Automated Alternative Compression/Traction of Lower Extremities AACT as a Musculoskeletal Countermeasure to Mitigate Bone Loss and Muscle Atrophy in Microgravity
Space Medicine and relevant sciences are still considered a new era; the first humankind steps toward the space took place since less than 60 years. It has been noticed the adverse effects of microgravity on the human body in different aspects, our concern here is the musculoskeletal aspect. On the ground we didn’t notice how we can stand up, or how our muscles and bones of the lower limbs can keep us standing up right. This is by a complicated process including the bones, the equilibrium, and the anti-gravitational muscles of the lower limbs which occurred without thinking about it. The force of Earth gravity against our bones of the lower limbs makes them harder and makes the muscles stronger, because they are interfacing the earth gravitational force every moment we are standing up, as per Newton’s third law (for every action in nature there is an equal and opposite reaction), such forces are unavailable in space and its effect being obvious on arrival to earth after long stay space flights, so being unable to keep standing upright easily on their arrival. On return to earth the routine medical examinations revealed loss of astronaut muscle mass and bone density particularly of their lower extremities because they did not use them in space for a long time. Currently, astronauts on board of ISS (International Space Station) they accomplish daily tasks including resistive exercises ARED “Advanced Resistive Exercise Device” in form of treadmill, ergometer, and weightlifting machine, to decrease the loss of bone density and muscle mass of their lower limbs. Despite their discipline to those exercises they still lose 1-2% of the muscle mass and bone density that give importance to add some protective measures to keep their muscles and bones healthy. Through this article, the idea is to make a device such AACT (Automated Alternative Compression/Traction) to be applied daily to the astronauts lower limbs as part of their daily exercise during space flight to give push/traction forces to astronauts lower limbs to prevent or at least decrease such loss, by AACT we are mimicking the gravitational force of earth on astounds lower limbs during long space flights to let them be healthy till they come back.
Sport specific assessment of inter-limb asymmetries: A way to reduce injuries
In recent years, lower inter-limb asymmetries have become a topic of increasing interest in sports research. Numerous studies have investigated the occurrence of between-limb differences in a variety of physical tests, ranging from strength, sprinting, and change of direction speed to jumping tasks. The main focus has been the association of asymmetries to either enhanced injury risk or reduced physical performance. Sport specific aspects and differences of lower limb asymmetries have not often been analysed. Additionally, most studies have been performed with male athletes. Women, however, present higher prevalence of lower limb asymmetries in strength, coordination, and postural control than men. These two aspects were therefore addressed in the present study. Female youth soccer (n=18, age: 16.7 ± 0.8 years) and floorball (n=18, age: 17.6 ± 0.9 years) players completed a test battery consisting of six unilateral jumping tasks in horizontal and lateral direction to detect sport specificity in inter-limb asymmetries. The test comprised the following hops: (1) Single Leg Hop for Distance and (2) a newly created version of it, (3) Single Leg Triple Hop, (4) Single Leg Crossover Hop, (5) Side Hop and (6) Single Leg 6-meters Timed Hop. The scores of every jump were calculated into Limb Symmetry Indexes for each participant. A linear mixed effect (LME) model (using function lmer in program R) was applied to evaluate the effects of sport and jump type on asymmetries. In terms of the whole test battery, there was a significantly higher magnitude of asymmetries in soccer compared to floorball (p=0.0067) with a mean difference of 1.9%. Three significant differences between the effects of different jump types were detected (5>2: p=0.027; 5>3: p6: p=0.014). Moreover, the results showed no significant effect on leg dominance. According to the findings of this study, soccer appears to be more asymmetric than floorball, leading to the suggestion that inter-limb asymmetries may not only be task-specific, but also sportspecific. Since no significant correlations were detected, this study suggests that inter-limb asymmetries are independent of leg dominance. Considering the possible reduction in athletic performance and increasing injury risk, strength and conditioning coaches are advised to assess athletes' inter-limb asymmetries using a broad, sport specific test battery and decrease them.
EIPCA : Electrocardiogram Interpretation Pattern for Cardiovascular Abnormalities Prediction
Cardiac Arrhythmia is one of the conditions in the group of heart and blood vessel diseases that can lead to sudden cardiac arrest (sudden death) and other conditions if not diagnosed quickly and accurately. According to research, heart and blood vessel diseases are the most common diseases and have a mortality rate of one-half of all non-communicable diseases. According to WHO statistics in 2012, it was found that there were 7.4 million deaths from heart and blood vessel diseases, and in 2017, the number of deaths increased to 177 million people, or about 94,444 people per day. Diagnosis of heart and blood vessel diseases can be done by measuring the electrical activity of the heart, and after the examination, a specialized physician will read and analyze the graph to find abnormal patterns. Currently, the shortage of qualified heart specialists to read the graph and screen for heart disease is a medical position shortage, which requires transferring data to hospitals with specialists, resulting in delays in diagnosis and treatment and even death. The project "EIPCA: Electrocardiogram Interpretation Pattern for Cardiovascular Abnormalities prediction" is an application program that assists in screening for fatal diseases that arise from abnormal heart rhythm. It employs artificial intelligence to aid in the screening and analysis of the electrical waveforms generated by an ECG machine, thus reducing diagnosis time and addressing the shortage of cardiology experts. EIPCA is comprised of two systems: (1) a system for screening and analyzing ECG waveforms using artificial intelligence to solve the problem of a shortage of specialized cardiology physicians, and (2) a system for risk assessment of fatal diseases by analyzing the ECG waveform data. The target group of the project is Rural hospitals, as well as health-related agencies. The project team hopes that the development of this project will significantly improve the efficiency and speed of screening for heart-related diseases, ultimately reducing the mortality rate from these diseases in the future.
Production of Nano-Composite Artificial Bone Tissue Using Bioceramic Synthesis from Bio-Waste
Certain specially structured ceramics, which can be used as biomaterials to replace bone, have recently started being utilized in the medical field. The aim of this study is to produce high-bioactivity silica from corn cob waste, a widely available organic material in nature, and combine it with calcium oxide (CaO) obtained by grinding organic mussel shell waste with high bioactivity. This combination is intended to synthesize dicalcium silicate (2CaO.SiO₂) to develop an alternative tissue scaffold with high bioactivity, capable of replacing bone, for existing titanium alloys. The goal is to incorporate this scaffold into PEEK (polyether ether ketone), a novel tissue scaffold material, at varying percentages to create a next-generation innovative bone substitute material. An additional objective is to demonstrate through biocompatibility tests that the produced ceramic-polymer biocomposite exhibits antibacterial activity against Staphylococcus aureus.
Natural resources utilization for the in-house production of fluorescence lipid nanoparticles
Nanotechnology, a transformative force, has steadily gained traction across multiple scientific disciplines, including physics, chemistry, engineering, and biology. It offers unprecedented capabilities, especially in the realm of nanoscale particles, ushering in new paradigms in various applications. One of the most revolutionary applications of nanotechnology is in the pharmaceutical sector. Here, nanoparticles have transformed drug and vaccine delivery systems, offering both efficacy and precision. Among these nanoparticles, lipid nanoparticles (LNPs) have stood out, especially for their role in delivering nucleic acid-based drugs and vaccines. These LNPs are intricate assemblies composed of lipids and nucleic acid complexes, offering an amalgamation of stability and deliverability. Such properties have rendered LNPs as invaluable tools in enhancing therapeutic efficacy while minimizing off-target side effects. The myriad of nanoparticles available includes the likes of silver, gold, and lipid nanoparticles. However, the emphasis of this research lies with lipid nanoparticles, given their widespread success in the pharmaceutical arena. LNPs have showcased their potential in delivering drugs with low therapeutic indices, emphasizing their capability to act as versatile platforms for novel drug development. Recent advances have further expanded the horizons of LNPs, paving the way for novel antisense oligonucleotides, innovative vaccines, and complex lipid nanoparticle formations. Characterizing these nanoparticles is paramount, not only for the development of novel drugs but also to comprehend their in vivo behavior. Their multifaceted nature, stemming from their unique excipients, core-bilayer design, and varying sizes, makes their characterization a critical step in the research and development pipeline.
In silico Investigation of Cyclosporine Conjugates as Potential Anti-angiogenic Agents via NFAT Inhibition
Calcineurin (CN) activation is a main cause of cancerous tumor formation, one of the leading causes of death globally. Cyclosporine-A (CsA) is a commercially available oral drug that inhibits CN activation; however, low bioavailability limits its use. Nine patented CsA conjugates are potential alternatives to CsA as they have improved cytotoxicities and bioavailabilities but unknown CN-binding affinity. This study aimed to identify the CNinhibition strength and bioavailability of CsA conjugates in silico drug-likeness evaluation via modified Lipinski’s Rule of Five was done on CsA, voclosporin, and CsA conjugates to test bioavailability. The binding affinities of bioavailable compounds were computed via docking to CN in five trials, and the binding affinities were compared. The Water-soluble, RVal, IIA, Alpha, and MeBmt 2 conjugates showed improved bioavailabilities compared to CsA as they passed the drug-likeness screening. After five trials of computational docking to CN, the IIA and RVal conjugates showed improved binding affinities at -15.8 kcal/mol and -15.2 kcal/mol, respectively, compared to CsA at -14.3 kcal/mol. Notably, IIA also showed an improved binding affinity compared to voclosporin at -15.5 kcal/mol. These results suggest that CsA conjugates may be better oral chemotherapeutic drugs than CsA.
Eradicating Cystic Fibrosis Biofilms by a Novel Non-Toxic, Multi-Pathway Salicylate Therapy
1.1. Cystic Fibrosis Biofilms Biofilms are bacterial aggregates in a matrix of polysaccharides, proteins and nucleic acids (Donlan, 2002). They account for 80% of all chronic infections and cause over 500,000 deaths annually. Cystic fibrosis (CF) is a genetic disorder characterized by mucus accumulation in the respiratory tracts (Morrison et al., 2020). This impairs mucociliary clearance, allowing chronic colonization by bacterial biofilms, leading to fatal respiratory failure, lung scarring, and necrosis of pulmonary epithelial tissues (Martin et al., 2021). 1.2. Obstacles in Current Treatments Three major therapies are used against CF biofilms: (1) aminoglycoside antibiotics like tobramycin, (2)non-aminoglycoside antibiotics such as ciprofloxacin and vancomycin, and (3) non-antibiotic therapies including flushing, chlorination, and ultraviolet disinfection. These have two major flaws. First, they are cytotoxic; 30% of patients experience acute kidney injury after three days of intravenous aminoglycoside therapy (Joyce et al., 2017). Furthermore, non-aminoglycoside therapies can cause phospholipid buildup in lysosomes of proximal tubule epithelial cells, accounting for 10-20% of acute renal failure cases. Second, antibiotic resistance due to horizontal gene transfer and mutations has significantly reduced treatment effectiveness. Therefore, cystic fibrosis biofilms remain a critical threat with few effective treatments. 1.3. Salicylate Derivatives This project tackled this issue using an innovative non-antibiotic approach with salicylate derivatives. Salicylates, a class of benzoic acids—benzene-based carboxylic acids (Figure 1)—used in painkillers and blood thinners, were investigated for their antibiofilm potential through a 3-step process: 1. Literature review: Identified three key biofilm therapeutic targets: quorum sensing, bacterial adhesion, and cell motility. Disrupting these pathways would result in biofilm eradication. 2. Molecule Identification: Recognized key molecules in each pathway: LasR, adhesins, and flagellin. Inhibiting these molecules would disrupt the pathways. 3. Screening: Found that salicylates could inhibit the identified molecules, though they had never been tested against cystic fibrosis biofilms.
Trojan Horses in the Fight against Skin Cancer
In photodynamic therapy (PDT), reactive oxygen species are generated within the cytoplasm to destroy cancer cells selectively. Using porphyrinic structures (PS) as photosensitizers holds promise for targeting cancer cells. However, direct incorporation of the porphyrins into cancer cells remains elusive. Hence, Dr. Martina Vermathen’s research introduced specific membranous phospholipid nanocarriers for topical porphyrin applications. However, since a sufficiently high enough concentration of PS in cancer cells has not yet been achieved, this study aimed to improve skin uptake of the nanocarriers. Two approaches were examined: (1) comparing polar and nonpolar porphyrins and (2) assessing the effect of a penetration enhancer, DMSO, through a neat and diluted application. The polarity of the porphyrins was first quantified with a log P test. The nanocarriers were assembled by incorporating two different PS compounds, either the mono- or tetra-4-carboxy substituted phenyl porphyrin. They were then characterized by 1D and 2D-NMR analysis. The porphyrin permeation was tested by Franz diffusion tests on pig ear skin. For the second approach, DMSO was added in the Franz diffusion test, either directly applied on the skin (“neat“) or diluted in the nanocarriers (“diluted”). The log P test for the mono- and the tetra-carboxyphenyl porphyrin resulted in values of 4.5 and -1.1, respectively. The more polar tetra-carboxyphenyl porphyrin exhibited 2.8 times better skin uptake compared to the mono-carboxyphenyl porphyrin. The neat DMSO application increased uptake by a factor of 5.5. The diluted DMSO application worsened skin uptake slightly. Analytical techniques revealed differences in porphyrin encapsulation: The mono-carboxyphenyl porphyrins were encapsulated in the centre, whereas tetra-carboxyphenyl porphyrins were localised around the nanocarriers. Results indicated potential instability of the nanocarriers. The more polar tetra-substituted porphyrins showed superior skin diffusion than the mono-substituted derivative. The neat DMSO application facilitated enhanced skin uptake by inducing membrane destabilization and pore formation but may have limited applicability. Further research is suggested to explore porphyrinic PS with alternative polar substitution patterns and tailored penetration enhancers for lipid-based delivery systems. Overall, the study underscores the importance of molecular properties of the PS system and demonstrates the potential of penetration enhancers in optimizing PDT for skin cancer treatment.