Hereditary epidermolysis bullosa: clinical-epidemiological profile of 278 patients at a tertiary hospital in São Paulo, Brazil.

Background: Epidermolysis bullosa (EB) is a group of rare hereditary diseases, characterized by fragility of the skin and mucous membranes. Epidemiological data on EB in Brazil are scarce.

Objectives: To describe epidemiological aspects of patients with EB diagnosed in the Dermatology Department of a tertiary hospital, from 2000 to 2022.

Association between frailty and clinical outcomes in patients undergoing craniotomy-systematic review and meta-analysis of observational studies.

Background: Frailty in patients undergoing craniotomy may affect perioperative outcomes. There have been a number of studies published in this field; however, evidence is yet to be summarized in a quantitative review format. We conducted a systematic review and meta-analysis to examine the effects of frailty on perioperative outcomes in patients undergoing craniotomy surgery.

Factors Influencing Acceptance of Grasshoppers and Other Insects as Food: A Comparison between Two Cities in Malaysia.

Entomophagy has recently sparked widespread attention worldwide. Although entomophagy is not a foreign dietary practice in Malaysia, acceptance of insects as food among Malaysians is still unclear. This study aimed to determine the acceptance of insects as food and its influencing factors among adults living in Klang Valley (Peninsular Malaysia) and Kuching, Sarawak (East Malaysia).

Load-induced regulation of tendon homeostasis by SPARC, a genetic predisposition factor for tendon and ligament injuries.

Tendons and tendon interfaces have a very limited regenerative capacity, rendering their injuries clinically challenging to resolve. Tendons sense muscle-mediated load; however, our knowledge on how loading affects tendon structure and functional adaption remains fragmentary. Here, we provide evidence that the matricellular protein secreted protein acidic and rich in cysteine (SPARC) is critically involved in the mechanobiology of tendons and is required for tissue maturation, homeostasis, and enthesis development.

Persistent hiccups and Horner's syndrome in a case of primary CNS lymphoma with diffuse cerebral, hypothalamic and lateral brainstem involvement - An exercise in clinical neuroanatomy.

We present a case of a 42-year-old male presenting with persistent hiccups and a Horner's syndrome, among other symptoms and signs of hypothalamic and brainstem dysfunction. He had a biopsy-proven diffuse infiltrative large primary CNS B-cell lymphoma involving the left fronto-temporal hemisphere, diencephalon and brainstem. The aim of this case report is to highlight key clinical and neuro-anatomical correlations that bring light to the art of the clinical examination.

Effect of the Presence and Type of Plate Augmentation on Postoperative Dysphagia Among Adult Patients Undergoing Elective Anterior Cervical Discectomy and Fusion for Spondylosis: A Randomized Trial.

Objective: To determine the effect of anterior plating on postoperative dysphagia (POD) among adult patients undergoing elective anterior cervical discectomy and fusion (ACDF) for cervical spondylosis and determine the potential role of demographic and clinical characteristics in the development of POD.

Methods: Consecutive adults undergoing an elective, single-level, ACDF were randomly assigned to receive a stand-alone CoRoent Cage or a CoRoent Cage with a Helix, or HelixMini plate. Patients with a history of cervical spine surgery were excluded.

Saprochaete Capitata Infection in an 80-Year Old Chronic Obstructive Pulmonary Disease (COPD) Patient: A Case Report.

Background: The fungal disease caused by invasive fungus Saprochaete capitata is becoming an increasingly popular infection. Fungal pathogens mainly occur in patients with immunocompromised disorders such as hematologic malignancies, acute myeloid leukemia, transplant patients.

Case Report: In this study, we presented a COPD patient infected with S.

Bullous Keratopathy Secondary to Anterior Chamber Angle Foreign Body.

Background: Penetrating ocular trauma with intraocular foreign body is a serious injury often resulting in loss of vision. Anterior chamber foreign bodies account for a considerable portion of all cases of all intraocular foreign bodies (up to 15%); however, they can be missed due to inconspicuous location.

Case Report: We report two cases of retained intraocular foreign bodies in the iridocorneal angle that was missed at the first ophthalmic examination.

Accuracy of K-Wireless Insertion of Percutaneous Pedicle Screws Using Computer-Assisted Spinal Navigation: A Systematic Review and Single-Center Experience.

Objective: This study sought to 1) describe the use K-wireless pedicle screw insertion among adults (age ≥18 years) undergoing a minimally invasive fusion and 2) perform a systematic review (SR) of all studies that describe a navigated, K-wireless technique with 3-dimensional fluoroscopy.

Methods: Patients undergoing a minimally invasive fusion requiring pedicle screw fixation for any indication were prospectively enrolled in the observational component of this study. An assessment of pedicle breach was performed independently and in duplicate based on a modification of the Belmont grading scale.

A feasibility study of the Nativis Voyager device in patients with recurrent glioblastoma in Australia.

Aim: Evaluation of the Nativis Voyager, an investigational medical device, as monotherapy for recurrent glioblastoma (rGBM).

Materials & Methods: A total of 15 patients with rGBM were treated with one of two Voyager ultra-low radio frequency energy cognates: A1A or A2HU. Safety and clinical utility were assessed every 2-4 months.

3D uniaxial mechanical stimulation induces tenogenic differentiation of tendon-derived stem cells through a PI3K/AKT signaling pathway.

The tendon is a mechanosensitive tissue, but little is known about how mechanical stimulation selectively signals tenogenic differentiation and neo-tendon formation. In this study, we compared the impact of uniaxial and biaxial mechanical loading on tendon-derived stem cells (TDSCs). Our data show that there are variations in cell signaling and cell differentiation of mouse TDSCs in response to uniaxial and biaxial loading in monolayer culture.

Minimally Invasive Direct Lateral Corpectomy of the Thoracolumbar Spine for Metastatic Spinal Cord Compression.

 To evaluate the feasibility, safety, clinical, and radiologic outcomes of a minimally invasive direct lateral-approach corpectomy (MIDLaC) for decompression and stabilization of symptomatic metastatic spinal cord compression (MSCC).  A retrospective study on a prospective cohort was conducted. Nineteen patients were consecutively treated with MIDLaC and posterior pedicle screw fixation between May 2012 and July 2014.

Cyclic mechanical stimulation rescues achilles tendon from degeneration in a bioreactor system.

Physiotherapy is one of the effective treatments for tendinopathy, whereby symptoms are relieved by changing the biomechanical environment of the pathological tendon. However, the underlying mechanism remains unclear. In this study, we first established a model of progressive tendinopathy-like degeneration in the rabbit Achilles.

Loss of c-Cbl E3 ubiquitin ligase activity enhances the development of myeloid leukemia in FLT3-ITD mutant mice.

Mutations in the Fms-like tyrosine kinase 3 (FLT3) receptor tyrosine kinase (RTK) occur frequently in acute myeloid leukemia (AML), with the most common involving internal tandem duplication (ITD) within the juxtamembrane domain. Fms-like tyrosine kinase 3-ITD mutations result in a mislocalized and constitutively activated receptor, which aberrantly phosphorylates signal transducer and activator of transcription 5 (STAT5) and upregulates the expression of its target genes. c-Cbl is an E3 ubiquitin ligase that negatively regulates RTKs, including FLT3, but whether it can downregulate mislocalized FLT3-ITD remains to be resolved.

Dasatinib targets B-lineage cells but does not provide an effective therapy for myeloproliferative disease in c-Cbl RING finger mutant mice.

This study aimed to determine whether the multi-kinase inhibitor dasatinib would provide an effective therapy for myeloproliferative diseases (MPDs) involving c-Cbl mutations. These mutations, which occur in the RING finger and linker domains, abolish the ability of c-Cbl to function as an E3 ubiquitin ligase and downregulate activated protein tyrosine kinases. Here we analyzed the effects of dasatinib in a c-Cbl RING finger mutant mouse that develops an MPD with a phenotype similar to the human MPDs.

A rare cause of postoperative paraplegia in minimally invasive spine surgery.

Study Design: A case report.

Objective: To present a patient who underwent a minimally invasive transforaminal lumbar interbody fusion who postoperatively developed paraplegia as a rare complication of a Kirschner wire (K-wire).

Summary Of Background Data: The few complications of K-wires that have been reported include, dural tears and damage to intra-abdominal structures.

Flt3 inhibitor AC220 is a potent therapy in a mouse model of myeloproliferative disease driven by enhanced wild-type Flt3 signaling.

High levels of expression of wild-type Flt3 characterize many hematopoietic proliferative diseases and neoplasms, providing a potential therapeutic target. Using the c-Cbl RING finger mutant mouse as a model of a myeloproliferative disease (MPD) driven by wild-type Flt3, in the present study, we show that treatment with the Flt3 kinase inhibitor AC220 blocks MPD development by targeting Flt3(+) multipotent progenitors (MPPs). We found that daily administration of AC220 caused a marked reduction in Flt3 expression, induction of quiescence, and a significant loss of MPPs within 4 days.

Incidence of c-Cbl mutations in human acute myeloid leukaemias in an Australian patient cohort.

Aim: The aim of this study was to investigate the incidence and characteristics of c-Cbl mutations in acute myeloid leukaemias (AMLs) from an Australian patient cohort. Two initial studies examining c-Cbl mutations in AML, one from Germany and one from the US, found vastly different incidences of mutations (0.6% compared to 33%, respectively).

Essential role of E3 ubiquitin ligase activity in Cbl-b-regulated T cell functions.

E3 ubiquitin ligases have been placed among the essential molecules involved in the regulation of T cell functions and T cell tolerance. However, it has never been experimentally proven in vivo whether these functions indeed depend on the catalytic E3 ligase activity. The Casitas B-cell lymphoma (Cbl) family protein Cbl-b was the first E3 ubiquitin ligase directly implicated in the activation and tolerance of the peripheral T cell.

Visualizing the role of Cbl-b in control of islet-reactive CD4 T cells and susceptibility to type 1 diabetes.

The E3 ubiquitin ligase Cbl-b regulates T cell activation thresholds and has been associated with protecting against type 1 diabetes, but its in vivo role in the process of self-tolerance has not been examined at the level of potentially autoaggressive CD4(+) T cells. In this study, we visualize the consequences of Cbl-b deficiency on self-tolerance to lysozyme Ag expressed in transgenic mice under control of the insulin promoter (insHEL). By tracing the fate of pancreatic islet-reactive CD4(+) T cells in prediabetic 3A9-TCR × insHEL double-transgenic mice, we find that Cbl-b deficiency contrasts with AIRE or IL-2 deficiency, because it does not affect thymic negative selection of islet-reactive CD4(+) cells or the numbers of islet-specific CD4(+) or CD4(+)Foxp3(+) T cells in the periphery, although it decreased differentiation of inducible regulatory T cells from TGF-β-treated 3A9-TCR cells in vitro.

Myeloid leukemia development in c-Cbl RING finger mutant mice is dependent on FLT3 signaling.

Although myeloid leukemias are primarily caused by leukemic stem cells, the molecular basis of their transformation remains largely unknown. Here, by analyzing mice with a mutation in the RING finger domain of c-Cbl, we show that the E3 ubiquitin ligase activity of c-Cbl is required to restrict myeloid leukemia development. These mice develop a myeloproliferative disease which progresses to leukemia and involves hematopoietic progenitors that exhibit augmented FLT3 signaling.

c-Cbl promotes T cell receptor-induced thymocyte apoptosis by activating the phosphatidylinositol 3-kinase/Akt pathway.

The ability of thymocytes to assess T cell receptor (TCR) signaling strength and initiate the appropriate downstream response is crucial for determining their fate. We have previously shown that a c-Cbl RING finger mutant knock-in mouse, in which the E3 ubiquitin ligase activity of c-Cbl is inactivated, is highly sensitive to TCR-induced death signals that cause thymic deletion. This high intensity signal involves the enhanced tyrosine phosphorylation of the mutant c-Cbl protein promoting a marked increase in the activation of Akt.