Pediatric Nemaline Myopathy: A Systematic Review Using Individual Patient Data

Nemaline myopathy is a skeletal muscle disease that affects 1 in 50 000 live births. The objective of this study was to develop a narrative synthesis of the findings of a systematic review of the latest case descriptions of patients with NM. A systematic search of MEDLINE, Embase, CINAHL, Web of Science, and Scopus was performed using Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines using the keywords pediatric, child, NM, nemaline rod, and rod myopathy. Case studies focused on pediatric NM and published in English between January 1, 2010, and December 31, 2020, in order to represent the most recent findings. Information was collected about the age of first signs, earliest presenting neuromuscular signs and symptoms, systems affected, progression, death, pathologic description, and genetic changes. Of a total of 385 records, 55 case reports or series were reviewed, covering 101 pediatric patients from 23 countries. We review varying presentations in children ranging in severity despite being caused by the same mutation, in addition to current and future clinical considerations relevant to the care of patients with NM. This review synthesizes genetic, histopathologic, and disease presentation findings from pediatric NM case reports. These data strengthen our understanding of the wide spectrum of disease seen in NM. Future studies are needed to identify the underlying molecular mechanism of pathology, to improve diagnostics, and to develop better methods to improve the quality of life for these patients

Love in the Time of COVID-19: Negligence in the Nicaraguan Response

The response of the Nicaraguan government to the coronavirus disease 2019 (COVID-19) pandemic has been perhaps the most erratic of any country in the world to date. Directly contradicting mitigation strategies recommended by WHO, President Daniel Ortega has refused to encourage any physical distancing measures. Vice President Rosario Murillo (Daniel Ortega\u27s wife) instead called on thousands of sympathisers to congregate in street marches under the slogan \u27love in the time of COVID-19\u27. By downplaying the danger of the pandemic and increasing the risk of community transmission in the second-poorest country in the western hemisphere, the Nicaraguan government is violating the human rights of its citizens

Don't Go Breaking My Heart: A Morphogenetic Role for FGF Signaling in Zebrafish Cardiac Jogging, Looping & Ballooning

The cellular events underlying proper cardiac development require the correct interpretation of signaling cues. Congenital heart defects, which affect 1 in 100 infants in the U.S. each year, arise from a failure of these events to occur. Using zebrafish as a model, we aim to better understand the links between errors in signaling, cellular aberrations, and heart malformation. To that end, we have investigated the role of Fibroblast Growth Factor (FGF) signaling, which is known to couple morphogenesis to cell migration events in zebrafish, in asymmetric heart development. We have uncovered three windows during which FGF signaling is necessary for the later stages of heart development, independent of the pathway’s earlier role in establishing left-right asymmetry. We find that FGF signaling is critical for proper tube extension (during cardiac jogging), chamber placement (cardiac looping) and chamber expansion (cardiac ballooning). We hypothesize that FGF signaling influences cardiac jogging through interactions with the actin cytoskeleton, cardiac looping by promoting the addition of a late-differentiating pool of cardiac progenitors (second/anterior heart field) to the arterial pole of the heart tube, and cardiac ballooning by regulating cell shape changes in the curvatures of the looped heart. This study helps us to better understand how signaling pathways regulate the complex processes involved in cardiac development and how disruptions in this process result in congenital heart defects