Novel KRIT1/CCM1 mutation in a patient with retinal cavernous hemangioma and cerebral cavernous malformation

Retinal cavernous hemangiomas are rare vascular anomalies, and can be associated with cerebral cavernous malformations (CCM). Distinct mutations have been reported in patients who have both CCMs and retinal cavernous hemangiomas. Fluorescein angiography, spectral domain optical coherence tomography, and genetic testing were performed on a patient with a retinal cavernous hemangioma and a CCM. Our patient was heterozygous in the KRIT1/CCM1 gene for a frameshift mutation, c.1088delC. This would be predicted to result in premature protein termination. We have identified a novel mutation in the KRIT1/CCM1 gene in a patient with both CCM and retinal cavernous hemangioma. We hypothesize that the occurrence of retinal cavernous hemangiomas and CCMs is underlaid by a common mechanism present in the KRIT1/CCM1 gene

Inhibition of Atrogin-1/MAFbx Mediated MyoD Proteolysis Prevents Skeletal Muscle Atrophy In Vivo

Ubiquitin ligase Atrogin1/Muscle Atrophy F-box (MAFbx) up-regulation is required for skeletal muscle atrophy but substrates and function during the atrophic process are poorly known. The transcription factor MyoD controls myogenic stem cell function and differentiation, and seems necessary to maintain the differentiated phenotype of adult fast skeletal muscle fibres. We previously showed that MAFbx mediates MyoD proteolysis in vitro. Here we present evidence that MAFbx targets MyoD for degradation in several models of skeletal muscle atrophy. In cultured myotubes undergoing atrophy, MAFbx expression increases, leading to a cytoplasmic-nuclear shuttling of MAFbx and a selective suppression of MyoD. Conversely, transfection of myotubes with sh-RNA-mediated MAFbx gene silencing (shRNAi) inhibited MyoD proteolysis linked to atrophy. Furthermore, overexpression of a mutant MyoDK133R lacking MAFbx-mediated ubiquitination prevents atrophy of mouse primary myotubes and skeletal muscle fibres in vivo. Regarding the complex role of MyoD in adult skeletal muscle plasticity and homeostasis, its rapid suppression by MAFbx seems to be a major event leading to skeletal muscle wasting. Our results point out MyoD as the second MAFbx skeletal muscle target by which powerful therapies could be developed

Barriers to successful recruitment of parents of overweight children for an obesity prevention intervention: a qualitative study among youth health care professionals

BACKGROUND: The recruitment of participants for childhood overweight and obesity prevention interventions can be challenging. The goal of this study was to identify barriers that Dutch youth health care (YHC) professionals perceive when referring parents of overweight children to an obesity prevention intervention. METHODS: Sixteen YHC professionals (nurses, physicians and management staff) from eleven child health clinics participated in semi-structured interviews. An intervention implementation model was used as the framework for conducting, analyzing and interpreting the interviews. RESULTS: All YHC professionals were concerned about childhood obesity and perceived prevention of overweight and obesity as an important task of the YHC organization. In terms of frequency and perceived impact, the most important impeding factors for referring parents of overweight children to an intervention were denial of the overweight problem by parents and their resistance towards discussing weight issues. A few YHC professionals indicated that their communication skills in discussing weight issues could be improved, and some professionals mentioned that they had low self-efficacy in raising this topic. CONCLUSIONS: We consider it important that YHC professionals receive more training to increase their self-efficacy and skills in motivating parents of overweight children to participate in obesity prevention interventions. Furthermore, parental awareness towards their child’s overweight should be addressed in future studies

Optic Nerve Sheath Fenestration in Cancer Patients: Indications and Surgical Technique

Optic nerve sheath fenestration (ONSF) entails cutting a window or making linear fenestrations in the retrobulbar optic nerve sheath, which releases pressure and often allows stabilization or improvement of vision. Indications for ONSF include visual loss due to pseudotumor cerebri, optic nerve sheath hemorrhage, dural sinus thrombosis, subdural hematoma, intradural arteriovenous malformation, arachnoiditis with increased intracranial pressure, and cryptococcal meningitis with papilledema due to AIDS. Indications for ONSF in cancer patients are not well established, but a few case reports have shown success of ONSF in patients with perineural metastasis of breast cancer, increased intracranial pressure with papilledema due to a brain tumor, lymphomatous infiltration of the optic nerve, and optic nerve sheath meningioma. ONSF can be performed with a medial orbitotomy approach with disinsertion of the medial rectus muscle, a superomedial eyelid crease incision without extraocular muscle disinsertion, a lateral orbitotomy approach with bone removal, or a lateral canthotomy incision without bone removal. ONSF is considered relatively safe when performed carefully; serious complications occur in about 1% of patients