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At least 1,045 records · Page 58

Knowledge Network Embedding of Transcriptomic Data From Spaceflown Mice Uncovers Signs and Symptoms Associated With Terrestrial Diseases

There has long been an interest in understanding how the hazards from spaceflight may trigger or exacerbate human diseases. With the goal of advancing our knowledge on physiological changes during space travel, NASA GeneLab provides an open-source repository of multi-omics data from real and simulated spaceflight studies. Alone, this data enables identification of biological changes during spaceflight, but cannot infer how that may impact an astronaut at the phenotypic level. To bridge this gap, SPOKE, a heterogeneous knowledge graph connecting biological and clinical data from over 30 databases, was used in combination with GeneLab transcriptomic data from six studies. This integration identified critical symptoms and physiological changes incurred during spaceflight.

spaceflight↗

Indices of Cardiovascular Disease Risk in Astronauts After Long-Duration Spaceflight in Low Earth Orbit

Current human spaceflight missions consist primarily of 4-6 month stays onboard the International Space Station (ISS), but in the future will include longer missions to the Moon and Mars. These missions will expose astronauts to increased risk of oxidative and inflammatory damage from a variety of sources (e.g., galactic cosmic radiation, psychological stress, reduced physical activity). Earth-based evidence suggests that increased oxidative stress and inflammation accelerates development of cardiovascular disease, but it is unclear if the spaceflight environment increases this risk in astronauts.

S M C Lee↗

Evaluation of the Spaceflight Cardiovascular Disease Risk using the Clinical Prediction Model Astro-Charm and the NASA Radiation Risk Model

Exposure to space radiation and other spaceflight hazards may pose an increased risk for cardiovascular diseases (CVD) during and after spaceflight [1], that should be quantified to plan future long-duration space missions such as the flight to Mars. The first CVD clinical prediction models (CPMs) for individuals were developed by the Framingham Heart Study investigators in the 1960’s. Since then, many CPMs have been developed and refined. The CPMs consider cardiovascular risk factors such as blood pressure, diabetes, cholesterol, and smoking. As there is a relationship between radiation-induced CVD risk and the background (non-exposed) CVD risk, it is possible to use CPMs to calculate a personalized risk for astronauts.

I. Plante↗

Automated diagnostic kiosk for diagnosing diseases

An automated and autonomous diagnostic apparatus that is capable of dispensing collection vials and collections kits to users interesting in collecting a biological sample and submitting their collected sample contained within a collection vial into the apparatus for automated diagnostic services. The user communicates with the apparatus through a touch-screen monitor. A user is able to enter personnel information into the apparatus including medical history, insurance information, co-payment, and answer a series of questions regarding their illness, which is used to determine the assay most likely to yield a positive result. Remotely-located physicians can communicate with users of the apparatus using video tele-medicine and request specific assays to be performed. The apparatus archives submitted samples for additional testing. Users may receive their assay results electronically. Users may allow the uploading of their diagnoses into a central databank for disease surveillance purposes.

60 APPLIED LIFE SCIENCES↗

Tracers for monitoring the activity of sodium/glucose cotransporters in health and disease

Radiolabeled tracers for sodium/glucose cotransporters (SGLTs), their synthesis, and their use are provided. The tracers are methyl or ethyl pyranosides having an equatorial hydroxyl group at carbon-2 and a C 1 preferred conformation, radiolabeled with .sup.18F, .sup.123I, or .sup.124I, or free hexoses radiolabeled with .sup.18F, .sup.123I, or .sup.124. Also provided are in vivo and in vitro techniques for using these and other tracers as analytical and diagnostic tools to study glucose transport, in health and disease, and to evaluate therapeutic interventions.

60 APPLIED LIFE SCIENCES↗

Methods of treating Parkinson's disease using viral vectors

Methods of delivering viral vectors, particularly recombinant adeno-associated virus (rAAV) virions, to the central nervous system (CNS) using convection enhanced delivery (CED) are provided. The rAAV virions include a nucleic acid sequence encoding a therapeutic polypeptide. The methods can be used for treating CNS disorders such as for treating Parkinson's Disease.

59 BASIC BIOLOGICAL SCIENCES↗

Clinical features and risk factors for adverse outcome in Ebola virus disease in Moyamba District Sierra Leone.

BACKGROUND The current outbreak of Ebola virus disease (EVD) in West Africa has attacked 24000 people, killed more than 10000 and disrupted social life. METHODS We studied retrospectively the clinical presentation and risk factors for fatal outcome in EVD among all patients admitted to the Ebola Treatment Center in Moyamba District, Sierra Leone. RESULTS Among a total of 88 admitted patients, eighty-two were tested by PCR and 31 (38%) were positive for Ebola virus. Ninety percent reported previous contact with EVD patients and 35% had participated in burials of EVD suspect deceased. No healthworkers were admitted. The most common symptoms on admission were weakness (97%), diarrhea (68%), fever (62%), loss of appetite (62%), vomiting (58%), pain in muscles (62%) and joints (55%), headache (55%), abdominal pain (45%) and conjunctivitis (42%). On admission, bleeding was present in one-third (11/31), while more than half (17/31) bled during the hospital stay. Fifty-eight percent (18/31) died, most within 4-11 days of onset. Significant predictors for fatal outcome were shorter time from onset to admission (P=0.02), high initial viral load (P<0.001), bleeding (P=0.004), and severe pain (P=0.001). The only two patients with hiccups died. CONCLUSIONS Bleeding was more common in our cohort than reported elsewhere during this epidemic, and predicted poor prognosis. Severe pain was common, particularly in fatal cases, and calls for improved and safe palliation, for instance with transdermal opiates. The lack of fever in one third of EBV cases may have implications for screening procedures and case definitions.

Haaskjold, Yngvar Lunde↗

Mosaic vaccines for serotype a foot-and-mouth disease virus

Synthetic foot-and-mouth disease virus (FMDV) mosaic polypeptides, and nucleic acid molecules encoding the mosaic polypeptides, are described. The mosaic polypeptides have greater T-cell epitope coverage than naturally occurring FMDV polypeptides, and include common FMDV epitopes, but exclude rare FMDV epitopes. When included as part of an FMDV genome, the mosaic polypeptides permit virus replication and assembly into FMDV particles. The mosaic polypeptide and nucleic acid compositions can be used to elicit immune responses that provide protection against a broad range of serotype A FMDV strains.

60 APPLIED LIFE SCIENCES↗

Lab Home Testing of Residential Isolation Space Control to Minimize Infectious Disease Transmission in Existing Single-Family Homes

Existing evidence strongly suggests that viral infectious diseases can be transmitted via an airborne route across distances in indoor environments. Accordingly, the risk of airborne transmission within homes should be managed. The public health emergency associated with SARS-CoV-2 makes controlling airborne transmission of respired viruses in indoor environments critical, especially in poorly ventilated indoor environments. The effectiveness of engineering interventions requiring minor efforts that create a negative-pressure isolation zone (IZ) for a contagious person has yet to be tested for existing residential homes. To mitigate the risk of airborne virus transmission and maximize health protection for the population in existing single-family homes, the relative effectiveness of several control strategies are investigated in this report. While very high-efficiency MERV filtration, high ventilation rates, and other controls can help be effective, most occupants are not likely to have the time or means for advanced measures found in hospitals. This project focused on testing relatively simple efforts that utilize existing or easy to acquire materials and simple processes.

30 DIRECT ENERGY CONVERSION↗

Genetically engineered Foot and Mouth Disease Virus and related proteins, polynucleotides, compositions, methods and systems

Genetically engineered Foot and Mouth Disease Virus (FMDV) and related engineered proteins and polynucleotides, nanolipoprotein particles, compositions, methods and systems are described. The genetically engineered FMDV is modified by the strategic insertion of a protein tag into select regions of the FMDV genome which encode viral proteins that are exposed on the surface of the FMDV viral capsid. The inserted protein tag is displayed as a decoration or attachment on the viral capsid surface.

Rieder, Aida Elizabeth↗

Genetically engineered foot and mouth disease virus and related proteins, polynucleotides, compositions, methods and systems

Genetically engineered Foot and Mouth Disease Virus (FMDV) and related engineered proteins and polynucleotides, nanolipoprotein particles, compositions, methods and systems are described. The genetically engineered FMDV is modified by the strategic insertion of a protein tag into select regions of the FMDV genome which encode viral proteins that are exposed on the surface of the FMDV viral capsid. The inserted protein tag is displayed as a decoration or attachment on the viral capsid surface.

Rieder, Aida E.↗

Discovery of 4-(5-(Cyclopropylcarbamoyl)-2-methylphenylamino)-5-methyl-N-propylpyrrolo[1,2-f][1,2,4]triazine-6-carboxamide (BMS-582949), a Clinical p38[alpha] MAP Kinase Inhibitor for the Treatment of Inflammatory Diseases

The discovery and characterization of 7k (BMS-582949), a highly selective p38{alpha} MAP kinase inhibitor that is currently in phase II clinical trials for the treatment of rheumatoid arthritis, is described. A key to the discovery was the rational substitution of N-cyclopropyl for N-methoxy in 1a, a previously reported clinical candidate p38{alpha} inhibitor. Unlike alkyl and other cycloalkyls, the sp{sup 2} character of the cyclopropyl group can confer improved H-bonding characteristics to the directly substituted amide NH. Inhibitor 7k is slightly less active than 1a in the p38{alpha} enzymatic assay but displays a superior pharmacokinetic profile and, as such, was more effective in both the acute murine model of inflammation and pseudoestablished rat AA model. The binding mode of 7k with p38{alpha} was confirmed by X-ray crystallographic analysis.

59 BASIC BIOLOGICAL SCIENCES↗

Current Status of Interventional Radiology Treatment of Infrapopliteal Arterial Disease

Treatment of infrapopliteal arteries has developed to a standard technique during the past two decades. With the introduction of innovative devices, a variety of techniques has been created and is still under investigation. Treatment options range from plain balloon angioplasty (POBA), all sorts of stent applications, such as bare metal, balloon expanding, self-expanding, coated and drug-eluting stents, and bio-absorbable stents, to latest developments, such as drug-eluting balloons. Regarding the scientific background, several prospective, randomized studies with relevant numbers of patients have been (or will be) published that are Level I evidence. In contrast to older studies, which primarily were based mostly on numeric parameters, such as diameters or residual stenoses, more recent study concepts focus increasingly on clinical features, such as amputation rate improvement or changes of clinical stages and quality of life standards. Although it is still not decided, which of the individual techniques might be the best one, we can definitely conclude that whatever treatment of infrapopliteal arteries will be used it is of substantial benefit for the patient. Therefore, the goal of this review is to give an overview about the current developments and techniques for the treatment of infrapopliteal arteries, to present clinical and technical results, to weigh individual techniques, and to discuss the recent developments.

62 RADIOLOGY AND NUCLEAR MEDICINE↗