The Transcription Factor Mohawk Facilitates Skeletal Muscle Repair via Modulation of the Inflammatory Environment.

Efficient repair of skeletal muscle relies upon the precise coordination of cells between the satellite cell niche and innate immune cells that are recruited to the site of injury. The expression of pro-inflammatory cytokines and chemokines such as TNFα, IFNγ, CXCL1, and CCL2, by muscle and tissue resident immune cells recruits neutrophils and M1 macrophages to the injury and activates satellite cells. These signal cascades lead to highly integrated temporal and spatial control of muscle repair. Despite the therapeutic potential of these factors for improving tissue regeneration after traumatic and chronic injuries, their transcriptional regulation is not well understood. The transcription factor Mohawk (Mkx) functions as a repressor of myogenic differentiation and regulates fiber type specification. Embryonically, Mkx is expressed in all progenitor cells of the musculoskeletal system and is expressed in human and mouse myeloid lineage cells. An analysis of mice deficient for Mkx revealed a delay in postnatal muscle repair characterized by impaired clearance of necrotic fibers and smaller newly regenerated fibers. Further, there was a delay in the expression of inflammatory signals such as Ccl2, Ifnγ, and Tgfß. This was coupled with impaired recruitment of pro-inflammatory macrophages to the site of muscle damage. These studies demonstrate that Mkx plays a critical role in adult skeletal muscle repair that is mediated through the initial activation of the inflammatory response.

Pharmacotherapeutic Approaches to Treatment of Muscular Dystrophies.

Muscular dystrophies are a heterogeneous group of genetic muscle-wasting disorders that are subdivided based on the region of the body impacted by muscle weakness as well as the functional activity of the underlying genetic mutations. A common feature of the pathophysiology of muscular dystrophies is chronic inflammation associated with the replacement of muscle mass with fibrotic scarring. With the progression of these disorders, many patients suffer cardiomyopathies with fibrosis of the cardiac tissue. Anti-inflammatory glucocorticoids represent the standard of care for Duchenne muscular dystrophy, the most common muscular dystrophy worldwide; however, long-term exposure to glucocorticoids results in highly adverse side effects, limiting their use. Thus, it is important to develop new pharmacotherapeutic approaches to limit inflammation and fibrosis to reduce muscle damage and promote repair. Here, we examine the pathophysiology, genetic background, and emerging therapeutic strategies for muscular dystrophies.

Occurrence of emerging contaminants in surface water bodies of a coastal province in Ecuador and possible influence of tourism decline caused by COVID-19 lockdown.

Emerging contaminants in water bodies is an issue of concern due to their impact on the ecosystem and human health. The COVID-19 pandemic has forced the implementation of protective measures such as social distancing, lockdowns, and remote work, which have affected the tourism influx. This study aimed to evaluate the occurrence of emerging pollutants in bodies of water in Esmeraldas, a coastal province of Ecuador, before and during the COVID-19 pandemic in a highly touristic region. For this purpose, surface waters from 14 beaches and ten river mouths were sampled at two-time points in November 2019 and November 2020. Compounds widely consumed in Ecuador: acetaminophen, caffeine, sodium diclofenac, trimethoprim, and sulfamethoxazole were extracted from water samples by solid phase extraction SPE and detected with a UPLC-QTOF-MS system. We found a decrease in the occurrence of caffeine from 100 % to 4.2 % of caffeine and 25 % to 0 % of diclofenac, likely related to the decline in tourist afflux due to the lockdown measures. Most of the compounds diminished in terms of frequency and/or concentration; however, as COVID-19 treatments make use of different pharmaceutical compounds such as antivirals, antibiotics, antiparasitics, or glucocorticoids, future studies should include these to assess their environmental impact.

Protein-lipid interactions and protein anchoring modulate the modes of association of the globular domain of the Prion protein and Doppel protein to model membrane patches.

The Prion protein is the molecular hallmark of the incurable prion diseases affecting mammals, including humans. The protein-only hypothesis states that the misfolding, accumulation, and deposition of the Prion protein play a critical role in toxicity. The cellular Prion protein (PrPC) anchors to the extracellular leaflet of the plasma membrane and prefers cholesterol- and sphingomyelin-rich membrane domains. Conformational Prion protein conversion into the pathological isoform happens on the cell surface. In vitro and in vivo experiments indicate that Prion protein misfolding, aggregation, and toxicity are sensitive to the lipid composition of plasma membranes and vesicles. A picture of the underlying biophysical driving forces that explain the effect of Prion protein - lipid interactions in physiological conditions is needed to develop a structural model of Prion protein conformational conversion. To this end, we use molecular dynamics simulations that mimic the interactions between the globular domain of PrPC anchored to model membrane patches. In addition, we also simulate the Doppel protein anchored to such membrane patches. The Doppel protein is the closest in the phylogenetic tree to PrPC, localizes in an extracellular milieu similar to that of PrPC, and exhibits a similar topology to PrPC even if the amino acid sequence is only 25% identical. Our simulations show that specific protein-lipid interactions and conformational constraints imposed by GPI anchoring together favor specific binding sites in globular PrPC but not in Doppel. Interestingly, the binding sites we found in PrPC correspond to prion protein loops, which are critical in aggregation and prion disease transmission barrier (ß2-α2 loop) and in initial spontaneous misfolding (α2-α3 loop). We also found that the membrane re-arranges locally to accommodate protein residues inserted in the membrane surface as a response to protein binding.

Diagnostico de la situacion del servicio de enfermeria en el Hospital San Vicente de Paul. Fomeque / Diagnosis of the situation of the nursing service in Hospital San Vicente de Paul. Fomeque

El hospital San Vicente de Paul de Fomeque (Cundinamarca) es un hospital local dependiente de la regional de Caqueza que ofrece 3 tipos de servicio: hospitalario, ambulatorio y extramural. El presente estudio de la situacion de enfermerria en el hospital, analizando los servicios, la organizacion y distribucion del personal, y los programas de salud en cuanto a fucionamiento, normas e infrestructura indica que los programas de salud se estan ejectuando en la institucion y se ajustan a las normas establecidos, con amplia cobertura. Sin embargo, hay fallas de infraestructra por falta de personal capacitado en el manetenimiento hospitalario, demuestra la ausencia de labores educativas a la comunidad, suplidas temporalmente con estrategias de participacion de la familia en el cuidado de los ninos hospitalizados. Desde el punto de vista de enfermeria anota alta rotacion de personal recien egresado sin programas a largo plazo. Se identifica como prioritario el entremanmeinto de las auxiliares de enfermeria para contribuir a la realizacion de los programas de salud..