How Does Fluid Flow Influence Drug Release from Drug Filled Implants?

Drug-filled implants (DFIs) have emerged as an innovative approach to control the delivery of drugs. These devices contain the drug within the structure of the implant itself and avoid the need to include additional drug carrier materials such as a polymers, which are often associated with inflammation and delayed healing/tissue regeneration at the implant site. One common feature of in vitro experiments to generate drug release profiles is stirring or agitation of the release medium. However, the influence of the resulting fluid flow on the rate of drug release from DFIs has yet to be quantified. In this paper we consider two DFIs, which although similar in shape and size, employ different strategies to control the release of drug: a porous pin with pores on the order of μm and a pin drilled with orifices of the order of mm. We develop a multiphysics mathematical model of drug release from these DFIs, subject to fluid flow induced through stirring and show that fluid flow greatly influences the drug release profile for the orifice pin, but that the porous pin drug release profile is relatively insensitive to flow. We demonstrate that drug release from the porous pin may adequately be described through a simplified radial 1D dissolution-diffusion model, while a 3D dissolution-advection-diffusion model is required to describe drug release from the orifice pin. A sensitivity analysis reveals that that the balance of reaction-advection-diffusion in terms of key nondimensional numbers governs the overall drug release. Our findings potentially have important implications in terms of devising the most relevant experimental protocol for quantifying drug release from DFIs.

Natural Fibers vs. Synthetic Fibers Reinforcement: Effect on Resistance of Mortars to Impact Loads

Given their specific properties, their natural and renewable sources and their low environmental impact in production, natural fibers offer an opportunity for the development of eco-friendly cement-based composites. The main objective of this experimental work is to evaluate the resistance to the impact load of mortars incorporating natural fibers or polypropylene fibers at 28 days. The assessment was carried out according to an experimental protocol developed in our laboratory. The method consists in dropping a metallic ball on a square shaped specimen of 30x30x2 cm3 to determine the energy supported by each sample. For each specimen, the number of blows required for the first crack initiation and for the total collapse of specimen are detected using a device allowing to measure the speed of ultrasonic waves. The device was fixed on the specimen itself. In order to fulfill the mechanical identity card of the composites, flexural and compression tests were also carried out at 28 days. In this experimental protocol, the pozzolanic binder was considered with different fiber percentages of polypropylene (0.25% and 0.5% by mass of binder) and of natural fibers (0.5% and 1% by mass of binder). All fibers have a length of 12 mm. Results show that natural fiber reinforcement could be considered as an ecological alternative to polypropylene fiber one to improve the resistance of mortars to impact loads.

Methods for estimating and modelling spruce budworm development rates at constant temperatures

We describe an experimental protocol for measuring the response of spruce budworm postdiapause larval development to temperature. This protocol is specifically designed to include measurements of development near their upper and lower thermal thresholds. The application of this protocol to a laboratory colony allowed for the first experimental evidence that spruce budworm larval development occurs at temperatures as low as 5 °C and as high as 35 °C, and it provides data to fit stage-specific development models. Our protocol is also designed to minimise mortality near the thermal development thresholds, thus allowing for multigenerational studies. We observed developmental plasticity in larvae reared at constant temperatures, particularly the occurrence of up to 42% of some individuals requiring only five instars to complete development compared to the expected six instars. The occurrence exhibited no clear relation to temperature. Although this protocol is specifically designed for spruce budworm, it provides a template for the study of other species’ developmental responses to temperature.

Evaluation of Oxidative Stress potential of some Nsaıds against Hydrogen Peroxide in experimental animal

Background: Oxidative stress is imbalance between aggressive and defensive system. Overproduction of oxidative stress contribute in pathogenesis of many diseasesincluding Parkinsonism, Alzheimer diseases, apoptosis, hepatic fibrosis ,chronic kidney failure and liver steatosis etc . There are several OTC drugs including NSAIDs that generate oxidative stress when administered. So there is a need to explore about these drugs. Therefore this study was designed to evaluate the oxidative stress potential of Acetaminophen, acetyl salicylic acid and Celecoxib NSAIDs. Objective: The present study is design to investigate the oxidative stress of NSAIDs of acetaminophen, aspirin and Celecoxib drug with reference to the hydrogen peroxide. Material and method: The Experimental protocol was designed for estimate the level of oxidative stress in NSAIDs treated animals against hydrogen peroxides. Animal of control group received only vehicle throughout experimental protocol. Rats of AAP group, ASA group ,CX group were exposed to acetaminophen (150mg/kg; orally) acetyl salicylic acid (300mg/kg ;orally) and Celecoxib (50mg/kg; orally) for forty two days . Rodent of HP group were challenged with Hydrogen peroxides (0.5%) with same schedule as above. At end of experimental protocols, all the animals were sacrificed and their organ were identified and collected for oxidative stress estimation and histological examination. Result: NSAIDs administration caused increase in oxidative stress measured in terms of SOD, CAT, MDA, GSH and GPx. HP administration produced maximum oxidative stress compare to all other groups. Oxidative parameter i.e. SOD, CAT, GSH and GPx were found to be decreased as compare to control rats. However MDA were found to be increased as compare to control rats. Additionally, CX produced less oxidative stress compare to other NDAIDs. Further, histological examinations support the biochemical results. Conclusion: From the above observations it can be concluded that NSAIDs have oxidative stress potential and generate oxidative stress and damage the organs when administrated chronically. Thus, these drugs should be used judiciously.

Depolarized Mitochondrial Membrane Potential and Protection with Duroquinone in Isolated Perfused Lungs from Rats Exposed to Hyperoxia

Dissipation of mitochondrial membrane potential (Δψm) is a hallmark of mitochondrial dysfunction. our objective was to use a previously developed experimental-computational approach to estimate tissue Δψm in intact lungs of rats exposed to hyperoxia, and to evaluate the ability of duroquinone (DQ) to reverse any hyperoxia-induced depolarization of lung Δψm. Rats were exposed to hyperoxia (>95% O2) or normoxia (room air) for 48 hrs, after which lungs were excised and connected to a ventilation-perfusion system. The experimental protocol consisted of measuring the concentration of the fluorescent dye rhodamine 6G (R6G) during three single-pass phases: loading, washing, and uncoupling, in which the lungs were perfused with and without R6G, and with the mitochondrial uncoupler FCCP, respectively. For normoxic lungs, the protocol was repeated with 1) rotenone (complex I inhibitor), 2) rotenone and either DQ or its vehicle (DMSO), and 3) rotenone, glutathione (GSH), and either DQ or DMSO added to the perfusate. Hyperoxic lungs were studied with and without DQ and GSH added to the perfusate. Computational modeling was used to estimate lung Δψm from R6G data. Rat exposure to hyperoxia resulted in partial depolarization (-33 mV) of lung Δψm, and complex I inhibition depolarized lung Δψm by -83 mV. Results also demonstrate the efficacy of DQ to fully reverse both rotenone-induced and hyperoxia-induced lung Δψm depolarization. This study demonstrates hyperoxia-induced Δψm depolarization in intact lungs, and the utility of this approach for assessing the impact of potential therapies such as exogenous quinones that target mitochondria in intact lungs.

Validity and Reliability of a Protocol to Establish Human Critical Environmental Limits (PSU HEAT)

The PSU HEAT protocol has been used to determine critical environmental limits, i.e., those combinations of ambient temperature and humidity above which heat stress becomes uncompensable and core temperature rises continuously. However, no studies have rigorously investigated the reliability and validity of this experimental protocol. Here, we assessed the (1) between-visit reliability and (2) validity of the paradigm. Twelve subjects (5M/7W; 25±4 yr) completed a progressive heat stress protocol during which they walked on a treadmill (2.2 mph, 3% gradient) in a controllable environmental chamber. After an equilibration period, either dry-bulb temperature (Tdb) was increased every 5 min while ambient water vapor pressure (Pa) was held constant (Tcrit experiments) or Pa was increased every 5 min while Tdb was held constant (Pcrit experiments) until an upward inflection in gastrointestinal temperature (Tgi) was observed. For reliability experiments, 11 subjects repeated the same protocol on a different day. For validity experiments, 10 subjects performed a Tcrit experiment at their previously determined Pcrit or vice versa. The between-visit reliability (intraclass correlation coefficient, ICC) for critical environmental limits was 0.98. Similarly, there was excellent agreement between original and validity trials for Tcrit (ICC = 0.95) and Pcrit (ICC = 0.96). Further, the wet-bulb temperature at the Tgi inflection point was not different during reliability (p = 0.78) or validity (p = 0.32) trials compared to original trials. These findings support the reliability and validity of this experimental paradigm for the determination of critical environmental limits for maintenance of human heat balance.

Artificial Selection on Microbiomes To Breed Microbiomes That Confer Salt Tolerance to Plants

We developed an experimental protocol that improves earlier methods of artificial selection on microbiomes and then tested the efficacy of our protocol to breed root-associated bacterial microbiomes that confer salt tolerance to a plant. Salt stress limits growth and seed production of crop plants, and artificially selected microbiomes conferring salt tolerance may ultimately help improve agricultural productivity.

Sensory Behaviours and Resting Parasympathetic Functions among Children with and without ADHD

Previous studies suggest that parasympathetic functions support sensory behaviours. However, the relationship between sensory behaviours and parasympathetic functions remain inconclusive and inconsistent among children with and without attention-deficit hyperactivity disorder (ADHD). This research aims to examine the sensory behaviours and resting parasympathetic functions among children with and without ADHD. We compared sensory behaviours and baseline parasympathetic functions of 64 participants, with 42 typically developing and 24 ADHD male children aged 7–12 years. Sensory behaviours were evaluated using the sensory profile. Baseline parasympathetic functions were indexed using the normalized unit of heart rate variability high-frequency bands (HF n.u.). Children underwent an experimental protocol consisting of watching a silent cartoon movie while HF n.u. is continuously monitored, within a controlled environment. The results of this research showed significantly lower HF n.u. (t(64) = 7.84, p < 0.01 ) and sensory processing total score (t(64) = 14.13 = p < 0.01 ) among children with ADHD compared to their typically developing peers. Likewise, a significant moderate positive correlation (r = 0.36, p < 0.05 ) was found between the HF n.u. and sensory profile total scores among children with ADHD. Children with ADHD have significantly lower resting state parasympathetic functions compared to their typically developing peers.

Optimization of training and measurement protocol for eNose analysis of urine headspace aimed at prostate cancer diagnosis

More than one million new cases of prostate cancer (PCa) were reported worldwide in 2020, and a significant increase of PCa incidence up to 2040 is estimated. Despite potential treatability in early stages, PCa diagnosis is challenging because of late symptoms’ onset and limits of current screening procedures. It has been now accepted that cell transformation leads to release of volatile organic compounds in biologic fluids, including urine. Thus, several studies proposed the possibility to develop new diagnostic tools based on urine analysis. Among these, electronic noses (eNoses) represent one of the most promising devices, because of their potential to provide a non-invasive diagnosis. Here we describe the approach aimed at defining the experimental protocol for eNose application for PCa diagnosis. Our research investigates effects of sample preparation and analysis on eNose responses and repeatability. The dependence of eNose diagnostic performance on urine portion analysed, techniques involved for extracting urine volatiles and conditioning temperature were analysed. 192 subjects (132 PCa patients and 60 controls) were involved. The developed experimental protocol has resulted in accuracy, sensitivity and specificity of 83% (CI95% 77–89), 82% (CI95% 73–88) and 87% (CI95% 75–94), respectively. Our findings define eNoses as valuable diagnostic tool allowing rapid and non-invasive PCa diagnosis.

Effects of Heat Stress on Mating Behavior and Colony Development in Bombus terrestris (Hymenoptera: Apidae)

Climate change is related to an increase in the frequency and intensity of extreme events such as heatwaves. In insect pollinators, heat exposure is associated with direct physiological perturbations, and in several species, could lead to a decrease of fitness related to a decrease in fertility. Here we developed a new experimental protocol in controlled conditions to assess if the exposure to high temperatures could modify the attractiveness and fertility of Bombus terrestris males. Our results show that virgin queens of B. terrestris do not have preferences between the pheromonal secretions of heat-exposed and control males. Moreover, mating with a heat-exposed male has no impact on the copulation behavior and the development of the nest (brood composition). We advise to extend trials to cover a range of wild and heat-sensitive species on multiple generations to better understand the impact of heat waves on the bumblebee communities.