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Abstract Interstitial cystitis/bladder pain syndrome (IC/BPS) is an intractable disease characterized by severe pelvic pain and urinary frequency. Mesenchymal stem cell (MSC) therapy is a promising approach to treat incurable IC/BPS. Here, we show greater therapeutic efficacy of human embryonic stem cell (hESC)-derived multipotent stem cells (M-MSCs) than adult bone-marrow (BM)-derived counterparts for treating IC/BPS and also monitor long-term safety and in vivo properties of transplanted M-MSCs in living animals. Controlled hESC differentiation and isolation procedures resulted in pure M-MSCs displaying typical MSC behavior. In a hydrochloric-acid instillation-induced IC/BPS animal model, a single local injection of M-MSCs ameliorated bladder symptoms of IC/BPS with superior efficacy compared to BM-derived MSCs in ameliorating bladder voiding function and histological injuries including urothelium denudation, mast-cell infiltration, tissue fibrosis, apoptosis, and visceral hypersensitivity. Little adverse outcomes such as abnormal growth, tumorigenesis, or immune-mediated transplant rejection were observed over 12-months post-injection. Intravital confocal fluorescence imaging tracked the persistence of the transplanted cells over 6-months in living animals. The infused M-MSCs differentiated into multiple cell types and gradually integrated into vascular-like structures. The present study provides the first evidence for improved therapeutic efficacy, long-term safety, and in vivo distribution and cellular properties of hESC derivatives in preclinical models of IC/BPS.

Purpose To evaluate the therapeutic effect of human embryonic stem cell (hESC)-derived multipotent mesenchymal stem cells (M-MSCs) on ketamine-induced cystitis (KC) in rats. Methods To induce KC, 10-week-old female rats were injected with 25-mg/kg ketamine hydrochloride twice weekly for 12 weeks. In the sham group, phosphate buffered saline (PBS) was injected instead of ketamine. One week after the final injection of ketamine, the indicated doses (0.25, 0.5, and 1×106 cells) of M-MSCs (KC+M-MSC group) or PBS vehicle (KC group) were directly injected into the bladder wall. One week after M-MSC injection, the therapeutic outcomes were evaluated via cystometry, histological analyses, and measurement of gene expression. Next, we compared the efficacy of M-MSCs at a low dose (1×105 cells) to that of an identical dose of adult bone marrow (BM)-derived MSCs. Results Rats in the KC group exhibited increased voiding frequency and reduced bladder capacity compared to rats of the sham group. However, these parameters recovered after transplantation of M-MSCs at all doses tested. KC bladders exhibited markedly increased mast cell infiltration, apoptosis, and tissue fibrosis. Administration of M-MSCs significantly reversed these characteristic histological alterations. Gene expression analyses indicated that several genes associated with tissue fibrosis were markedly upregulated in KC bladders. However the expression of these genes was significantly suppressed by the administration of M-MSCs. Importantly, M-MSCs ameliorated bladder deterioration in KC rats after injection of a low dose (1×105) of cells, at which point BM-derived MSCs did not substantially improve bladder function. Conclusions This study demonstrates for the first time the therapeutic efficacy of hESC-derived M-MSCs on KC in rats. M-MSCs restored bladder function more effectively than did BM-derived MSCs, protecting against abnormal changes including mast cell infiltration, apoptosis and fibrotic damage.

BackgroundMetformin is considered the first choice oral treatment for type 2 diabetes patients in the absence of contraindications. Rarely, life-threatening complications associated with metformin treatment are seen in some patients with underlying diseases. The aim of this study was to further investigate the clinical profiles and risk factors for metformin-associated lactic acidosis (MALA) and the treatment modalities according to survival.MethodsTo identify MALA, we performed a retrospective study in seven diabetic patients who were taking metformin and had been diagnosed with lactic acidosis at Inha University Hospital between 1995 and 2012. For each patient, we recorded the age, sex, daily metformin dosage, laboratory test results, admission diagnosis, and risk factors. Also, concurrent conditions, treatment modalities, and outcomes were evaluated.ResultsSix patients had risk factors for lactic acidosis before admission. All patients had renal impairment on admission as a precipitating risk factor. Five patients survived and two patients died despite early renal replacement therapy. Older patients tended to have a poorer prognosis.ConclusionRenal function must be monitored in elderly type 2 diabetes mellitus patients with underlying diseases and conditions causing renal impairment who begin metformin treatment. Accurate recognition of MALA and initiation of renal replacement are essential for treatment.

Phlegmonous esophagogastritis is a rare bacterial infection that has been reported to result in mortality. The pathophysiology of phlegmonous gastrointestinal infection is unclear, but some predisposing factors are reported. Those include immunocompromised status, alcohol abuse, malignancy and uncontrolled diabetes mellitus. We report two cases of phlegmonous esophagogastritis with newly diagnosed diabetes mellitus. A 26-year-old woman and a 56-year-old woman individually visited our hospital for sore throat, neck pain and fever. The laboratory findings of both patients demonstrated leukocytosis, and elevated serum glucose levels. HbA1c of both patients was above 11%. Enhanced computed tomography of young woman showed submucosal edema with intramural abscess along the esophagus and stomach, and that of older woman showed the same defined to esophagus. In both cases, empirical antibiotic therapy with intravenous third generation cephalosporin and metronidazole were started. Later, we identified Klebsiella pneumonia through pus culture in both cases. The symptoms of case 1 improved with conservative management with antibiotics only. However, case 2 required surgical drainage and esophagectomy. Early radiologic diagnosis of this disease and accurate identification of pathogens are important factors for good prognosis. Therefore, we emphasize suspicion of such a rare disease is needed, especially when the patient has risk factors such as diabetes mellitus. [ABSTRACT FROM AUTHOR]

Paraganglioma is a tumor originating from the extra adrenal chromaffin cells, and functional paraganglioma causes paroxysmal hypertension, headache and tachycardia, due to excess excretion of catecholamine. However, rarely, ARDS, acute myocardial infarction, heart failure, arrhythmia, and pulmonary edema are also seen in patients with paraganglioma and clinical manifestations are depending on the patient's intravascular volume status. Seventy one years old male was presented with hypotension and pulmonary edema after intravenous midazolam injection during colonoscopy under conscious sedation. The patient was initially suspected with anaphylactic shock, due to midazolam injection. However, later, he was diagnosed with paraganglioma, and blood pressure was successfully controlled with alpha adrenergic blockade. We suggest that when we encounter heart failure, pulmonary edema and shock of unknown origin, pheochromocytoma must be taken into consideration. [ABSTRACT FROM AUTHOR]

To better prepare themselves for authentic teaching situations, pre- and in-service teachers should become familiarized with the application of curriculum-development theory in their training programs. The authors will detail how they have become more prepared to face the challenges of course development by outlining their own experience designing a curriculum for an English for Art Purposes course for a leading art school. Being inexperienced teachers themselves and outsiders to curriculum design, the authors outline and share what they learned about creating materials, tasks, and assessment instruments that not only addressed the specific needs and interests of the students, which differ from those of other academic disciplines, but also fulfilled the educational objectives of the art institution itself. Involving preservice teachers in curriculum design will help them to internalize second language teaching theory and have a deeper connection to their own curricula. The authors believe that it is through this curriculum-development process that teachers can experience professional growth and empowerment. [ABSTRACT FROM AUTHOR]