Genetic landscape of hearing loss in prelingual deaf patients of eastern Iran: Insights from exome sequencing analysis.

Hearing loss is one of the most prevalent genetic disorders in humans. Locus and allelic heterogeneity cause fundamental challenges in hearing loss genetic diagnosis and management of patients and their families. This study examined the genetic profile of patients with prelingual hearing loss who were referred to the Genetic Foundation of Khorasan Razavi spanning over a decade. Deleterious variants in GJB2 were evaluated through Sanger sequencing among 745 non-syndromic hearing loss patients. Furthermore, exome sequencing was applied in 250 patients with negative GJB2 sequencing results and 30 patients with syndromic hearing loss. The findings revealed a relatively low frequency of GJB2 variants among the studied patients. Exome sequencing successfully identified the genetic causes of hearing loss in 70% of the patients. Moreover, variants in 10 genes, namely SLC26A4, MYO15A, TMPRSS3, TMC1, OTOF, CDH23, PJVK, MYO7A, TECTA, and PCDH15, accounted for 66% of the positive exome sequencing findings in this study. At least three prevalent founder alleles in the hearing-impaired population of eastern Iran were identified. This study emphasizes the efficiency of exome sequencing as a powerful tool for determining the etiology of prelingual hearing loss in the eastern Iranian population.

Non-coding RNAs as potential therapeutic targets for receptor tyrosine kinase signaling in solid tumors: current status and future directions.

This review article presents an in-depth analysis of the current state of research on receptor tyrosine kinase regulatory non-coding RNAs (RTK-RNAs) in solid tumors. RTK-RNAs belong to a class of non-coding RNAs (nc-RNAs) responsible for regulating the expression and activity of receptor tyrosine kinases (RTKs), which play a critical role in cancer development and progression. The article explores the molecular mechanisms through which RTK-RNAs modulate RTK signaling pathways and highlights recent advancements in the field. This include the identification of potential new RTK-RNAs and development of therapeutic strategies targeting RTK-RNAs. While the review discusses promising results from a variety of studies, encompassing in vitro, in vivo, and clinical investigations, it is important to acknowledge the challenges and limitations associated with targeting RTK-RNAs for therapeutic applications. Further studies involving various cancer cell lines, animal models, and ultimately, patients are necessary to validate the efficacy of targeting RTK-RNAs. The specificity of ncRNAs in targeting cellular pathways grants them tremendous potential, but careful consideration is required to minimize off-target effects, the article additionally discusses the potential clinical applications of RTK-RNAs as biomarkers for cancer diagnosis, prognosis, and treatment. In essence, by providing a comprehensive overview of the current understanding of RTK-RNAs in solid tumors, this review emphasizes their potential as therapeutic targets for cancer while acknowledging the associated challenges and limitations.

The first Iranian patient with You-Hoover-Fong syndrome and a review of the literature on 27 cases: expanding the genotypic and phenotypic spectrum.

BACKGROUND: The ultra-rare autosomal recessive genetic disorder, You-Hoover-Fong Syndrome (YHFS), is caused by defects in the TELO2 gene and is characterized by intellectual disability, developmental delay, and ocular impairments. This study aims to contribute to a better understanding of YHFS by reviewing previous cases and introducing a novel variant in a new case. METHODS: Whole exome sequencing (WES) was conducted on the proband to identify genetic variants, and Sanger sequencing was used to confirm variants within the family. This article presents a comprehensive collection of reported cases of YHFS, incorporating both molecular and clinical data, through an extensive literature search and analysis of English-language studies published until June 2023. RESULTS: Using WES, a novel homozygous missense variant, c.1799A > G (p. Tyr600Cys), was identified in the TELO2 gene in a 4-year-old Iranian male patient. Novel clinical features, including choanal atresia and clubfoot, were also identified. A comprehensive literature review identified 27 patients with YHFS, with 20 variants in the TELO2 gene. Missense pathogenic variants were the most common type of pathogenic variant, and the most common features were microcephaly and intellectual impairment. CONCLUSION: This study presents the first case of pathogenic variants in TELO2 gene in Iran, expands the genotypic and phenotypic spectrum of YHFS and contributes to the growing body of literature pertaining to YHFS. Furthermore, our findings highlight the importance of genetic testing for non-consanguineous carrier screening, as compound heterozygosity may be a significant factor in the development of YHFS. Further research is needed to clarify the molecular mechanisms underlying YHFS pathogenesis.

Broadening the Phenotype and Genotype Spectrum of Glycogen Storage Disease by Unraveling Novel Variants in an Iranian Patient Cohort.

Glycogen storage diseases (GSDs) are a group of rare inherited metabolic disorders characterized by clinical, locus, and allele heterogeneity. This study aims to investigate the phenotype and genotype spectrum of GSDs in a cohort of 14 families from Iran using whole-exome sequencing (WES) and variant analysis. WES was performed on 14 patients clinically suspected of GSDs. Variant analysis was performed to identify genetic variants associated with GSDs. A total of 13 variants were identified, including six novel variants, and seven previously reported pathogenic variants in genes such as AGL, G6PC, GAA, PYGL, PYGM, GBE1, SLC37A4, and PHKA2. Most types of GSDs observed in the cohort were associated with hepatomegaly, which was the most common clinical presentation. This study provides valuable insights into the phenotype and genotype spectrum of GSDs in a cohort of Iranian patients. The identification of novel variants adds to the growing body of knowledge regarding the genetic landscape of GSDs and has implications for genetic counseling and future therapeutic interventions. The diverse nature of GSDs underscores the need for comprehensive genetic testing methods to improve diagnostic accuracy. Continued research in this field will enhance our understanding of GSDs, ultimately leading to improved management and outcomes for individuals affected by these rare metabolic disorders.

Associations between the perception of dental pain and pain anxiety, mental pain, and dental anxiety in Iranian sample.

OBJECTIVE: This study examined the perception of dental pain and its relationship to pain anxiety, dental anxiety, and mental pain. METHODS: This cross-sectional study was conducted on 328 patients referred to dental clinics in Kermanshah (Iran) from 2020 to 2021. The instruments used in this study included scales assessing pain anxiety, dental anxiety, mental pain, and pain perception. RESULTS: There was a significant relationship (p = .001) between pain perception with dental anxiety (r = .38), pain anxiety (r = .45), and mental pain (r = .25). CONCLUSION: Psychological factors are associated with the perception of dental pain. Given the importance of dental care to overall health, psychological interventions may help to reduce the perception of dental pain and fear of seeing dentists in Iran.

Preemptive and non-preemptive multi-skill multi-mode resource-constrained project scheduling problems considering sustainability and energy consumption: A comprehensive mathematical model.

Modern project managers cope with significant challenges to schedule and control projects considering dynamic environments, frequent uncertainties, strict project deadlines, and stricter sustainable requirements above all. Sustainability taking into account resource utilization has been recently associated with project management. Hence, this paper presents a new mixed-integer linear programming (MILP) model with two objectives for a resource-constrained project scheduling problem (RCPSP) with multiple skills and multiple modes, assuming preemptive and non-preemptive activities in an uncertain environment. Given the importance of sustainable developments in projects, the considered objectives are to maximize job opportunities and minimize project duration, resource costs, and total energy consumption. To deal with the model, an AUGNMECON2VIKOR algorithm is utilized to create Pareto solutions. In this model, project activities can be crashed by allocating extra resources. Furthermore, multi-skill resources are used to perform project activities. This study also investigates the impact of these resources on project scheduling. To deal with uncertain circumstances, a fuzzy chance-constrained programming method is employed to develop a robust possibilistic programming model. With respect to the increasing significance of sustainability in project management, this study pioneers the examination of the impact of sustainable factors on project scheduling. Finally, the proposed formulation is validated using instances from the well-known PSPLIB and MMLIB test sets. Finally, a comparison is drawn between the presented solution method considering AUGMECON2VIKOR and AUGMECON2.

Effect of muscular fatigue on the cumulative lumbar damage during repetitive lifting task: a comparative study of damage calculation methods.

Several methods have been put forward to quantify cumulative loads; however, limited evidence exists as to the subsequent damages and the role of muscular fatigue. The present study assessed whether muscular fatigue could affect cumulative damage imposed on the L5-S1 joint. Trunk muscle electromyographic (EMG) activities and kinematics/kinetics of 18 healthy male individuals were evaluated during a simulated repetitive lifting task. A traditional EMG-assisted model of the lumbar spine was modified to account for the effect of erector spinae fatigue. L5-S1 compressive loads for each lifting cycle were estimated based on varying (i.e. actual), fatigue-modified, and constant Gain factors. The corresponding damages were integrated to calculate the cumulative damage. Moreover, the damage calculated for one lifting cycle was multiplied by the lifting frequency, as the traditional approach. Compressive loads and the damages obtained through the fatigue-modified model were predicted in close agreement with the actual values. Similarly, the difference between actual damages and those driven by the traditional approach was not statistically significant (p = 0.219). However, damages based on a constant Gain factor were significantly greater than those based on the actual (p = 0.012), fatigue-modified (p = 0.017), and traditional (p = 0.007) approaches.Practitioner summary: In this study, we managed to include the effect of muscular fatigue on cumulative lumbar damage calculations. Including the effect of muscular fatigue leads to an accurate estimation of cumulative damages while eliminating computational complexity. However, using the traditional approach also appears to provide acceptable estimates for ergonomic assessments.

Development of a newly designed biosensor using multi-walled carbon nanotubes (MWCNTs) with gold nanoparticles (AuNPs) in the presence of acetaminophen for detection of Escherichia coli.

Escherichia coli is one of the main indicators in the quality control of water, pharmaceuticals, and other samples. Compared with the time-consuming and high prices of the classical methods, with their high risks in the case of insensitive, contamination and offline detections, biosensors have long been a fast and accurate approach for identifying different bacteria. The present study reports the development of a newly electrochemical biosensor using a glassy carbon electrode (GCE) modified by multi-walled carbon nanotubes/AuNPs/E. coli polyclonal antibody/Bovine Serum Albumin in 0.1 M phosphate-buffered saline ( pH 7) in the presence of acetaminophen, for the detection of E. coli in pharmaceuticals and some real samples. Acetaminophen was added as an indicator for the detection of E. coli by changes in conductivity and current. To identify E. coli, square-wave voltammetry (SWV), differential pulse voltammetry (DPV), and cyclic voltammetry (CV) techniques were used. According to the obtained results of square-wave voltammetry, a limit of 3.02 CFU/ml E. coli detection in 3 min with desirable sensitivity, repeatability, and reproducibility was found with the designed biosensor. This biosensor could be a powerful tool for the detection of indicator bacteria in the food industry, drug safety, quality control, clinical diagnostics, and environmental monitoring.

Correlated downregulation of VDR and CYP3A4 in colorectal cancer.

BACKGROUND: The evidence obtained from experimental studies suggests the tumor-suppressive effects of vitamin D by controlling the differentiation, proliferation, and apoptosis in cancerous cells. Furthermore, the deregulation of genes involved in vitamin D metabolism has been reported in several types of cancer. METHODS: In the present study, we investigated the expression level of vitamin D metabolic pathway genes, including VDR, CYP3A4, RXRα, and GC, in colorectal cancer (CRC) samples compared with the adjacent tissues by using quantitative RT-PCR. RESULTS: The results indicated significant downregulation of CYP3A4 and VDR genes in CRC tissues compared with the adjacent control tissues (p < 0.01). RXRA and GC expression levels did not show any significant alteration among the studied samples. Moreover, a positive correlation was observed between the expression level of CYP3A4 and VDR genes (p < 0.0001). ROC curve analysis also revealed the potential diagnostic power of CYP3A4 and VDR genes in CRC samples. CONCLUSION: Reduction in the expression of both CYP3A4 and VDR plays an important role in CRC due to the possible impairment in vitamin D metabolism. Further studies concerning the relationship between the expression of these genes and colorectal cancer pathogenesis and treatment are recommended.

Alopecia areata-like pattern of baldness: the most recent update and the expansion of novel phenotype and genotype in the CTNNB1 gene.

Neurodevelopmental disorder with spastic diplegia and visual defects (NEDSDV) is a rare autosomal dominant genetic disorder caused by genetic alterations in the CTNNB1 gene. CTNNB1 is a gene that encodes ß-catenin, an effector protein in the canonical Wnt pathway involved in stem cell differentiation and proliferation, synaptogenesis, and a wide range of essential cellular mechanisms. Mutations in this gene are also found in specific malignancies as well as exudative vitreoretinopathy. To date, only a limited number of cases of this disease have been reported, and though they share some phenotypic manifestations such as intellectual disability, developmental delay, microcephaly, behavioral abnormalities, and dystonia, the variety of phenotypic traits of these patients shows extreme heterogeneity. In this study, two cases of NEDSDV with de novo CTNNB1 mutations: c.1420C>T(p.R474X) and c.1377_1378Del(p.Ala460Serfs*29), found with whole exome sequencing (WES) have been reported and the clinical and paraclinical characteristics of these patients have been described. Due to such a wide range of clinical characteristics, the identification of new patients and novel variants is of great importance in order to establish a more complete phenotypic spectrum, as well as to conclude the genotype-phenotype correlations in these cases.

Extending and outlining the genotypic and phenotypic spectrum of novel mutations of NALCN gene in IHPRF1 syndrome: identifying recurrent urinary tract infection.

Infantile hypotonia with psychomotor retardation and characteristic facies 1 (IHPRF1) is caused by biallelic mutations in the NALCN gene, the major ion channel responsible for the background Na + conduction in neurons. Through whole-exome sequencing (WES), we report three novel homozygous variants in three families, including c.1434 + 1G > A, c.3269G > A, and c.2648G > T, which are confirmed and segregated by Sanger sequencing. Consequently, intron 12's highly conserved splice donor location is disrupted by the pathogenic c.1434 + 1G > A variation, most likely causing the protein to degrade through nonsense-mediated decay (NMD). Subsequently, a premature stop codon is thus generated at amino acid 1090 of the protein as a result of the pathogenic c.3269G > A; p.W1090* variation, resulting in NMD or truncated protein production. Lastly, the missense mutation c.2648G > T; p.G883V can play a critical role in the interplay of functional domains. This study introduces recurrent urinary tract infections for the first time, broadening the phenotypic range of IHPRF1 syndrome in addition to the genotypic spectrum. This trait may result from insufficient bladder emptying, which may be related to the NALCN channelosome's function in background Na + conduction. This work advances knowledge about the molecular genetic underpinnings of IHPRF1 and introduces a novel phenotype through the widespread use of whole exome sequencing.

Prognostic factors in pediatric cochlear implant: an outcome-based study.

OBJECTIVE: To determine the prognostic factors in the pediatric cochlear implant (CI) outcome. MATERIALS AND METHODS: This prospective cohort study was conducted on 289 pediatric cases with prelingual hearing loss who received cochlear implantation. Several possible salient factors have been recorded. Auditory and speech evaluations were performed before CI, as well as 6 and 12 months after surgery, using Categories of Auditory Performance (CAP) and Speech Intelligibility Rating (SIR) tests. RESULTS: According to univariate analysis, age at the time of surgery was a statistically significant factor. Neurological problems in the child, history of newborn infectious diseases, history of hearing aid use, proper parental cooperation, and round window approach were all significantly related to better auditory or speech outcomes. On the other hand, good parental cooperation and age (for CAP) and good parental cooperation, age, history of infectious disease, and hearing aids use (for SIR) are the significant factors in the multivariate setting. CONCLUSION: As evidenced by the obtained results, age, background diseases, history of rehabilitation with hearing aids, and surgical details are essential factors to be taken into account in the case-selection process.

Identification of a novel de novo mutation in the CTNNB1 gene in an Iranian patient with intellectual disability.

CTNNB1 encodes for the ß-catenin protein, a component of the cadherin adhesion complex, which regulates cell-cell adhesion and gene expression in the canonical Wnt signaling pathway. Mutations in CTNNB1 have been reported to be associated with cancer and mental disorders. Recently, loss-of-function mutations in CTNNB1 have been observed in patients with intellectual disability and some other clinical manifestations including motor and language delays, microcephaly, and mild visual defects. We report an 8-year-old Iranian girl with intellectual disability, hypotonia, impaired vision such as vitreomacular adhesion, motor delay, and speech delay. A novel, de novo nonsense mutation (c.1014G > A; p.Trp338Ter) in exon 7 of the CTNNB1 (NM_001904) gene was detected and confirmed by whole-exome sequencing and Sanger sequencing, respectively. This study helps to expand the growing list of loss-of-function mutations known in the CTNNB1 gene.

Autophagy ATG16L1 rs2241880 impacts the colorectal cancer risk: A case-control study.

BACKGROUND: Despite many efforts to discover the important role of the autophagy process in the pathogenesis of colorectal cancer (CRC), the exact involved molecular mechanism still remains to be elucidated. Recently, a limited number of studies have been employed to discover the impact of autophagy genes' variants on the development and progression of CRC. Here, we evaluated the association between two single-nucleotide polymorphisms (SNPs) in the main components of the autophagy genes, ATG16L1 rs2241880, and ATG5 rs1475270, and the CRC risk in an Iranian population. METHODS: During this investigation, a total of 369 subjects, including 179 CRC patients and 190 non-cancer controls have been genotyped using Tetra-primer amplification refractory mutation system-polymerase chain reaction (TP-ARMS-PCR) method. RESULT: The results demonstrated that the T allele of the ATG16L1 rs2241880 was significantly associated with the increased risk of CRC in the studied population (OR 1.64, 95% CI: 1.21-2.22, p = 0.0015). Moreover, ATG16L1 rs2241880 TT genotype increased the susceptibility to CRC (OR 3.31, 95% CI: 1.64-6.69, p = 0.0008). Furthermore, a significant association was observed under the recessive and dominant inheritance models (p = 0.0015 and p = 0.017, respectively). No statistically significant differences were found in the ATG5 rs1475270 alleles and genotypes between the cases and controls. CONCLUSION: The results of the present study may be helpful concerning the risk stratification in CRC patients based on the genotyping approach of autophagy pathways and emphasize the need for further investigations among different populations and ethnicities to refine our conclusions.

Development of modified rapid entire body assessment (MOREBA) method for predicting the risk of musculoskeletal disorders in the workplaces.

BACKGROUND: Rapid Entire Body Assessment (REBA) technique is one of the tools developed for predicting the risk of musculoskeletal disorders based on the effective risk factors. This method has several limitations. The present study was aimed to develop the Modified Rapid Entire Body Assessment (MOREBA) method to more accurately predict the risk of musculoskeletal disorders. MATERIALS: This cross-sectional study was performed on 300 male workers of a steel factory with a variety of job tasks in Iran. Then, the information related to the various physical risk factors was extracted through observation of their duties and conversation with them. Also, the subjects were asked to complete the Persian version of Cornell musculoskeletal discomfort questionnaires (CMDQ). Then, a theoretical model was drawn in AMOS software. Computed coefficients were used to develop the MOREBA equation. In the end, the final scores were categorized by ROC curves, and the validation of the novel method was investigated using linear regression analysis. RESULTS: The parameters evaluated in the MOREBA method included contact stress, rapid and sudden movement, throwing motion, hand-arm vibration, whole-body vibration, temperature, and work-rest cycle in addition to the parameters of the REBA method, including awkward posture, coupling, force, load, static activity, and repetitive activity. The results showed that the strain produced by the physical risk factors with the total effect coefficient of 0.783 could significantly affect the musculoskeletal symptoms. The computed coefficients of the risk factors were applied to develop a novel index. The final score of the MOREBA method was categorized into four levels by optimal cut-off points of 12.37, 16.51, and 24.35. Based on the results, the MOREBA and REBA methods could justify 67 and 55% of the variations of musculoskeletal symptoms, respectively. CONCLUSIONS: The results revealed that modifications conducted in the REBA method were effective, and the MOREBA method can provide a more accurate prediction of the risk of musculoskeletal disorders.

The Prediction of Chronicity in Patients With Acute and Subacute Nonspecific Low Back Pain and Associated Risk Factors: A Case-Control Study.

BACKGROUND: Chronic low back pain is one of the most common musculoskeletal disorders in different countries. AIMS: This study aimed to predict the chronicity of nonspecific acute and nonspecific low back pain (LBP) and related risk factors among cases referred to physiotherapy clinics. DESIGN: A case-control and cross-sectional study. SETTINGS: Two physiotherapy centers in Tehran, Iran. PARTICIPANTS: This study included 502 patients with acute, subacute and chronic LBP. METHOD: This study included 502 patients with acute, subacute and chronic LBP. Data were obtained using the Fear-Avoidance Beliefs Questionnaire, Patient Health Questionnaire, Pain Catastrophic Scale, Tampa Scale for Kinesiophobia, Pittsburgh Sleep Quality Index, Walker's Health-Promoting Lifestyle Questionnaire, Roland Morris Disability Questionnaire, and Numerical Pain Rating Scale. Data analysis was performed by applying independent sample t test, χ2, and multiple logistic regression in SPSS software version 25. IBM Amos version 22 was used for path analysis. RESULTS: It was found that some demographic parameters (i.e., weight, BMI, job, type of occupational task performance, history of low back pain, work shift, underlying diseases and income), some cognitive parameters (i.e., fear-avoidance beliefs, kinesiophobia, catastrophic pain, and depression), some lifestyle parameters (i.e., health responsibility, physical activity, and interpersonal relationships), sleep quality and pain related disability were among the most critical risk factors in the chronicity of acute and subacute LBP (p < .05). CONCLUSIONS: Personal, psychological, and psychosocial parameters can be among the most critical predictors in the chronicity of acute and subacute nonspecific LBP. Hence, paying attention to all the mentioned factors at the beginning of patients' treatment to create a targeted treatment algorithm and prevent the conversion of acute and subacute into chronic LBP has particular importance.

Risk factors of dislocation after total hip arthroplasty in patients with developmental dysplasia of the hip.

PURPOSE: Dislocation following total hip arthroplasty (THA) is a well-known complication. However, there is little data on its rate and predictors in patients with developmental dysplasia of the hip (DDH). The current study is aimed to determine the rate and specific risk factors of dislocation following THA in DDH patients. METHODS: All the medico-surgical records of primary THAs from January 2014 to January 2019 were retrospectively reviewed. They were categorized into three main groups: primary OA, DDH, and others. Pre-operative and post-operative radiographs, past medical and surgical history, and surgical notes were reviewed in DDH cases. RESULTS: In a total of 171 patients with DDH, 21 suffered from dislocation after THA (12%) which was significantly more frequent than those with primary OA. In univariate analysis, higher grade of dysplasia, smaller head size, intra-operative fracture, Wagner Cone stem, failure of offset restoration, and implanting the cup outside the Lewinnek's safe zone were identified as predictors of dislocation. In multiple regression analysis, however, only higher Crowe grade, intra-operative fracture, and post-operative acetabular offset less than 16 mm were independent predictors of dislocation. CONCLUSION: Dysplastic hips can be more prone to post-THA dislocation than those with primary OA. Higher grades of dysplasia, failure of offset restoration, and intra-operative fracture can increase the rate of dislocation in this group of patients.

A phase I study of the anaplastic lymphoma kinase inhibitor ceritinib in combination with gemcitabine-based chemotherapy in patients with advanced solid tumors.

In this phase I, dose-escalation study, we sought to determine the maximum tolerated dose (MTD) of the anaplastic lymphoma kinase/c-ROS oncogene 1 receptor (ALK/ROS1) inhibitor ceritinib in combination with gemcitabine-based chemotherapy in patients with advanced solid tumors. Secondary objectives were characterization of the safety profile, pharmacokinetics and preliminary efficacy of these combinations, and identification of potential biomarkers of efficacy. Ceritinib was combined with gemcitabine (Arm 1), gemcitabine/nab-paclitaxel (Arm 2) or gemcitabine/cisplatin (Arm 3). Drug concentrations in plasma were measured by tandem mass spectrometric detection (LC-MS/MS). We analyzed archival tumor tissue for ALK, ROS1, hepatocyte growth factor receptor (c-MET) and c-Jun N-terminal kinase (JNK) expression by immunohistochemistry. Arm 2 closed early secondary to toxicity. Twenty-one patients were evaluable for dose-limiting toxicity (DLT). There was one DLT in Arm 1 (grade 3 ALT increase) and three DLTs in Arm 3 (grade 3 acute renal failure, grade 3 thrombocytopenia, grade 3 dyspnea). The MTD of ceritinib was determined to be 600 mg (Arm 1) and 450 mg orally daily (Arm 3). Main toxicities were hematologic, constitutional and gastrointestinal as expected by the chemotherapy backbone. The apparent clearance for ceritinib decreased substantially after repeated dosing; cisplatin did not significantly affect the pharmacokinetics of ceritinib. The overall response rate was 20%; the median progression-free survival was 4.8 months. Three out of five response-evaluable cholangiocarcinoma patients had clinical benefit. Increased expression of c-MET was associated with a lack of clinical benefit. Ceritinib in combination with gemcitabine and gemcitabine/cisplatin has a manageable toxicity profile. Further development of this strategy in tumors with ALK or ROS1 fusions is warranted.

The study of stress conditions on growth and proteome of Raoultella planticola: a new emerging pathogen.

All bacteria can survive and adapt to different stresses, such as fluctuations in temperature, pH oxidative, and osmotic pressure occurring in their surrounding environments. This study aims to evaluate the effects of a variety of stress conditions on the growth, and proteome of Raoultella planticola PTCC 1598. R. planticola cells were exposed to different values of temperatures, sodium chloride, pH, and hydrogen peroxide stresses. Among the stress conditions, oxidative stress, upon exposure to hydrogen peroxide (H2O2) at 4000 ppm concentration was selected for proteomics analysis in detail. Approximately, 1400 spots were identified in two-dimensional gel electrophoresis (2-DE). Among the identified spots, 85 spots were repeatable using 2D-Platinum software and eye confirmation and, nine protein spots were differentially expressed. Among nine proteins, six proteins identified successfully with an MASCOT score greater than 40 (p < 0.05) were 2,3-dihydroxybenzoate-2,3-dehydrogenase (oxidoreductase family), hypothetical protein G787-04832, periplasmic D-galactose-binding protein, uridine phosphorylase (glycosyltransferases), a single peptide match to cysteine-binding periplasmic protein, and NADP(H) nitroreductase. All identified proteins showed decreased level expression. Based on the obtained results, we concluded that hydrogen peroxide as an antiseptic compound could affect cell growth and proteomics of R. planticola. Therefore, we recommend using an antiseptic solution containing H2O2 to prevent the spread of R. planticola as a new emerging pathogen.

Antimicrobial activity of bacteriocin produced by a new Latilactobacillus curvatus sp.LAB-3H isolated from traditional yogurt.

In recent years, the use of bacteriocin-producing Lactobacillus species has received much attention in different areas, including using as probiotics, food preservation, and as broad antimicrobial spectrum activity. In this study, a bacteriocin-producing Lactobacillus strain was isolated from traditional yogurt. The isolate was identified by morphological, biochemical, 16S rRNA analyses, and designated as Latilactobacillus curvatus LAB-3H. The primary antimicrobial activity of the isolate was evaluated on Micrococcus luteus PTCC 1408 by the agar gel diffusion method. The growth of L. curvatus LAB-3H in MRS broth at 37 °C and its antimicrobial activity against Lactobacillus casei ATCC 39,392 was evaluated. In batch culture analysis, bacteriocin production starts at the early exponential growth phase and continues to the middle of the stationary phase about (660 AU/ml) at 28 h and pH 3.8. Bacteriocin produced by L. curvatus LAB-3H showed antibacterial activity against some selected foodborne pathogens, including Listeria monocytogenes PTCC1294, Bacillus cereus PTCC1857, Staphylococcus aureus PTCC1917, and Escherichia coli PTCC1276. For purification of bacteriocin, ammonium sulfate precipitation and cation exchange chromatography methods were used. The maximum antimicrobial activity observed was about 3985.15 AU/mg of protein, which was a 249.22-fold increase, and 5.21% yield compared with that in the cell-free supernatant. The molecular weight of bacteriocin was approximately 55 kDa by SDS-PAGE. The obtained results in this study demonstrate that bacteriocin from L. curvatus LAB-3H is a potential candidate for controlling microbial contaminations and can be used in different sectors, such as food industries.