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

Hyperparathyroidism subsequent to radioactive iodine therapy for Graves\u27 disease

BACKGROUND: The development of primary hyperparathyroidism (PHPT) after radioactive iodine (RAI) treatment for thyroid disease is poorly characterized. The current study is the largest reported cohort and assesses the disease characteristics of patients treated for PHPT with a history of RAI exposure. METHODS: A retrospective analysis comparing patients, with and without a history of RAI treatment, who underwent surgery for PHPT. RESULTS: Twenty-eight of the 469 patients had a history of RAI treatment, all for Graves\u27 disease. Patients with a history of RAI exposure had similar disease characteristics compared to control; however, patients with a history of RAI treatment had a higher rate of recurrence (7.4% vs 1.2%, p = 0.012). CONCLUSION: PHPT in patients with a history of RAI treatment can be approached in the same manner as RAI naive PHPT patients; however, the risk of recurrence of PHPT in RAI exposed patients may be higher

How stigma impacts on people with psychosis: The mediating effect of self-esteem and hopelessness on subjective recovery and psychotic experiences

This study aimed to examine how stigma impacts on symptomatic and subjective recovery from psychosis, both concurrently and longitudinally. We also aimed to investigate whether self-esteem and hopelessness mediated the observed associations between stigma and outcomes. 80 service-users with psychosis completed symptom (Positive and Negative Syndrome Scale) and subjective recovery measures (Process of Recovery Questionnaire) at baseline and 6-months later, and also completed the King Stigma Scale, the Self-Esteem Rating Scale and the Beck Hopelessness Scale at baseline. In cross sectional regression and multiple mediation analyses of the baseline data, we found that stigma predicted both symptomatic and subjective recovery, and the effects of stigma on these outcomes were mediated by hopelessness and self-esteem. When the follow-up data were examined, stigma at baseline continued to predict recovery judgements and symptoms. However, self-esteem only mediated the effect of stigma on PANSS passive social withdrawal. Self-esteem and hopelessness should be considered in interventions to reduce the effects of stigma. Interventions that address the current and long-term effects of stigma may positively affect outcome for people being treated for psychosis

Epigenetic and neurological effects and safety of high-dose nicotinamide in patients with Friedreich's ataxia: an exploratory, open-label, dose-escalation study

Background: Friedreich's ataxia is a progressive degenerative disorder caused by deficiency of the frataxin protein. Expanded GAA repeats within intron 1 of the frataxin (FXN) gene lead to its heterochromatinisation and transcriptional silencing. Preclinical studies have shown that the histone deacetylase inhibitor nicotinamide (vitamin B3) can remodel the pathological heterochromatin and upregulate expression of FXN. We aimed to assess the epigenetic and neurological effects and safety of high-dose nicotinamide in patients with Friedreich's ataxia. Methods: In this exploratory, open-label, dose-escalation study in the UK, male and female patients (aged 18 years or older) with Friedreich's ataxia were given single doses (phase 1) and repeated daily doses of 2–8 g oral nicotinamide for 5 days (phase 2) and 8 weeks (phase 3). Doses were gradually escalated during phases 1 and 2, with individual maximum tolerated doses used in phase 3. The primary outcome was the upregulation of frataxin expression. We also assessed the safety and tolerability of nicotinamide, used chromatin immunoprecipitation to investigate changes in chromatin structure at the FXN gene locus, and assessed the effect of nicotinamide treatment on clinical scales for ataxia. This study is registered with ClinicalTrials.gov, number NCT01589809. Findings: Nicotinamide was generally well tolerated; the main adverse event was nausea, which in most cases was mild, dose-related, and resolved spontaneously or after dose reduction, use of antinausea drugs, or both. Phase 1 showed a dose-response relation for proportional change in frataxin protein concentration from baseline to 8 h post-dose, which increased with increasing dose (p=0·0004). Bayesian analysis predicted that 3·8 g would result in a 1·5-times increase and 7·5 g in a doubling of frataxin protein concentration. Phases 2 and 3 showed that daily dosing at 3·5–6 g resulted in a sustained and significant (p<0·0001) upregulation of frataxin expression, which was accompanied by a reduction in heterochromatin modifications at the FXN locus. Clinical measures showed no significant changes. Interpretation: Nicotinamide was associated with a sustained improvement in frataxin concentrations towards those seen in asymptomatic carriers during 8 weeks of daily dosing. Further investigation of the long-term clinical benefits of nicotinamide and its ability to ameliorate frataxin deficiency in Friedreich's ataxia is warranted

Robotic Laser-Adaptive-Optics Imaging of 715 Kepler Exoplanet Candidates using Robo-AO

The Robo-AO Kepler Planetary Candidate Survey is designed to observe every Kepler planet candidate host star with laser adaptive optics imaging to search for blended nearby stars, which may be physically associated companions and/or responsible for transit false positives. In this paper we present the results from the 2012 observing season, searching for stars close to 715 representative Kepler planet candidate hosts. We find 53 companions, 44 of which are new discoveries. We detail the Robo-AO survey data reduction methods including a method of using the large ensemble of target observations as mutual point-spread-function references, along with a new automated companion-detection algorithm designed for large adaptive optics surveys. Our survey is sensitive to objects from 0.15" to 2.5" separation, with contrast ratios up to delta-m~6. We measure an overall nearby-star-probability for Kepler planet candidates of 7.4% +/- 1.0%, and calculate the effects of each detected nearby star on the Kepler-measured planetary radius. We discuss several KOIs of particular interest, including KOI-191 and KOI-1151, which are both multi-planet systems with detected stellar companions whose unusual planetary system architecture might be best explained if they are "coincident multiple" systems, with several transiting planets shared between the two stars. Finally, we detect 2.6-sigma evidence for <15d-period giant planets being 2-3 times more likely be found in wide stellar binaries than smaller close-in planets and all sizes of further-out planets.Comment: Accepted by ApJ. Minor updates & improved statistical analysis; no changes to results. 15 pages, 13 figure

Assessment of Hydration Thermodynamics at Protein Interfaces with Grid Cell Theory

Molecular dynamics simulations have been analyzed with the Grid Cell Theory (GCT) method to spatially resolve the binding enthalpies and entropies of water molecules at the interface of 17 structurally diverse proteins. Correlations between computed energetics and structural descriptors have been sought to facilitate the development of simple models of protein hydration. Little correlation was found between GCT-computed binding enthalpies and continuum electrostatics calculations. A simple count of contacts with functional groups in charged amino acids correlates well with enhanced water stabilization, but the stability of water near hydrophobic and polar residues depends markedly on its coordination environment. The positions of X-ray-resolved water molecules correlate with computed high-density hydration sites, but many unresolved waters are significantly stabilized at the protein surfaces. A defining characteristic of ligand-binding pockets compared to nonbinding pockets was a greater solvent-accessible volume, but average water thermodynamic properties were not distinctive from other interfacial regions. Interfacial water molecules are frequently stabilized by enthalpy and destabilized entropy with respect to bulk, but counter-examples occasionally occur. Overall detailed inspection of the local coordinating environment appears necessary to gauge the thermodynamic stability of water in protein structures

Does wage rank affect employees' well-being?

How do workers make wage comparisons? Both an experimental study and an analysis of 16,000 British employees are reported. Satisfaction and well-being levels are shown to depend on more than simple relative pay. They depend upon the ordinal rank of an individual's wage within a comparison group. “Rank” itself thus seems to matter to human beings. Moreover, consistent with psychological theory, quits in a workplace are correlated with pay distribution skewness

Intraoperative PTH Monitoring in Normohormonal Primary Hyperparathyroidism

Background: A subset of patients with primary hyperparathyroidism present with inappropriately normal PTH levels despite elevated serum calcium, called normohormonal primary hyperparathyroidism (NHPHP). This disease variant presents a clinical dilemma regarding intraoperative parathyroid hormone (IOPTH) monitoring during parathyroidectomy when using the standard criteria of a ≥ 50% reduction in IOPTH from baseline to determine surgical success. This study aimed to determine what percent reduction in post-excision IOPTH from baseline in NHPHP patients would yield a high cure rate similar to that of classic primary hyperparathyroidism. Methods: This was a single surgeon, single institution retrospective cohort study of patients that underwent parathyroidectomy between July 2013 and February 2020. Demographic, preoperative, intraoperative, and postoperative metrics were collected. Patients with NHPHP were compared to those with classic primary hyperparathyroidism. Results: 496 patients were included in the study. 66 (13.3%) were of the normohormonal variant based on preoperative intact PTH levels and 28 (5.6%) based on baseline IOPTH levels. The cure rates in the normohormonal groups were not significantly different from their classic counterparts: 98.4% and 100.0% vs 97.1% and 97.1%, p = 1.000. The median percent decline in post-excision IOPTH from baseline that achieved cure in the normohormonal groups were 82.8% and 80.4% compared to their respective controls of 87.3% and 87.1%, p = 0.017 and p=0.001. Conclusion: A ≥ 75% decline in 15-minute post-excision IOPTH level from baseline can be used as a more stringent criterion for achieving high rates of cure in patients with NHPHP that undergo parathyroidectomy