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.

Identification of novel mutations in TPK1 and SLC19A3 genes in families exhibiting thiamine metabolism dysfunction syndrome.

Background and aims: The occurrence of thiamine metabolism dysfunction syndrome (THMD), a rare autosomal recessive condition, may be linked to various mutations found in the TPK1 and SLC19A3 genes. The disease chiefly manifests through ataxia, muscle hypotonia, abrupt or subacute onset encephalopathy, and a decline in developmental milestones achieved during the early stages of infancy. We present findings from an investigation that involved two individuals from Iran, both of whom experienced seizures along with ataxia and hypotonia. The underlying genetic causes were found with the use of next-generation sequencing (NGS) technology, which has facilitated the detection of causal changes in a variety of genetic disorders. Material and methods: The selection of cases for this study was based on the phenotypic and genetic information that was obtainable from the Center for Comprehensive Genetic Services. The genetic basis for the problems observed among the participants was determined through the application of whole-exome sequencing (WES). Subsequently, sanger sequencing was employed as a means of validating any identified variations suspected to be causative. Results: The first patient exhibited a homozygous mutation in the TPK1 gene, NM_022445.4:c.224 T > A:p.I75 N, resulting in the substitution of isoleucine for asparagine at position 75 (p.I75 N). In our investigation, patient 2 exhibited a homozygous variant, NM_025243.4:c.1385dupA:pY462X, within the SLC19A3 gene. Conclusions: Collectively, when presented with patients showcasing ataxia, encephalopathy, and basal ganglia necrosis, it is essential to account for thiamine deficiency in light of the potential advantages of prompt intervention. At times, it may be feasible to rectify this deficiency through the timely administration of thiamine dosages. Accordingly, based on the results of the current investigation, these variations may be useful for the diagnosis and management of patients with THMD.

Evaluation of the efficacy of mesenchymal stem cells derived conditioned medium in the treatment of striae distensae: a double blind randomized clinical trial.

BACKGROUND: Striae distensae is a disfiguring atrophic skin condition that impairs the body's aesthetic image. Despite the variety of conducted studies, there is controversy regarding the best modalities. Human mesenchymal stem cells are considered a rich source for scar treatment. Skin needling is among the most efficient and safe aesthetic and therapeutic devices. This study aimed to evaluate the efficacy of the combination of needling and intradermal injection of mesenchymal stem cells compared to skin needling alone for treating striae distensae. METHOD: This study was a randomized, double-blind clinical trial involving 10 women aged 18-60. Each striae lesion was divided into two parts, with one side receiving needling and intradermal injection of conditioned medium, while the other side received needling and intradermal injection of normal saline. This treatment was administered in three sessions with three-week intervals. Patients were evaluated before the first intervention and three months after the final session. Three months after the completion of the intervention, patients' lesions were evaluated using biometric criteria, physician evaluation, and patient self-assessment. RESULTS: The results demonstrated a significant improvement in dermal and complete thickness and skin density in patients treated with microneedling. All skin ultrasound parameters improved significantly in patients receiving the combination of needling and conditioned medium. When comparing the two groups, significantly higher physician and patient satisfaction was observed in the combination group. However, the comparison of biometric indices improvement wasn't significant between these groups. CONCLUSION: The combination of human mesenchymal stem cells with microneedling could be considered a novel effective option for stretch marks.

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 novel mutations in pontocerebellar hypoplasia with a comprehensive molecular literature review.

BACKGROUND: Pontocerebellar hypoplasia is an umbrella term describing a heterogeneous group of prenatal neurodegenerative disorders mostly affecting the pons and cerebellum, with 17 types associated with 25 genes. However, some types of PCH lack sufficient information, which highlights the importance of investigating and introducing more cases to further elucidate the clinical, radiological, and biochemical features of these disorders. The aim of this study is to provide an in-depth review of PCH and to identify disease genes and their inheritance patterns in 12 distinct Iranian families with clinically confirmed PCH. METHODS: Cases included in this study were selected based on their phenotypic and genetic information available at the Center for Comprehensive Genetic Services. Whole-exome sequencing (WES) was used to discover the underlying genetic etiology of participants' problems, and Sanger sequencing was utilized to confirm any suspected alterations. We also conducted a comprehensive molecular literature review to outline the genetic features of the various subtypes of PCH. RESULTS: This study classified and described the underlying etiology of PCH into three categories based on the genes involved. Twelve patients also were included, eleven of whom were from consanguineous parents. Ten different variations in 8 genes were found, all of which related to different types of PCH. Six novel variations were reported, including SEPSECS, TSEN2, TSEN54, AMPD2, TOE1, and CLP1. Almost all patients presented with developmental delay, hypotonia, seizure, and microcephaly being common features. Strabismus and elevation in lactate levels in MR spectroscopy were novel phenotypes for the first time in PCH types 7 and 9. CONCLUSIONS: This study merges previously documented phenotypes and genotypes with unique novel ones. Due to the diversity in PCH, we provided guidance for detecting and diagnosing these heterogeneous groups of disorders. Moreover, since certain critical conditions, such as spinal muscular atrophy, can be a differential diagnosis, providing cases with novel variations and clinical findings could further expand the genetic and clinical spectrum of these diseases and help in better diagnosis. Therefore, six novel genetic variants and novel clinical and paraclinical findings have been reported for the first time. Further studies are needed to elucidate the underlying mechanisms and potential therapeutic targets for PCH.

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.

Comprehensive review and expanding the genetic landscape of Cornelia-de-Lange spectrum: insights from novel mutations and skin biopsy in exome-negative cases.

BACKGROUND: Cornelia de Lange Syndrome (CdLS) is a rare genetic disorder characterized by a range of physical, cognitive, and behavioral abnormalities. This study aimed to perform a comprehensive review of the literature on CdLS and investigate two cases of CdLS with distinct phenotypes that underwent WES to aid in their diagnosis. METHODS: We conducted a comprehensive review of the literature on CdLS along with performing whole-exome sequencing on two CdLS patients with distinct phenotypes, followed by Sanger sequencing validation and in-silico analysis. RESULTS: The first case exhibited a classic CdLS phenotype, but the initial WES analysis of blood-derived DNA failed to identify any mutations in CdLS-related genes. However, a subsequent WES analysis of skin-derived DNA revealed a novel heterozygous mutation in the NIPBL gene (NM_133433.4:c.6534_6535del, p.Met2178Ilefs*8). The second case was presented with a non-classic CdLS phenotype, and WES analysis of blood-derived DNA identified a heterozygous missense variant in the SMC1A gene (NM_006306.4:c.2320G>A, p.Asp774Asn). CONCLUSIONS: The study shows the importance of considering mosaicism in classic CdLS cases and the value of WES for identifying genetic defects. These findings contribute to our understanding of CdLS genetics and underscore the need for comprehensive genetic testing to enhance the diagnosis and management of CdLS patients.

In vitro Antibacterial Activity and Wound Healing Effects of Achillea millefolium Essential Oil in Rat.

Objectives: In this study we aimed to evaluate the in vitro antibacterial activity and wound healing properties of Achillea millefolium essential oil (AMEO) in full-thickness wound model in rat. The antibacterial activity of AMEO was evaluated against Staphylococcus aureus and Pseudomonas aeruginosa using the broth dilution method. Methods: The 2 cm × 2 cm full-thickness excisional wounds were created on the back of animals. Topical therapy was applied twice a day using 1%, 2%, and 3% w/w AMEO ointments, and the measurement of the wounds area was carried out every 3 days, after that the wound closure percentage was calculated in these days. Hydroxyproline content and histopathological evaluation of wound tissue samples were carried out on day 7 and 14 post wounding. Eucerin was used for the treatment of vehicle control group and negative control group received no treatment. Results: Our results revealed the bacteriostatic activity of AMEO against S. aureus and P. aeruginosa. Wound healing activity evaluation of AMEO showed the significant increase (p < 0.05) in the wound closure percentages in rats treated with AMEO 1% and 2% comparing to those of non-treatment group. In addition, hydroxyproline contents of tissue significantly (p < 0.01) increased in AMEO 1% and 2% comparing to non-treatment group. Histopathological evaluations of wound tissue samples on day 7 and 14 demonstrated higher accumulation of collagen fibers, reduction of edema and inflammation and also formation of tissue appendages in 1% and 2% AMEO treated groups in comparison with non-treatment group. Conclusion: The results of this study indicated that AMEO has the potential to be used as a safe and effective wound healing agent.

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.

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.

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.

Analysis of Cytogenetic Abnormalities in Iranian Patients with Syndromic Autism Spectrum Disorder: A Case Series.

Objective: Autism spectrum disorder (ASD) is a heterogeneous neuropsychiatric group of pervasive developmental disorders mainly diagnosed through the complex behavioral phenotype. According to strong genetic involvement, detecting the chromosome regions and the key genes linked to autism can help to elucidate its etiology. The present study aimed to investigate the value of cytogenetic analysis in syndromic autism and find an association between autism and chromosome abnormalities. Materials & Methods: Thirty-six autistic patients from 30 families were recruited, clinically diagnosed with the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5). The syndromic patients with additional clinical features (including development delay, attention deficit, hyperactivity disorder, seizure, and language and intellectual impairment) were selected due to elevating the detection rate. Cytogenetics analysis was performed using GTG banding on the patients' cultured fibroblasts. Moreover, array-comparative genomic hybridization (CGH) was also performed for patients with a de novo and novel variant. Results: Karyotype analysis in 36 syndromic autistic patients detected chromosomal abnormalities in 2 (5.6%) families, including 46,XY,dup(15)(q11.1q11.2) and 46,XX,ins(7)(q11.1q21.3)dn. In the latter, array-CGH detected 3 abnormalities on chromosome 7, including deletion and insertion on both arms: 46,XX,del(7)(q21.11q21.3),dup(7)(p11.2p14.1p12.3)dn. Conclusion: We reported a novel and de novo cytogenetic abnormality on chromosome 7 in an Iranian patient diagnosed with syndromic autism. However, the detection rate in syndromic autism was low, implying that it cannot be utilized as the only diagnostic procedure.

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.

CREB-binding protein (CREBBP) and preeclampsia: a new promising target gene.

Preeclampsia (PE) is a major complication of pregnancy and remains a leading cause of neonatal and maternal mortality worldwide. Several studies have revealed that the incidence of preeclampsia is high in mothers who carried a fetus with Rubinstein-Taybi Syndrome due to the mutation in CREBBP. We aimed to compare the expression level of the CERBBP gene between preeclamptic and healthy placenta in our study. The expression level of CREBBP gene was evaluated in a total of one hundred placental biopsies from PE patients and healthy pregnant women after delivery using quantitative real-time polymerase chain reaction (qRT-PCR). Moreover, the differential expression of CREBBP was assessed between the maternal and fetal sides of the placenta. Expression of the CREBBP gene was higher in preeclampsia patients compared with the controls (Fold change = 2.158; P = 0.018). Moreover, the gene expression was slightly higher in the fetal side of the placenta, although it was not significantly different (Fold change = 1.713, P = 0.254). Our findings show a role for CREBBP in the pathogenesis of PE. Due to the important role of CREBBP in angiogenesis and hypoxia, the gene may serve as a promising target in future studies.

Strategies for sustaining and enhancing nursing students' engagement in academic and clinical settings: a narrative review.

Students' engagement in academic-related learning activities is one of the important determinants of students' success. Identifying the best teaching strategies to sustain and promote nursing students' engagement in academic and clinical settings has always been a challenge for nurse educators. Hence, it is essential to provide a set of strategies for maintaining and enhancing the academic engagement of nursing students. The purpose of this review was to explore and summarize the strategies that nurse educators use to sustain and promote nursing students' engagement in academic and clinical settings. A narrative literature review was conducted. CINAHL (nursing content), ProQuest, Medline, the Cochrane, Google Scholar, and Scopus were searched. Of 1,185 retrieved articles, 32 teaching strategies were identified and extracted from the nursing literature. We used thematic analysis approach to organize these strategies into five main categories as follows: technology-based strategies (15 articles), collaborative strategies (10 articles), simulation-based strategies (two articles), research-based strategies (two articles), and miscellanea learning strategies (three articles). As a general comment, these strategies have the potential to promote nursing students' engagement. Among the strategies discussed in this review, the use of technology, particularly the response system and online learning, was more common among nursing educators, which is in line with today's advances in smart technologies. The collection presented in this review can be used as a starting point for future research to evaluate the effectiveness of an educational intervention on the academic engagement of nursing students. Nevertheless, due to the lack of experimental studies, the optimal strategies remain to be elucidated through future high-quality experimental study.

Student-related factors affecting academic engagement: A qualitative study exploring the experiences of Iranian undergraduate nursing students.

BACKGROUND AND AIM: Academic engagement is an important indicator of quality of higher education. This study aimed to explain the experiences of undergraduate nursing students in terms of student-related factors affecting academic engagement. METHODS: This qualitative study was conducted in 2017 at Mashhad University of Medical Sciences in Iran. Data were collected using semi-structured interviews and focus groups with 7 and 16 undergraduate nursing students at Mashhad School of Nursing and Midwifery; respectively. Undergraduate nursing students of both genders who enrolled in different academic semesters with various academic achievements were selected. Data were analyzed using conventional content analysis approach proposed by Graneheim and Lundman, with the support of MAXQDA software. RESULTS: After analyzing the data, 374 initial codes were extracted, which ultimately conceptualized within six main categories including: "learning motivation", "interest in learning", "student participation in extracurricular scientific programs", "self-directedness", "mental concentration", and "demonstration of emotions". CONCLUSION: The findings of this study indicated that student-related factors such as individual motivation and interest, mental concentration, participation in extracurricular activities, and self-directedness in learning, as well as students' sense of satisfaction with learning could play important roles in the creation of academic engagement in undergraduate nursing students that need to be of interest to nursing educators and planners.

Challenges ahead of emergency medical technician graduates in the workplace in Iran: a qualitative study.

OBJECTIVE: Emergency medical technicians (EMTs) in Iran enter the workplace after a short academic education. Their workplace has high emotional fluctuations and imposes high pressure. The aim of this study was to assess the challenges faced by EMT graduates in Iran. DESIGN: This applied study was conducted using qualitative content analysis. Twelve paramedics and graduates with 2 to 3 years of service were interviewed and their responses were analyzed by content analysis. RESULTS: Findings were presented in five themes: organizational pressure, educational style, professional communication, emotional load, and misunderstanding of others. CONCLUSION: Several problems confront EMTs in Iran. Educators and educational planners in this discipline could help resolve these problems by revising problematic points in the education and management of EMT graduates and by revising educational methods and human resource management to provide better services and save lives.