Study protocol and rationale of "the UP project": evaluating the effectiveness of active breaks on health indicators in desk-based workers.

Background: Excessive sedentary time has been negatively associated with several health outcomes, and physical activity alone does not seem to fully counteract these consequences. This panorama emphasizes the essential of sedentary time interruption programs. "The Up Project" seeks to assess the effectiveness of two interventions, one incorporating active breaks led by a professional and the other utilizing a computer application (self-led), of both equivalent duration and intensity. These interventions will be compared with a control group to evaluate their impact on physical activity levels, sedentary time, stress perception, occupational pain, and cardiometabolic risk factors among office workers. Methods: This quasi-experimental study includes 60 desk-based workers from universities and educational institutes in Valparaiso, Chile, assigned to three groups: (a) booster breaks led by professionals, (b) computer prompts that are unled, and (c) a control group. The intervention protocol for both experimental groups will last 12 weeks (only weekdays). The following measurements will be performed at baseline and post-intervention: cardiometabolic risk based on body composition (fat mass, fat-free mass, and bone mass evaluated by DXA), waist circumference, blood pressure, resting heart rate, and handgrip strength. Physical activity and sedentary time will be self-reported and device-based assessed using accelerometry. Questionnaires will be used to determine the perception of stress and occupational pain. Discussion: Governments worldwide are addressing health issues associated with sedentary behavior, particularly concerning individuals highly exposed to it, such as desk-based workers. Despite implementing certain strategies, there remains a noticeable gap in comprehensive research comparing diverse protocols. For instance, studies that contrast the outcomes of interventions led by professionals with those prompted by computers are scarce. This ongoing project is expected to contribute to evidence-based interventions targeting reduced perceived stress levels and enhancing desk-based employees' mental and physical well-being. The implications of these findings could have the capacity to lay the groundwork for future public health initiatives and government-funded programs.

Preclinical Evaluation of the FGFR-Family Inhibitor Futibatinib for Pediatric Rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma. Despite decades of clinical trials, the overall survival rate for patients with relapsed and metastatic disease remains below 30%, underscoring the need for novel treatments. FGFR4, a receptor tyrosine kinase that is overexpressed in RMS and mutationally activated in 10% of cases, is a promising target for treatment. Here, we show that futibatinib, an irreversible pan-FGFR inhibitor, inhibits the growth of RMS cell lines in vitro by inhibiting phosphorylation of FGFR4 and its downstream targets. Moreover, we provide evidence that the combination of futibatinib with currently used chemotherapies such as irinotecan and vincristine has a synergistic effect against RMS in vitro. However, in RMS xenograft models, futibatinib monotherapy and combination treatment have limited efficacy in delaying tumor growth and prolonging survival. Moreover, limited efficacy is only observed in a PAX3-FOXO1 fusion-negative (FN) RMS cell line with mutationally activated FGFR4, whereas little or no efficacy is observed in PAX3-FOXO1 fusion-positive (FP) RMS cell lines with FGFR4 overexpression. Alternative treatment modalities such as combining futibatinib with other kinase inhibitors or targeting FGFR4 with CAR T cells or antibody-drug conjugate may be more effective than the approaches tested in this study.

Lipid Hydroperoxidation Effect on the Dynamical Evolution of the Conductance Process in Bilayer Lipid Membranes: A Condition Toward Criticality.

Cell membranes are one of the main targets of oxidative processes mediated by reactive oxygen species (ROS). These chemical species interact with unsaturated fatty acids of membrane lipids, triggering an autocatalytic chain reaction, producing lipid hydroperoxides (LOOHs) as the first relatively stable product of the ROS-mediated lipid peroxidation (LPO) process. Numerous biophysical and computational studies have been carried out to elucidate the LPO impact on the structure and organization of lipid membranes. However, although LOOHs are the major primary product of LPO of polyunsaturated fatty acids (PUFAs), to the best of our knowledge, there is no experimental evidence on the effects of the accumulation of these LPO byproducts on the electrical properties and the underlying dynamics of lipid membranes. In this work, bilayer lipid membranes (BLMs) containing 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocoline (POPC) with increasing hydroperoxidized POPC (POPC-OOH) molar proportions (BLMPC/PC-OOH) are used as model membranes to investigate the effect of LOOH-mediated LPO propagation on the electrical behavior of lipid bilayers. Voltage-induced ion current signals are analyzed by applying the fractal method of power spectrum density (PSD) analysis. We experimentally prove that, when certain LOOH concentration and energy threshold are overcome, oxidized membranes evolve toward a critical state characterized by the emergence of non-linear electrical behavior dynamics and the pore-type metastable structures formation. PSD analysis shows that temporal dynamics exhibiting "white" noise (non-time correlations) reflects a linear relationship between the input and output signals, while long-term correlations (ß > 0.5) begin to be observed closely to the transition (critical point) from linear (Ohmic) to nonlinear (non-Ohmic) behavior. The generation of lipid pores appears to arise as an optimized energy dissipation mechanism based on the system's ability to self-organize and generate ordered structures capable of dissipating energy gradients more efficiently under stressful oxidative conditions.

Probing Thermotropic Phase Behavior of Dipalmitoylphosphatidylcholine Bilayers from Electrical and Topographic Data in a Horizontal Black Lipid Membrane Model.

Here, a homemade device allowed preparing horizontal lipid bilayer membranes (hBLMs) for recording electrical and topographical data simultaneously and in real-time, under temperature (T)-controlled conditions along a cooling process of dipalmitoylphosphatidylcholine (DPPC) bilayers. Electrical parameters (ionic current intensity, I, and transmembrane resistance, R = ΔV/I) plotted against T exhibited discontinuities at the main transition (TPß'→Lα) and pretransition (TLß→Pß') temperatures of DPPC. The T-dependent sensitivity to ΔV-induced electrostriction was revealed by capacitance measurements. The patterns of I fluctuation described long-range correlations reflected by 1/f-type noise in the ripple phase (Pß') and Brownian-type fluctuations in the liquid-crystalline (Lα) phase at voltage intensities lower than a voltage threshold (ΔVth = ±160 mV), indicating that autocorrelations arise from an underlying structural connectivity that takes place within ordered phases. At |V| ≥ Vth, the fluctuation dynamics exhibited a 1/f behavior over the whole temperature range analyzed, suggesting that upon a certain intensity of external electrical perturbation, the membrane system evolves toward a voltage-induced percolated-pore state. At T > TPß'→Lα, differential interference contrast micrographs showed droplet-like structures, probably containing solvent traces of the lipid solution, which were reverted upon cooling. However, droplets did not interfere with the thermotropic equilibrium of the bilayer phase. This suggested that the temperature-induced changes in the electrical properties of the bilayer, as well as in the complexity of the fluctuation patterns (emergency of long- and short-range correlations), were strongly associated with the characteristic thermotropic behavior of DPPC, without significant deviations induced by the presence of residual n-decane in the bilayer. Our hBLM model membrane proved useful for correlating thermotropic phase changes with electro-biophysical and topographical information.

[Effect of "Super 8 Law" implementation on body composition of schoolchildren during the National Holidays in Chile. Longitudinal-ecological study]. / Efecto de la implementación de la "Ley Súper 8" sobre la composición corporal de escolares durante las vacaciones de Fiestas Patrias en Chile. Estudio longitudinal-ecológico.

INTRODUCTION: several public health programs are being implemented to combat childhood obesity in the world. However, the impact of Chilean Law n.o 20,606, which regulates the sale and advertising of foods high in critical nutrients ("Super 8 Law") about a critical period in the increase of body weight in schoolchildren, such as National Holiday (NH), has not yet been evaluated. OBJECTIVE: establish the effect of NH on various body composition indicators before and after the implementation of the Super 8 Law. METHODS: 110 schoolchildren between 10 and 13 years of age participated in this study, and 48 finished it after one year of follow-up (23 children and 25 girls). Body weight, body mass index (Zscore-BMI), triponderal mass index (TMI), fat mass index (FMI), percentage of fat mass and muscle mass during the four weeks of September 2015 (without law) and 2016 (with law). An ANOVA for repeated measures and adjusted for covariates was applied. RESULTS: body weight (0.327 and 0.556 kg), Zscore-BMI (0.057 and 0.085) and fat percentage (0.1 and 0.9%) increased significantly during both NH (without and with law, respectively). Compared to 2015, FMI and TMI do not show significant increases during 2016, however, there are no significant differences in any of the variables studied after the implementation of the law. CONCLUSION: despite observing slight advances in certain parameters of body composition between one year and another, the implementation of the Super 8 Law in Chile does not seem to generate a preventive effect during NH.

Introducción: diversos programas de salud pública están siendo implementados para combatir la obesidad infantil en el mundo. No obstante, el impacto de la Ley chilena n.o 20.606 que regula la venta y publicidad de alimentos altos en nutrientes críticos ("Ley Súper 8") sobre un periodo crítico en el aumento de peso corporal en escolares, como son las vacaciones de Fiestas Patrias (VFP) aún no ha sido evaluado.Objetivo: establecer el efecto de las VFP sobre diversos indicadores de composición corporal antes y después de la implementación de la Ley Súper 8.Metodología: participaron 110 escolares entre 10 y 13 años de edad y finalizaron 48 tras 1 año de seguimiento (23 niños y 25 niñas). Se evaluó el peso corporal, índice de masa corporal (Zscore-IMC), índice de masa triponderal (IMT), índice de masa grasa (IMG), porcentaje de masa grasa y masa muscular durante las 4 semanas del mes de septiembre de 2015 (sin ley) y de 2016 (con ley). Se aplicó un ANOVA para medidas repetidas y ajustada a covariables.Resultados: el peso corporal (0,327 y 0,556 kg), Zscore-IMC (0,057 y 0,085) y porcentaje de grasa (0,1 y 0,9%) aumentan significativamente durante ambas VFP (sin y con ley, respectivamente). En comparación a 2015, el IMG e IMT no muestran aumentos significativos durante 2016, sin embargo, no existen diferencias significativas en ninguna de las variables estudiadas tras la implementación de la ley.Conclusión: a pesar de observar ligeros avances en ciertos parámetros de composición corporal entre un año y otro, la implementación de la Ley Súper 8 en Chile no parece generar un efecto preventivo durante las VFP.

Langmuir films of dipalmitoyl phosphatidylethanolamine grafted poly(ethylene glycol). In-situ evidence of surface aggregation at the air-water interface.

The molecular packing-dependent interfacial organization of polyethylene glycol grafted dipalmitoylphosphatidylethanolamine (PE-PEGs) Langmuir films was studied. The PEG chains covered a wide molecular mass range (350, 1000 and 5000Da). In surface pressure-area (π-A), isotherms PE-PEG1000 and PE-PEG5000 showed transitions (midpoints at πm,t1∼11mN/m, "t1"), which appeared as a long non-horizontal line region. Thus, t1 cannot be considered a first-order phase transition but may reflect a transition within the polymer, comprising its desorption from the air-water interface and compaction upon compression. This is supported by the increase in the νs(C-O-C) PM-IRRAS signal intensity and the increasing surface potentials at maximal compression, which reflect thicker polymeric layers. Furthermore, changes in hydrocarbon chain (HC) packing and tilt with respect to the surface led to reorientation in the PO2- group upon compression, indicated by the inversion of the νasym(PO2-) PM-IRRAS signal around t1. The absence of a t1 in PE-PEG350 supports the requisite of a critical polymer chain length for this transition to occur. In-situ epifluorescence microscopy revealed 2D-domain-like structures in PE-PEG1000 and PE-PEG5000 around t1, possibly associated with gelation/dehydration of the polymeric layer and appearing at decreasing π as the polymeric tail became longer. Another transition, t2, appearing in PE-PEG350 and PE-PEG1000 at πm,t2=29.4 and 34.8mN/m, respectively, was associated with HC condensation and was impaired in PE-PEG5000 due to steric hindrance imposed by the large size of its polymer moiety. Two critical lengths of polymer chains were found, one of which allowed the onset of polymeric-tail gelation and the other limited HC compaction.

Cholesterol favors the emergence of a long-range autocorrelated fluctuation pattern in voltage-induced ionic currents through lipid bilayers.

The present paper was aimed at evaluating the effect of cholesterol (CHO) on the voltage-induced lipid pore formation in bilayer membranes through a global characterization of the temporal dynamics of the fluctuation pattern of ion currents. The bilayer model used was black lipid membranes (BLMs) of palmitoyloleoylphosphatidylethanolamine and palmitoyloleoylphosphatidylcholine (POPE:POPC) at a 7:3 molar ratio in the absence (BLM0) or in the presence of 30 (BLM30), 40 (BLM40) or 50(BLM50)mol% of cholesterol with respect to total phospholipids. Electrical current intensities (I) were measured in voltage (ΔV) clamped conditions at ΔV ranging between 0 and ±200mV. The autocorrelation parameter α derived from detrended fluctuation analysis (DFA) on temporal fluctuation patterns of electrical currents allowed discriminating between non-correlated (α=0.5, white noise) and long-range correlated (0.5<α<1) behaviors. The increase in |ΔV| as well as in cholesterol content increased the number of conductance states, the magnitude of conductance level, the capacitance of the bilayers and increased the tendency towards the development of long-range autocorrelated (fractal) processes (0.5<α<1) in lipid channel generation. Experiments were performed above the phase transition temperature of the lipid mixtures, but compositions used predicted a superlattice-like organization. This leads to the conclusion that structural defects other than phase coexistence may promote lipid channel formation under voltage clamped conditions. Furthermore, cholesterol controls the voltage threshold that allows the percolation of channel behavior where isolated channels become an interconnected network.

Stereo-selective activity of menthol on GABA(A) receptor.

Menthol is a naturally occurring compound, which has three chiral centers that define eight possible optically actives stereoisomers. Neuroactivity of menthol and related agents by affecting neuronal intracellular signaling or by modulation of neurotransmitter-gated currents has been reported. Furthermore, stereo-selectivity of menthol in its analgesic activity as well as in its sensory properties and other biological activities was also described. The present study is the first contribution to the description of stereo-selectivity of GABA(A) receptor against the most possible isomers of menthol, discussed in terms of their chirality. The results showed that only (+)-menthol, among the five stereoisomers analyzed, was active, stimulating in a dose-response manner the binding of an allosteric GABA(A) receptor ligand. Taking into account these results, and comparing them with those of some active phenolic compounds, it is strongly suggested that the existence of a relative spatial location of its substituents with respect to the ring (equatorial position of all substituents and (1S,2R,5S)-configuration) as well as the presence in the cyclic molecule of an aliphatic non polar group (isopropyl) with free rotation near to a polar group (hydroxyl) are crucial points to demonstrate activity on the receptor.