Virginia Wotring - Academia.edu (original) (raw)

Papers by Virginia Wotring

Research paper thumbnail of Muscle Atrophy Phenotype Gene Expression During Spaceflight Is Linked to a Metabolic Stress Crosstalk Between the Liver and the Muscle in Mice

Research paper thumbnail of The Future of Personalized Medicine in Space: From Observations to Countermeasures

Frontiers in Bioengineering and Biotechnology, 2021

The aim of personalized medicine is to detach from a “one-size fits all approach” and improve pat... more The aim of personalized medicine is to detach from a “one-size fits all approach” and improve patient health by individualization to achieve the best outcomes in disease prevention, diagnosis and treatment. Technological advances in sequencing, improved knowledge of omics, integration with bioinformatics and new in vitro testing formats, have enabled personalized medicine to become a reality. Individual variation in response to environmental factors can affect susceptibility to disease and response to treatments. Space travel exposes humans to environmental stressors that lead to physiological adaptations, from altered cell behavior to abnormal tissue responses, including immune system impairment. In the context of human space flight research, human health studies have shown a significant inter-individual variability in response to space analogue conditions. A substantial degree of variability has been noticed in response to medications (from both an efficacy and toxicity perspectiv...

Research paper thumbnail of Physiological adaptations affecting drug pharmacokinetics in space: what do we really know? A critical review of the literature

British Journal of Pharmacology, 2022

As human spaceflight continues with extended mission durations, the demand of effective and safe ... more As human spaceflight continues with extended mission durations, the demand of effective and safe drugs is going to increase. To date, the medications used during missions (for space motion sickness, sleep disturbances, allergies, pain and sinus congestion) are administered under the assumption that they act similarly as on the Earth. During spaceflights however fluid shifts, muscle and bone loss, immune system dysregulation and changes in the gastrointestinal tract and metabolism are documented. These alterations may change the pharmacokinetics (PK) and pharmacodynamics. The information gained from bed-rest studies and from inflight observations is partial and demonstrates variability in drug PK. The objectives of this review are to report: i) the impact of the space environmental stressors on human physiology in relation to PK; ii) the state-of-the-art on experimental data in space and/or in ground-based models; iii) the validation of ground-based models for PK studies; and iv) the identification of possible research gaps.

Research paper thumbnail of Astropharmacy: Pushing the boundaries of the pharmacists’ role for sustainable space exploration

Research in Social and Administrative Pharmacy, 2022

BACKGROUND Human physiology undergoes extensive changes in space potentially leading to alteratio... more BACKGROUND Human physiology undergoes extensive changes in space potentially leading to alterations in the way a medication functions. Understanding the efficacy behind Pharmacological Countermeasures (PCMs) and deliverable pharmacy services is imperative for the future presence of humans in space. However, while the pharmacist plays an integral role for human health terrestrially, pharmacist input has been minimal for human health in the space sector. Here, we explore the pharmacist's potential role in larger medical teams for future missions. OBJECTIVE To explore pharmacy and space sector stakeholder perspectives regarding the pharmacist's role in the space sector. METHODS Semi-structured interviews and focus groups were conducted with pharmacy (n = 31) and human health-related space sector stakeholders (n = 26) across the globe from governmental, commercial, industry and academic sectors. Purposive and snowball sampling were used to identify stakeholders. Interviews and focus groups were audio recorded, transcribed verbatim and thematically analysed. RESULTS Three themes - medication management, medication-related research and medication and health information - were generated. The importance of medication optimisation within commercial and federal spaceflight participant medication regimens was cited as necessary for sustainable space exploration. Both groups advocated for pharmacists' involvement with in-situ medication manufacturing and medication-related research, particularly regarding space-based pharmacokinetic and pharmacodynamic drug profiling. Other essential roles included the pharmacist's role in providing medication information to spaceflight participants and other healthcare professionals on their health status and medication use risk in the context of space. CONCLUSIONS With the advancement of accessible, commercial space travel and humans becoming an inter-planetary species, the opportunity to tackle PCM needs via a more extensive and comprehensive collaborative effort between the space, medical and pharmacy sectors is essential for sustainable space exploration.

Research paper thumbnail of Spaceflight Pharmacology

Principles of Clinical Medicine for Space Flight, 2019

Research paper thumbnail of Career Exploration Program Exit Presentation

Mouse liver cells on short-term shuttle flights (STS- 135) have been shown to exhibit changes. By... more Mouse liver cells on short-term shuttle flights (STS- 135) have been shown to exhibit changes. By replicating aspects of spaceflight in the laboratory, we can conduct experiments without impacting mission resources. Astronauts are on a high-iron diet during spaceflight. Galactic Cosmic Rays (GCRs) and Solar Particle Events (SPEs) are ionizing radiation sources that can alter physiological functions. Preliminary medication usage data from the International Space Station (ISS) crew shows that the most common reasons for using medications in space are the same for healthy people on earth.

Research paper thumbnail of Space Pharmacology: How Space Affects Pharmacology

Drug Discovery and Evaluation: Methods in Clinical Pharmacology, 2018

Research paper thumbnail of Developing, Implementing, and Applying Novel Techniques During Systematic Reviews of Primary Space Medicine Data

Aerospace Medicine and Human Performance, 2021

BACKGROUND: The Aerospace Medicine Systematic Review Group was set up in 2016 to facilitate high ... more BACKGROUND: The Aerospace Medicine Systematic Review Group was set up in 2016 to facilitate high quality and transparent synthesis of primary data to enable evidence-based practice. The group identified many research methods specific to space medicine that need consideration for systematic review methods. The group has developed space medicine specific methods to address this and trialed usage of these methods across seven published systematic reviews. This paper outlines evolution of space medicine synthesis methods and discussion of their initial application.METHODS: Space medicine systematic review guidance has been developed for protocol planning, quantitative and qualitative synthesis, sourcing gray data, and assessing quality and transferability of space medicine human spaceflight simulation study environments.RESULTS: Decision algorithms for guidance and tool usage were created based on usage. Six reviews used quantitative methods in which no meta-analyses were possible due t...

Research paper thumbnail of Supplying a pharmacy for NASA exploration spaceflight: challenges and current understanding

npj Microgravity, 2019

In order to maintain crew health and performance during long-duration spaceflight outside of low-... more In order to maintain crew health and performance during long-duration spaceflight outside of low-Earth orbit, NASA and its international partners must be capable of providing a safe and effective pharmacy. Given few directed studies of pharmaceuticals in the space environment, it is difficult to characterize pharmaceutical effectiveness or stability during spaceflight; this in turn makes it challenging to select an appropriate formulary for exploration. Here, we present the current state of literature regarding pharmaceutical stability, metabolism, and effectiveness during spaceflight. In particular, we have attempted to highlight the gaps in current knowledge and the difficulties in translating terrestrial-based drug studies to a meaningful interpretation of drug stability, safety, and effectiveness in space. We hope to identify high-yield opportunities for future research that might better define and mitigate pharmaceutical risk for exploration missions.

Research paper thumbnail of Limitations in predicting radiation-induced pharmaceutical instability during long-duration spaceflight

npj Microgravity, 2019

As human spaceflight seeks to expand beyond low-Earth orbit, NASA and its international partners ... more As human spaceflight seeks to expand beyond low-Earth orbit, NASA and its international partners face numerous challenges related to ensuring the safety of their astronauts, including the need to provide a safe and effective pharmacy for long-duration spaceflight. Historical missions have relied upon frequent resupply of onboard pharmaceuticals; as a result, there has been little study into the effects of long-term exposure of pharmaceuticals to the space environment. Of particular concern are the long-term effects of space radiation on drug stability, especially as missions venture away from the protective proximity of the Earth. Here we highlight the risk of space radiation to pharmaceuticals during exploration spaceflight, identifying the limitations of current understanding. We further seek to identify ways in which these limitations could be addressed through dedicated research efforts aimed toward the rapid development of an effective pharmacy for future spaceflight endeavors.

Research paper thumbnail of Dose Tracker: an iOS app for collection of medication use data from volunteer crewmembers on the International Space Station

Frontiers in Physiology, 2018

Research paper thumbnail of Biomedical findings from NASA's Project Mercury: a case series

NPJ microgravity, 2018

The United States first sent humans into space during six flights of Project Mercury from May 196... more The United States first sent humans into space during six flights of Project Mercury from May 1961 to May 1963. These flights were brief, with durations ranging from about 15 min to just over 34 h. A primary purpose of the project was to determine if humans could perform meaningful tasks while in space. This was supported by a series of biomedical measurements on each astronaut before, during (when feasible), and after flight to document the effects of exposure to the spaceflight environment. While almost all of the data presented here have been published in technical reports, this is the first integrated summary of the main results. One unexpected finding emerges: the major physiological changes associated with these short-term spaceflights are correlated more strongly with time spent by the astronaut in a spacesuit than with time spent in space per se. Thus, exposure to the direct stressors of short-duration (up to 34 h) spaceflight was not the dominant factor influencing human he...

Research paper thumbnail of The Role of Acetylcholine and Its Receptors in Retinal Processing☆

Reference Module in Neuroscience and Biobehavioral Psychology, 2017

Research paper thumbnail of Menstrual Cycle Control in Female Astronauts and the Associated Risk of Venous Thromboembolism

Venous thromboembolism (VTE) is a common and serious condition affecting approximately 12 per 100... more Venous thromboembolism (VTE) is a common and serious condition affecting approximately 12 per 1000 people in the USA every year. There have been no documented case reports of VTE in female astronauts during spaceflight in the published literature. Some female astronauts use hormonal contraception to control their menstrual cycles and it is currently unknown how this affects their risk of VTE. Current terrestrial risk prediction models do not account for the spaceflight environment and the physiological changes associated with it. We therefore aim to estimate a specific risk score for female astronauts who are taking hormonal contraception for menstrual cycle control, to deduce whether they are at an elevated risk of VTE. A systematic review of the literature was conducted in order to identify and quantify known terrestrial risk factors for VTE. Studies involving analogues for the female astronaut population were also reviewed, for example, military personnel who use the oral contraceptive pill for menstrual suppression. Well known terrestrial risk factors, for example, obesity or smoking would not be applicable to our study population as these candidates would have been excluded during astronaut selection processes. Other risk factors for VTE include hormonal therapy, lower limb paralysis, physical inactivity, hyperhomocysteinemia, low methylfolate levels and minor injuries, all of which potentially apply to crew members LSAH data will be assessed to identify which of these risk factors are applicable to our astronaut population. Using known terrestrial risk data, an overall estimated risk of VTE for female astronauts using menstrual cycle control methods will therefore be calculated. We predict this will be higher than the general population but not significantly higher requiring thromboprophylaxis. This study attempts to delineate what is assumed to be true of our astronaut population, for example, they are known to be a healthy fit cohort of individuals, and combine physiological impacts of spaceflight (cephalic fluid shifts, lower limb inactivity) to understand specific risks associated with hormonal contraception.

Research paper thumbnail of Hormone Therapy and Venous Thromboembolism Risk During Space Travel

Research paper thumbnail of Therapeutic Options for Controlling Fluids in the Visual System

Visual Impairment/Intracranial Pressure (VIIP) is a newly recognized risk at NASA. The VIIP proje... more Visual Impairment/Intracranial Pressure (VIIP) is a newly recognized risk at NASA. The VIIP project examines the effect of long-term exposure to microgravity on vision of crewmembers before and after they return to Earth. Diamox (acetazolamide) is a medication which is used to decrease intraocular pressure; however, it carries a 3% risk of kidney stones. Astronauts are at a higher risk of kidney stones during spaceflight and the use Diamox would only increase the risk; therefore alternative therapies were investigated. Histamine 2 (H2) antagonist acid blockers such as cimetidine, ranitidine, famotidine and nizatidine are typically used to relieve the symptoms of gastroesophageal reflux disease (GERD). H2 receptors have been found in the human visual system, which has led to research on the use of H2 antagonist blockers to control fluid production in the human eye. Another potential therapeutic strategy is targeted at aquaporins, which are water channels that help maintain fluid homeostasis. Aquaporin antagonists are also known to affect intracranial pressure which can in turn alter intraocular pressure. Studies on aquaporin antagonists suggest high potential for effective treatment. The primary objective of this investigation is to review existing research on alternate medications or therapy to significantly reduce intracranial and intraocular pressure. A literature review was conducted. Even though we do not have all the answers quite yet, a considerable amount of information was discovered, and findings were narrowed, which should allow for more conclusive answers to be found in the near future.

Research paper thumbnail of Menstrual Cycle Control and Venous Thromboembolism Risk in Female Astronauts

Total number of humans in space 534 10.6% Total females in space 57 Total US astronauts in space ... more Total number of humans in space 534 10.6% Total females in space 57 Total US astronauts in space 330 14.5% Total US female astronauts in space 48 Age range at US selection 26-47 yrs Mean age US ASCAN* finalist 32 yrs Mean age US female astronaut at first flight 38 yrs 2013 selected female ASCANs* 50% *ASCAN-astronaut candidate Menstrual Suppression Similar contraceptive efficacy and safety profiles to cyclic use Fewer hormonal side effects Aids endometriosis, menorrhagia, dysmenorrhea Pregnancy delays selection process Pregnancy contraindicated for most training activities Contraindicated for spaceflight Waste management systems on board station Microgravity environment

Research paper thumbnail of New Pharmacology Studies on the ISS

It is known that medications degrade over time and that extreme storage conditions will hasten th... more It is known that medications degrade over time and that extreme storage conditions will hasten their degradation. This is the basis of the HRP Risk of Ineffective or Toxic Medications Due to Long Term Storage. Gaps include questions about the effects of the spaceflight environment and about the potential for safe use of medications beyond their expiration dates. There are also open questions regarding effects of the spaceflight environment on human physiology and subsequent changes in how medications act on the body; these unanswered questions gave rise to the HRP Concern of Clinically Relevant Unpredicted Effects of Medication. Studies designed to address this Risk and Concern are described below.

Research paper thumbnail of Medically induced amenorrhea in female astronauts

npj Microgravity, 2016

Medically induced amenorrhea can be achieved through alterations in the normal regulatory hormone... more Medically induced amenorrhea can be achieved through alterations in the normal regulatory hormones via the adoption of a therapeutic agent, which prevents menstrual flow. Spaceflight-related advantages for medically induced amenorrhea differ according to the time point in the astronaut's training schedule. Pregnancy is contraindicated for many pre-flight training activities as well as spaceflight, therefore effective contraception is essential. In addition, the practicalities of menstruating during pre-flight training or spaceflight can be challenging. During long-duration missions, female astronauts have often continuously taken the combined oral contraceptive pill to induce amenorrhea. Long-acting reversible contraceptives (LARCs) are safe and reliable methods used to medically induce amenorrhea terrestrially but as of yet, not extensively used by female astronauts. If LARCs were used, daily compliance with an oral pill is not required and no upmass or trash would need disposal. Military studies have shown that high proportions of female personnel desire amenorrhea during deployment; better education has been recommended at recruitment to improve uptake and autonomous decision-making. Astronauts are exposed to similar austere conditions as military personnel and parallels can be drawn with these results. Offering female astronauts up-to-date, evidence-based, comprehensive education, in view of the environment in which they work, would empower them to make informed decisions regarding menstrual suppression while respecting their autonomy.

Research paper thumbnail of Recent Pharmacology Studies on the International Space Station

The environment on the International Space Station (ISS) includes a variety of potential stressor... more The environment on the International Space Station (ISS) includes a variety of potential stressors including the absence of Earth's gravity, elevated exposure to radiation, confined living and working quarters, a heavy workload, and high public visibility. The effects of this extreme environment on pharmacokinetics, pharmacodynamics, and even on stored medication doses, are not yet understood. Dr. Wotring will discuss recent analyses of medication doses that experienced long duration storage on the ISS and a recent retrospective examination of medication use during longduration spaceflights. She will also describe new pharmacology experiments that are scheduled for upcoming ISS missions. Dr. Virginia E. Wotring is a Senior Scientist in the Division of Space Life Sciences in the Universities Space Research Association, and Pharmacology Discipline Lead at NASA's Johnson Space Center, Human Heath and Countermeasures Division. She received her doctorate in Pharmacological and Physiological Science from Saint Louis University after earning a B.S. in Chemistry at Florida State University. She has published multiple studies on ligand gated ion channels in the brain and spinal cord. Her research experience includes drug mechanisms of action, drug receptor structure/function relationships and gene & protein expression. She joined USRA (and spaceflight research) in 2009. In 2012, her book reviewing pharmacology in spaceflight was published by Springer: Space Pharmacology, Space Development Series.

Research paper thumbnail of Muscle Atrophy Phenotype Gene Expression During Spaceflight Is Linked to a Metabolic Stress Crosstalk Between the Liver and the Muscle in Mice

Research paper thumbnail of The Future of Personalized Medicine in Space: From Observations to Countermeasures

Frontiers in Bioengineering and Biotechnology, 2021

The aim of personalized medicine is to detach from a “one-size fits all approach” and improve pat... more The aim of personalized medicine is to detach from a “one-size fits all approach” and improve patient health by individualization to achieve the best outcomes in disease prevention, diagnosis and treatment. Technological advances in sequencing, improved knowledge of omics, integration with bioinformatics and new in vitro testing formats, have enabled personalized medicine to become a reality. Individual variation in response to environmental factors can affect susceptibility to disease and response to treatments. Space travel exposes humans to environmental stressors that lead to physiological adaptations, from altered cell behavior to abnormal tissue responses, including immune system impairment. In the context of human space flight research, human health studies have shown a significant inter-individual variability in response to space analogue conditions. A substantial degree of variability has been noticed in response to medications (from both an efficacy and toxicity perspectiv...

Research paper thumbnail of Physiological adaptations affecting drug pharmacokinetics in space: what do we really know? A critical review of the literature

British Journal of Pharmacology, 2022

As human spaceflight continues with extended mission durations, the demand of effective and safe ... more As human spaceflight continues with extended mission durations, the demand of effective and safe drugs is going to increase. To date, the medications used during missions (for space motion sickness, sleep disturbances, allergies, pain and sinus congestion) are administered under the assumption that they act similarly as on the Earth. During spaceflights however fluid shifts, muscle and bone loss, immune system dysregulation and changes in the gastrointestinal tract and metabolism are documented. These alterations may change the pharmacokinetics (PK) and pharmacodynamics. The information gained from bed-rest studies and from inflight observations is partial and demonstrates variability in drug PK. The objectives of this review are to report: i) the impact of the space environmental stressors on human physiology in relation to PK; ii) the state-of-the-art on experimental data in space and/or in ground-based models; iii) the validation of ground-based models for PK studies; and iv) the identification of possible research gaps.

Research paper thumbnail of Astropharmacy: Pushing the boundaries of the pharmacists’ role for sustainable space exploration

Research in Social and Administrative Pharmacy, 2022

BACKGROUND Human physiology undergoes extensive changes in space potentially leading to alteratio... more BACKGROUND Human physiology undergoes extensive changes in space potentially leading to alterations in the way a medication functions. Understanding the efficacy behind Pharmacological Countermeasures (PCMs) and deliverable pharmacy services is imperative for the future presence of humans in space. However, while the pharmacist plays an integral role for human health terrestrially, pharmacist input has been minimal for human health in the space sector. Here, we explore the pharmacist's potential role in larger medical teams for future missions. OBJECTIVE To explore pharmacy and space sector stakeholder perspectives regarding the pharmacist's role in the space sector. METHODS Semi-structured interviews and focus groups were conducted with pharmacy (n = 31) and human health-related space sector stakeholders (n = 26) across the globe from governmental, commercial, industry and academic sectors. Purposive and snowball sampling were used to identify stakeholders. Interviews and focus groups were audio recorded, transcribed verbatim and thematically analysed. RESULTS Three themes - medication management, medication-related research and medication and health information - were generated. The importance of medication optimisation within commercial and federal spaceflight participant medication regimens was cited as necessary for sustainable space exploration. Both groups advocated for pharmacists' involvement with in-situ medication manufacturing and medication-related research, particularly regarding space-based pharmacokinetic and pharmacodynamic drug profiling. Other essential roles included the pharmacist's role in providing medication information to spaceflight participants and other healthcare professionals on their health status and medication use risk in the context of space. CONCLUSIONS With the advancement of accessible, commercial space travel and humans becoming an inter-planetary species, the opportunity to tackle PCM needs via a more extensive and comprehensive collaborative effort between the space, medical and pharmacy sectors is essential for sustainable space exploration.

Research paper thumbnail of Spaceflight Pharmacology

Principles of Clinical Medicine for Space Flight, 2019

Research paper thumbnail of Career Exploration Program Exit Presentation

Mouse liver cells on short-term shuttle flights (STS- 135) have been shown to exhibit changes. By... more Mouse liver cells on short-term shuttle flights (STS- 135) have been shown to exhibit changes. By replicating aspects of spaceflight in the laboratory, we can conduct experiments without impacting mission resources. Astronauts are on a high-iron diet during spaceflight. Galactic Cosmic Rays (GCRs) and Solar Particle Events (SPEs) are ionizing radiation sources that can alter physiological functions. Preliminary medication usage data from the International Space Station (ISS) crew shows that the most common reasons for using medications in space are the same for healthy people on earth.

Research paper thumbnail of Space Pharmacology: How Space Affects Pharmacology

Drug Discovery and Evaluation: Methods in Clinical Pharmacology, 2018

Research paper thumbnail of Developing, Implementing, and Applying Novel Techniques During Systematic Reviews of Primary Space Medicine Data

Aerospace Medicine and Human Performance, 2021

BACKGROUND: The Aerospace Medicine Systematic Review Group was set up in 2016 to facilitate high ... more BACKGROUND: The Aerospace Medicine Systematic Review Group was set up in 2016 to facilitate high quality and transparent synthesis of primary data to enable evidence-based practice. The group identified many research methods specific to space medicine that need consideration for systematic review methods. The group has developed space medicine specific methods to address this and trialed usage of these methods across seven published systematic reviews. This paper outlines evolution of space medicine synthesis methods and discussion of their initial application.METHODS: Space medicine systematic review guidance has been developed for protocol planning, quantitative and qualitative synthesis, sourcing gray data, and assessing quality and transferability of space medicine human spaceflight simulation study environments.RESULTS: Decision algorithms for guidance and tool usage were created based on usage. Six reviews used quantitative methods in which no meta-analyses were possible due t...

Research paper thumbnail of Supplying a pharmacy for NASA exploration spaceflight: challenges and current understanding

npj Microgravity, 2019

In order to maintain crew health and performance during long-duration spaceflight outside of low-... more In order to maintain crew health and performance during long-duration spaceflight outside of low-Earth orbit, NASA and its international partners must be capable of providing a safe and effective pharmacy. Given few directed studies of pharmaceuticals in the space environment, it is difficult to characterize pharmaceutical effectiveness or stability during spaceflight; this in turn makes it challenging to select an appropriate formulary for exploration. Here, we present the current state of literature regarding pharmaceutical stability, metabolism, and effectiveness during spaceflight. In particular, we have attempted to highlight the gaps in current knowledge and the difficulties in translating terrestrial-based drug studies to a meaningful interpretation of drug stability, safety, and effectiveness in space. We hope to identify high-yield opportunities for future research that might better define and mitigate pharmaceutical risk for exploration missions.

Research paper thumbnail of Limitations in predicting radiation-induced pharmaceutical instability during long-duration spaceflight

npj Microgravity, 2019

As human spaceflight seeks to expand beyond low-Earth orbit, NASA and its international partners ... more As human spaceflight seeks to expand beyond low-Earth orbit, NASA and its international partners face numerous challenges related to ensuring the safety of their astronauts, including the need to provide a safe and effective pharmacy for long-duration spaceflight. Historical missions have relied upon frequent resupply of onboard pharmaceuticals; as a result, there has been little study into the effects of long-term exposure of pharmaceuticals to the space environment. Of particular concern are the long-term effects of space radiation on drug stability, especially as missions venture away from the protective proximity of the Earth. Here we highlight the risk of space radiation to pharmaceuticals during exploration spaceflight, identifying the limitations of current understanding. We further seek to identify ways in which these limitations could be addressed through dedicated research efforts aimed toward the rapid development of an effective pharmacy for future spaceflight endeavors.

Research paper thumbnail of Dose Tracker: an iOS app for collection of medication use data from volunteer crewmembers on the International Space Station

Frontiers in Physiology, 2018

Research paper thumbnail of Biomedical findings from NASA's Project Mercury: a case series

NPJ microgravity, 2018

The United States first sent humans into space during six flights of Project Mercury from May 196... more The United States first sent humans into space during six flights of Project Mercury from May 1961 to May 1963. These flights were brief, with durations ranging from about 15 min to just over 34 h. A primary purpose of the project was to determine if humans could perform meaningful tasks while in space. This was supported by a series of biomedical measurements on each astronaut before, during (when feasible), and after flight to document the effects of exposure to the spaceflight environment. While almost all of the data presented here have been published in technical reports, this is the first integrated summary of the main results. One unexpected finding emerges: the major physiological changes associated with these short-term spaceflights are correlated more strongly with time spent by the astronaut in a spacesuit than with time spent in space per se. Thus, exposure to the direct stressors of short-duration (up to 34 h) spaceflight was not the dominant factor influencing human he...

Research paper thumbnail of The Role of Acetylcholine and Its Receptors in Retinal Processing☆

Reference Module in Neuroscience and Biobehavioral Psychology, 2017

Research paper thumbnail of Menstrual Cycle Control in Female Astronauts and the Associated Risk of Venous Thromboembolism

Venous thromboembolism (VTE) is a common and serious condition affecting approximately 12 per 100... more Venous thromboembolism (VTE) is a common and serious condition affecting approximately 12 per 1000 people in the USA every year. There have been no documented case reports of VTE in female astronauts during spaceflight in the published literature. Some female astronauts use hormonal contraception to control their menstrual cycles and it is currently unknown how this affects their risk of VTE. Current terrestrial risk prediction models do not account for the spaceflight environment and the physiological changes associated with it. We therefore aim to estimate a specific risk score for female astronauts who are taking hormonal contraception for menstrual cycle control, to deduce whether they are at an elevated risk of VTE. A systematic review of the literature was conducted in order to identify and quantify known terrestrial risk factors for VTE. Studies involving analogues for the female astronaut population were also reviewed, for example, military personnel who use the oral contraceptive pill for menstrual suppression. Well known terrestrial risk factors, for example, obesity or smoking would not be applicable to our study population as these candidates would have been excluded during astronaut selection processes. Other risk factors for VTE include hormonal therapy, lower limb paralysis, physical inactivity, hyperhomocysteinemia, low methylfolate levels and minor injuries, all of which potentially apply to crew members LSAH data will be assessed to identify which of these risk factors are applicable to our astronaut population. Using known terrestrial risk data, an overall estimated risk of VTE for female astronauts using menstrual cycle control methods will therefore be calculated. We predict this will be higher than the general population but not significantly higher requiring thromboprophylaxis. This study attempts to delineate what is assumed to be true of our astronaut population, for example, they are known to be a healthy fit cohort of individuals, and combine physiological impacts of spaceflight (cephalic fluid shifts, lower limb inactivity) to understand specific risks associated with hormonal contraception.

Research paper thumbnail of Hormone Therapy and Venous Thromboembolism Risk During Space Travel

Research paper thumbnail of Therapeutic Options for Controlling Fluids in the Visual System

Visual Impairment/Intracranial Pressure (VIIP) is a newly recognized risk at NASA. The VIIP proje... more Visual Impairment/Intracranial Pressure (VIIP) is a newly recognized risk at NASA. The VIIP project examines the effect of long-term exposure to microgravity on vision of crewmembers before and after they return to Earth. Diamox (acetazolamide) is a medication which is used to decrease intraocular pressure; however, it carries a 3% risk of kidney stones. Astronauts are at a higher risk of kidney stones during spaceflight and the use Diamox would only increase the risk; therefore alternative therapies were investigated. Histamine 2 (H2) antagonist acid blockers such as cimetidine, ranitidine, famotidine and nizatidine are typically used to relieve the symptoms of gastroesophageal reflux disease (GERD). H2 receptors have been found in the human visual system, which has led to research on the use of H2 antagonist blockers to control fluid production in the human eye. Another potential therapeutic strategy is targeted at aquaporins, which are water channels that help maintain fluid homeostasis. Aquaporin antagonists are also known to affect intracranial pressure which can in turn alter intraocular pressure. Studies on aquaporin antagonists suggest high potential for effective treatment. The primary objective of this investigation is to review existing research on alternate medications or therapy to significantly reduce intracranial and intraocular pressure. A literature review was conducted. Even though we do not have all the answers quite yet, a considerable amount of information was discovered, and findings were narrowed, which should allow for more conclusive answers to be found in the near future.

Research paper thumbnail of Menstrual Cycle Control and Venous Thromboembolism Risk in Female Astronauts

Total number of humans in space 534 10.6% Total females in space 57 Total US astronauts in space ... more Total number of humans in space 534 10.6% Total females in space 57 Total US astronauts in space 330 14.5% Total US female astronauts in space 48 Age range at US selection 26-47 yrs Mean age US ASCAN* finalist 32 yrs Mean age US female astronaut at first flight 38 yrs 2013 selected female ASCANs* 50% *ASCAN-astronaut candidate Menstrual Suppression Similar contraceptive efficacy and safety profiles to cyclic use Fewer hormonal side effects Aids endometriosis, menorrhagia, dysmenorrhea Pregnancy delays selection process Pregnancy contraindicated for most training activities Contraindicated for spaceflight Waste management systems on board station Microgravity environment

Research paper thumbnail of New Pharmacology Studies on the ISS

It is known that medications degrade over time and that extreme storage conditions will hasten th... more It is known that medications degrade over time and that extreme storage conditions will hasten their degradation. This is the basis of the HRP Risk of Ineffective or Toxic Medications Due to Long Term Storage. Gaps include questions about the effects of the spaceflight environment and about the potential for safe use of medications beyond their expiration dates. There are also open questions regarding effects of the spaceflight environment on human physiology and subsequent changes in how medications act on the body; these unanswered questions gave rise to the HRP Concern of Clinically Relevant Unpredicted Effects of Medication. Studies designed to address this Risk and Concern are described below.

Research paper thumbnail of Medically induced amenorrhea in female astronauts

npj Microgravity, 2016

Medically induced amenorrhea can be achieved through alterations in the normal regulatory hormone... more Medically induced amenorrhea can be achieved through alterations in the normal regulatory hormones via the adoption of a therapeutic agent, which prevents menstrual flow. Spaceflight-related advantages for medically induced amenorrhea differ according to the time point in the astronaut's training schedule. Pregnancy is contraindicated for many pre-flight training activities as well as spaceflight, therefore effective contraception is essential. In addition, the practicalities of menstruating during pre-flight training or spaceflight can be challenging. During long-duration missions, female astronauts have often continuously taken the combined oral contraceptive pill to induce amenorrhea. Long-acting reversible contraceptives (LARCs) are safe and reliable methods used to medically induce amenorrhea terrestrially but as of yet, not extensively used by female astronauts. If LARCs were used, daily compliance with an oral pill is not required and no upmass or trash would need disposal. Military studies have shown that high proportions of female personnel desire amenorrhea during deployment; better education has been recommended at recruitment to improve uptake and autonomous decision-making. Astronauts are exposed to similar austere conditions as military personnel and parallels can be drawn with these results. Offering female astronauts up-to-date, evidence-based, comprehensive education, in view of the environment in which they work, would empower them to make informed decisions regarding menstrual suppression while respecting their autonomy.

Research paper thumbnail of Recent Pharmacology Studies on the International Space Station

The environment on the International Space Station (ISS) includes a variety of potential stressor... more The environment on the International Space Station (ISS) includes a variety of potential stressors including the absence of Earth's gravity, elevated exposure to radiation, confined living and working quarters, a heavy workload, and high public visibility. The effects of this extreme environment on pharmacokinetics, pharmacodynamics, and even on stored medication doses, are not yet understood. Dr. Wotring will discuss recent analyses of medication doses that experienced long duration storage on the ISS and a recent retrospective examination of medication use during longduration spaceflights. She will also describe new pharmacology experiments that are scheduled for upcoming ISS missions. Dr. Virginia E. Wotring is a Senior Scientist in the Division of Space Life Sciences in the Universities Space Research Association, and Pharmacology Discipline Lead at NASA's Johnson Space Center, Human Heath and Countermeasures Division. She received her doctorate in Pharmacological and Physiological Science from Saint Louis University after earning a B.S. in Chemistry at Florida State University. She has published multiple studies on ligand gated ion channels in the brain and spinal cord. Her research experience includes drug mechanisms of action, drug receptor structure/function relationships and gene & protein expression. She joined USRA (and spaceflight research) in 2009. In 2012, her book reviewing pharmacology in spaceflight was published by Springer: Space Pharmacology, Space Development Series.