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At least 19 records

The Central Nervous Connections Involved in the Vomiting Reflex

The vomiting reflex may be elicited by a number of different types or classes of stimuli involving many varieties of receptor structures and considerable diversity in afferent pathways and central connections. Central relay or mediating structures thus may vary widely according to the type of initial emetic stimulus. The emetic circuits which have been most completely delineated to date are probably those in which the Chemoreceptor Trigger Zone (CTZ) in the Area Postrema (AP) functions as a key mediating structure. Even in this system, however, there are large gaps in our knowledge of the nerve tracts and central nervous connections involved. Knowledge of most other emetic circuits subserving the emetic reflex resulting from many diverse types of stimuli such, for example, as emotional stress (e.g. psychogenic vomiting, Wruble et al. 1982), pain (e.g. testicular trauma), and chemical or mechanical irritation of the gastrointestinal tract or urinary tract is quite incomplete at this time, thus precluding any very adequate description of their central connections at present. One physiological system, however, which has received considerable attention recently in relation to the vomiting reflex elicited by motion stimuli is the vestibular system. Due to the paucity of data on central nervous connections of several or the non-vestibular types of emetic stimuli cited above, we will devote most of our attention in this brief review to the central connections of the vestibular system which seem likely to be involved in the vomiting response to motion stimuli. However, the latter part of the review will be concerned with the concept of the reticular vomiting centre in relation to the ParviCellular Reticular Formation (PCRF), and will thus probably pertain to all of the many classes of emetic stimuli since it will address the question of the final common emetic pathway.

Brizzee, K. R.↗

Cutting Head for Ultrasonic Lithotripsy

Kidney stones lodged in urinary tract disintegrated with increased safety and efficiency by cutting head attached to end of vibrated wire probe. Aligns probe with stone and enables probe to vibrate long enough to disintegrate stone. Design of cutting head reduces risk of metal-fatigue-induced breakage of probe tip leaving metal fragments in urinary tract. Teeth of cutting head both seat and fragment kidney stone, while extension of collar into catheter lessens mechanical strain in probe wire, increasing probe life and lessening danger of in situ probe breakage.

Angulo, E. D.↗

Pathology effects at radiation doses below those causing increased mortality

Mortality data from experiments conducted at the Argonne National Laboratory (ANL) on the long-term effects of external whole-body irradiation on B6CF(1) mice were used to investigate radiation-induced effects at intermediate doses of (60)Co gamma rays or fission-spectrum neutrons either delivered as a single exposure or protracted over 60 once-weekly exposures. Kaplan-Meier analyses were used to identify the lowest dose in the ANL data (within radiation quality, pattern of exposure, and sex) at which radiation-induced mortality caused by primary tumors could be detected (approximately 1-2 Gy for gamma rays and 10-15 cGy for neutrons). Doses at and below these levels were then examined for radiation-induced shifts in the spectrum of pathology detected at death. To do this, specific pathology events were pooled into larger assemblages based on whether they were cancer, cardiovascular disease or non-neoplastic diseases detected within the lungs and pleura, liver and biliary tract, reproductive organs, or urinary tract. Cancer and cardiovascular disease were further subdivided into categories based on whether they caused death, contributed to death, or were simply observed at death. Counts of how often events falling within each of these combined pathology categories occurred within a mouse were then used as predictor variables in logistic regression to determine whether irradiated mice could be distinguished from control mice. Increased pathology burdens were detected in irradiated mice at doses lower than those causing detectable shifts in mortality-22 cGy for gamma rays and 2 cGy for neutrons. These findings suggest that (1) models based on mortality data alone may underestimate radiation effects, (2) radiation may have adverse health consequences (i.e. elevated health risks) even when mortality risks are not detected, and (3) radiation-induced pathologies other than cancer do occur, and they involve multiple organ systems.

Non-NASA Center↗

Protecting Space Travelers from Kidney Stones: Renal Stone Risk During Space Flight

Renal stones, popularly known as kidney or bladder stones, are small rock-like objects formed in the kidneys or urinary tract by deposits of calcium and other minerals. The problem arises when the stones block the drainage of the kidney, resulting in urinary obstruction and pain. Passing these stones can be one of the most painful experiences a person will endure so doctors often prescribe pain relievers to ease the experience. Drinking plenty of fluids, which help flush waste out of the body, and eating a well-balanced diet are the first steps to preventing stones. For individuals at risk, this may not be enough, and a doctor may recommend a special diet and medications. Unfortunately, approximately 60 percent of people who have had a renal stone will experience a recurrence. This is particularly true of men, who are four to five times more likely to develop stones than women. Renal stones do not discriminate based on age; even children are at risk. Astronauts are particularly at risk of developing renal stones because they lose bone and muscle mass; calcium, other minerals, and protein normally used for bone and muscle end up in the bloodstream and then in the kidneys. Without plenty of fluid to wash them away, crystals can form and then grow into stones. This factor compounds the risk for astronauts, since they also perceive that they are less thirsty in space and will drink less than normal during the mission. To minimize all of these factors, doctors must instead treat the stone-forming compounds with medication. This study will use potassium citrate to reduce the risk of stone formation. Renal stones are never convenient, but they are a particular concern for astronauts who have limited access to treatment during flight. Researchers are examining how earthbound preventions for renal stone formation work in flight, ensuring missions are not ended prematurely due to this medical condition. During STS-107, earthbound preventions and treatments become astronauts' gain.

Whitson, Peggy↗

NASA Astronaut Urinary Conditions Associated with Spaceflight

INTRODUCTION: Spaceflight is associated with many factors which may promote kidney stone formation, urinary retention, and/or Urinary Tract Infection (UTI). According to ISS mission predictions supplied by NASA's Integrated Medical Model, kidney stone is the second and sepsis (urosepsis as primary driver) the third most likely reason for emergent medical evacuation from the International Space Station (ISS). METHODS: Inflight and postflight medical records of NASA astronauts were reviewed for urinary retention, UTI and kidney stones during Mercury, Gemini, Apollo, Mir, Shuttle, and ISS expeditions 1-38. RESULTS: NASA astronauts have had 7 cases of kidney stones in the 12 months after flight. Three of these cases occurred within 90 to 180 days after landing and one of the seven cases occurred in the first 90 days after flight. There have been a total of 16 cases (0.018 events per person-flights) of urinary retention during flight. The event rates per mission are nearly identical between Shuttle and ISS flights (0.019 vs 0.021 events per person-flights). In 12 of the 16 cases, astronauts had taken at least one space motion sickness medication. Upon further analysis, it was determined that the odds of developing urinary retention in spaceflight is 3 times higher among astronauts who took promethazine. The female to male odds ratio for inflight urinary retention is 11:14. An astronaut with urinary retention is 25 times more likely to have a UTI with a 17% infection rate per mission. There have been 9 reported UTIs during spaceflight. DISCUSSION: It is unclear if spaceflight carries an increased post-flight risk of kidney stones. Regarding urinary retention, the female to male odds ratio is higher during flight compared to the general population where older males comprise almost all cases due to prostatic hypertrophy. This female prevalence in spaceflight is even more concerning given the fact that there have been many more males in space than females. Terrestrial medications with a known side effect of urinary retention are also associated with urinary retention during flight. However, not all cases of urinary retention surrounded medication use inflight. It is also known that UTI is a terrestrial cause of urinary retention. Furthermore, the treatment of urinary retention with a urinary catheter may be more likely to initiate a UTI in space than on the ground, as aseptic techniques can be particularly challenging with an inexperienced provider in a free-floating environment. Inflight urinary retention and UTI have proven to be highly associated and urinary risks should be considered collectively when planning for space flight.

Law, Jennifer↗

The examination of urine samples for pathogenic microbes by the luciferase assay for ATP. 1: The effect of the presence of fungi, fungal like bacteria and kidney cells in urine samples

A method for accurately determining urinary tract infections in man is introduced. The method is based on adenosine triphosphate (ATP) concentration in urine samples after removing nonbacterial ATP. Adenosine triphosphate concentration is measured from the bioluminescent reaction of luciferase when mixed with ATP. An examination was also made of the effectiveness of rupturing agents on monkey kidney cells Candia albicans, a Rhodotorula species, and a Streptomyces species in determining whether these cells could contribute ATP to the bacterial ATP value of a urine sample.

Bush, V. N.↗

Application of firefly luciferase assay for adenosine triphosphate (ATP) to antimicrobial drug sensitivity testing

The development of a rapid method for determining microbial susceptibilities to antibiotics using the firefly luciferase assay for adenosine triphosphate (ATP) is documented. The reduction of bacterial ATP by an antimicrobial agent was determined to be a valid measure of drug effect in most cases. The effect of 12 antibiotics on 8 different bacterial species gave a 94 percent correlation with the standard Kirby-Buer-Agar disc diffusion method. A 93 percent correlation was obtained when the ATP assay method was applied directly to 50 urine specimens from patients with urinary tract infections. Urine samples were centrifuged first to that bacterial pellets could be suspended in broth. No primary isolation or subculturing was required. Mixed cultures in which one species was predominant gave accurate results for the most abundant organism. Since the method is based on an increase in bacterial ATP with time, the presence of leukocytes did not interfere with the interpretation of results. Both the incubation procedure and the ATP assays are compatible with automation.

Picciolo, G. L.↗

DNA Probe Design for Preflight and Inflight Microbial Monitoring

Crew health is a dominant issue in manned space flight. Microbiological concerns, in particular, have repeatedly emerged as determinants of flight readiness. For example, in at least one case, suspected contamination of the potable water supply nearly forced a launch delay. In another instance, a crew member's urinary tract infection nearly led to early termination of the mission, in part due to the difficulty of accurately diagnosing the nature of the infection in-flight. Microbial problems are an increasing concern with the trend towards longer-duration missions. It is essential to the success of such missions that systems that deliver acceptable quality of air and water during the anticipated lifetime of the spacecraft be available. As mission duration and resupply intervals increase, it will be necessary to rely on advanced life support systems which incorporate both biological and physical-chemical recycling methods for air and water as well as provide food for the crew. It therefore is necessary to develop real-time, robust, in-flight monitoring procedures that are sensitive enough to detect less than 100 CFU (colony forming units) of bacteria per 100 milliliters of water. It would be desirable if the monitoring system could be readily "reprogrammed" to identify specific pathogens if an in-flight incident were to occur. Thus, the monitoring technology must simultaneously detect many organisms of interest, be subject to miniaturization and be highly automated The long range goal of project is to develop such monitoring systems.

Fox, George E.↗

Space Motion Sickness - Analysis of Medical Debriefs Data for Incidence and Treatment

Astronauts use medications for the treatment of a variety of illnesses during space travel. Data mining efforts to assess minor clinical conditions occurring during Shuttle flights STS-1 through STS-94 revealed that space motion sickness (SMS) was the most common ailment during early flight days, occurring in approx.40% of crewmembers, followed by digestive system disturbances (9%) and infectious diseases, which most commonly involved the respiratory or urinary tracts. A more recent analysis of postflight medical debriefs data to examine trends with respect to medication use by astronauts during spaceflights indicated that ~37% of all prescriptions recorded was for pain followed by sleep (22%), SMS (18%), decongestion (14%), and all others (14%). Further analysis revealed that about 150 of 317 crewmembers experienced symptoms of SMS. Nearly all (132 of 150) crewmembers took medication for the treatment of symptoms with a total of 387 doses. Promethazine was taken most often (201 doses); in most cases this resulted in alleviation of symptoms with 130 crewmembers (65%) reporting feeling much or somewhat better. Although fewer total doses of the combination of promethazine and dextroamphetamine (Phen/Dex) were taken (45 doses), slightly more than half of these doses resulted in improvement. The combination of scopolamine and dextroamphetamine (Scop/Dex) was reported to be effective in only 37% of cases, with 36 of 97 total doses resulting in improvement. A higher percentage (24%) of Scop/Dex doses was reported to be ineffective compared with promethazine alone or as Phen/Dex (10% and 7%, respectively). Comparisons of the effectiveness of the different dosage forms of promethazine revealed that intramuscular injection was most effective in alleviating symptoms with 55% feeling much better, 16% feeling somewhat better, and only 7% feeling no effect or worse. Overall, it appears that promethazine alone was used more frequently during flight and was reported effective for the treatment of SMS.

Putcha, Lakshmi↗

NASA FACTS: E. coli AntiMicrobial Satellite (EcAMSat)

The E. coli AntiMicrobial Satellite(EcAMSat) mission will investigate space microgravity affects on the antibiotic resistance of E. coli, a bacterial pathogen responsible for urinary tract infection in humans and animals. EcAMSat is being developed through a partnership between NASAs Ames Research Center and the Stanford University School of Medicine. Dr. A.C. Matin is the Stanford University Principal Investigator. EcAMSat will investigate spaceflight effects on bacterial antibiotic resistance and its genetic basis. Bacterial antibiotic resistance may pose a danger to astronauts in microgravity, where the immune response is weakened. Scientists believe that the results of this experiment could help design effective countermeasures to protect astronauts health during long duration human space missions.

Spremo, Stevan↗

Efficacy of Antimicrobials on Bacteria Cultured in a Spaceflight Analogue

As humans travel in space, they will interact with microbial flora from themselves, other crewmembers, their food, and the environment. While evaluations of microbial ecology aboard the Mir and ISS suggest a predominance of common environmental flora, the presence of (and potential for) infectious agents has been well documented. Likewise, pathogens have been detected during preflight monitoring of spaceflight food, resulting in the disqualification of that production lot from flight. These environmental and food organisms range from the obligate pathogen, Salmonella enterica serovar Typhimurium (S. Typhimurium), which has been responsible for disqualification and removal of food destined for ISS and has previously been reported from Shuttle crew refuse, to the opportunistic pathogen Staphylococcus aureus, isolated numerous times from ISS habitable compartments and the crew. Infectious disease events have affected spaceflight missions, including an upper respiratory infection that delayed the launch of STS-36 and an incapacitating Pseudomonas aeruginosa urinary tract infection of a crewmember during Apollo 13. These observations indicate that the crew has the potential to be exposed to obligate and opportunistic pathogens. This risk of exposure is expected to increase with longer mission durations and increased use of regenerative life support systems. As antibiotics are the primary countermeasure after infection, determining if their efficacy during spaceflight missions is comparable to terrestrial application is of critical importance. The NASA Rotating Wall Vessel (RWV) culture system has been successfully used as a spaceflight culture analogue to identify potential alterations in several key microbial characteristics, such as virulence and gene regulation, in response to spaceflight culture. We hypothesized that bacteria cultured in the low fluid shear RWV environment would demonstrate changes in efficacy of antibiotics compared to higher fluid shear controls. This study investigated the response of three medically significant microorganisms grown in the RWV to antibiotics that could be used on spaceflight missions. Our findings suggest potential alterations in antibiotic efficacy during spaceflight and indicate that future studies on the antibiotic response require additional basic research using the RWV and/or true spaceflight. However, while this analogue has reinforced these potential alterations, the results suggest the best approach for applied forward work is evaluating an in vivo system during spaceflight, including human and rodent studies. The complex nature of the analysis for many antibiotics and organism suggests the best approach to determine in vivo responses during pharmaceutical treatment is evaluating an in vivo system during spaceflight.

Nickerson, CA↗

EcAMSat: Effect of Space-Flight on Antibiotic Resistance of a Pathogenic Bacterium and its Genetic Basis

Human immune response is compromised in space and incidence of urinary tract infections (UTI) in astronauts has been reported. We have found that the causative agent of UTI, the uropathogenic Escherichia coli, becomes more resistant to gentamicin (Gm), which is commonly used to treat this disease, under modeled microgravity conditions (MMG), the increase being controlled by the stress response master regulator, σs. While the wild type bacterium becomes virtually invincible under MMG, the strain missing this sigma factor barely survives. We report here preparatory ground work for testing this finding in space flight on a nanosatellite. We have shown that the effect of Gm treatment on culture viability is directly correlated to increased Alamar Blue (AB) reduction; we have identified conditions to keep the experimental elements - the bacterial cultures, Gm, and AB - in a state of viability and potency to permit successful spaceflight experimentation given the necessary constraints. Spaceflight kinetics of AB reduction will be transmitted from the satellite via telemetry. The PharmaSat hardware previously used for space experimentation with yeast was modified to permit studies with bacteria by reducing the filter pore size and increasing fluidics volume to enable more fluid exchanges. Several verification tests have been run using the nanosatellite's flight software and prototype hardware. Cells were grown to stationary phase to induce the σs-controlled stress resistance and treated with Gm. Without Gm, the mutant took longer than the wild type to reduce the AB; this time difference increased almost 8 fold at 55 μg/mL Gm concentration. Thus, using flight hardware the mutant shows similarly increased sensitivity to Gm compared to the wild type to that found in our pilot microtiter plate experiments. Previous inflight experiments have given contradictory results concerning bacterial antibiotic resistance; none has yet explored the involvement of specific genes in this phenomenon. With our system ready to fly in late 2015/early 2016, these questions can be approached

uropathogenic E. coli↗

Hollow Fiber Membrane Bioreactor Systems for Wastewater Processing: Effects of Environmental Stresses Including Dormancy Cycling and Antibiotic Dosing

Membrane-aerated biofilm reactors (MABRs) have been studied for a number of years as an alternate approach for treating wastewater streams during space exploration. While the technology provides a promising pre-treatment for lowering organic carbon and nitrogen content without the need for harsh stabilization chemicals, several challenges must be addressed before adoption of the technology in future missions. One challenge is the transportation of bioreactors containing intact, active biofilms as a means for rapid start-up on the International Space Station or beyond. Similarly, there could be a need for placing these biological systems into a dormant state for extended periods when the system is not in use, along with the ability for rapid restart. Previous studies indicated that there was little influence of storage condition (4 or 25 C, with or without bulk fluid) on recovery of bioreactors with immature biofilms (48 days old), but that an extensive recovery time was required (20+ days). Bioreactors with fully established biofilms (13 months) were able to recover from a 7-month dormancy within 4 days (approximately 1 residence). Further dormancy and recovery testing is presented here that examines the role of biofilm age on recovery requirements, repeated dormancy cycle capabilities, and effects of long-duration dormancy cycles (8-9 months) on HFMB systems. Another challenge that must be addressed is the possibility of antibiotics entering the wastewater stream. Currently, for most laboratory tests of biological water processors, donors providing urine may not contribute to the study when taking antibiotics because the effects on the system are yet uncharacterized. A simulated urinary tract infection event, where an opportunistic, pathogenic organism, E. coli, was introduced to the HFMBs followed by dosing with an antibiotic, ciprofloxacin, was completed to study the effect of the antibiotic on reactor performance and to also examine the development of antibiotic-resistant communities within the system.

Bioreactor Systems↗

Payload Hardware and Experimental Protocol for Testing the Effect of Space Microgravity on the Resistance to Gentamicin of Stationary-Phase Uropathogenic Escherichia Coli and Its Sigma (sup S)-Deficient Mutant

Human immune response is compromised and bacteria can become more antibiotic resistant in space microgravity (MG). We report that under low-shear modeled microgravity (LSMMG) stationary-phase uropathogenic Escherichia coli (UPEC) become more resistant to gentamicin (Gm). UPEC causes urinary tract infections (UTIs), reported to afflict astronauts; Gm is a standard treatment, so these findings could impact astronaut health. Because LSMMG has been shown to differ from MG, we report here preparations to examine UPEC's Gm sensitivity during spaceflight using the E. coli Anti-Microbial Satellite (EcAMSat) on a free flying nanosatellite in low Earth orbit. Within EcAMSats payload, a 48-microwell fluidic card contains and supports study of bacterial cultures at constant temperature; optical absorbance changes in cell suspensions are made at three wavelengths for each microwell and a fluid-delivery system provides growth medium and predefined Gm concentrations. Performance characterization is reported for spaceflight prototypes of this payload system. Using conventional microtiter plates, we show that Alamar Blue (AB) absorbance changes due to cellular metabolism accurately reflect E. coli viability changes: measuring AB absorbance onboard EcAMSat will enable telemetry of spaceflight data to Earth. Laboratory results using payload prototypes are consistent with wellplate and flask findings of differential sensitivity of UPEC and its delta rpoS strain to Gm. Space MG studies using EcAMSat should clarify inconsistencies from previous space experiments on bacterial antibiotic sensitivity. Further, if sigma (sup s) plays the same role in space MG as in LSMMG and Earth gravity, EcAMSat results would facilitate utilizing our previously developed terrestrial UTI countermeasures in astronauts.

Matin, A. C.↗

E. coli AntiMicrobial Satellite (EcAMSat)

The E. coli AntiMicrobial Satellite(EcAMSat) mission will investigate space microgravity affects on the antibiotic resistance of E. coli, a bacterial pathogen responsible for urinary tract infection in humans and animals. EcAMSat is being developed through a partnership between NASA Ames Research Center and the Stanford University School of Medicine. Scientists believe that the results of this experiment could help design effective countermeasures to protect astronauts health during long duration human space missions.

e. Coli↗

Space Biofilms - Phenotypic and Transcriptomic Behaviour of Pseudomonas Aeruginosa Biofilms on Board the International Space Station

Bacterial biofilms in space can have a positive or negative impact on the success of a mission. For example, in some instances, biofilms can improve plant growth, facilitate synthesis/recovery of metals from regolith, or bioremediate wastewater. On the other hand, biofilms can deteriorate or cause malfunctions of spaceflight hardware. Biofilms have been found on the wastewater tank of the Environmental Control and Life Support System (ECLSS), which poses a risk to the system. Even more alarming, some biofilms cause infections that may threaten astronauts’ health, like urinary tract infections that if left unclear could cause permanent damage to the kidneys. Given that biofilms can contribute to or hinder the efforts of space exploration, it is necessary to understand the effects of microgravity on biofilm behaviour. The Space Biofilms experiment intends to contribute to such understanding by analysing the morphology and transcriptomic profiles of Pseudomonas aeruginosa PA14 biofilms grown in spaceflight compared to matched ground controls. P. aeruginosa biofilms were grown onboard the International Space Station for 1, 2, or 3 days at 37°C over six surface materials: Stainless Steel 316 (SS316), passivated SS316, and a novel Lubricant Impregnated Surface (LIS) were grown in rich media supplemented with potassium nitrate (LBK) to simulate wastewater. While cellulose membrane, catheter grade silicone, and silicone with special nanotopography (DLIP) were grown in modified Artificial Urine Media supplemented with glucose and high phosphate (mAUMg-hi Pi) to simulate urine. Asynchronous ground controls replicated spaceflight procedures. Morphology analysis revealed that flight samples had a significant decrease in mass, thickness and surface area coverage in LBK. Additionally, biofilm surface coverage on LIS was only 11% of the equivalent samples on SS316 (p<0.001). Associated preliminary transcriptomic data will also be addressed.

Pamela Flores↗