Nanomedicine, a valuable tool for skeletal muscle disorders: Challenges, promises, and limitations

Muscular dystrophies are a group of rare genetic disorders characterized by progressive muscle weakness, which, in the most severe forms, leads to the patient's death due to cardiorespiratory problems. There is still no cure available for these diseases and significant effort is being placed into developing new strategies to either correct the genetic defect or to compensate muscle loss by stimulating skeletal muscle regeneration. However, the vast anatomical extension of the target tissue poses great challenges to these goals, highlighting the need for complementary strategies. Nanomedicine is an actively evolving field that merges nanotechnologies with biomedical and pharmaceutical sciences. It holds great potential in regenerative medicine, both in supporting tissue engineering and regeneration, and in optimizing drug and oligonucleotide delivery and gene therapy strategies. In this review, we will summarize the state-of-the-art in the field of nanomedicine applied to skeletal muscle regeneration. We will discuss the recent work toward the development of nanopatterned scaffolds for tissue engineering, the efforts in the synthesis of organic and inorganic nanoparticles for gene therapy and drug delivery applications, as well as their use as immune modulators. Although nanomedicine holds great promise for muscle and other degenerative diseases, many challenges still need to be systematically addressed to assure a smooth transition from the bench to the bedside. This article is categorized under: Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement

Algorithms and Experiments for the Webgraph This work is dedicated to the memory of Jop F. Sibeyn.

In this paper we present an experimental study of the statistical and topological properties of the Webgraph. This work has required the development of a set of external and semi-external algorithms for computing properties of massive graphs, and for the large scale simulation of stochastic graph models. We use these algorithms for running experiments on a large crawl from 2001 of 200M pages and about 1.4 billion edges made available by the WebBase project at Stanford [19], and on synthetic graphs obtained by the large scale simulation of stochastic graph models for the Webgraph

Restoration of ER proteostasis attenuates remote apoptotic cell death after spinal cord injury by reducing autophagosome overload

The pathogenic mechanisms that underlie the progression of remote degeneration after spinal cord injury (SCI) are not fully understood. In this study, we examined the relationship between endoplasmic reticulum (ER) stress and macroautophagy, hereafter autophagy, and its contribution to the secondary damage and outcomes that are associated with remote degeneration after SCI. Using a rat model of spinal cord hemisection at the cervical level, we measured ER stress and autophagy markers in the axotomized neurons of the red nucleus (RN). In SCI animals, mRNA and protein levels of markers of ER stress, such as GRP78, CHOP, and GADD34, increased 1 day after the injury, peaking on Day 5. Notably, in SCI animals, the increase of ER stress markers correlated with a blockade in autophagic flux, as evidenced by the increase in microtubule-associated protein 2 light chain 3 (LC3-II) and p62/SQSTM1 (p62) and the decline in LAMP1 and LAMP2 levels. After injury, treatment with guanabenz protected neurons from UPR failure and increased lysosomes biogenesis, unblocking autophagic flux. These effects correlated with greater activation of TFEB and improved neuronal survival and functional recovery—effects that persisted after suspension of the treatment. Collectively, our results demonstrate that in remote secondary damage, impairments in autophagic flux are intertwined with ER stress, an association that contributes to the apoptotic cell death and functional damage that are observed after SCI

The complications of enteral nutrition in medical wards (Le complicanze della nutrizione enterale nei reparti di medicina)

Introduction. The effects of Enteral Nutrition (EN) in patients unable to feed themselves have been widely explo-red although studies in low-/mean-intensity words are lacking. Aim. To measure the prevalence of EN side effects in medical wards and to explore their risk factors. Metodi. Observational, retrospective study on matched patients. All patients in the medical departments of the Azienda Ospe-daliero-Universitaria Senese were enrolled (81 cases and 162 controls) from 1 August 2018 to 1 September 2019, aged over 50 years and hospitalized for longer than 4 days. The NE side effects such as diarrhea, vomiting, gastric stagna-tion and abdominal pain were collected from clinical records The presence of EN, age of patients, mobilization and use of antibiotics during hospitalization were considered risk fac-tors. Results. The prevalence of diarrhea, vomiting, gastric and abdominal pain ranged from 4.9% to 11.1%. The EN was not a significant risk factor for the onset of gastrointestinal disorders, and these complications were always lower than in the controls. Vomiting, diarrhea and abdominal pain were more frequently, though not significantly, associated to antibiotic treatments; the age of subjects significantly predicted the diarrhea, showing a protective effect with the age increase. Conclusions. The study shows a low prevalence of diarrhoea, vomiting and abdominal pain com-pared to the literature. These symptoms were not significantly associated to the EN, that cannot be considered a risk factor