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At least 37 records · Page 2

Advances in multi-dimensional cellulose-based fluorescent carbon dot composites

Recently, fluorescent materials composed of carbon dots (CDs) have attracted increasing attention in diverse fields, including the environment, food, biology, and medicine. Cellulose has emerged as a promising class of materials for carriers due to its low cost, fascinating biodegradability, and various morphologies, especially in available different dimensions. By taking advantage of the respective superiority of fluorescent materials and cellulose carriers, the performance of fluorescence composite materials can be optimized and their application may be extended. Here, in this review, the study emphasizes the synthesis and applications of cellulose-based fluorescent materials with different dimensions. Moreover, some effective strategies and potential challenges for further development of cellulose-based fluorescent materials are discussed. A deeper understanding will provide a guide for the materials with ideal fluorescent performances.

42 ENGINEERING↗

Training Ultrasound Image Classification Deep-Learning Algorithms for Pneumothorax Detection Using a Synthetic Tissue Phantom Apparatus

Ultrasound (US) imaging is a critical tool in emergency and military medicine because of its portability and immediate nature. However, proper image interpretation requires skill, limiting its utility in remote applications for conditions such as pneumothorax (PTX) which requires rapid intervention. Artificial intelligence has the potential to automate ultrasound image analysis for various pathophysiological conditions. Training models require large data sets and a means of troubleshooting in real-time for ultrasound integration deployment, and they also require large animal models or clinical testing. Here, we detail the development of a dynamic synthetic tissue phantom model for PTX and its use in training image classification algorithms. The model comprises a synthetic gelatin phantom cast in a custom 3D-printed rib mold and a lung mimicking phantom. When compared to PTX images acquired in swine, images from the phantom were similar in both PTX negative and positive mimicking scenarios. We then used a deep learning image classification algorithm, which we previously developed for shrapnel detection, to accurately predict the presence of PTX in swine images by only training on phantom image sets, highlighting the utility for a tissue phantom for AI applications.

Boice, Emily N. (ORCID:0000000171802842)↗

Ultrathin Boron Growth onto Nanodiamond Surfaces via Electrophilic Boron Precursors

Diamond as a templating substrate is largely unexplored, and the unique properties of diamond, including its large bandgap, thermal conductance, and lack of cytotoxicity, makes it versatile in emergent technologies in medicine and quantum sensing. Surface termination of an inert diamond substrate and its chemical reactivity are key in generating new bonds for nucleation and growth of an overlayer material. Oxidized high-pressure high temperature (HPHT) nanodiamonds (NDs) are largely terminated by alcohols that act as nucleophiles to initiate covalent bond formation when an electrophilic reactant is available. In this work, we demonstrate a templated synthesis of ultrathin boron on ND surfaces using trigonal boron compounds. Boron trichloride (BCl 3 ), boron tribromide (BBr 3 ), and borane (BH 3 ) were found to react with ND substrates at room temperature in inert conditions. BBr 3 and BCl 3 were highly reactive with the diamond surface, and sheet-like structures were produced and verified with electron microscopy. Surface-sensitive spectroscopies were used to probe the molecular and atomic structure of the ND constructs’ surface, and quantification showed the boron shell was less than 1 nm thick after 1–24 h reactions. Observation of the reaction supports a self-terminating mechanism, similar to atomic layer deposition growth, and is likely due to the quenching of alcohols on the diamond surface. X-ray absorption spectroscopy revealed that boron-termination generated midgap electronic states that were originally predicted by density functional theory (DFT) several years ago. DFT also predicted a negative electron surface, which has yet to be confirmed experimentally here. The boron-diamond nanostructures were found to aggregate in dichloromethane and were dispersed in various solvents and characterized with dynamic light scattering for future cell imaging or cancer therapy applications using boron neutron capture therapy (BNCT). The unique templating mechanism based on nucleophilic alcohols and electrophilic trigonal precursors allows for covalent bond formation and will be of interest to researchers using diamond for quantum sensing, additive manufacturing, BNCT, and potentially as an electron emitter.

36 MATERIALS SCIENCE↗

Development and Characterization of a Self-Tightening Tourniquet System

Uncontrolled hemorrhage remains a leading cause of death in both emergency and military medicine. Tourniquets are essential to stopping hemorrhage in these scenarios, but they suffer from subjective, inconsistent application. Here, we demonstrate how tourniquet application can be automated using sensors and computer algorithms. The auto-tourniquet self-tightens until blood pressure oscillations are no longer registered by the pressure sensor connected to the pneumatic pressure cuff. The auto-tourniquet’s performance in stopping the bleed was comparable to manual tourniquet application, but the time required to fully occlude the bleed was longer. Application of the tourniquet was significantly smoother, and less variable, for the automatic tourniquet compared to manual tourniquet application. This proof-of-concept study highlights how automated tourniquets can be integrated with sensors to provide a much more consistent application and use compared to manual application, even in controlled, low stress testing conditions. Future work will investigate different sensors and tourniquets to improve the application time and repeatability.

Vega, Saul J.↗

Biomaterials and Magnetic fields for Cancer Therapy

The field of biomaterials has emerged as an important topic in the purview of NASA s new vision of research activities in the Microgravity Research Division. Although this area has an extensive track record in the medical field as borne out by the routine use of polymeric sutures, implant devices, and prosthetics, novel applications such as tissue engineering, artificial heart valves and controlled drug delivery are beginning to be developed. Besides the medical field, biomaterials and bio-inspired technologies are finding use in a host of emerging interdisciplinary fields such as self-healing and self-assembling structures, biosensors, fuel systems etc. The field of magnetic fluid technology has several potential applications in medicine. One of the emerging fields is the area of controlled drug delivery, which has seen its evolution from the basic oral delivery system to pulmonary to transdermal to direct inoculations. In cancer treatment by chemotherapy for example, targeted and controlled drug delivery has received vast scrutiny and substantial research and development effort, due to the high potency of the drugs involved and the resulting requirement to keep the exposure of the drugs to surrounding healthy tissue to a minimum. The use of magnetic particles in conjunction with a static magnetic field allows smart targeting and retention of the particles at a desired site within the body with the material transport provided by blood perfusion. Once so located, the therapeutical aspect (radiation, chemotherapy, hyperthermia, etc.) of the treatment, now highly localized, can be implemented.

Ramachandran, Narayanan↗

State-of-the-art γ-ray assay of 86 Y for medical imaging

An emerging direction in nuclear medicine is the coupling of a therapeutic isotope with an imaging isotope to form a so-called theranostic pair, which allows one to quantitatively track and image the delivery of the therapeutic isotope. 90 Y is used in several therapy applications and a convenient candidate imaging partner is the positron emitter 86 Y. A 27.6 MBq source of 86 Y was produced at the University of Wisconsin and assayed with the Gammasphere array at Argonne National Laboratory. Over 200 γ-ray transitions were identified, more than double that which was previously known. In conclusion, the positron emission probability inferred from the present level scheme leads to 27.9(12)%, an important (≈14%) reduction with respect to the previously recommended value.

59 ≤ A ≤ 89↗

Application of an Electronic Medical Record in Space Medicine

Electronic Medical Records (EMR) have been emerging over the past decade. Today, they are replacing the paper chart in clinics throughout the nation. Approximately three years ago, the NASA-JSC Flight Medicine Clinic initiated an assessment of the EMRs available on the market. This assessment included comparing these products with the particular scope of practice at JSC. In 1998, the Logician EMR from Medicalogic was selected for the JSC Flight Medicine Clinic. This presentation reviews the process of selection and implementation of the EMR into the unique practice of aerospace medicine at JSC.

McGinnis, Patrick J.↗

Physiological effects of light on the human circadian pacemaker

The physiology of the human circadian pacemaker and its influence and on the daily organization of sleep, endocrine and behavioral processes is an emerging interest in science and medicine. Understanding the development, organization and fundamental properties underlying the circadian timing system may provide insight for the application of circadian principles to the practice of clinical medicine, both diagnostically (interpretation of certain clinical tests are dependent on time of day) and therapeutically (certain pharmacological responses vary with the time of day). The light-dark cycle is the most powerful external influence acting upon the human circadian pacemaker. It has been shown that timed exposure to light can both synchronize and reset the phase of the circadian pacemaker in a predictable manner. The emergence of detectable circadian rhythmicity in the neonatal period is under investigation (as described elsewhere in this issue). Therefore, the pattern of light exposure provided in the neonatal intensive care setting has implications. One recent study identified differences in both amount of sleep time and weight gain in infants maintained in a neonatal intensive care environment that controlled the light-dark cycle. Unfortunately, neither circadian phase nor the time of day has been considered in most clinical investigations. Further studies with knowledge of principles characterizing the human circadian timing system, which governs a wide array of physiological processes, are required to integrate these findings with the practice of clinical medicine.

Review, Tutorial↗

Optic Nerve Sheath Diameter: Translating a Terrestrial Focused Technique into a Clinical Monitoring Tool for Spaceflight

Ultrasonography is increasingly used to quickly measure optic nerve sheath diameter (ONSD) when increased intracranial pressure (ICP) is suspected. NASA Space and Clinical Operations Division has been using ground and on‐orbit ultrasound since 2009 as a proxy for ICP in non‐acute monitoring for space medicine purposes. In the terrestrial emergency room population, an ONSD greater than 0.59 cm is considered highly predictive of elevated intracranial pressure. However, this cut‐off limit is not applicable to the spaceflight setting since over 50% of US Operating Segment (USOS) astronauts have an ONSD greater than 0.60 cm even before launch. Crew Surgeon clinical decision‐making is complicated by the fact that many astronauts have history of previous spaceflights. Our data characterize the distribution of baseline ONSD in the astronaut corps, its longitudinal trends in long‐duration spaceflight, and the predictive power of this measure related to increased ICP outcomes.

Mason, Sara↗

Providing Housing, Food and Medical Support for 25,000 Katrina Evacuees with 12 Hours Notice: The Harris County Medical Support of the Superdome Evacuees

Hurricane Katrina was responsible for trapping 25,000 people in the New Orleans Superdome and isolating many others throughout Louisiana and Mississippi. The transport of these evacuees to the Reliant Park (Houston, Texas) used 500 buses each containing about 55 people. Processing the arriving evacuees included addressing their health status and medical needs as follows: an initial triage at disembarkation, a secondary triage in the Reliant Astrodome and Center, and definitive clinical care in the Reliant Arena "Katrina" Clinic. Baylor College of Medicine (BCM) physicians boarded buses and identified the sickest for emergency transport to Harris County Hospital District (HCHD) hospitals. BCM departments represented included pediatrics, family and community medicine, internal medicine, radiology, obstetrics and gynecology, orthopedics, surgery, and psychiatry. Astrodome and Center triage was managed by BCM physicians and staffed by HCHD Nurses and volunteers from Texas and beyond. The Reliant Astrodome, Center and Arena reached peak headcounts of 15,000,4500, and 2500, respectively Most evacuees visiting the triage sites in the Astrodome and Center were treated using "over-the-counter" medications with the remaining being transported to the "Katrina" clinic. The clinic was equipped with a lab, pharmacy, digital X-ray, and ultrasound machines in addition to electronic patient records created using 80 computer terminals. The Katrina clinic saw more than 15,000 patients during 15 days of operations (2,000 on the first full day), administered 10,000 tetanus shots, and filled thousands of prescriptions. At the peak of operations, the clinic saw 150 patients/hour with 25 physicians scheduled for each 12-hour shift. Approximately 900 people were transported to hospital emergency rooms. Within 3 weeks of arriving at the Reliant Park facilities, more than 90% of the families found permanent housing, enrolled children in schools, and found work. Using data obtained from manual and electronic medical records, this presentation will document the major milestones and lessons learned from this extraordinary project to help the Katrina evacuees.

Hamilton, Douglas↗

Radioarsenic: A promising theragnostic candidate for nuclear medicine

Molecular imaging is a non-invasive process that enable the visualization, characterization, and quantitation of biological processes at the molecular and cellular level. With the emergence of theragnostic agents to diagnose and treat disease for personalized medicine there is a growing need for matched pairs of isotopes. Matched pairs offer the unique opportunity to obtain patient specific information from SPECT or PET diagnostic studies to quantitate in vivo function or receptor density to inform and tailor therapeutic treatment. There are several isotopes of arsenic that have emissions suitable for either or both diagnostic imaging and radiotherapy. Their half-lives are long enough to pair them with peptides and antibodies which take longer to reach maximum uptake to facilitate improved patient pharmacokinetics and dosimetry then can be obtained with shorter lived radionuclides. Arsenic-72 even offers availability from a generator that can be shipped to remote sites and thus enhances availability. Arsenic has a long history as a diagnostic agent, but until recently has suffered from limited availability, lack of suitable chelators, and concerns about toxicity have inhibited its use in nuclear medicine. However, new production methods and novel chelators are coming online and the use of radioarsenic in the pico and nanomolar scale is well below the limits associated with toxicity. This manuscript will review the production routes, separation chemistry, radiolabeling techniques and in vitro/in vivo studies of three medically relevant isotopes of arsenic (arsenic-74, arsenic-72, and arsenic-77).

07 ISOTOPE AND RADIATION SOURCES↗

Multidrug Efflux Pumps and the Two-Faced Janus of Substrates and Inhibitors

Antibiotics are miracle drugs that can cure infectious bacterial diseases. However, their utility is challenged by antibiotic resistant bacteria emerging in clinics and straining the modern medicine and our ways of life. Certain bacteria such as Gram-negative (Gram(- )) and Mycobacteriales species are intrinsically resistant to most clinical antibiotics and can further gain multidrug resistance through mutations and plasmid acquisition. These species stand out by the presence of an additional external lipidic membranes (the outer membrane, OM) that are composed of unique glycolipids. Although formidable, the OM is a passive permeability barrier that can reduce penetration of antibiotics but cannot affect intracellular steady-state concentrations of drugs. The two-membrane envelopes are further reinforced by active efflux transporters that expel antibiotics from cells against their concentration gradients. The major mechanism of antibiotic resistance in Gram(-) pathogens is the active efflux of drugs, which acts synergistically with the low permeability barrier of the OM and other mutational and plasmid-borne mechanisms of antibiotic resistance.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Global transcriptome profile of the developmental principles of in vitro iPSC-to-motor neuron differentiation

Abstract Background Human induced pluripotent stem cells (iPSC) have opened new avenues for regenerative medicine. Consequently, iPSC-derived motor neurons have emerged as potentially viable therapies for spinal cord injuries and neurodegenerative disorders including Amyotrophic Lateral Sclerosis. However, direct clinical application of iPSC bears in itself the risk of tumorigenesis and other unforeseeable genetic or epigenetic abnormalities. Results Employing RNA-seq technology, we identified and characterized gene regulatory networks triggered by in vitro chemical reprogramming of iPSC into cells with the molecular features of motor neurons (MNs) whose function in vivo is to innervate effector organs. We present meta-transcriptome signatures of 5 cell types: iPSCs, neural stem cells, motor neuron progenitors, early motor neurons, and mature motor neurons. In strict response to the chemical stimuli, along the MN differentiation axis we observed temporal downregulation of tumor growth factor-β signaling pathway and consistent activation of sonic hedgehog, Wnt/β-catenin, and Notch signaling. Together with gene networks defining neuronal differentiation (neurogenin 2, microtubule-associated protein 2, Pax6, and neuropilin-1), we observed steady accumulation of motor neuron-specific regulatory genes, including Islet-1 and homeobox protein HB9. Interestingly, transcriptome profiling of the differentiation process showed that Ca 2+ signaling through cAMP and LPC was downregulated during the conversion of the iPSC to neural stem cells and key regulatory gene activity of the pathway remained inhibited until later stages of motor neuron formation. Pathways shaping the neuronal development and function were well-represented in the early motor neuron cells including, neuroactive ligand-receptor interactions, axon guidance, and the cholinergic synapse formation. A notable hallmark of our in vitro motor neuron maturation in monoculture was the activation of genes encoding G-coupled muscarinic acetylcholine receptors and downregulation of the ionotropic nicotinic acetylcholine receptors expression. We observed the formation of functional neuronal networks as spontaneous oscillations in the extracellular action potentials recorded on multi-electrode array chip after 20 days of differentiation. Conclusions Detailed transcriptome profile of each developmental step from iPSC to motor neuron driven by chemical induction provides the guidelines to novel therapeutic approaches in the re-construction efforts of muscle innervation.

59 BASIC BIOLOGICAL SCIENCES↗

Tropical medicine: Telecommunications and technology transfer

The potential for global outbreaks of tropical infectious diseases, and our ability to identify and respond to such outbreaks is a major concern. Rapid, efficient telecommunications is viewed as part of the solution to this set of problems - the means to link a network of epidemiological field stations via satellite with U.S. academic institutions and government agencies, for purposes of research, training in tropical medicine, and observation of and response to epidemic emergencies. At a workshop, telecommunications and technology transfer were addressed and applications of telecommunications technology in long-distance consultation, teaching and disaster relief were demonstrated. Applications in teaching and consultation in tropical infectious diseases is discussed.

Legters, Llewellyn J.↗

The microbicidal potential of visible blue light in clinical medicine and public health

Visible blue light of wavelengths in the 400–470 nm range has been observed to have microbicidal properties. A widely accepted hypothesis for the mechanism of microbial inactivation by visible blue light is that the light causes photoexcitation of either endogenous (present within the microbe) or, exogenous (present in the biological medium surrounding the microbe) photosensitizers such as porphyrins and flavins, which leads to the release of reactive oxygen species that subsequently manifests microbicidal activity. Some of the factors that have been observed to be associated with enhanced microbicidal action include increased duration of exposure, and either pre- or co-treatment with quinine hydrochloride. In case of bacteria, repetitive exposure to the blue light shows no significant evidence of resistance development. Additionally, visible blue light has exhibited the ability to inactivate fungal and viral pathogens and, multidrug-resistant bacteria as well as bacterial biofilms. Visible blue light has demonstrated efficacy in eliminating foodborne pathogens found on food surfaces and exposed surfaces in the food processing environment as well as in the decontamination of surfaces in the clinical environment to minimize the spread of nosocomial infections. We conclude from reviewing existing literature on the application of the blue light in clinical medicine and public health settings that this microbicidal light is emerging as a safer alternative to conventional ultraviolet light-based technologies in multiple settings. However, further comprehensive studies and thorough understanding of the mechanism of microbicidal action of this light in different scenarios is warranted to determine its place in human health and disease.

60 APPLIED LIFE SCIENCES↗

A goldilocks computational protocol for inhibitor discovery targeting DNA damage responses including replication-repair functions

While many researchers can design knockdown and knockout methodologies to remove a gene product, this is mainly untrue for new chemical inhibitor designs that empower multifunctional DNA Damage Response (DDR) networks. Here, we present a robust Goldilocks (GL) computational discovery protocol to efficiently innovate inhibitor tools and preclinical drug candidates for cellular and structural biologists without requiring extensive virtual screen (VS) and chemical synthesis expertise. By computationally targeting DDR replication and repair proteins, we exemplify the identification of DDR target sites and compounds to probe cancer biology. Our GL pipeline integrates experimental and predicted structures to efficiently discover leads, allowing early-structure and early-testing (ESET) experiments by many laboratories. By employing an efficient VS protocol to examine protein-protein interfaces (PPIs) and allosteric interactions, we identify ligand binding sites beyond active sites, leveraging in silico advances for molecular docking and modeling to screen PPIs and multiple targets. A diverse 3,174 compound ESET library combines Diamond Light Source DSI-poised, Protein Data Bank fragments, and FDA-approved drugs to span relevant chemotypes and facilitate downstream hit evaluation efficiency for academic laboratories. Two VS per library and multiple ranked ligand binding poses enable target testing for several DDR targets. This GL library and protocol can thus strategically probe multiple DDR network targets and identify readily available compounds for early structural and activity testing to overcome bottlenecks that can limit timely breakthrough drug discoveries. By testing accessible compounds to dissect multi-functional DDRs and suggesting inhibitor mechanisms from initial docking, the GL approach may enable more groups to help accelerate discovery, suggest new sites and compounds for challenging targets including emerging biothreats and advance cancer biology for future precision medicine clinical trials.

59 BASIC BIOLOGICAL SCIENCES↗

Risk of Performance and Behavioral Health Decrements Due to Inadequate Cooperation, Coordination, and Psychosocial Adaptions within a Team

The Risk of Performance and Behavioral Health Decrements Due to Inadequate Cooperation, Coordination, Communication, and Psychosocial Adaptation within a Team (the Team Risk) is primarily performance-focused, with a secondary emphasis on behavioral health outcomes resulting from team performance and interpersonal interactions. Monitoring tools, measures, and countermeasures are aimed at enhancing team processes and team composition configurations to optimize team performance and functioning. Long-duration exploration missions (LDEMs) will include major challenges that could affect team performance, including social isolation, physical confinement, a small and diverse crew, communication delays between crew and ground, limited or no crew rotation or evacuation options, limited or no resupply, and a high-consequence environment. Each of these conditions will affect the crew’s coordination, cooperation, psychological well-being, and performance. Although the International Space Station (ISS) remains important for studies that require spaceflight testing and validation, the current conditions on the ISS do not adequately mimic the exploration environment that is required for National Aeronautics and Space Administration (NASA) teams research, and thus access to terrestrial or ground-based analogs of LDEM conditions is paramount. The emphasis on analogs for research is reflected in this updated evidence review of the Team Risk, and includes data from studies conducted at isolated, confined, extreme (ICE) environments (e.g., Antarctic stations), and from several mission simulation analogs such as the Human Exploration Research Analog (HERA) (HERA Experiment Information Package, 2014), also known as isolated, confined, controlled (ICC) environments. These studies have characterized many team factors regarding LDEMs, and the Team Risk has now matured from risk characterization to focusing more on countermeasure development. Because spaceflight evidence for team-level research is lacking, no reliable data is available to quantify the impact of team-level variables on individual and team-level outcomes during spaceflight missions. Until recently, no systematic attempt had been undertaken to measure the performance effects of team cohesion, team composition, team training, or team-related psychosocial adaptation during spaceflight. The Team Risk is a relatively young research area for NASA, with substantial growth only since the 2000s, and with limited access to spaceflight performance data. As a result, spaceflight evidence is lacking to identify specifically what team composition, level of training, amount of cohesion, or quality of psychosocial adaptation is necessary to reduce the risk of performance errors in space. However, astronaut journals and interviews and reports from spaceflight subject matter experts (SMEs) provide testimonies that team performance during spaceflight is important for mission success and to maintain crew health. Team spaceflight data is now being collected as part of the Spaceflight Standard Measures task (Clement, 2021)—a set of core measurements related to many human spaceflight risks that are collected from astronauts before, during, and after long-duration missions. The team-related standard measures focus on team cohesion, team performance, group living, team climate, and team processes. Collection of standard measures data is ongoing and published data is not yet available. Finally, although spaceflight evidence is lacking, evidence gleaned from ground studies and spaceflight analog studies will help close the gaps outlined in the Team Risk. Ground-based studies provide quantitative evidence for team functioning in ICE environments. Academic research on teams has produced dozens of meta-analyses that can be used to understand the general relationships among team inputs (e.g., team member characteristics and skills, job context), team processes, and emergent states (e.g., coordination, communication, cooperation, cohesion, trust, shared cognition), and team outcomes (e.g., effectiveness, errors, adaptation). Teams are complex, incorporating individual characteristics of team members, but also existing at a level that is greater than the sum of its parts. Therefore, the Team Risk must be integrated with other individual-focused NASA Human Research Program (HRP) risks, including Behavioral Medicine (BMed), Sleep, and Human-Systems Integration Architecture (HSIA), and emerging research indicates more integration may needed between the Team Risk and the physiologically oriented risks. Much of this integration occurs through the Human Systems Risk Board (HSRB). A lack of team functioning may be a stressor in some circumstances, but the team often acts as a countermeasure. For example, support for team leaders and teammates can facilitate individual functioning and encourage psychological and physically healthy behaviors and attitudes. However, more research is needed regarding teams during LDEMs and the remaining gaps in the research are described in the current report.

Lauren Blackwell Landon↗