Development of a High Sensitive Multiplex Lateral Flow Immunoassay (LFIA) System for Rapid Detection of Methicillin-Resistant Staphylococcus Aureus (MRSA).

Background: Methicillin-resistant Staphylococcus aureus (MRSA) has become a worldwide concern as an epidemic bacterium and a cause of nosocomial and community-acquired infections. One of the major problems in the prevention and treatment of infections caused by MRSA strains is their multi-drug resistant trait, which causes the spread of infections and increases the mortality rate. Therefore, a rapid and accurate method is needed to identify MRSA strains, initiate appropriate antibiotic therapy, and control its infection. The aim of this study was to develop a twin lateral flow immunoassay system to detect methicillin-resistant Staphylococcus aureus (MRSA). Methods: First, BSA blocked AuNPs-anti-peptidoglycan antibody and AuNPs-anti-BSA antibody were used to detect Staphylococcus aureus (S. aureus). Then, AuNPs-anti-PBP2a antibody was used to specifically detect MRSA. Sensitivity, specificity and limit of detection of this twin immunoassay system were assessed using MRSA, methicillin susceptible S. aureus and clinical samples. Results were compared to those of cefoxitin disc diffusion (FOX30) and Polymerase Chain Reaction (PCR) as gold standards. Results: The Limit of Detection (LOD) of this twin system were 103 and 104 CFU/ml for the first and second strips, respectively. Sensitivity and specificity of this innovative assay in detecting MRSA were 92.30 and 97.36%, compared to FOX30 and PCR, respectively. Conclusion: High rates of sensitivity and specificity of this initiative system show its high potentials for rapid and accurate detection of MRSA.

Developmental and epileptic encephalopathy 89: A novel bi-allelic variant, molecular dynamics simulation, and a comprehensive clinical and molecular profile.

OBJECTIVE: Gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the adult central nervous system, plays an important role during embryonic neural network formation. GAD67 is the rate-limiting enzyme in GABA synthesis, and its deficiency leads to developmental and epileptic encephalopathy 89 (DEE 89). Patients who suffered from this syndrome generally manifested severe to profound neurodevelopmental delay, seizures, and often congenital anomalies such as the cleft palate or/and omphalocele. Up to now, only three papers on this syndrome have been published, and our knowledge about the disease's clinical course and pathophysiology is in its infancy. METHODS: We used whole-exome sequencing (WES) and multiple in-silico tools to detect a potential causative variant in a patient with severe neurodevelopmental delay and refractory epilepsy. Moreover, by molecular docking and molecular dynamics simulation, we investigate the effect of the candidate variant on the GAD67 function and structure. RESULTS: WES data analysis revealed a novel deleterious variant (NM_000817.3: c.850C>T; p.Leu284Phe) in the GAD1 gene, which encodes the GAD67 enzyme. Molecular docking and molecular dynamics simulation showed that this variant has deleterious effects on the structure and function of the GAD67. This study's patient, in addition to typical symptoms of the DEE89, showed microcephaly and clonus in the toe, which were novel clinical findings. SIGNIFICANCE: Our findings expand the mutational and clinical spectrum of DEE 89. Also, by gathering clinical symptoms and genetic findings of previously reported cases, moreover providing a comprehensive clinical picture of the disease, we found that there was no common drug therapy among patients whose epilepsy was controlled. Furthermore, the comparison of clinical symptoms between patients with missense and truncating mutations did not show any significant clinical difference, except that patients with missense mutations did not show cleft palates or omphaloceles.

A Novel Biallelic Variant in CDH23 Gene in a Family with Atypical USH1D Manifestation: A Literature Review and Investigation of Genotype-Phenotype Correlation.

INTRODUCTION: Usher syndrome (USH) is an autosomal recessive disorder that predominantly affects hearing, vision, and, in some cases, vestibular function. USH, according to the onset age, severity, and progression of symptoms, is categorized into four main types. In addition, there are a significant number of reports that patients' manifestations deviate from canonical phenotypic criteria of main types of USH, which are named atypical USH. CDH23 is the second most common USH gene in which its defects result in USH1D, non-syndromic autosomal recessive deafness-12 (DFNB12), and in a few cases, atypical USH1D. While some studies have suggested that missense and truncating damaging variants in the CDH23 gene cause DFNB12 and USH1D, respectively, no genotype-phenotype correlation for atypical USH1D has been established. METHODS: Using whole-exome sequencing, we studied an Iranian family with two affected siblings who manifested congenital bilateral hearing loss, late-onset nyctalopia, retinitis pigmentosa, and normal vestibular function, indicating that their clinical symptoms are consistent with USH2. RESULTS: Whole-exome data analysis revealed a novel bi-allelic nonsense variant (c.6562G>T; p.Glu2188Ter) in the CDH23 gene, which was confirmed by Sanger sequencing. Surprisingly, CDH23 is a member of the USH1 genes; therefore, our patients suffered from atypical USH1D. Also, by conducting a literature review, we provided a clinical and mutational profile of all reported patients with atypical manifestations or those who refuted the claimed genotype-phenotype correlation. CONCLUSION: By reporting a novel damaging variant, we expand the mutational spectrum of the CDH23 gene that leads to atypical USH1D. Also, reviewing the literature shows that, contrary to previous claims, different genotypes occur in the CDH23 gene allelic disorders, and there is no clear-cut genotype-phenotype correlation.

Griscelli syndrome type 1: a novel pathogenic variant, and review of literature.

Griscelli syndrome type 1 (GS1) is a rare inherited autosomal recessive disease caused by a deleterious variant in the MYO5A gene and characterized by general hypopigmentation, neurological symptoms, motor disability, hypotonia, and vision abnormality. Only nine pathogenic variants in the MYO5A gene have been confirmed in association with the GS1. All of the reported pathogenic variants are truncating. Herein, two siblings from a consanguineous Iranian family with abnormal pigmentation and neurological symptoms were referred for genetic counseling. Whole-exome sequencing (WES) revealed a novel homozygous truncating variant c.1633_1634delAA (p.Asn545Glnfs*10) in the MYO5A gene, which was completely co-segregated with the phenotype in all affected and unaffected family members. Computational analysis and protein modeling demonstrated the deleterious effects of this variant on the structure and function of the protein. The variant, according to ACMG guidelines, was classified as pathogenic. Besides the novelty of the identified variant, our patients manifested more severe clinical symptoms and presented distal hyperlaxity in all four limbs, which was a new finding. In conclusion, we expanded the mutational and phenotypic spectrum of the GS1. Moreover, by studying clinical manifestations in all molecularly confirmed reported cases, provided a comprehensive overview of clinical presentation, and attempted to find a genotype-phenotype correlation.

The brilliance of nanoscience over cancer therapy: Novel promising nanotechnology-based methods for eradicating glioblastoma.

Given the limited sensitivity of screening methods and the lack of effective therapeutic interventions for malignant brain tumors such as glioblastoma multiforme (also known as GBM), diagnostic and therapeutic procedures for these tumors are rarely performed on a routine basis. Nanostructures with great selectivity, including silica-based nanovehicles, metallic nanostructures, lipid nanoparticles, quantum dots, and polymeric nanoparticles, have been demonstrated to have excellent potential for passing the BBB efficiently. Based on tumor-derived cells, surface modification, encapsulation of contrast agent, bio composition, and functionalities by appropriate coating materials can all be used to take advantage of the photodynamic, magnetic, and optical capabilities of nanostructures. As a result, nanotechnology has revolutionized the detection, screening, as well as treatment of malignancies and brain tumors. In recent years, nanostructures with biomimetic activities have been designed for uptake by tumors in deep cancer regions, with the goal of monitoring and treating the disease. Also, nanostructures are exceptional nano-vehicles for delivering therapeutic agents to their targeted areas due to their special physicochemical properties, which include nanosized dimensions, larger surface area, specific geometrical characteristics, and the capabilities to encompass various substances within their inner parts or on their exterior surface. This paper describes the current developments of several nanostructures such as dendrimers, liposomes, carbon dots, carbon nanotubes, micelles, and metallic nanoparticles for efficient detection of GBM as well as drug delivery in GBM treatment. The importance of metallic nanoparticle-based radiosensitization, as well as immunotherapy, as good ways to fight metastasis and GBM growth, will also be discussed.

Economic Inequality in Visual Impairment: A Study in Deprived Rural Population of Iran.

PURPOSE: To determine economic inequality in visual impairment (VI) and its determinants in the rural population of Iran. METHODS: In this population-based, cross-sectional study, 3850 individuals, aged 3-93 years were selected from the north and southwest regions of Iran using multi-staged stratified cluster random sampling. The outcome was VI, measured in 20 feet. Economic status was constructed using principal component analysis on home assets. The concentration index (C) was used to determine inequality, and the gap between low and high economic groups was decomposed to explained and unexplained portions using the Oaxaca-Blinder decomposition method. RESULTS: Of the 3850 individuals that were invited, 3314 participated in the study. The data of 3095 participants were finally analyzed. The C was -0.248 (95% confidence interval [CI]: -0.347 - -0.148), indicating a pro-poor inequality (concentration of VI in low economic group). The prevalence (95% CI) of VI was 1.72% (0.92-2.52) in the high economic group and 10.66% (8.84-12.48) in the low economic group with a gap of 8.94% (6.95-10.93) between the two groups. The explained and unexplained portions comprised 67.22% and 32.77% of the gap, respectively. Among the study variables, age (13.98%) and economic status (80.70%) were significant determinants of inequality in the explained portion. The variables of education (coefficient: -4.41; P < 0.001), age (coefficient: 14.09; P < 0.001), living place (coefficient: 6.96; P: 0.006), and economic status (coefficient: -7.37; P < 0.001) had significant effects on inequality in the unexplained portion. CONCLUSIONS: The result showed that VI had a higher concentration in the low economic group, and the major contributor of this inequality was economic status. Therefore, policymakers should formulate appropriate interventions to improve the economic status and alleviate economic inequality.