Fetal lower urinary tract obstruction (LUTO) is a congenital condition in which the bladder fails to excrete urine through the urethra. The primary goal of prenatal treatment for LUTO is the prevention of renal impairment and pulmonary hypoplasia. Vesico-amniotic shunt (VAS) has been the fetal intervention of choice; however, VAS has some limitations, including excretion of urine through an unphysiologic bypass and the need for postnatal corrective reoperation. In this study, we present a novel fetal intervention, a “retro-cystoscopic urethral approach,” performed on a male fetus at 20 weeks gestation diagnosed with enlarged bladder and bilateral hydronephrosis. This approach aims to dilate the narrowed urethra by inserting a urinary catheter using guidewire through a fetal cysto scope. The whole procedure was monitored under real-time ultrasonographic guidance. Despite prenatal intervention, the fetus required multiple cystocenteses, and the bladder dilation persisted.Postnatally, he was diagnosed with megacystis microcolon intestinal hypoperistalsis syndrome, a non-obstructive condition which is relatively rare in male infants. Our case emphasizes the compl exity of diagnosing LUTO during the prenatal period. Further studies exploring novel prenatal interven tions should pay more attention to candidate selection. Additionally, a thorough evaluation of organ systems beyond the urinary tract is necessary.

Fetal lower urinary tract obstruction (LUTO) is a congenital condition in which the bladder fails to excrete urine through the urethra. The primary goal of prenatal treatment for LUTO is the prevention of renal impairment and pulmonary hypoplasia. Vesico-amniotic shunt (VAS) has been the fetal intervention of choice; however, VAS has some limitations, including excretion of urine through an unphysiologic bypass and the need for postnatal corrective reoperation. In this study, we present a novel fetal intervention, a “retro-cystoscopic urethral approach,” performed on a male fetus at 20 weeks gestation diagnosed with enlarged bladder and bilateral hydronephrosis. This approach aims to dilate the narrowed urethra by inserting a urinary catheter using guidewire through a fetal cysto scope. The whole procedure was monitored under real-time ultrasonographic guidance. Despite prenatal intervention, the fetus required multiple cystocenteses, and the bladder dilation persisted.Postnatally, he was diagnosed with megacystis microcolon intestinal hypoperistalsis syndrome, a non-obstructive condition which is relatively rare in male infants. Our case emphasizes the compl exity of diagnosing LUTO during the prenatal period. Further studies exploring novel prenatal interven tions should pay more attention to candidate selection. Additionally, a thorough evaluation of organ systems beyond the urinary tract is necessary.

Fetal lower urinary tract obstruction (LUTO) is a congenital condition in which the bladder fails to excrete urine through the urethra. The primary goal of prenatal treatment for LUTO is the prevention of renal impairment and pulmonary hypoplasia. Vesico-amniotic shunt (VAS) has been the fetal intervention of choice; however, VAS has some limitations, including excretion of urine through an unphysiologic bypass and the need for postnatal corrective reoperation. In this study, we present a novel fetal intervention, a “retro-cystoscopic urethral approach,” performed on a male fetus at 20 weeks gestation diagnosed with enlarged bladder and bilateral hydronephrosis. This approach aims to dilate the narrowed urethra by inserting a urinary catheter using guidewire through a fetal cysto scope. The whole procedure was monitored under real-time ultrasonographic guidance. Despite prenatal intervention, the fetus required multiple cystocenteses, and the bladder dilation persisted.Postnatally, he was diagnosed with megacystis microcolon intestinal hypoperistalsis syndrome, a non-obstructive condition which is relatively rare in male infants. Our case emphasizes the compl exity of diagnosing LUTO during the prenatal period. Further studies exploring novel prenatal interven tions should pay more attention to candidate selection. Additionally, a thorough evaluation of organ systems beyond the urinary tract is necessary.

Fetal lower urinary tract obstruction (LUTO) is a congenital condition in which the bladder fails to excrete urine through the urethra. The primary goal of prenatal treatment for LUTO is the prevention of renal impairment and pulmonary hypoplasia. Vesico-amniotic shunt (VAS) has been the fetal intervention of choice; however, VAS has some limitations, including excretion of urine through an unphysiologic bypass and the need for postnatal corrective reoperation. In this study, we present a novel fetal intervention, a “retro-cystoscopic urethral approach,” performed on a male fetus at 20 weeks gestation diagnosed with enlarged bladder and bilateral hydronephrosis. This approach aims to dilate the narrowed urethra by inserting a urinary catheter using guidewire through a fetal cysto scope. The whole procedure was monitored under real-time ultrasonographic guidance. Despite prenatal intervention, the fetus required multiple cystocenteses, and the bladder dilation persisted.Postnatally, he was diagnosed with megacystis microcolon intestinal hypoperistalsis syndrome, a non-obstructive condition which is relatively rare in male infants. Our case emphasizes the compl exity of diagnosing LUTO during the prenatal period. Further studies exploring novel prenatal interven tions should pay more attention to candidate selection. Additionally, a thorough evaluation of organ systems beyond the urinary tract is necessary.

Fetal lower urinary tract obstruction (LUTO) is a congenital condition in which the bladder fails to excrete urine through the urethra. The primary goal of prenatal treatment for LUTO is the prevention of renal impairment and pulmonary hypoplasia. Vesico-amniotic shunt (VAS) has been the fetal intervention of choice; however, VAS has some limitations, including excretion of urine through an unphysiologic bypass and the need for postnatal corrective reoperation. In this study, we present a novel fetal intervention, a “retro-cystoscopic urethral approach,” performed on a male fetus at 20 weeks gestation diagnosed with enlarged bladder and bilateral hydronephrosis. This approach aims to dilate the narrowed urethra by inserting a urinary catheter using guidewire through a fetal cysto scope. The whole procedure was monitored under real-time ultrasonographic guidance. Despite prenatal intervention, the fetus required multiple cystocenteses, and the bladder dilation persisted.Postnatally, he was diagnosed with megacystis microcolon intestinal hypoperistalsis syndrome, a non-obstructive condition which is relatively rare in male infants. Our case emphasizes the compl exity of diagnosing LUTO during the prenatal period. Further studies exploring novel prenatal interven tions should pay more attention to candidate selection. Additionally, a thorough evaluation of organ systems beyond the urinary tract is necessary.

Background/Aims: We evaluated the clinical significance and prognostic power of functional luminal imaging probe (FLIP) panometry in patients with achalasia treated with peroral endoscopic myotomy (POEM), and examined the clinical parameters associated with symptomatic improvement and the presence of contractility (POC) following POEM. Methods: We reviewed the electronic medical records of patients with achalasia treated with FLIP panometry and POEM at a tertiary teaching hospital in Seoul, Republic of Korea. Follow-up examination was composed of esophageal manometry and questionnaires on symptoms. We analyzed the FLIP data by interpolating using the cubic spline method in MATLAB. Results: We retrospectively analyzed 33 men and 35 women (mean age: 52 ± 17 years), of whom 14, 39, and 15 patients were diagnosed with achalasia types I, II, and III, respectively. The FLIP panometry diagnoses were reduced esophagogastric junction opening (REO) with a retrograde contractile response (n = 43); REO with an absent contractile response (n = 5); REO with a normal contractile response (n = 11); and a retrograde contractile response (n = 9). Overall, the patients showed improvements in Eckardt scores following POEM from 6.48 ± 2.20 to 1.16 ± 1.15 (P < 0.01). Post-POEM symptomatic improvement was not significantly associated with any of the clinical parameters, including panometry diagnosis. Conversely, post-POEM POC was significantly associated with the presence of repetitive antegrade contractions and achalasia subtypes (both P < 0.01). Conclusion While FLIP panometry was not significantly associated with the clinical course of achalasia, FLIP panometry was associated with POC following POEM and may complement manometry in the functional evaluation of esophageal motility disorders.

In a search for effective PPAR-γ agonists, 110 clinical drugs were screened via molecular docking, and 9 drugs, including parecoxib, were selected for subsequent biological evaluation. Molecular docking of parecoxib to the ligand-binding domain of PPAR-γ showed high binding affinity and relevant binding conformation compared with the PPAR-γ ligand/antidiabetic drug rosiglitazone. Per the docking result, parecoxib showed the best PPAR-γ transactivation in Ac2F rat liver cells. Further docking simulation and a luciferase assay suggested parecoxib would be a selective (and partial) PPAR-γ agonist. PPAR-γ activation by parecoxib induced adipocyte differentiation in 3T3-L1 murine preadipocytes. Parecoxib promoted adipogenesis in a dose-dependent manner and enhanced the expression of adipogenesis transcription factors PPAR-γ, C/EBPα, and C/EBPβ. These data indicated that parecoxib might be utilized as a partial PPAR-γ agonist for drug repositioning study.

In a search for effective PPAR-γ agonists, 110 clinical drugs were screened via molecular docking, and 9 drugs, including parecoxib, were selected for subsequent biological evaluation. Molecular docking of parecoxib to the ligand-binding domain of PPAR-γ showed high binding affinity and relevant binding conformation compared with the PPAR-γ ligand/antidiabetic drug rosiglitazone. Per the docking result, parecoxib showed the best PPAR-γ transactivation in Ac2F rat liver cells. Further docking simulation and a luciferase assay suggested parecoxib would be a selective (and partial) PPAR-γ agonist. PPAR-γ activation by parecoxib induced adipocyte differentiation in 3T3-L1 murine preadipocytes. Parecoxib promoted adipogenesis in a dose-dependent manner and enhanced the expression of adipogenesis transcription factors PPAR-γ, C/EBPα, and C/EBPβ. These data indicated that parecoxib might be utilized as a partial PPAR-γ agonist for drug repositioning study.

Alzheimer's Disease (AD) is a progressive neurodegenerative disease, which is pathologically defined by the accumulation of amyloid plaques and hyper-phosphorylated tau aggregates in the brain. Mitochondrial dysfunction is also a prominent feature in AD, and the extracellular Aβ and phosphorylated tau result in the impaired mitochondrial dynamics. In this study, we generated an induced pluripotent stem cell (iPSC) line from an AD patient with amyloid precursor protein (APP) mutation (Val715Met; APP-V715M) for the first time. We demonstrated that both extracellular and intracellular levels of Aβ were dramatically increased in the APP-V715M iPSC-derived neurons. Furthermore, the APP-V715M iPSC-derived neurons exhibited high expression levels of phosphorylated tau (AT8), which was also detected in the soma and neurites by immunocytochemistry. We next investigated mitochondrial dynamics in the iPSC-derived neurons using Mito-tracker, which showed a significant decrease of anterograde and retrograde velocity in the APP-V715M iPSC-derived neurons. We also found that as the Aβ and tau pathology accumulates, fusion-related protein Mfn1 was decreased, whereas fission-related protein DRP1 was increased in the APP-V715M iPSC-derived neurons, compared with the control group. Taken together, we established the first iPSC line derived from an AD patient carrying APP-V715M mutation and showed that this iPSC-derived neurons exhibited typical AD pathological features, including a distinct mitochondrial dysfunction.
Alzheimer Disease ; Amyloid ; Brain ; Carisoprodol ; Humans ; Immunohistochemistry ; Mitochondrial Dynamics ; Neurites ; Neurodegenerative Diseases ; Neurons ; Pathology ; Plaque, Amyloid ; Pluripotent Stem Cells

PURPOSE: Many recent studies have reported that successful percutaneous coronary intervention (PCI) with drug-eluting stents (DESs) for chronic total occlusion (CTO) has more beneficial effects than failed CTO-PCI; however, there are only limited data available from comparisons of successful CTO-PCI with medical therapy (MT) in the Korean population. MATERIALS AND METHODS: A total of 840 consecutive CTO patients who underwent diagnostic coronary angiography, receiving either PCI with DESs or MT, were enrolled. Patients were divided into two groups according to the treatment assigned. To adjust for potential confounders, propensity score matching (PSM) analysis was performed using logistic regression. Individual major clinical outcomes and major adverse cardiac events, a composite of total death, myocardial infarction (MI), stroke, and revascularization, were compared between the two groups up to 5 years. RESULTS: After PSM, two propensity-matched groups (265 pairs, n=530) were generated, and the baseline characteristics were balanced. Although the PCI group showed a higher incidence of target lesion and vessel revascularization on CTO, the incidence of MI tended to be lower [hazard ratio (HR): 0.339, 95% confidence interval (CI): 0.110 to 1.043, p=0.059] and the composite of total death or MI was lower (HR: 0.454, 95% CI: 0.224 to 0.919, p=0.028), compared with the MT group up to 5 years. CONCLUSION: In this study, successful CTO PCI with DESs was associated with a higher risk of repeat PCI for the target vessel, but showed a reduced incidence of death or MI.
Coronary Angiography ; Drug-Eluting Stents* ; Humans ; Incidence ; Logistic Models ; Myocardial Infarction ; Percutaneous Coronary Intervention* ; Propensity Score ; Stroke