Skeletal muscle has remarkable regeneration capabilities, mainly due to its resident muscle stem cells (MuSCs). In this review, we introduce recently developed technologies and the mechanistic insights they provide to the understanding of MuSC biology, including the re-definition of quiescence and Galert states. Additionally, we present recent studies that link MuSC function with cellular heterogeneity, highlighting the complex regulation of self-renewal in regeneration, muscle disorders and aging. Finally, we discuss MuSC metabolism and its role, as well as the multifaceted regulation of MuSCs by their niche. The presented conceptual advances in the MuSC field impact on our general understanding of stem cells and their therapeutic use in regenerative medicine.

The reconstructive armamentarium of head and neck surgeons involved in hypopharyngeal and cervical esophagus reconstruction should encompass every option described herein in order to appropriately deal with specific clinical needs and patient requirements. However, fasciocutaneous free flaps (especially ALT) seem to play an ever greater role in restoration of pharyngoesophageal continuity.

Microvascular reconstruction in the elderly can be performed with high success rates, even though medical complications can occur more frequently compared to younger patients. Minor and major surgical complications in the elderly appear to be comparable to those in the younger population and do not affect final outcome or the perioperative mortality rate. Flap outcome does not seem to be significantly affected by age. Careful preoperative assessment and postoperative monitoring are mandatory to prevent adverse events, and prompt management is warranted whenever present.

Oral tongue and floor of mouth cancer needs to be classified according to a revised TNM staging system in which 'depth of infiltration' should be taken into account. An 'ideal cut off' for distinguishing 'low' (T1-T2) from 'high-risk' (T3-T4) categories has been proposed based on the literature review, but needs retrospective as well as large prospective trials before its validation.

Muscular dystrophies are severe disorders due to mutations in structural genes, and are characterized by skeletal muscle wasting, compromised patient mobility, and respiratory functions. Although previous works suggested enhancing regeneration and muscle mass as therapeutic strategies, these led to no long-term benefits in humans. Mice lacking the transcription factor Nfix have delayed regeneration and a shift toward an oxidative fiber type. Here, we show that ablating or silencing the transcription factor Nfix ameliorates pathology in several forms of muscular dystrophy. Silencing Nfix in postnatal dystrophic mice, when the first signs of the disease already occurred, rescues the pathology and, conversely, Nfix overexpression in dystrophic muscles increases regeneration and markedly exacerbates the pathology. We therefore offer a proof of principle for a novel therapeutic approach for muscular dystrophies based on delaying muscle regeneration.

SummarySox6 belongs to the Sox gene family and plays a pivotal role in fiber type differentiation, suppressing transcription of slow-fiber-specific genes during fetal development. Here, we show that Sox6 plays opposite roles in MyHC-I regulation, acting as a positive and negative regulator of MyHC-I expression during embryonic and fetal myogenesis, respectively. During embryonic myogenesis, Sox6 positively regulates MyHC-I via transcriptional activation of Mef2C, whereas during fetal myogenesis, Sox6 requires and cooperates with the transcription factor Nfix in repressing MyHC-I expression. Mechanistically, Nfix is necessary for Sox6 binding to the MyHC-I promoter and thus for Sox6 repressive function, revealing a key role for Nfix in driving Sox6 activity. This feature is evolutionarily conserved, since the orthologs Nfixa and Sox6 contribute to repression of the slow-twitch phenotype in zebrafish embryos. These data demonstrate functional cooperation between Sox6 and Nfix in regulating MyHC-I expression during prenatal muscle development.

4. Laryngoscope, 127:2731-2737, 2017.

Angular branch-based osteomuscular scapular free flaps represent a major advance in palatomaxillary reconstruction: their versatility, long pedicle with large caliber donor vessels, morphologic similarity with maxillary bony structures, and limited donor-site morbidity compare favorably with those of other osteomuscular and osteomusculocutaneous free flaps described for such challenging reconstructive purposes.