Nonsense mutation-associated Becker muscular dystrophy: interplay between exon definition and splicing regulatory elements within the DMD gene

Nonsense mutations are usually predicted to function as null alleles due to premature termination of protein translation. However, nonsense mutations in the DMD gene, encoding the dystrophin protein, have been associated with both the severe Duchenne Muscular Dystrophy (DMD) and milder Becker Muscular Dystrophy (BMD) phenotypes. In a large survey, we identified 243 unique nonsense mutations in the DMD gene, and for 210 of these we could establish definitive phenotypes. We analyzed the reading frame predicted by exons flanking those in which nonsense mutations were found, and present evidence that nonsense mutations resulting in BMD likely do so by inducing exon skipping, confirming that exonic point mutations affecting exon definition have played a significant role in determining phenotype. We present a new model based on the combination of exon definition and intronic splicing regulatory elements for the selective association of BMD nonsense mutations with a subset of DMD exons prone to mutation-induced exon skipping.     

Side-to-side arteriovenous fistula at the elbow with perforating vein ligation

OBJECTIVE: We postulated that ligation of a consistent perforating venous branch at the elbow would improve distention and flow in the superficial veins about the elbow. This would also lesson the likelihood of arterial steal enabling a favorable outcome following a brachial artery medial antecubital or cephalic vein arterio-venous fistula (AVF). METHODS: Pressure measurements were made from the radial artery after side-to-side brachial artery antecubital or cephalic vein AVF in 20 patients. Clamping of the perforating vein increased radial artery pressure significantly indicating that a considerable amount of flow from the side-to-side AVF was diverted into the deep system and away from the accessible superficial veins. Encouraged by this finding, we studied the outcome of brachial cephalic or brachial antecubital AVF with ligation of the deep branch in 134 patients who were not candidates for radio-cephalic AVF. The end point of the study was successful hemodialysis using the fistula. RESULTS: Of the 134 patients treated, 24 died, and 11 were lost to follow-up and were censored from analysis of fistula performance at that time point. The primary fistula success rate was 89.7% +/- 2.66% and 83.7% +/- 3.5% at 1 and 2 years by life table analysis. No patient developed significant arterial steal or venous hypertension. CONCLUSION: We recommend this simple one-stage procedure for patients requiring hemodialysis whose cephalic vein at the wrist is unsuitable.     

Coronary artery aneurysm: a review

Coronary artery ectasia (CAE) is found in 0.3-5% of patients undergoing coronary angiography. Atherosclerosis is the main cause, followed by Kawasaki disease and infectious emboli. The exact pathogenesis has not been diagnosed as yet, but an inflammatory process is underlying. Symptoms, if present, are usually related to myocardial ischemia. Angiography is the mainstay for diagnosis. The prognosis is generally favorable. Thromboembolic complications are rare with antiplatelet therapy, and spontaneous rupture generally is rare but occurs more commonly in Kawasaki disease. Management varies from antithrombotic therapy to surgical ligation. Controlling coronary heart disease risk factors sharply affects the prognosis in patients with CAE.     

Compressive and Thermal Properties of Non-Structural Lightweight Concrete Containing Industrial Byproduct Aggregates

This study aimed to investigate the recycling opportunities for industrial byproducts and their contribution to innovative concrete manufacturing processes. The attention was mainly focused on municipal solid waste incineration fly ash (MSWI-FA) and its employment, after a washing pre-treatment, as the main component in artificially manufactured aggregates containing cement and ground granulated blast furnace slag (GGBFS) in different percentages. The produced aggregates were used to produce lightweight concrete (LWC) containing both artificial aggregates only and artificial aggregates mixed with a relatively small percentage of recycled polyethylene terephthalate (PET) in the sand form. Thereby, the possibility of producing concrete with good mechanical properties and enhanced thermal properties was investigated through effective PET reuse with beneficial impacts on the thermal insulation of structures. Based on the obtained results, the samples containing artificial aggregates had lower compressive strength (up to 30%) but better thermal performance (up to 25%) with respect to the reference sample made from natural aggregates. Moreover, substituting 10% of recycled aggregates with PET led to a greater reduction in resistance while improving the thermal conductivity. This type of concrete could improve the economic and environmental aspects by incorporating industrial wastes—mainly fly ash—thereby lowering the use of cement, which would lead to a reduction in CO₂ emissions.     

Best practices in surgical and nonsurgical management of head and neck Merkel cell carcinoma: An update

Merkel cell carcinoma (MCC) is a rare, highly aggressive cutaneous neuroendocrine carcinoma. Controversy exists regarding optimal management of MCC as high-quality randomized studies and clinical trials are limited, and physicians are bound to interpret highly heterogeneous, retrospective literature in their clinical practice. Furthermore, the rising incidence and notably poor prognosis of MCC urges the establishment of best practices for optimal management of the primary tumor and its metastases. Herein, we summarized the relevant evidence and provided an algorithm for decision-making in MCC management based on the latest 2021 National Comprehensive Cancer Network guidelines. Additionally, we report current active MCC clinical trials in the United States. The initial management of MCC is dependent upon the pathology of the primary tumor and presence of metastatic disease. Patients with no clinical evidence of regional lymph node involvement generally require sentinel node biopsy (SLNB) while clinically node-positive patients should undergo fine needle aspiration (FNA) or core biopsy and full imaging workup. If SLNB or FNA/core biopsy are positive, a multidisciplinary team should be assembled to discuss if additional node dissection or adjuvant therapy is necessary. Wide local excision is optimal for primary tumor management and SLNB remains the preferred staging and predictive tool in MCC. The management of MCC has progressively improved in the last decade, particularly due to the establishment of immunotherapy as a new treatment option in advanced MCC. Ongoing trials and prospective studies are needed to further establish the best practices for MCC management.