medical condition, hereditary disorder, or major anomaly as well as to document parental sociodemographic characteristics and compliance with follow-up schedules of fetal medicine and clinical genetic clinics. STUDY DESIGN: This prospective 2-year cohort study of neonates and infants reported the referral indications, investigations, and diagnoses obtained through prenatal and postnatal examinations. It also reported their parental follow-up vigilance. RESULTS: Of the 811 infants of high risk females referred 460 (56.7%) came for assessment. Mean parental consanguinity and endogamy were 67 and 71.3%, respectively. All pregnant mothers underwent first-trimester biochemical testing (plasma protein-A, α-fetoprotein [AFP], human chorionic gonadotropin [hCG]) and serial ultrasound examinations. Seventy mothers needed second-trimester biochemical testing (AFP, hCG, and estriol). Sixty-two mothers underwent amniocentesis where G-banding karyotype, fluorescence in situ hybridization and targeted molecular testing for the specific gene mutation of single gene disorders were conducted according to suspected disorders. High quality fetal ultrasound was performed when brain malformations were suspected, while 16 fetuses required brain MRI examination. Mean age of newborns at first examination was 26.5 days. They were grouped according to the maternal indication for referral. Upon examination, 18 neonates had confirmed congenital malformations/genetic disorders. Five of them were diagnosed prenatally. In four other fetuses with single gene disorder, the molecular diagnosis of their affected siblings was not established prior to this pregnancy; thus, prenatal diagnosis was not possible. The remaining nine cases were diagnosed postnatally. CONCLUSION: Parental consanguinity and endogamy were increased among high-risk pregnancies. Public awareness about potential adverse effects of consanguineous marriages and the importance of genetic testing are imperative. A structured multidisciplinary team of specialists in fetal medicine, clinical genetics, and neonatology provides good genetic services. Expansion and financial support of these services are urgently required. KEY POINTS: · A multidisciplinary team provides good genetic services in high-risk pregnancies.. · Parental consanguinity and endogamy are increased among high-risk pregnancies.. · Increased public awareness about genetic testing importance and financial support are imperative..

Systemic quinolones and risk of retinal detachment I: analysis of data from the US FDA adverse event reporting system.

BACKGROUND: Quinolones comprise a class of antibiotics that are globally preferred for treating a wide range of bacterial infections due to their potency, broad coverage, favorable pharmacologic profile, and mostly mild to moderate adverse reactions. Spontaneous reports on adverse drug events (ADE) and data from some pharmacoepidemiologic studies have raised concerns regarding quinolones and risk of retinal detachment (RD). This study examined ADE reports submitted to FDA adverse event reporting system (FAERS) for evidence on quinolone-associated RD risk. RESEARCH DESIGN AND METHODS: We identified all RD reports in FAERS between 2010-2019. We compared ADE signals between quinolones and selected medications that were previously associated with RD, and with reference medications not known to cause RD. For signal detection, we used two techniques: the proportional reporting ratio (PRR) and multi-item gamma Poisson shrinker (MGPS), which are known for their higher sensitivity and specificity for ADE signal detection, respectively. RESULTS: Moxifloxacin showed a positive and significant PRR signal for RD [PRR: 2.54 (1.60, 4.04)], and a marginally significant EBGM signal [EBGM: 2.21 (1.41, 3.02)]. CONCLUSION: Moxifloxacin is the only quinolone showing a positive disproportionality signal for RD. Further epidemiologic research is needed to clarify the association between moxifloxacin and RD risk.