Muscle wasting is an unmet medical need which leads to a reduction of myofiber diameter and a negative impact on the functional performance of daily activities. We previously found that a new ...neuroprotective drug called NeuroHeal reduced muscle atrophy produced by transient denervation. Aiming to decipher whether NeuroHeal has a direct role in muscle biology, we used herein different models of muscle atrophy: one caused by chronic denervation, another caused by hindlimb immobilization, and lastly, an in vitro model of myotube atrophy with Tumor Necrosis Factor-α (TNFα). In all these models, we observed that NeuroHeal reduced muscle atrophy and that SIRT1 activation seems to be required for that. The treatment downregulated some critical markers of protein degradation: Muscle Ring Finger 1 (MuRF1), K48 poly-Ub chains, and p62/SQSTM1. Moreover, it seems to restore the autophagy flux associated with denervation. Hence, we envisage a prospective use of NeuroHeal at clinics for different myopathies.
Musculoskeletal injuries represent a challenging medical problem. Although the skeletal muscle is able to regenerate and recover after injury, the process engaged with conservative therapy can be ...inefficient, leading to a high re-injury rate. In addition, the formation of scar tissue implies an alteration of mechanical properties in muscle. There is still a need for new treatments of the injured muscle. NeuroHeal may be one option. Published studies demonstrated that it reduces muscle atrophy due to denervation and disuse. The main objective of the present work was to assess the potential of NeuroHeal to improve muscle regeneration after traumatic injury. Secondary objectives included characterizing the effect of NeuroHeal treatment on satellite cell biology. We used a rat model of sport-induced injury in the gastrocnemius and analyzed the effects of NeuroHeal on functional recovery by means of electrophysiology and tetanic force analysis. These studies were accompanied by immunohistochemistry of the injured muscle to analyze fibrosis, satellite cell state, and fiber type. In addition, we used an in vitro model to determine the effect of NeuroHeal on myoblast biology and partially decipher its mechanism of action. The results showed that NeuroHeal treatment advanced muscle fiber recovery after injury in a preclinical model of muscle injury, and significantly reduced the formation of scar tissue. In vitro, we observed that NeuroHeal accelerated the formation of myotubes. The results pave the way for novel therapeutic avenues for muscle/tendinous disorders.
Olive ridley sea turtles, Lepidochelys olivacea, exhibit a polymorphic reproductive behavior, nesting solitarily or in mass aggregations termed “arribadas”, where thousands of individuals nest ...synchronously. Arribada nesting provides fitness benefits including mate finding during nearshore aggregations and predator satiation at the time of hatching, but it is unknown if such benefits come with a physiological cost. We used plasma metabolite profiling, stable isotope analysis, biochemical and endocrine assays to test whether metabolic parameters differ between nesting modes, and if arribada nesting is associated with increased levels of oxidative damage compared to solitary nesting. Arribada nesters were bigger and had higher circulating thyroid hormone levels than solitary nesters. Similarly, pathways related to phospholipid and amino acid metabolism, catabolic processes, and antioxidant defense were enriched in individuals nesting in arribada. Stable isotope signatures in skin samples showed differences in feeding zones with arribada nesters likely feeding on benthic and potentially more productive grounds. Arribada nesters had increased levels of plasma lipid peroxidation and protein oxidation products compared to solitary nesters. These results suggest that metabolic profiles differ between nesting modes and that oxidative stress is a trade-off for the fitness benefits associated with arribada nesting.
Microlitiasis alveolar pulmonar García-Marmolejo, Juan Pablo; Mayoral-Valencía, Manuel Davíd
AMC. Acta médica Colombiana,
04/2021, Letnik:
46, Številka:
2
Journal Article
La microlitiasis alveolar pulmonar es una enfermedad hereditaria infrecuente causada por mutaciones en el gen SCL34A2 que codifica el cotransportador de fosfato en células alveolares tipo 2. Esto ...resulta en un aumento de fosfato y calcio en el surfactante pulmonar que conlleva a la formación y depósito de microlitos intraalveolares. El diagnóstico definitivo necesita la identificación histológica de los microlitos. Reportamos el caso de un paciente masculino de 67 años con antecedente de EPOC y tabaquismo pesado, quien consultó a nuestra institución por empeoramiento progresivo de disnea desde hace una semana, asociado a tos seca y alzas térmicas no cuantificadas en casa. La radiografía de tórax mostró micronodulaciones calcificadas bilaterales. La tomografía computarizada de alta resolución confirmó estos hallazgos. El diagnóstico fue confirmado por los resultados histológicos del lavado bronco alveolar identificándose los microlitos laminares característicos.
(1) Background: the use of Mesenchymal Stromal Cells (MSC) in emerging therapies for spinal cord injury (SCI) hold the potential to improve functional recovery. However, the development of cell-based ...medicines is challenging and preclinical studies addressing quality, safety and efficacy must be conducted prior to clinical testing; (2) Methods: herein we present (i) the characterization of the quality attributes of MSC from the Wharton’s jelly (WJ) of the umbilical cord, (ii) safety of intrathecal infusion in a 3-month subchronic toxicity assessment study, and (iii) efficacy in a rat SCI model by controlled impaction (100 kdynes) after single (day 7 post-injury) and repeated dose of 1 × 106 MSC,WJ (days 7 and 14 post-injury) with 70-day monitoring by electrophysiological testing, motor function assessment and histology evaluation; (3) Results: no toxicity associated to MSC,WJ infusion was observed. Regarding efficacy, recovery of locomotion was promoted at early time points. Persistence of MSC,WJ was detected early after administration (day 2 post-injection) but not at days 14 and 63 post-injection. (4) Conclusions: the safety profile and signs of efficacy substantiate the suitability of the presented data for inclusion in the Investigational Medicinal Product Dossier for further consideration by the competent Regulatory Authority to proceed with clinical trials.
La actividad física (AF) puede influir en el rendimiento académico de estudiantes universitarios. Estudios científicos han identificado que los estudiantes universitarios practican poca actividad ...física y presentan hábitos sedentarios que afectan la adquisición de comportamientos saludables e influyen en sus logros académicos. Objetivo principal: Determinar la relación entre el nivel de actividad física y el rendimiento académico en estudiantes de una institución universitaria. Metodología: Participaron 486 estudiantes de una institución universitaria, con sedes en cuatro ciudades de Colombia, Enfoque de investigación cuantitativo, de corte transversal y de tipo descriptivo. Se utilizó el cuestionario internacional de actividad física (IPAQ), un cuestionario de caracterización sociodemográfico y el promedio de calificaciones como indicador del rendimiento académico. Resultado: Las mujeres realizan más actividad física de intensidad leve mientras que los hombres realizan más actividad física de intensidad moderada; los estudiantes pertenecientes a estratos socioeconómicos bajos tienen un nivel de actividad física leve, mientras que estudiantes pertenecientes a los estratos medios o altos suelen tener en su mayoría un nivel de actividad física moderada. Se encontró que tener un nivel de actividad física moderada o vigorosa aumenta dos veces la posibilidad de que un estudiante obtenga un promedio académico superior a 3.7 (en una escala de 0 - 5).Conclusión: Existe una relación positiva entre el nivel de actividad física y el rendimiento académico, reflejando la necesidad de sensibilizar a los estudiantes sobre la importancia de realizar actividad física.
Palabras claves: Actividad física, Rendimiento académico, Estudiantes, Sedentarismo.
Abstract. Physical activity (PA) may influence the academic performance of university students. Scientific studies have identified that university students practice little physical activity and exhibit sedentary habits that affect the acquisition of healthy behaviors and influence their academic performance. Main objective: To determine the relationship between the level of physical activity and academic performance in students of a university institution. Methodology: 486 students from a university institution with campuses in four Colombian cities participated. The research approach was quantitative, cross-sectional and descriptive. The International Physical Activity Questionnaire (IPAQ), a sociodemographic characterization questionnaire and grade point average as an indicator of academic performance were used. Results: Women perform more physical activity of mild intensity while men perform more physical activity of moderate intensity; students belonging to low socioeconomic strata have a mild level of physical activity, while students belonging to the middle or high strata tend to have mostly a moderate level of physical activity. It was found that having a moderate or vigorous level of physical activity increases twice the possibility of a student obtaining a GPA higher than 3.7 (on a scale of 0 - 5). Conclusion: There is a positive relationship between the level of physical activity and academic performance, reflecting the need to sensitize students to the importance of physical activity.
Keywords: Physical activity, Academic performance, Students, Sedentary lifestyle.
The early diagnosis of neurodevelopmental conditions such as autism spectrum disorder (ASD), is an unmet need. One difficulty is the identification of a biological signal that relates to the ASD ...phenotype. The electroretinogram (ERG) waveform has been identified as a possible signal that could categorize neurological conditions such as ASD. The ERG waveform is derived from the electrical activity of photoreceptors and retinal neurons in response to a brief flash of light and provides an indirect 'window' into the central nervous system. Traditionally, the waveform is analyzed in the time-domain, but more recently time-frequency spectrum (TFS) analysis of ERG has been successfully carried out using discrete wavelet transformation (DWT) to characterize the morphological features of the signal. In this study, we propose the use of a high resolution TFS technique, namely variable frequency complex demodulation (VFCDM), to decompose the ERG waveform based on two signal flash strengths to build machine learning (ML) models to categorize ASD. ERG waveforms from N = 217 subjects (71 ASD, 146 control), at two different flash strengths, 446 and 113 Troland seconds (Td.s), from both right and left eyes were included. We analyzed the raw ERG waveforms using DWT and VFCDM. We computed features from the TFSs and trained ML models such as Random Forest, Gradient Boosting, Support Vector Machine to classify ASD from controls. ML models were validated using a subject independent validation strategy, and we found that the ML models with VFCDM features outperformed models using the DWT, achieving an area under the receiver operating characteristics curve of 0.90 (accuracy = 0.81, sensitivity = 0.85, specificity = 0.78). We found that the higher frequency range (80–300 Hz) included more relevant information for classifying ASD compared to the lower frequencies. We also found that the stronger flash strength of 446 Td.s in the right eye provided the best classification result which supports VFCDM analysis of the ERG waveform as a potential tool to aid in the identification of the ASD phenotype.
•Variable Frequency Complex Demodulation (VFCDM) of Electroretinogram (ERG) for autism spectrum disorder (ASD) detection.•Machine learning models trained on VFCDM features performed better than other time-frequency spectrum analysis methods.•The higher frequency range identified with VFCDM analysis offers the most relevant information for ASD classification.
Although the automated image acquisition with the focused ion beam scanning electron microscope (FIB-SEM) provides volume reconstructions, volume analysis of large samples remains challenging. Here, ...we present a workflow that combines a modified sample protocol of the classical transmission electron microscope with FIB-SEM volume imaging. The proposed workflow enables efficient 3D structural surveys of rabbit ovaries collected at consecutive developmental stages. The precise trimming of the region of interest adds the time dimension to the volume, constructing a virtual 4D electron microscopy. We found filopodia-like processes emitted by oocyte cysts allowing contact between oocytes not previously observed.
To ascertain if the photopic negative response of the electroretinogram is different in autism spectrum disorder as a potential clinical marker.
Visual function can be atypical in autism spectrum ...disorder and structural imaging of the ganglion cell layers has been reported to differ in these individuals. Therefore, we sought to investigate if the photopic negative response of the full field electroretinograms, a measure of ganglion cell function, could help explain the visual perceptual differences in autism spectrum disorder and support the structural changes observed.
Participants (n = 55 autism spectrum disorder, aged 5.4-26.7 years) and control (n = 87, aged 5.4-27.3 years) were recruited for the study. Full-field light-adapted electroretinograms using a Troland protocol with 10 flash strengths from −0.367 to 1.204 log photopic cd.s.m
−2
were recorded in each eye. The photopic negative response amplitudes at Tmin and at t = 72 ms were compared between groups along with the a- and b-wave values.
There were no significant interactions between groups for the Photopic Negative Response measures of amplitude or time (p > 0.30). There was a group interaction between groups and flash strengths for the b-wave amplitude as previously reported (p < 0.001).
The photopic negative response results suggest that there are no significant differences in the summed retinal ganglion cell responses produced by a full-field stimulus.
Herein, we report two new charge-transfer organic cocrystals, CP-TCNQ and CP-TFBQ. The two cocrystals exhibit broad absorption, good thermal stability, and low photoluminescence quantum yields, the ...necessary requirements to show the photothermal conversion (PTC) effect. Indeed, the two cocrystals exhibit distinct PTC efficiencies of 11.0 ± 1.4% (CP-TCNQ) and 17.0 ± 1.0% (CP-TFBQ). The 55% improvement in the observed efficiencies is attributed to the fast in-plane reorientations of the TFBQ fragment, as determined by detailed ssNMR spectroscopy and DFT calculations. This work provides for the first time experimental and computational evidence that the molecular motion of a cocrystal coformer increases its PTC efficiency, paving the way to the design of new crystalline materials with PTC as a regulated property.
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