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BACKGROUND AND AIMS: Hearing loss (HL) is the most common sensorineural disorder and one of the most common human defects. HL can be classified according to main criteria, including: the site (conductive, sensorineural and mixed), onset (pre-lingual and post-lingual), accompanying signs and symptoms (syndromic and non-syndromic), severity (mild, moderate, severe and profound) and mode of inheritance (Autosomal recessive, autosomal dominant, X-linked and mitochondrial). Autosomal recessive non-syndromic HL (ARNSHL) forms constitute a major share of the HL cases. In the present study, next-generation sequencing (NGS) was applied to investigate the underlying etiology of HL in a multiplex ARNSHL family from Khuzestan province, southwest Iran. METHODS: In this descriptive study, 20 multiplex ARNSHL families from Khuzestan province, southwest of Iran were recruited. After DNA extraction, genetic linkage analysis (GLA) was applied to screen for a panel of more prevalent loci. One family, which was not linked to these loci, was subjected to Otogenetics deafness Next Generation Sequencing (NGS) panel. RESULTS: NGS results showed a novel deletion-insertion variant (c.1555delinsAA) in the MARVELD2 gene. The variant which is a frameshift in the seventh exon of the MARVELD2 gene fulfills the criteria of being categorized as pathogenic according to the American College of Medical Genetics and Genomics (ACMG) guideline. CONCLUSION: NGS is very promising to identify the molecular etiology of highly heterogeneous diseases such as HL. MARVELD2 might be important in the etiology of HL in this region of Iran.
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Surdez/genética , Proteína 2 com Domínio MARVEL/genética , Adulto , Surdez/patologia , Feminino , Genes Recessivos , Humanos , Mutação INDEL , Masculino , LinhagemRESUMO
BACKGROUND AND OBJECTIVES: Hereditary hearing loss (HL) is known by a very high genetic heterogeneity, which makes a molecular diagnosis problematic. Next-generation sequencing (NGS) is a new strategy that can overcome this problem. METHOD: A comprehensive family history was obtained, and clinical evaluations and pedigree analysis were performed in the family with 3 affected members. After excluding mutations in the GJB2 and 7 other most common autosomal recessive nonsyndromic HL genes via Sanger sequencing and genetic linkage analysis in the family, we applied the Otogenetics deafness NGS panel in the proband of this family. RESULTS: NGS results showed a novel rare variant (c.7720C>T) in the MYO15A gene. This nonsense variant in the exon 40 of the MYO15A gene fulfills the criteria of being categorized as pathogenic according to the American College of Medical Genetics and Genomics guideline. CONCLUSIONS: New DNA sequencing technologies could lead to identification of the disease causing variants in highly heterogeneous disorders such as HL.
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Surdez/genética , Perda Auditiva Neurossensorial/genética , Miosinas/genética , Adolescente , Adulto , Audiometria de Tons Puros , Criança , Códon sem Sentido , Simulação por Computador , Consanguinidade , Exoma , Feminino , Ligação Genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Irã (Geográfico) , Masculino , Linhagem , Análise de Sequência de DNA , Adulto JovemRESUMO
Co-infection of COVID-19 with other diseases increases the challenges related to its treatment management. COVID-19 co-infection with parasites is studied with low frequency. Here, we systematically reviewed the cases of parasitic disease co-infection with COVID-19. All articles on COVID-19 co-infected with parasites (protozoa, helminths, and ectoparasites), were screened through defined inclusion/exclusion criteria. Of 2190 records, 35 studies remained for data extraction. The majority of studies were about COVID-19 co-infected with malaria, followed by strongyloidiasis, amoebiasis, chagas, filariasis, giardiasis, leishmaniasis, lophomoniasis, myiasis, and toxoplasmosis. No or low manifestation differences were reported between the co-infected cases and naïve COVID-19 or naïve parasitic disease. Although there was a relatively low number of reports on parasitic diseases-COVID-19 co-infection, COVID-19 and some parasitic diseases have overlapping symptoms and also COVID-19 conditions and treatment regimens may cause some parasites re-emergence, relapse, or re-activation. Therefore, more attention should be paid to the on-time diagnosis of COVID-19 and the co-infected parasites.
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Background and Aims: The study aimed to collect and compare clinical and laboratory findings of children with severe and nonsevere COVID-19 in Kermanshah City, located in the west of Iran. Methods: The study was conducted on 500 children with COVID-19 hospitalized in Mohammad-Kermanshahi Hospital in Kermanshah City. Pediatric COVID-19 was confirmed by reverse transcription-polymerase chain reaction (RT-PCR) test using respiratory secretion samples. Medical records were reviewed and information related to demographic characteristics, underlying diseases, clinical manifestations, laboratory findings, and chest computed tomography (CT) scans were all extracted from electronic and paper records. Patients were divided into three groups according to the severity of the disease: mild, moderate, and severe. Clinical and laboratory findings were compared between the groups and the collected data were analyzed by statistical methods. Results: Out of 500 patients, 286 were boys and 214 were girls. Of the patients, 321 cases were only COVID-19, while 179 patients were diagnosed as Multisystem Inflammatory Syndrome in Children (MIS-C) positive. The average age of COVID-19 patients was 3.85 ± 4.48 and of MIS-C patients was 3.1 ± 3.5. In order, fever, cough, and heart disorders were the most common symptoms in patients with COVID-19 and MIS-C, respectively. In terms of disease severity, 246 patients had mild disease, 19 patients had moderate disease, and 56 patients had severe disease. In severe patients, the average number of white blood cells (WBC) was higher, while the average number of lymphocytes was lower. Also, in these patients, the average age was lower, and most of them had respiratory distress. In mild patients, often cough, diarrhea, and vomiting were observed. Conclusion: The results of our study showed that laboratory factors such as WBC count, lymphocyte count, CT findings, Respiratory distress, cough, diarrhea, and vomiting can be used to evaluate the severity of COVID-19 in children.
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Klebsiella pneumoniae (K. pneumoniae) is a causative agent of severe infections in humans. There is no publically available vaccine for K. pneumoniae infections yet. Here, using comprehensive immunoinformatics methods, T-cell-specific epitopes of four type 1 fimbriae antigens of K. pneumoniae were predicted and evaluated as potential vaccine candidates. Both CD8+ (class I) and CD4+ (class II) T-cell-specific epitopes were predicted and the epitopes similar to human proteome were excluded. Subsequently, the windows of class-II epitopes containing class-I epitopes were determined. The immunogenicity, IFN-γ production and population coverage were also estimated. Using the 3D structure of HLA and epitopes, molecular docking was carried out. Two best epitopes were selected for molecular dynamics studies. Our prediction and analyses resulted in the several dominant epitopes for each antigen. The docking results showed that all selected epitopes can bind to their restricted HLA molecules with high affinity. The molecular dynamics results indicated the stability of system with minimum possible deviation, suggesting the selected epitopes can be promising candidates for stably binding to HLA molecules. Altogether, our results suggest that the selected T-cell-specific epitopes of K. pneumoniae fimbriae antigens, particularly the two epitopes confirmed by molecular dynamics, can be applied for vaccine development. However, the in vitro and in vivo studies are required to authenticate the results of the present study.Communicated by Ramaswamy H. Sarma.
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Epitopos de Linfócito T , Klebsiella pneumoniae , Biologia Computacional , Humanos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Linfócitos T , Vacinas de Subunidades AntigênicasRESUMO
Klebsiella pneumoniae causes various human infections. Ferric enterobactin protein (FepA) is a conserved protein of K. pneumoniae with high immunogenicity. In the present study, using comprehensive in silico approaches the T and B cell-specific epitopes of K. pneumoniae FepA were identified. The T (both class I and class II) and B (both linear and conformational) epitopes of FepA were predicted using prediction tools. The predicted epitopes were screened for human similarity, immunogenicity, antigenicity, allergenicity, toxicity, conservancy, structural and physicochemical suitability, and in case of T epitopes binding to HLA alleles, using numerous immune-informatics, homology modeling, and molecular docking approaches. These analyses led to introduce the most dominant FepA epitopes that are appropriate for vaccine development. Furthermore, we introduced an antigenic peptide containing both T and B epitopes which comprises suitable structural and physiochemical properties needed for vaccine development and it is conserved in many bacteria. Altogether, here the highly immunogenic T and B epitopes of FepA as well as a final epitopic peptide containing both T and B epitopes were found and introduced for future vaccine development studies. It is suggested that the actual efficiency and efficacy of our final epitopic peptide be investigated by in vitro/in vivo testing. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10989-021-10247-3.
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OBJECTIVES: Natural disasters (NDs) may increase the outbreaks and transmissions of vector-borne diseases such as cutaneous leishmaniasis (CL) and visceral leishmaniasis (VL). However, the relationship between leishmaniases and NDs has not yet been clearly established. Here, we systematically reviewed all reported articles in this field to answer whether NDs increase the frequency of leishmaniases. METHODS: All the related articles published during January 2000 till January 2020 were reviewed. Moreover, all NDs and the associated leishmaniases frequencies reports in 17 leishmaniases endemic countries were searched to find any ND-leishmaniases relationship. RESULTS: After the initial screening, 39 articles on ND-leishmaniases were selected and systematically reviewed. These articles showed different frequencies of CL in the endemic areas before and after NDs in some regions of Pakistan and Iran and in case of VL in Brazil, Ethiopia, and Sudan. After thorough deliberation, four studies for CL-ND and five studies for VL-ND relationships were selected for meta-analysis. The results showed increases in the leishmaniases incidences after NDs, although not robustly. CONCLUSION: The lack of a strong leishmaniases-ND relationship could be attributed to the local compilations of such data in scattered regions of the endemic countries. Therefore, currently a substantial knowledge gap on leishmaniases-ND relationship is apparent.
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Leishmaniose Cutânea/epidemiologia , Leishmaniose Visceral/epidemiologia , Desastres Naturais , Brasil/epidemiologia , Surtos de Doenças , Etiópia/epidemiologia , Saúde Global , Humanos , Incidência , Irã (Geográfico)/epidemiologia , Paquistão/epidemiologia , Fatores de Risco , Sudão/epidemiologiaRESUMO
Objective: Current therapy strategies of leishmaniasis have some problems such as high cost, toxicity and side effects. Plant extracts can be a source of drugs to control leishmaniasis. In this study, the effect of hydroalcoholic and chloroformic extracts of Vigna radiata, Tamarix ramosissima, and Carthamus lanatus on Leishmania major and L. tropica was studied. Methods: The plant samples were collected from west of Iran and their extracts were prepared. Anti-promastigote activity assay of all extracts was done using tetrazolium-dye assay. Results: Only high concentrations of V. radiata and C. lanatus were able to inhibit Leishmania, while both high and low concentrations of T. ramosissima had antileishmanial effect. No difference was observed between hydroalcoholic with chloroformic extract of each plant. Conclusion: Altogether, the results revealed the antileishmanial activity of T. ramosissima extracts against L. major and L. tropica, indicating its potential as an antileishmanial agent.