Insights into the pathogenesis of ATP1A1‐related CMT disease using patient‐specific iPSCs

The development of patient‐specific induced pluripotent stem cells (iPSCs) offered interesting insights in modeling the pathogenesis of Charcot‐Marie‐Tooth (CMT) disease and thus we decided to explore the phenotypes of iPSCs derived from a single CMT patient carrying a mutant ATP1A1 allele (p.Pro600Ala). iPSCs clones generated from CMT and control fibroblasts, were induced to differentiate into neural precursors and then into post‐mitotic neurons. Control iPSCs differentiated into neuronal precursors and then into post‐mitotic neurons within 6‐8 days. On the contrary, the differentiation of CMT iPSCs was clearly defective. Electrophysiological properties confirmed that post‐mitotic neurons were less mature compared to the normal counterpart. The impairment of in vitro differentiation of CMT iPSCs only concerned with the neuronal pathway, because they were able to differentiate into mesendodermal cells and other ectodermal derivatives. ATP1A1 was undetectable in the few neuronal cells derived from CMT iPSCs. ATP1A1 gene mutation (p.Pro600Ala), responsible for a form of axonal CMT disease, is associated in vitro with a dramatic alteration of the differentiation of patient‐derived iPSCs into post‐mitotic neurons. Thus, the defect in neuronal cell development might lead in vivo to a decreased number of mature neurons in ATP1A1‐CMT disease.     

Copanlisib for the treatment of adults with relapsed follicular lymphoma

ABSTRACT

Introduction

Follicular lymphoma (FL) is the second most common histotype of lymphoma and is considered an incurable disease. The need for new treatment options has led to the development of innovative targeted agents, including inhibitors of the phosphatidylinositol-3-kinase (PI3K) pathway.     

TLR2 activation in corneal stromal cells by Staphylococcus aureus‐induced keratitis

The Toll‐Like Receptor 2 (TLR2) plays an active and important role in Staphylococcus aureus‐induced chronic ocular inflammation. The aim of this study was to investigate the expression and function of TLR2 of corneal stromal cells in ex vivo rabbit model of S. aureus keratitis. Corneal buttons with sclera rims placed in an ex vivo air‐interface organ culture were assigned to two groups: corneas with epithelial and stromal abrasions. Each group was then divided into two sub‐groups exposed to UV‐killed S. aureus ATCC 6538P and S. aureus ATCC 29213, respectively. TLR2 and IL‐8 mRNA expressions were analyzed by quantitative real‐time RT‐PCR. TLR2 localization was visualized by immunofluorescence analysis. The results demonstrated that TLR2 and IL‐8 mRNA were significantly expressed in the stromal cells of the groups exposed to S. aureus strains. Moreover, it has been demonstrated that, after corneal injury, keratocytes differentiated into myofibroblasts became able to express TLR2 only when exposed to S. aureus. Identification of mechanisms regulation of corneal TLRs may lead to development of therapeutic interventions aimed at controlling corneal inflammation. This ex vivo model can be used to clarify the molecular events of bacterial‐corneal tissue interactions and their inflammatory consequences.     

Follow-Up Study of Over Three Years of Patients with Uveitis after Cataract Phacoemulsification: Outcomes and Complications

Purpose: To evaluate the rate and onset of intraoperative and postoperative complications post-phacoemulsification. Methods: One hundred sixty-two eyes of 145 patients with uveitis who underwent phacoemulsification between 2006 and 2009 were identified through surgical record review. Fifty-nine eyes of 46 patients met the inclusion criteria. Hazard ratio (HR) and Kaplan-Meier survival probability were calculated for each class of uveitis. Results: Macular edema (ME) resulted to be associated to chronic postoperative inflammation (r?=?0.6; p?=?0.00) and mostly related to patients who presented more than one postoperative relapse/year (r?=?0.2; p?=?0.02). Fuchs uveitis resulted to be a risk factor for posterior capsule opacification (PCO) (HR 3.36 IC95%1.0-10.5; p?=?0.03). Hypotony and elevated intraocular pressure (IOP) were detected in the anterior uveitis group (0.02 EY). Conclusion: The HR to develop ME was significantly related to chronic anterior uveitis. PCO and elevated IOP are most frequent in Fuchs uveitis. The postoperative visual acuity result was good among all the uveitis groups.     

Rituximab or Cyclophosphamide in the Treatment of Membranous Nephropathy: The RI-CYCLO Randomized Trial

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Necrotic lesions of the oral cavity in chronic leukemia. Treatment with CO2 laser

The main characteristics of oral necrotic lesions in leukemia and the treatment and consequence of these pathologies are described. These lesions are classified as noma-like lesions, necrotic gangrenous ulcers of the oral cavity mucosa appearing in severe organic diseases. A new therapeutical approach in the treatment of oral necrotic lesions in chronic leukemia by the use of CO2 laser is tried and a case with the results obtained is presented.     

Bone resorption around dental implants placed in grafted sinuses: clinical and radiologic follow-up after up to 4 years

PURPOSE: The long-term results of endosseous implants depend on the maintenance of bone support. The aim of this study was to evaluate radiologically bone resorption around dental implants placed in grafted sinuses after up to 4 years of function. MATERIALS AND METHODS: Between 1997 and 2001, augmentation of the maxillary sinus floor with alloplastic (Biostite) or xenogenic (Bio-Oss) materials was performed in 34 patients. RESULTS: Eighteen patients participated in the study. Twenty-six sinus augmentations were performed on these 18 patients, and they received 37 implants. The change in marginal bone level around the implants at the mesial side was 1 mm during the first year after the abutment connection, followed by an annual loss of 0.1 mm. The change in marginal bone level around the implants at the distal side was 1.1 mm during the first year after the abutment connection followed by an annual loss of 0.2 mm. DISCUSSION: The implant survival rate observed in this study is in line with data previously reported for patients treated with implants in the posterior maxilla without bone atrophy. The results for implants placed into sinuses grafted with Bio-Oss were similar to the results for implants placed in sinuses grafted with Biostite. CONCLUSION: Although this study involved a limited number of procedures, it confirmed that alloplastic and xenogenic materials can be reliable for bone regeneration in subantral cavities. The angular defects present both at the distal and mesial sides of the implants were comparable to those observed at implants placed in native bone.