Identification of a Novel Deletion Variant (c.2999_3005delTGTGTGT/p.Asn1000SerfsTer4) in NPHP4 Associated With Nephronophthisis-4.

BACKGROUND: Nephronophthisis-4 (NPHP4) is an inherited renal ciliopathy described by renal fibrosis and progressive impairment of kidney function. This study aimed to investigate the genetic basis and clinical manifestations of NPHP4 in two Iranian siblings. METHODS: The proband was a 27-year-old male with features of end-stage renal disease, including anemia, uremia, polyuria, and polydipsia. It is worth mentioning that he has a 22-year-old sister with a similar presentation. Clinical diagnosis procedures, such as renal biopsy, brain imaging, blood and urine tests, cardiac evaluation, ophthalmic inspection, and auditory function assessment, were carried out to evaluate organ involvement and potential comorbidities. Whole-exome sequencing (WES) and segregation analysis were performed to identify and confirm genetic variants associated with the condition. Computational variant analysis was conducted to evaluate the pathogenicity of the candidate variant. Furthermore, the SWISS-MODEL server was utilized for protein modeling. RESULTS: The brain, cardiac, ocular, and auditory functions were normal. Renal biopsy of the proband showed chronic interstitial inflammation and fibrosis. We found a novel homozygous 7-base pair deletion (c.2999_3005delTGTGTGT/ p.Asn1000SerfsTer4) in exon 21 of NPHP4 by WES. Segregation analysis confirmed homozygosity for the NPHP4 variant in affected individuals and heterozygous carrier status in parents, supporting autosomal recessive inheritance. 3D protein modeling indicated significant structural changes due to the variant. CONCLUSION: This study expands the genetic causes and phenotypic spectrum of nephronophthisis-4 and reveals the importance of genetic analysis in diagnosing and managing rare inherited kidney disorders, particularly those involving consanguinity.

The emergence of novel Iranian variants in sheeppox and goatpox viral envelope proteins with remarkably altered putative binding affinities with the host receptor.

The outbreak of Sheep and goat pox (SGP) viral infections have increasingly been reported despite vaccinating the majority of sheep populations in Iran. The objective of this study was to predict the impacts of the SGP P32/envelope variations on the binding with host receptors as a candidate tool to assess this outbreak. The targeted gene was amplified in a total of 101 viral samples, and the PCR products were subjected to Sanger sequencing. The polymorphism and phylogenetic interactions of the identified variants were assessed. Molecular docking was performed between the identified P32 variants and the host receptor and the effects of these variants were evaluated. Eighteen variations were identified in the investigated P32 gene with variable silent and missense effects on the envelope protein. Five groups (G1-G5) of amino acid variations were identified. While there were no amino acid variations in the G1 (wild-type) viral protein, G2, G3, G4, and G5 proteins had seven, nine, twelve, and fourteen SNPs, respectively. Based on the observed amino acid substitutions, multiple distinct phylogenetic places were occupied from the identified viral groups. Dramatic alterations were identified between G2, G4, and G5 variants with their proteoglycan receptor, while the highest binding was revealed between goatpox G5 variant with the same receptor. It was suggested that the higher severity of goatpox viral infection originated from its higher affinity to bind with its cognate receptor. This firm binding may be explained by the observed higher severity of the SGP cases from which G5 samples were isolated.

Histological and stereological approaches for detection of tissues and fraud in some meat products.

Meat and meat products are highly important sources of protein in the diet. Nowadays, the consumption of meat and meat products has increased owing to modern manufacturing techniques. Due to the economic value of meat, the use of unauthorized tissue is possible in meat products. In some cases, there is fraud in the percentage of meat in meat products to reduce prices. In this study, 34 samples of minced meat, hamburger and sausage were randomly collected from the markets in the northeast of Iran. Then, sections were stained using Hematoxylin and Eosin (H & E), Verhoeff-van-Gieson, Masson's trichrome and periodic acid-Schiff-Alcian blue stains. In this regard, for the first time, the efficacy of stereological technique to determine the percentage of meat listed in sausages and the possible existence of fraud was evaluated. The results showed that, due to the presence of some unusual tissues, histological technique could determine different tissues in meat products. The stereological results of control samples showed a very slight difference; whereas, the results for the samples collected from the city stores showed a distinctive difference regarding the percentage of meat compared to the percentage of label. Skeletal and smooth muscles, blood vessels, nerve, gizzard, adipose tissue, glandular tissue, cartilage, bone, tendon, skin, lymphatic tissues and plant materials were observed. It was confirmed that stereology was a reliable method to determine and confirm the percentage of meat used in meat products.

Perceived Child Abuse and Neglect in Hospitalized Children with Special Health Care Needs in Iran.

BACKGROUND: Child Abuse and Neglect (CAN) is an important public health concern. Nurses play a key role in caring for the children and keeping them safe from abuse and neglect. The aim of this study was to determine the rate of perceived CAN in Hospitalized Children with Special Health Care Needs (CSHCN) as well as the relationship between the rate and some effective factors. MATERIALS AND METHODS: This is a descriptive cross-sectional study on 199 CSHCN aged 6-18 years old, admitted to the pediatric wards in an educational hospital, in Isfahan, Iran, in 2018. Children were selected through convenience sampling method and assessed for CAN through a child abuse questionnaire. The Pearson correlation coefficient and Kruskal-Wallis and Mann-Whitney U tests were used to analyze the data. The p values smaller than 0.05 were regarded as significant. RESULTS: According to the findings, 173 children (86.93%) had perceived CAN, the average total score of which was 9.36 contributing commonly to malnutrition 3.01 (2.36) followed by psycho-emotional abuse 2.71 (1.76), neglect 1.62 (1.23), and physical 1.52 (1.08) and sexual 0.54 (0.31) abuse based on mean (SD). Statistical analysis indicated a significant effect of child's age, economic situation of the family, mother's education and occupation, and parents' illness on the total score of perceived CAN (p < 0.05). CONCLUSIONS: Malnutrition was found to be the most common type of perceived CAN. Therefore, parents and the health system are advised to prioritize nutritional needs when planning their nutrition.

Dysregulation of Ovine Toll-Like Receptors 2 and 4 Expression by Hydatid Cyst-Derived Antigens.

BACKGROUND: Cystic echinococcosis (CE) is a zoonotic disease caused by infection with Echinococcus granulosus. Toll-like receptors (TLRs) as the first line of defense against various parasites play a critical role in sensing and triggering anti-parasite responses. METHODS: The study was conducted at the Department of Pathobiology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Iran in 2019. Ovine peripheral blood mononuclear cells (PBMCs) were stimulated with hydatid cyst-derived antigens including hydatid cyst fluid (HCF), germinal layer antigens (GL), somatic and excretory/secretory (ES) products of protoscoleces (PSC). To investigate whether the expression of TLR2 and TLR4 was altered during exposure to these antigens, PBMCs were stimulated with two different concentrations at different time points. RESULTS: After exposure of PBMCs to ES and somatic antigens of protoscoleces (PSC) the expression of TLR2 and TLR4 was down-regulated in comparison with control group. Similarly, HCF markedly down-regulated TLR2 and TLR4 transcripts independent of dose and time. GL antigens significantly down-regulated TLR2, while TLR4 expression was up-regulated as compared with control group. CONCLUSION: Hydatid cyst-derived antigens could dysregulate the expression of TLR2 and TLR4 in ovine PBMCs, suggesting a possible mechanism to suppress host immunity to establish chronic infection.

Vancomycin Infusion Methods on Phlebitis Prevention in Children.

BACKGROUND: Hospitalized children require antibiotic therapy. The most common side effect of intravenous injections is Phlebitis. Due to high usage of Vancomycin in children and subsequent phlebitis in their intravenous lines, the current study aimed at comparing the effects of two intervention and routine vancomycin infusion methods in preventing phlebitis in hospitalized children. MATERIALS AND METHODS: The current study is a quasi-experimental study investigating 74 individuals between ages of 1 month and 6 years undergoing treatment using vancomycin. First, 37 children, hospitalized in internal medicine ward of Isfahan Paediatrics' Hospital, Iran with vancomycin infusion orders, were placed in control group, and another 37 children were placed in the intervention group through matching with control group. The intervention group used phlebitis prevention guidelines, created by the authors, while control group used routine infusion method of the hospital. Data were analyzed by SPSS software, and statistical significance was set at 5%. RESULTS: The occurrence of phlebitis was 45.90% in intervention and 89.10% in control group. Results showed that the frequency of phlebitis in intervention group was significantly lower than control group (χ2= 15.79, df = 1, p < 0.001) and the average time of phlebitis onset in control group was also significantly lower than that of the intervention group (t 72= 2.99, p = 0.004). CONCLUSIONS: According to the results, intervention vancomycin infusion method is more effective in reducing phlebitis as a result of intravenous catheter, compared to the routine vancomycin infusion method.

Genetic Analysis of Iranian Patients with Familial Hypercholesterolemia

Background: Familial hypercholesterolemia (FH) is a frequent autosomal dominant disorder of lipoprotein metabolism. This disorder is generally caused by mutations in low-density lipoprotein receptor (LDLR), apolipoprotein B 100 (APOB), and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. In the present study, we aimed at identifying the common LDLR and APOB gene mutations in an Iranian population. Methods: Eighty unrelated Iranian patients with FH entered the study, based on Simon Broome diagnostic criteria. All samples were screened for two common APOB gene mutations, including R3500Q and R3500W, by the means of ARMS-PCR and PCR- RFLP assays, respectively. In addition, exons 3, 4, 9, and 10 of LDLR gene were sequenced in all patients. Results: A novel mutation in exon 3 (C95W) and a previously described mutation in exon 4 (D139H) of LDLR gene were found. Three previously reported polymorphisms in LDLR gene as well as three novel polymorphisms were detected in the patients. However, in the studied population, no common mutations were observed in APOB gene. Conclusion: The results of our study imply that the genetic basis of FH in Iranian patients is different from other populations.

The Association of Panton-Valentine leukocidin and mecA Genes in Methicillin-Resistant Staphylococcus aureus Isolates From Patients Referred to Educational Hospitals in Ahvaz, Iran.

BACKGROUND: Staphylococcus aureus, an important human pathogen is one of the main causative agents of nosocomial infection. Virulence genes play a major role in the pathogenicity of this agent and its infections. Methicillin-Resistant Staphylococcus aureus (MRSA) isolates are major challenge among infectious agents that can cause severe infections and mortality. Methicillin-resistant S. aureus produces a unique type of Penicillin Binding Protein 2a (PBP2a) that has low affinity for ß-lactam antibiotics. Most of the MRSA bacterial strains can also produce a leukotoxin as Panton-Valentine Leukocidin (PVL) that increases the virulence of MRSA strains and can cause severe necrotic pneumonia. The presence of pvl gene is a genetic marker for the MRSA populations. OBJECTIVES: The aim of this study was to explore the association of pvl and mecA genes in clinical isolates of MRSA. MATERIALS AND METHODS: Fifty MRSA isolates were collected from 200 clinical samples from three different educational hospitals in Ahvaz, Iran, and identified by biochemical tests including catalase, oxidase, tube coagulase, mannitol fermentation, and sensitivity to furazolidone, resistance to bacitracin, PYR test and Voges-Proskauer test. Their resistance to methicillin was evaluated using the disc diffusion method. DNA was extracted by boiling and then the presence of pvl and mecA genes was investigated by the polymerase chain reaction method using specific primers. RESULTS: The results revealed that mecA and pvl genes were positive for 15 (30%) and 3 (6%) of the isolates, respectively. None of mecA positive isolates was positive for pvl gene. CONCLUSIONS: It can be concluded from these results that fortunately the prevalence of pvl gene is low in MRSA isolates in this region and there is no association between the presence of pvl and mecA genes in these isolates.