Microfluidic-Assisted Preparation of Targeted pH-Responsive Polymeric Micelles Improves Gemcitabine Effectiveness in PDAC: In Vitro Insights

Pancreatic ductal adenocarcinoma (PDAC) represents a great challenge to the successful delivery of the anticancer drugs. The intrinsic characteristics of the PDAC microenvironment and drugs resistance make it suitable for therapeutic approaches with stimulus-responsive drug delivery systems (DDSs), such as pH, within the tumor microenvironment (TME). Moreover, the high expression of uPAR in PDAC can be exploited for a drug receptor-mediated active targeting strategy. Here, a pH-responsive and uPAR-targeted Gemcitabine (Gem) DDS, consisting of polymeric micelles (Gem@TpHResMic), was formulated by microfluidic technique to obtain a preparation characterized by a narrow size distribution, good colloidal stability, and high drug-encapsulation efficiency (EE%). The Gem@TpHResMic was able to perform a controlled Gem release in an acidic environment and to selectively target uPAR-expressing tumor cells. The Gem@TpHResMic displayed relevant cellular internalization and greater antitumor properties than free Gem in 2D and 3D models of pancreatic cancer, by generating massive damage to DNA, in terms of H2AX phosphorylation and apoptosis induction. Further investigation into the physiological model of PDAC, obtained by a co-culture of tumor spheroids and cancer-associated fibroblast (CAF), highlighted that the micellar system enhanced the antitumor potential of Gem, and was demonstrated to overcome the TME-dependent drug resistance. In vivo investigation is warranted to consider this new DDS as a new approach to overcome drug resistance in PDAC.

SCALING OF SENSATIONS DURING THE PERFORMANCE OF VISUAL TASKS IN RELATION TO HUMAN CENTRIC LIGHTING

Currently, programs for lighting calculation based on computer graphics (CG) allows us to move to a fundamentally new approach to a assessing the quality of lighting. A designing based on illuminance can be complement with designing based on synthetic images or on lighting design. Modern CG programs can calculate the spatial-angular distribution of luminance (SADL). However, to make the assessment of the quality of lighting using SADL a new criterion is needed. This paper considers constructing a physiological model of the visual perception scale based on experimental data and on neural network for simple scene as light source viewed on a uniform background with different luminance levels. Scale based on threshold contrasts of luminance for each sensation can be a fundament of new criterion. The article offers the method of construction the map for each sensation using the example of «discomfort» and «unpleasant» maps that can easily applied in programs.

Comparison of Aspiration Catheters with Modified Standard Catheters for Treatment of Large Pulmonary Embolism Using an In-vitro Patho-Physiological Model

Purpose The presented in-vitro study provides a comparison of various catheters for mechanical treatment of large-burden pulmonary embolism (PE) under standardized conditions, using a new test rig. Dedicated aspiration catheters (JETi®, Penumbra Indigo®, Aspirex®) were compared with standard catheters (Pigtail, Multi-Purpose, Balloon Catheter) applied for embolus fragmentation. Materials and Methods Emboli prepared from porcine blood were washed into the test rig which consists of anatomical models of the pulmonary artery (PA) and of the right heart in combination with a pulsatile drive system. For all catheters, the duration of the recanalization procedure and the weight percentage (wt%) of the remaining, removed and washed-down clot fractions were evaluated. For aspiration catheters, the aspirated volume was measured. Results All catheters achieved full or partial recanalization. The aspiration catheters showed a significantly (p < 0.05) lower procedure time (3:15 min ± 4:26 min) than the standard fragmentation catheters (7:19 min ± 4:40 min). The amount of thrombus removed by aspiration was significantly (p < 0.001) higher than that by fragmentation, averaging 86.1 wt% ± 15.6 wt% and 31.7 wt% ± 3.8 wt%, respectively. Nonetheless, most of the residue was fragmented into pieces of ≥ 1 mm and washed down. Only in 2 of 36 tests, a residual thrombus of 11.9 wt% ± 5.1 wt% remained in the central PA. Conclusion Comparison under standardized in-vitro patho-physiological conditions showed that embolus fragmentation with standard catheters is clearly inferior to aspiration with dedicated catheters in the treatment of large-burden PE, but can still achieve considerable success. Level of Evidence No level of evidence, experimental study.

Clutch may predict growth of hatchling Burmese pythons better than food availability or sex

ABSTRACT Identifying which environmental and genetic factors affect growth pattern phenotypes can help biologists predict how organisms distribute finite energy resources in response to varying environmental conditions and physiological states. This information may be useful for monitoring and managing populations of cryptic, endangered, and invasive species. Consequently, we assessed the effects of food availability, clutch, and sex on the growth of invasive Burmese pythons (Python bivittatus Kuhl) from the Greater Everglades Ecosystem in Florida, USA. Though little is known from the wild, Burmese pythons have been physiological model organisms for decades, with most experimental research sourcing individuals from the pet trade. Here, we used 60 hatchlings collected as eggs from the nests of two wild pythons, assigned them to High or Low feeding treatments, and monitored growth and meal consumption for 12 weeks, a period when pythons are thought to grow very rapidly. None of the 30 hatchlings that were offered food prior to their fourth week post-hatching consumed it, presumably because they were relying on internal yolk stores. Although only two clutches were used in the experiment, we found that nearly all phenotypic variation was explained by clutch rather than feeding treatment or sex. Hatchlings from clutch 1 (C1) grew faster and were longer, heavier, in better body condition, ate more frequently, and were bolder than hatchlings from clutch 2 (C2), regardless of food availability. On average, C1 and C2 hatchling snout-vent length (SVL) and weight grew 0.15 cm d−1 and 0.10 cm d−1, and 0.20 g d−1 and 0.03 g d−1, respectively. Additional research may be warranted to determine whether these effects remain with larger clutch sample sizes and to identify the underlying mechanisms and fitness implications of this variation to help inform risk assessments and management. This article has an associated First Person interview with the first author of the paper.

ANATOMICAL AND PHYSIOLOGICAL FOUNDATIONS OF MEDITATION

В статье приводится физиологическая модель активности подсознательных процессов, оказывающих значительное влияние на здоровье и сознание. Разбираются возможные механизмы сознательного влияния на эти процессы. В качестве такого воздействия моделируется медитативный процесс по методу Марка Яковлевича Пальчика. The article presents a physiological model of the activity of subconscious processes that have a significant impact on health and consciousness. Possible mechanisms of conscious influence on these processes are analyzed. As such an impact, the meditative process is modeled according to the method of Mark Yakovlevich Palchik.

Model adaptation mechanisms of cultivated plants in extreme conditions

This study presents a new mathematical model of the physiology of the plant open system development in the conditions far from equilibrium. Unlike existing approaches, our model is based on the equations describing competition for the substrate between the three main compartments of cultivated plants - the root, stem and leaf system in extreme conditions. Exchange with the external environment occurs through two channels - through the leaves and the root system. The internal control channel is defined as a function of limiting the plant biomass through the biomass of the individual structural parts. The model viability was tested on the example of physiological model of tomato development. The system’s behavior was studied under two varieties of extreme conditions - a lack of nutrients in the soil and a low level or lack of solar radiation. In the first case, the model shows the restructuring of the system after several levels of vibrations to a stable state with a low consumption of substrate and a redistribution of the leaves, stem and root masses. In the second case, the calculations show a significant suppression of leaf cover biomass and mass redistribution in favor of the stem and root. However, even in this case, after a period of instability, the system comes to a stable state with the mass of the stem exceeding the mass of other structures. For each case, phase trajectories of the biomass and substrates behavior are constructed.

Study on a thermophysiological model for health assessment of showering environment in China

In China, the thermal environment of family showers in old communities is quite different from that of other living spaces, especially when the thermal environment changes drastically during showering, which can easily cause health problems. The human thermal physiological model is an effective tool to predict and evaluate the non-uniform and unstable shower thermal environment and human health risks. In this research, the showering experiment was carried out in a typical bathroom in an old community in China, during which environmental parameters such as air temperature, wall temperature and water temperature of the bathroom during the showering were recorded, and physiological parameters such as skin temperature, core temperature and blood pressure during the whole showering process were detected. Based on the multi-node numerical human body model of Stowljik and a cardiovascular control model with human body temperature as the driving force, a temperature-blood pressure coupling prediction model was established. The validity of the proposed model was examined for blood circulation. This predictive model can accurately reflect changes in physiological parameters and is verified as suitable for the health assessment of showering environment in residential buildings.

A physiological model of human mobility: A global study

The movement of people has led to several challenges in terms of traffic congestion, energy consumption, emissions and climate change. Human mobility modelling is currently described mainly through socio-economic variables, such as travel time, travel costs, income and car-ownership. The overall objective of this paper is to relate mobility behaviour based on measurable entities of travel time and distance and the entities of speed. A simple underlying mechanism of human mobility is presented based on the human energy expended. The energy is related firstly to the average values of travel modes. Explicit formulas for the distribution within each travel mode are developed and the concept is also shown to apply to multi-modal mobility. The approach is described in its most basic and fundamental form, but opens up perspectives for new applications and analyses approaches to transport modelling, planning and appraisals. The approach shows that travel time and distance are consistently inversely proportional and limited by the physiological power consumption. The basic hypothesis and the related verifications is shown on all modal combinations of daily mobility with a median R2 of around 0.8. The approach is validated using national travel surveys of Germany, Switzerland, UK and US, spanning over five decades to 2018.

Questioning the renoprotective role of L-type calcium channel blockers in chronic kidney disease using physiological modeling

Our physiological model replicates clinical trial results and provides unique insights into possible mechanisms that play a role in glomerular injury and hypertensive kidney disease progression during chronic calcium channel blocker (CCB) therapy. Specifically, these simulations predict the temporal changes in renal function with CCB treatment and demonstrate important roles for tubuloglomerular feedback and efferent arteriolar conductance in the control of chronic kidney disease progression.