Prevalence of congenital anomalies and related factors in live births in Zahedan, Southeast of Iran: A cross-sectional study.

Background: The term congenital anomalies (CAs) refers to structural or functional abnormalities at the time of conception. Approximately 12 deaths related to congenital disabilities occur in every 10,000 babies born. Objective: This study aimed to evaluate the prevalence and associated factors of single and multiple CAs in live births in Zahedan, Southeast Iran. Materials and Methods: This cross-sectional study was conducted on 59,087 live births in a referral hospital in Zahedan located in the southeast of Iran from 2009 to 2019. All live births were examined by pediatricians and the CAs and categorized based on the international classification of diseases. Results: Of 59,085 live births, at least 883 had a significant anomaly, and the prevalence rate of CAs was about 149 per 10,000. Anomalies of the nervous (24.1%) and cardiovascular systems (21.10%) were the most frequent, occurring in 213 and 187 of the live births, respectively. Spina bifida is the most common anomaly of the central nervous system. The most common anomalies in the cardiovascular system were unspecified heart malformations (17.1%), cardiovascular malformations (18.7%), and patent ductus arteriosus (11.7%). Significant correlations were found between the parent's consanguinity marriage, the mother's age, an existing anomaly in the family, and relatives in single and multiple CAs (p = 0.02, p = 0.02, p < 0.001, p = 0.01, respectively). Conclusion: The prevalence of CAs was 149 per 10,000 live births. The highest prevalence of CAs was related to the central nervous system. Increasing the public's knowledge about fetal defects can reduce the prevalence of CAs.

Ablation of Projection Glutamatergic Neurons in the Lateral Cerebellar Nuclei Alters Motor Coordination in Vglut2-Cre+ Mice.

Cerebellar nuclei (CN) constitute the sole cerebellar output to the rest of the central nervous system and play a central role in cerebellar circuits. Accumulating evidence from both human genetics and animal studies point to a crucial role for CN connectivity in neurological diseases, including several types of ataxia. However, because of the compact and restricted topography and close functional connection between the CN and the cerebellar cortex, identifying cerebellar deficits exclusively linked to CN is challenging. In this study, we have experimentally ablated large projection glutamatergic neurons of the lateral CN and evaluated the impact of this selective manipulation on motor coordination in mice. To this end, through stereotaxic surgery, we injected the lateral CN of Vglut2-Cre+ mice with an adeno-associated virus (AAV) encoding a Cre-dependent diphtheria toxin receptor (DTR), followed by an intraperitoneal injection of diphtheria toxin (DT) to ablate the glutamatergic neurons of the lateral nucleus. Double immunostaining of cerebellar sections with anti-SMI32 and -GFP antibodies revealed GFP expression and provided evidence of SMI32+ neuron degeneration at the site of AAV injection in the lateral nucleus of Vglut2-Cre+ mice. No changes were observed in Vglut2-Cre negative mice. Analysis of motor coordination by rotarod test indicated that the latency to fall was significantly different before and after AAV/DT injection in the Vglut2-Cre+ group. Elapsed time and number of steps in the beam walking test were significantly higher in AAV/DT injected Vglut2-Cre+ AAV/DT mice compared to controls. We demonstrate for the first time that partial degeneration of glutamatergic neurons in the lateral CN is sufficient to induce an ataxic phenotype.

Stimulating olfactory epithelium mitigates mechanical ventilation-induced hippocampal inflammation and apoptosis.

Mechanical ventilation (MV), as a life-saving procedure in critical patients, is a risk factor to develop of neurocognitive dysfunction and triggers of inflammation and apoptosis in the brain. Since diversion of breathing route to the tracheal tube diminishes brain activity entrained by physiological nasal breathing, we hypothesized that simulating nasal breathing using rhythmic air-puff (AP) into the nasal cavity of mechanically ventilated rats can reduce hippocampal inflammation and apoptosis in association with restoring respiration-coupled oscillations. We found that stimulating olfactory epithelium through applying rhythmic nasal AP, in association with reviving respiration-coupled brain rhythm, mitigates MV-induced hippocampal apoptosis and inflammation involving microglia and astrocytes. The current translational study opens a window for a novel therapeutic approach to reduce neurological complications induced by MV.

The possible impact of DNA-binding chromodomain-helicase 5 polymorphisms on male infertility: A case-control study.

BACKGROUND: Chromodomain-helicase 5 (CHD5) is a conventional tumor-suppressing gene in many tumors. The CHD5 gene, as a key factor in the chromatin density process during sperm maturation, can affect the risk of infertility. This study aimed to determine whether CHD5 variants contribute to the risk of male infertility. METHODS: Gene variants were identified using tetra primer-ARMS-PCR method on nonobstructive azoospermia and severe oligozoospermia in a case-control study. SPSS software 20 (SPSS Inc. Chicago, IL, USA) was used for data recording and statistical analysis. RESULTS: In the codominant pattern, the rs12067480 TT variant versus CC significantly increased the risk of disease, and also, in the recessive pattern, TT variant versus CC + CT and T allele versus C. The rs2273032 variant was associated with the risk of infertility in codominant pattern AA versus GG and recessive pattern AA versus GG + GA and allele. We discovered that the rs12067480 T and rs2273032 A alleles increase the risk of male infertility. Also, the interaction of the CT/GA, CT/AA, TT/GA genotypes and rs12067480T/rs2273032A and rs12067480T/rs2273032G haplotypes significantly increased the risk of infertility. CONCLUSIONS: Our results suggest that the CHD5 gene polymorphisms contribute to the risk of male infertility. Our findings can be valuable in improving the diagnosis and treatment of infertility.

The effect of dopaminergic neuron transplantation and melatonin co-administration on oxidative stress-induced cell death in Parkinson's disease.

A gradual degeneration of the striatum and loss of nigral dopamine cells are characteristic of Parkinson's disease. Nowadays, combination therapy for neurodegenerative disease is considered. This study aimed to investigate the effects of melatonin and dopaminergic neurons derived from adipose tissue stem cells (ADSCs) in a rat model of Parkinson's disease. Parkinson's disease was induced in rats using neurotoxin 6-Hydroxydopamine. The treatment was performed using melatonin and dopaminergic neurons transplantation. Subsequently, behavioral tests, western blot analysis for Caspase-3 expression, GSH (Glutathione) content and stereology analysis for the volume and cell number of substantia nigra and striatum were performed. Treatment with melatonin and dopaminergic neuron transplantation increased the number of neurons in substantia nigra and striatum while the number of glial cell and the volume of substantia nigra and striatum did not show significant change between groups. Western blot analysis for caspase 3 indicated the significant differences between groups. The results also indicated the increased level of glutathione (GSH) content in treatment groups. this study showed that combination therapy with melatonin and dopaminergic neurons could greatly protect the neurons, reduce oxidative stress and improve the symptoms of PD.

mRNA expression and epigenetic-based role of chromodomain helicase DNA-binding 5 in hepatocellular carcinoma.

OBJECTIVE: Chromodomain helicase DNA-binding 5 (CHD5) acts as a tumor suppressor gene in some cancers. CHD5 expression levels may affect an individual's susceptibility to hepatocellular carcinoma (HCC). This study aimed to evaluate the methylation pattern of the CHD5 promoter region and the gene's corresponding mRNA expression in HCC patients compared with healthy individuals. METHODS: In this case-control study, CHD5 mRNA gene expression levels and DNA methylation patterns were analyzed in 81 HCC patients and 90 healthy individuals by quantitative reverse transcription polymerase chain reaction and methylation-specific polymerase chain reaction, respectively. RESULTS: The CHD5 gene was hypermethylated in 61.8% of the HCC patients and 54.4% of the controls, and this difference was statistically significant. The CHD5 mRNA expression levels were significantly lower in the HCC patient group. CONCLUSIONS: Hypermethylation of the CHD5 promoter region may significantly lower the expression of this gene, affecting the incidence and severity of HCC. The methylation status of CHD5 can also be further studied as a prognostic factor in HCC.

Interleukin 22 Expression During the Implantation Window in the Endometrium of Women with Unexplained Recurrent Pregnancy Loss and Unexplained Infertility Compared to Healthy Parturient Individuals.

We evaluated the expression of interleukin-22 (IL-22) in the endometrium of women with unexplained recurrent pregnancy loss (uRPL) and unexplained infertility (UI) compared to the women with normal pregnancies. Endometrial tissues were collected from 20 women with UI, 20 women with uRPL, and 24 healthy women as a control group. Immunohistochemical expression and gene expression of IL-22 were analyzed by immunohistochemistry (IHC) and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) methods. The controls showed lower IL-22 expression than the uRPL group (P > 0.05) using PCR. It was also found that patients with UI had lower levels of IL-22 expression compared to the uRPL group (P > 0.05). Although IL-22 expression in the endometrium of patients with UI was higher than the control group, this difference was not statistically significant (P < 0.05). IL-22 immunoreactivity was observed in the endometrial glands and stromal tissues using IHC. We found the lowest IL-22 expression in the control group and the highest in uRPL samples (P < 0.05). Our findings suggest that a significant increase in IL-22 expression in uRPL patients may affect fertility and pregnancy outcomes or even have a considerable impact on immune function deficits. Further studies on the critical function of IL-22 during pregnancy are suggested.

Cannabinoid receptor type-1 and its correlation with CB1 gene polymorphism-1359G/A in ectopic pregnancy compared to the control group.

AIM: Ectopic pregnancy (EP) is one of the most important causes of maternal mortality. This study aimed to evaluate the immunohistochemical (IHC) expression of the cannabinoid receptor type-1 (CB1) and its association with CB1-1359G/A gene polymorphism (rs1049353) in the fallopian tubes in EP compared to controls. METHODS: In this case-control study, 100 women with EP (cases) and 100 women that underwent abdominal surgery due to the hysterectomy or uterine tubal ligation (healthy controls) were included. Genotyping of CB1-1359G/A polymorphism, tissue expression of CB1 at the protein and mRNA levels were studied using restriction fragment length polymorphism, IHC method, and quantitative real-time polymerase chain reaction (qRT-PCR) analysis. RESULTS: Genotyping showed that in EP, the frequency of AA, AA+AG genotypes, and A allele was significantly higher than healthy control subjects (p = 0.001). Also, patients with EP had significantly increased IHC expression of CB-1 compared to the control samples (p = 0.016). Patients with AA and AG genotypes had a significantly higher IHC expression of CB-1 compared to the GG genotype. qRT-PCR analysis showed that patients with EP had significantly increased expression of CB-1 compared to the control samples (p < 0.001). Patients with AA and AG genotypes had higher significant mRNA expression of CB-1 compared to the GG genotype. CONCLUSIONS: CB1 is likely to be effective in creating innate immunity in humans and can affect the process of EP in the fallopian tube. CB1 is also a pathological valuable factor in identifying the pathway of inflammation during ectopic implantation.

Upregulation of elafin expression in the fallopian tube of ectopic tubal pregnancies compared to the normal tubes.

BACKGROUND: Ectopic pregnancy is one of the most important causes of maternal deaths and fallopian tubes are the location of 95% of ectopic pregnancies. Elafin is a natural antimicrobial molecule that plays an important role as an anti-inflammatory agent in mucosal surfaces and has been found in the female reproductive tract. OBJECTIVES: The aim of this study was to investigate elafin expression, in the fallopian tube mucosa of ectopic pregnancies compared to the normal tubes using immunohistochemistry (IHC) techniques and quantitative reverse transcription (qRT)-PCR. METHODS: In this case-control study, uterine tube samples were obtained from patients with an indication for surgical removal of the tubes. The case group (n = 20) consisted of patients who were undergoing salpingectomy due to an ectopic pregnancy, the control group (n = 20) included patients who had a salpingectomy and hysterectomy. Using qRT-PCR and IHC, the expression of elafin was investigated in both study groups. RESULTS: Immunohistochemical expression of elafin in the epithelium and connective tissue was significantly increased in the implantation site of the patients in comparison with the control group (P < 0.001). The level of elafin mRNA increased in the mucous membrane of the fallopian tube from patients with the ectopic pregnancy compared to the normal mucosa (P < 0.001). CONCLUSION: Increasing expression of elafin during an ectopic pregnancy may be a mechanism for enhancing innate immune response and be involved in related pathological conditions such as infection and ectopic implantation.

A Prevalence Study of Hearing Loss among Primary School Children in the South East of Iran.

Hearing impairment substantially affects child's ability to normally acquire the spoken language. Such negative effects create problems for the child not only in terms of communication but also in terms of achievement in school as well as social and emotional growth. The aim of this research is to study the prevalence of hearing disorders and its relationship to age and gender among primary school students of Zahedan, Iran. In this cross-sectional and descriptive analytical study, 1500 students from elementary schools were screened for hearing loss. The selection of samples was performed using multistage sampling method. Primary information was obtained through direct observation, otoscopy, and audiometric and tympanometric screenings. Data was obtained and analyzed via ANOVA test. Statistical analysis showed a significant correlation between the age and the prevalence of middle ear abnormal function. Conductive hearing loss in males and females was 8.8% and 7.1%, respectively. In addition, 1% and 0.7% of male and female students, respectively, suffered from sensorineural hearing loss. Results indicated that 20.2% of students of elementary schools in Zahedan needed medical treatment for their problems. Therefore, it is recommended that the hearing screening of school-age children should be included in annual school health programs in this region.