Priorities and Public Safety II: Adopting Effective Probation Practices

Outlines the structural problems of Massachusetts' corrections, the role of probation in public safety, best practices in community supervision in other states, and the elements of an evidence-based probation system, including inter-agency collaboration

Doğumsal kalp hastalığı nedeniyle ameliyat edilen çocuk hastalarda postperikardiyotomi sendromu ve perikardiyal efüzyon sıklığı, risk faktörleri, prognozu

Postperikardiyotomi sendromu (PPS), tanı ve tedavi yöntemlerindeki tüm gelişmelere rağmen gelişmiş ülkelerde bile kardiyak cerrahi sonrası morbiditenin başta gelen sebeplerindendir. En erken klinik bulgusu ameliyat sonrası perikardiyal efüzyon gelişimidir. Biz bu retrospektif çalışmada kardiyak cerrahi geçiren pediyatrik hastalarda perikardiyal efüzyon sıklığını belirlemeyi, risk faktörlerini incelemeyi, ameliyat süresinin, kardiyopulmoner “bypass” süresinin, konjenital kalp hastalığının tanısının efüzyon üzerine etkisini incelemeyi amaçladık. Çalışmaya Mart 2011 ile Mart 2012 tarihleri arasında bir yıllık süre içerisinde hastanemiz Kalp Damar Cerrahisi Ana Bilim Dalında konjenital kalp hastalığı nedeniyle opere edilmiş 469 hastadan perikardiyal efüzyon varlığı gösterilen 66 hasta dahil edildi. Bu süre içerisinde ameliyat sonrası perikardiyal efüzyon oranı %14, PPS oranı ise %13.7 olarak bulundu. Olgularımızın 34’ü (%52) kız, 32’si (%48) erkekti. Olguların tanılara göre dağılımlarına bakıldığında 19’unun (%28.8) TOF, 23’ünün (%34.8) VSD olduğu görülmektedir. Efüzyon gelişen olguların %11.6’sında efüzyon ilk haftada gelişmiştir. Perikardiyosentez yapılan olguların perikard sıvısı inceleme sonuçlarına bakıldığında transuda niteliğinde efüzyon sıklığı (%66.6) olup iki hastada şilöz efüzyon gelişmesi nedeniyle (%22.2) sandostatin kullanılmıştır. Sonuç olarak çalışmamızda kardiyak cerrahi geçiren hastaların %14.1’inde perikardiyal efüzyon geliştiğini ve perikardiyal efüzyon gelişen hastalarda en sık rastlanan tanının %34.8 ile VSD olduğunu saptadık(Tüm hastalar içinde VSD en sıktır. Bu çıkarım doğru olmayabilir). Ameliyat süresinin, pompa süresinin, konjenital kalp hasalığının türünün ameliyat sonrası perikardiyal efüzyon açısından risk olabileceğini saptadık. Ameliyat sonrası dönemde ilk bir ay yakın, dördüncü aya kadar aralıklı izlenmesi gerektiğini belirledik

Author Correction: Myoblasts and macrophages are required for therapeutic morpholino antisense oligonucleotide delivery to dystrophic muscle

The originally published version of this Article contained an error in Figure 6. In panel b, the top graph (BrdU 21–24d) and the bottom graph (BrdU 28–31d) were inadvertently swapped. This error has now been corrected in both the PDF and HTML versions of the Article

Myoblasts and macrophages are required for therapeutic morpholino antisense oligonucleotide delivery to dystrophic muscle

Exon skipping is a promising therapeutic strategy for Duchenne muscular dystrophy (DMD), employing morpholino antisense oligonucleotides (PMO-AO) to exclude disruptive exons from the mutant DMD transcript and elicit production of truncated dystrophin protein. Clinical trials for PMO show variable and sporadic dystrophin rescue. Here, we show that robust PMO uptake and efficient production of dystrophin following PMO administration coincide with areas of myofiber regeneration and inflammation. PMO localization is sustained in inflammatory foci where it enters macrophages, actively differentiating myoblasts and newly forming myotubes. We conclude that efficient PMO delivery into muscle requires two concomitant events: first, accumulation and retention of PMO within inflammatory foci associated with dystrophic lesions, and second, fusion of PMO-loaded myoblasts into repairing myofibers. Identification of these factors accounts for the variability in clinical trials and suggests strategies to improve this therapeutic approach to DMD

Morpholino-induced exon skipping stimulates cell-mediated and humoral responses to dystrophin in mdx mice.

Exon skipping is a promising genetic therapeutic strategy for restoring dystrophin expression in the treatment of Duchenne muscular dystrophy (DMD). The potential for newly synthesized dystrophin to trigger an immune response in DMD patients, however, is not well established. We have evaluated the effect of chronic phosphorodiamidate morpholino oligomer (PMO) treatment on skeletal muscle pathology and asked whether sustained dystrophin expression elicits a dystrophin-specific autoimmune response. Here, two independent cohorts of dystrophic mdx mice were treated chronically with either 800 mg/kg/month PMO for 6 months (n = 8) or 100 mg/kg/week PMO for 12 weeks (n = 11). We found that significant muscle inflammation persisted after exon skipping in skeletal muscle. Evaluation of humoral responses showed serum-circulating antibodies directed against de novo dystrophin in a subset of mice, as assessed both by Western blotting and immunofluorescent staining; however, no dystrophin-specific antibodies were observed in the control saline-treated mdx cohorts (n = 8) or in aged (12-month-old) mdx mice with expanded ‘revertant’ dystrophin-expressing fibers. Reactive antibodies recognized both full-length and truncated exon-skipped dystrophin isoforms in mouse skeletal muscle. We found more antigen-specific T-cell cytokine responses (e.g. IFN-g, IL-2) in dystrophin antibody-positive mice than in dystrophin antibody-negative mice. We also found expression of major histocompatibility complex class I on some of the dystrophin-expressing fibers along with CD8+ and perforin-positive T cells in the vicinity, suggesting an activation of cell-mediated damage had occurred in the muscle. Evaluation of complement membrane attack complex (MAC) deposition on the muscle fibers further revealed lower MAC deposition on muscle fibers of dystrophin antibody-negative mice than on those of dystrophin antibody-positive mice. Our results indicate that de novo dystrophin expression after exon skipping can trigger both cell-mediated and humoral immune responses in mdx mice. Our data highlights the need to further investigate the autoimmune response and its long-term consequences after exon-skipping therapy. Copyright © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd

Boletín de Segovia: Número 132 - 1914 noviembre 4

Copia digital. Madrid : Ministerio de Cultura. Subdirección General de Coordinación Bibliotecaria, 200

Additional file 5: of Elusive sources of variability of dystrophin rescue by exon skipping

Dystrophin protein expression detected by IF and WB after 7 days of PMO delivery. Four mice were treated with one high dose of PMO (800 mg/kg) and sacrificed at 7 days. Tibialis anterior muscles were dissected and analyzed by IF and WB. We observed low levels of dystrophin protein by both quantification methods as compared to saline-treated mice. (PDF 265 kb