Purpose: We aimed to identify the genetic causes of hypospadias in children using targeted gene panel sequencing for disorders of sex development (DSD). Materials and Methods: This study included 18 twin boys with hypospadias: seven and two pairs were monozygotic and dizygotic twins, respectively, and six were discordant and three were concordant twins. Targeted gene panel sequencing for 67 known DSD genes was performed. Sequence variants were classified into five different categories, pathogenic, likely pathogenic, variants of uncertain significance, likely benign, and benign, following the American College of Medical Genetics and Genomics Standards and Guidelines. Results: The mean gestational age and birth weight were 35.3±2.0 weeks and 1.96±0.61 kg, respectively, with seven patients being small for gestational age. Hypospadias was present in 12 patients, with posterior type in 33.3% and anterior type in 66.7%.In three families with twins, both siblings had hypospadias. In addition, cryptorchidism was observed in one subject. Surgical correction of hypospadias was performed at a mean age of 22.1 months. Molecular analysis identified 12 different genetic variants, including two pathogenic mutations in the AMH (p.E389*) and SRD5A2 (p.R246Q) genes, found in subjects with hypospadias, respectively. However, only heterozygous mutations were detected. Conclusions This study did not identify a definitive genetic component contributing to the development of hypospadias; however, the findings suggest that intrauterine growth retardation may play a significant role.

Purpose: We aimed to identify the genetic causes of hypospadias in children using targeted gene panel sequencing for disorders of sex development (DSD). Materials and Methods: This study included 18 twin boys with hypospadias: seven and two pairs were monozygotic and dizygotic twins, respectively, and six were discordant and three were concordant twins. Targeted gene panel sequencing for 67 known DSD genes was performed. Sequence variants were classified into five different categories, pathogenic, likely pathogenic, variants of uncertain significance, likely benign, and benign, following the American College of Medical Genetics and Genomics Standards and Guidelines. Results: The mean gestational age and birth weight were 35.3±2.0 weeks and 1.96±0.61 kg, respectively, with seven patients being small for gestational age. Hypospadias was present in 12 patients, with posterior type in 33.3% and anterior type in 66.7%.In three families with twins, both siblings had hypospadias. In addition, cryptorchidism was observed in one subject. Surgical correction of hypospadias was performed at a mean age of 22.1 months. Molecular analysis identified 12 different genetic variants, including two pathogenic mutations in the AMH (p.E389*) and SRD5A2 (p.R246Q) genes, found in subjects with hypospadias, respectively. However, only heterozygous mutations were detected. Conclusions This study did not identify a definitive genetic component contributing to the development of hypospadias; however, the findings suggest that intrauterine growth retardation may play a significant role.

Purpose: We aimed to identify the genetic causes of hypospadias in children using targeted gene panel sequencing for disorders of sex development (DSD). Materials and Methods: This study included 18 twin boys with hypospadias: seven and two pairs were monozygotic and dizygotic twins, respectively, and six were discordant and three were concordant twins. Targeted gene panel sequencing for 67 known DSD genes was performed. Sequence variants were classified into five different categories, pathogenic, likely pathogenic, variants of uncertain significance, likely benign, and benign, following the American College of Medical Genetics and Genomics Standards and Guidelines. Results: The mean gestational age and birth weight were 35.3±2.0 weeks and 1.96±0.61 kg, respectively, with seven patients being small for gestational age. Hypospadias was present in 12 patients, with posterior type in 33.3% and anterior type in 66.7%.In three families with twins, both siblings had hypospadias. In addition, cryptorchidism was observed in one subject. Surgical correction of hypospadias was performed at a mean age of 22.1 months. Molecular analysis identified 12 different genetic variants, including two pathogenic mutations in the AMH (p.E389*) and SRD5A2 (p.R246Q) genes, found in subjects with hypospadias, respectively. However, only heterozygous mutations were detected. Conclusions This study did not identify a definitive genetic component contributing to the development of hypospadias; however, the findings suggest that intrauterine growth retardation may play a significant role.

Purpose: We aimed to identify the genetic causes of hypospadias in children using targeted gene panel sequencing for disorders of sex development (DSD). Materials and Methods: This study included 18 twin boys with hypospadias: seven and two pairs were monozygotic and dizygotic twins, respectively, and six were discordant and three were concordant twins. Targeted gene panel sequencing for 67 known DSD genes was performed. Sequence variants were classified into five different categories, pathogenic, likely pathogenic, variants of uncertain significance, likely benign, and benign, following the American College of Medical Genetics and Genomics Standards and Guidelines. Results: The mean gestational age and birth weight were 35.3±2.0 weeks and 1.96±0.61 kg, respectively, with seven patients being small for gestational age. Hypospadias was present in 12 patients, with posterior type in 33.3% and anterior type in 66.7%.In three families with twins, both siblings had hypospadias. In addition, cryptorchidism was observed in one subject. Surgical correction of hypospadias was performed at a mean age of 22.1 months. Molecular analysis identified 12 different genetic variants, including two pathogenic mutations in the AMH (p.E389*) and SRD5A2 (p.R246Q) genes, found in subjects with hypospadias, respectively. However, only heterozygous mutations were detected. Conclusions This study did not identify a definitive genetic component contributing to the development of hypospadias; however, the findings suggest that intrauterine growth retardation may play a significant role.

Malnutrition and inflammation are related to high rates of morbidity and mortality in hemodialysis patients. Resistin is associated with nutrition and inflammation. We attempted to determine whether resistin levels may predict clinical outcomes in hemodialysis patients. We conducted a prospective evaluation of 100 outpatients on hemodialysis in a single dialysis center (male, 46%; mean age, 53.7 +/- 16.4 yr). We stratified the patients into 4 groups according to quartiles of serum resistin levels. During the 18-month observational period, patients with the lowest quartile of serum resistin levels had poor hospitalization-free survival (log rank test, P = 0.016). After adjustment of all co-variables, patients with the lowest quartile of serum resistin levels had poor hospitalization-free survival, compared with reference resistin levels. Higher levels of interleukin-6 were an independent predictor of poor hospitalization-free survival. In contrast, serum resistin levels were not correlated with interleukin-6 levels. The current data showed that low resistin levels may independently predict poor hospitalization free survival in hemodialysis patients.
Adult ; Aged ; Diabetes Complications ; Female ; Hospitalization ; Humans ; Interleukin-6/blood ; Kidney Failure, Chronic/blood/*mortality ; Male ; Middle Aged ; Proportional Hazards Models ; Prospective Studies ; *Renal Dialysis ; Resistin/*blood ; Survival Analysis

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a disorder which can be caused by treatment with a diverse collection of drugs, and it is characterized by fever, rash, lymphadenopathy, and internal organ involvement with eosinophilia. Although ethambutol and rifampin are popularly used to treat tuberculosis, there has been only one reported case of DRESS syndrome associated with ethambutol. DRESS syndrome associated with administration of rifampin have not been reported. In this report and discussion, we present the case of a patient suffering from DRESS syndrome induced by both ethambutol and rifampin.
Eosinophilia ; Ethambutol ; Exanthema ; Fever ; Humans ; Lymphatic Diseases ; Rifampin ; Stress, Psychological ; Tuberculosis

Background: Gene therapy shows the ability to restore neuronal dysfunction via therapeutic gene expression. The efficiency of gene expression and delivery to hypoxic injury sites is important for successful gene therapy. Therefore, we established a gene/stem cell therapy system using neuron-specific enolase promoter and induced neural stem cells in combination with valproic acid to increase therapeutic gene expression in hypoxic spinal cord injury. Methods: To examine the effect of combined method on enhancing gene expression, we compared neuronal cell-inducible luciferase levels under normoxia or hypoxia conditions in induced neural stem cells with valproic acid. Therapeutic gene, vascular endothelial growth factor, expression with combined method was investigated in hypoxic spinal cord injury model. We verified gene expression levels and the effect of different methods of valproic acid administration in vivo. Results: The results showed that neuron-specific enolase promoter enhanced gene expression levels in induced neural stem cells compared to Simian Virus 40 promoter under hypoxic conditions. Valproic acid treatment showed higher gene expression of neuron-specific enolase promoter than without treatment. In addition, gene expression levels and cell viability were different depending on the various concentration of valproic acid. The gene expression levels were increased significantly when valproic acid was directly injected with induced neural stem cells in vivo. Conclusion In this study, we demonstrated that the combination of neuron-specific enolase promoter and valproic acid induced gene overexpression in induced neural stem cells under hypoxic conditions and also in spinal cord injury depending on valproic acid administration in vivo. Combination of valproic acid and neuron-specific enolase promoter in induced neural stem cells could be an effective gene therapy system for hypoxic spinal cord injury.

Background: Gene therapy shows the ability to restore neuronal dysfunction via therapeutic gene expression. The efficiency of gene expression and delivery to hypoxic injury sites is important for successful gene therapy. Therefore, we established a gene/stem cell therapy system using neuron-specific enolase promoter and induced neural stem cells in combination with valproic acid to increase therapeutic gene expression in hypoxic spinal cord injury. Methods: To examine the effect of combined method on enhancing gene expression, we compared neuronal cell-inducible luciferase levels under normoxia or hypoxia conditions in induced neural stem cells with valproic acid. Therapeutic gene, vascular endothelial growth factor, expression with combined method was investigated in hypoxic spinal cord injury model. We verified gene expression levels and the effect of different methods of valproic acid administration in vivo. Results: The results showed that neuron-specific enolase promoter enhanced gene expression levels in induced neural stem cells compared to Simian Virus 40 promoter under hypoxic conditions. Valproic acid treatment showed higher gene expression of neuron-specific enolase promoter than without treatment. In addition, gene expression levels and cell viability were different depending on the various concentration of valproic acid. The gene expression levels were increased significantly when valproic acid was directly injected with induced neural stem cells in vivo. Conclusion In this study, we demonstrated that the combination of neuron-specific enolase promoter and valproic acid induced gene overexpression in induced neural stem cells under hypoxic conditions and also in spinal cord injury depending on valproic acid administration in vivo. Combination of valproic acid and neuron-specific enolase promoter in induced neural stem cells could be an effective gene therapy system for hypoxic spinal cord injury.

BACKGROUND: Autologous nerve grafts are the gold standard treatment for peripheral nerve injury treatment. However, this procedure cannot avoid sacrificing other nerves as a major limitation. The aim of the present study was to evaluate the potential of olfactory ensheathing cells (OECs) embedded in a nerve conduit. METHODS: A 10-mm segment of the sciatic nerve was resected in 21 rats, and the nerve injury was repaired with one of the following (n = 7 per group): autologous nerve graft, poly (ε-caprolactone) (PCL) conduit and OECs, and PCL conduit only. The consequent effect on nerve regeneration was measured based on the nerve conduction velocity (NCV), amplitude of the compound muscle action potential (ACMAP), wet muscle weight, histomorphometric analysis, and nerve density quantification. RESULTS: Histomorphometric analysis revealed nerve regeneration and angiogenesis in all groups. However, there were significant differences (p < 0.05) in the ACMAP nerve regeneration rate of the gastrocnemius and tibialis anterior muscles between the autologous graft (37.9 ± 14.3% and 39.1% ± 20.4%) and PCL only (17.8 ± 8.6% and 13.6 ± 5.8%) groups, and between the PCL only and PCL + OECs (46.3 ± 20.0% and 34.5 ± 14.6%) groups, with no differences between the autologous nerve and PCL + OEC groups (p > 0.05). No significant results in NCV, wet muscle weight, and nerve density quantification were observed among the 3 groups. CONCLUSION A PCL conduit with OECs enhances the regeneration of injured peripheral nerves, offering a good alternative to autologous nerve grafts.

BACKGROUND: Autologous nerve grafts are the gold standard treatment for peripheral nerve injury treatment. However, this procedure cannot avoid sacrificing other nerves as a major limitation. The aim of the present study was to evaluate the potential of olfactory ensheathing cells (OECs) embedded in a nerve conduit. METHODS: A 10-mm segment of the sciatic nerve was resected in 21 rats, and the nerve injury was repaired with one of the following (n = 7 per group): autologous nerve graft, poly (ε-caprolactone) (PCL) conduit and OECs, and PCL conduit only. The consequent effect on nerve regeneration was measured based on the nerve conduction velocity (NCV), amplitude of the compound muscle action potential (ACMAP), wet muscle weight, histomorphometric analysis, and nerve density quantification. RESULTS: Histomorphometric analysis revealed nerve regeneration and angiogenesis in all groups. However, there were significant differences (p < 0.05) in the ACMAP nerve regeneration rate of the gastrocnemius and tibialis anterior muscles between the autologous graft (37.9 ± 14.3% and 39.1% ± 20.4%) and PCL only (17.8 ± 8.6% and 13.6 ± 5.8%) groups, and between the PCL only and PCL + OECs (46.3 ± 20.0% and 34.5 ± 14.6%) groups, with no differences between the autologous nerve and PCL + OEC groups (p > 0.05). No significant results in NCV, wet muscle weight, and nerve density quantification were observed among the 3 groups. CONCLUSION A PCL conduit with OECs enhances the regeneration of injured peripheral nerves, offering a good alternative to autologous nerve grafts.