Preliminary Study on the Effect of an Early Physical Therapy Intervention after Sentinel Lymph Node Biopsy: A Multicenter Non-Randomized Controlled Trial

Selective sentinel lymph node biopsy (SLNB) represents a minimally invasive surgery in patients with breast cancer. The purpose of this study was to explore the possible effect of an early physiotherapy intervention for the recovery of the upper limb and the surgical scars after SLNB in comparison with usual care. A total of 40 patients were enrolled in either the control group (n = 20) or the experimental group (n = 20). The intervention group performed an early physiotherapy program based on functional exercises, scar manual therapy, and educational tips. The control group received usual care. Shoulder range of motion (ROM), grip strength, upper limb pain and disability (SPADI), scar recovery (POSAS), myofascial adhesions (MAP-BC), quality of life (EORTCQLA-BR-23) and the presence of axillary web syndrome (AWS) and lymphoedema were assessed at baseline and immediately after intervention. A follow-up period of 6 months was performed for lymphoedema surveillance. Between groups significant differences in favor of the intervention were found for ROM (r = 0.43), grip strength (r = 0.32), SPADI (d = 0.45), POSAS (d = 1.28), MAP-BC (d = 1.82) and EORTCQLQ-BR 23 general function subscale (d = 0.37) (p < 0.05 for all variables). Our results suggest that an early physical therapy program seems to be more effective than usual care in women after SLNB. However, results should be interpreted with caution and future randomized trial with a larger sample size is neededThis research was partially supported by ICPFA. Grant number 04722/19P/MA. The funder had no role in the design of the study and collection, analysis, and interpretation of data, and in writing the manuscript. Partial funding for open access charge: Universidad de Málag

UPRmt activation improves pathological alterations in cellular models of mitochondrial diseases

Background: Mitochondrial diseases represent one of the most common groups of genetic diseases. With a prevalence greater than 1 in 5000 adults, such diseases still lack effective treatment. Current therapies are purely palliative and, in most cases, insufficient. Novel approaches to compensate and, if possible, revert mitochondrial dysfunction must be developed. Results: In this study, we tackled the issue using as a model fibroblasts from a patient bearing a mutation in the GFM1 gene, which is involved in mitochondrial protein synthesis. Mutant GFM1 fibroblasts could not survive in galactose restrictive medium for more than 3 days, making them the perfect screening platform to test several compounds. Tetracycline enabled mutant GFM1 fibroblasts survival under nutritional stress. Here we demonstrate that tetracycline upregulates the mitochondrial Unfolded Protein Response (UPR), a compensatory pathway regulating mitochondrial proteostasis. We additionally report that activation of UPR improves mutant GFM1 cellular bioenergetics and partially restores mitochondrial protein expression. Conclusions: Overall, we provide compelling evidence to propose the activation of intrinsic cellular compensatory mechanisms as promising therapeutic strategy for mitochondrial diseases.This work was supported by FIS PI16/00786 (2016) and FIS PI19/00377 (2019) grants, the Ministerio de Sanidad, Spain and the Fondo Europeo de Desarrollo Regional (FEDER Unión Europea), Spanish Ministry of Education, Culture and Sport. This activity has been co-financed by the European Regional Development Fund (ERDF) and by the Regional Ministry of Economic Transformation, Industry, Knowledge and Universities of the Junta de Andalucía, within the framework of the ERDF Andalusia operational program 2014–2020 Thematic objective "01—Reinforcement of research, technological development and innovation" through the reference research project CTS-5725 and PY18-850

Neurodegeneration, Mitochondria, and Antibiotics

Neurodegenerative diseases are characterized by the progressive loss of neurons, synapses, dendrites, and myelin in the central and/or peripheral nervous system. Actual therapeutic options for patients are scarce and merely palliative. Although they affect millions of patients worldwide, the molecular mechanisms underlying these conditions remain unclear. Mitochondrial dysfunction is generally found in neurodegenerative diseases and is believed to be involved in the pathomechanisms of these disorders. Therefore, therapies aiming to improve mitochondrial function are promising approaches for neurodegeneration. Although mitochondrial-targeted treatments are limited, new research findings have unraveled the therapeutic potential of several groups of antibiotics. These drugs possess pleiotropic effects beyond their anti-microbial activity, such as anti-inflammatory or mitochondrial enhancer function. In this review, we will discuss the controversial use of antibiotics as potential therapies in neurodegenerative diseases.This project was supported by FIS PI19/00377 (2019) and FIS PI22/00142 (2022) grants, Instituto de Salud Carlos III, Spain; and the Fondo Europeo de Desarrollo Regional (FEDER Unión Europea), Spanish Ministry of Education, Culture, and Sport. This activity was co-financed by the European Regional Development Fund (ERDF) and by the Regional Ministry of Economic Transformation, Industry, Knowledge, and Universities of the Junta de Andalucía, within the framework of the ERDF Andalusia operational program 2014–2020 Thematic objective “01—Reinforcement of research, technological development and innovation” through the reference research project CTS-5725 and PY18-850.Peer reviewe