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Multi-region pain during adolescence is associated with a higher symptom burden and lower quality of life. The purpose of this study was to describe and compare the biopsychosocial attributes of single-region and multi-region pain among healthy young adolescents.We analyzed data from 10,320 children aged 10.6 to 14 years who self-reported pain in the Adolescent Brain and Cognitive Development Study. Pain was coded as single-region or multi-region based on body map data.One in 5 young adolescents indicated recent multi-region pain. Sequential regression supported improved model fit when psychological and sociocultural factors were added to a biological model of pain; however, these models improved the classification of multi-region but not single-region pain. A significant interaction effect of sex and puberty remained constant across models with increased odds of pain at each advancing pubertal stage for both sexes compared with prepuberty, but no difference between girls and boys at late puberty (adjusted odds ratio [OR]=2.45 [1.72, 3.49] and adjusted OR=1.63 [1.20, 2.23], respectively). Psychological factors improved the classification of multi-region pain with significant effects of anxiety, somatic symptoms, and somnolence. Finally, compared with White and non-Hispanic children, Black and Hispanic children were less likely to report pain (adjusted OR=0.70 [0.61, 0.80]; adjusted OR=0.88 [0.78, 0.99], respectively) but had significantly higher pain interference when pain was present (adjusted OR=1.49 [1.29, 1.73] and adjusted OR=1.20 [1.06, 1.35], respectively).Pain is a biopsychosocial phenomenon, but psychological and sociocultural features may be more relevant for multi-region compared with single-region pain during early adolescence.

Background Astronauts on long-duration spaceflight missions may develop changes in ocular structure and function, which can persist for years after the return to normal gravity. Chronic exposure to elevated intracranial pressure during spaceflight is hypothesized to be a contributing factor, however, the etiologic causes remain unknown. Purpose To investigate the intracranial effects of microgravity by measuring combined changes in intracranial volumetric parameters, pituitary morphologic structure, and aqueductal cerebrospinal fluid (CSF) hydrodynamics relative to spaceflight and to establish a comprehensive model of recovery after return to Earth. Materials and Methods This prospective longitudinal MRI study enrolled astronauts with planned long-duration spaceflight. Measures were conducted before spaceflight followed by 1, 30, 90, 180, and 360 days after landing. Intracranial volumetry and aqueductal CSF hydrodynamics (CSF peak-to-peak velocity amplitude and aqueductal stroke volume) were quantified for each phase. Qualitative and quantitative changes in pre- to postflight (day 1) pituitary morphologic structure were determined. Statistical analysis included separate mixed-effects models per dependent variable with repeated observations over time. Results Eleven astronauts (mean age, 45 years ± 5 [standard deviation]; 10 men) showed increased mean volumes in the brain (28 mL; P < .001), white matter (26 mL; P < .001), mean lateral ventricles (2.2 mL; P < .001), and mean summated brain and CSF (33 mL; P < .001) at postflight day 1 with corresponding increases in mean aqueductal stroke volume (14.6 μL; P = .045) and mean CSF peak-to-peak velocity magnitude (2.2 cm/sec; P = .01). Summated mean brain and CSF volumes remained increased at 360 days after spaceflight (28 mL; P < .001). Qualitatively, six of 11 (55%) astronauts developed or showed exacerbated pituitary dome depression compared with baseline. Average midline pituitary height decreased from 5.9 to 5.3 mm (P < .001). Conclusion Long-duration spaceflight was associated with increased pituitary deformation, augmented aqueductal cerebrospinal fluid (CSF) hydrodynamics, and expansion of summated brain and CSF volumes. Summated brain and CSF volumetric expansion persisted up to 1 year into recovery, suggesting permanent alteration. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Lev in this issue.

Adolescent substance use has been identified as our nation's number one public health problem. Screening, brief intervention, and referral to treatment (SBIRT) is an evidence-based approach to identify and address adolescent substance use. Despite recommendations for universal implementation, adolescent SBIRT training has been notably absent from undergraduate nursing curricula. This project describes and evaluates the effectiveness of using an interactive computer simulation for adolescent SBIRT in an undergraduate nursing program.Undergraduate nursing students (n = 144) completed an adolescent SBIRT interactive computer simulation (SBI with Adolescents, Kognito). Self-perceived competence, confidence, and readiness to deliver adolescent SBIRT were measured via pre- and post-survey items. Student attitudes toward substance use and simulation-based learning were also studied. At the end of the simulation, students received an automatic assessment challenge score based on performance. We compared the pre- and post-SBIRT scores using the Wilcoxon signed rank test and the sign test for repeated measures using 2-tailed α = 0.05.We saw significant (p .05) improvement in overall student competence, confidence, and readiness to deliver SBIRT. Positive quantitative and qualitative feedback were also received regarding the simulation experience.Adolescent SBIRT training was successfully integrated into an undergraduate nursing curriculum. There were significant improvements in self-reported competence, confidence, and readiness to deliver adolescent SBIRT.This project provided further support for the potential benefits of an interactive computer-based simulation in an undergraduate nursing curriculum.

Background Effective interventions for overdose survivors are needed in the emergency departments (EDs). One promising model is the use of peer recovery coaches to engage with survivors in EDs, followed by partnering with community case management navigators to connect survivors to recovery support and treatment services. This paper describes the evaluation of a pilot program, the Recovery Opioid Overdose Team (ROOT), a warm hand-off system that links survivors to treatment services post-ED discharge. Methods The ROOT program is composed of a peer recovery coach who is in long-term recovery, and a case management navigator who specializes in mental health care and provides guidance for accessing community services. After an overdose reversal, law enforcement contacts a county 24/7 Crisis Team, who then notifies ROOT. The peer recovery coach engages with the survivor in the ED, and then follow up continues with the case management navigator and the peer recovery coach for up to 90 days post-ED discharge. Retrospective chart reviews were conducted to evaluate ROOT in two Midwest EDs from September 2017 through March 2019. Results Of the 122 referrals, 77.0% ( n = 94) of the survivors initially engaged with ROOT in the ED or in the community. The remaining 23.0% ( n = 28) left the ED against medical advice or were unengaged. The majority of overdose survivors were male (63.9%; n = 78), White (43.4%; n = 53), had housing (80.2%; n = 48), and access to transportation (48.4%; n = 59). From the 122 referrals, 33.6% ( n = 41) received ongoing treatment services ( n = 20 outpatient, n = 17 residential, n = 2 detoxification facility, n = 1 recovery housing, n = 1 medication treatment for opioid use disorder), 2.5% ( n = 3) were incarcerated, 2.5% ( n = 3) died, and 61.5% ( n = 75) declined services. Conclusions The ROOT, a community-wide coordinated program in the EDs, shows promise in linking overdose survivors to recovery support and treatment services post-overdose.

BACKGROUND/OBJECTIVES: Exercise is a front-line countermeasure used to maintain astronaut health during long-duration spaceflight; however, reductions in metabolic health still occur. Accordingly, we evaluated serial changes in metabolic parameters in a spaceflight analog and evaluated the efficacy of exercise with or without the addition of low-dose testosterone treatment on mitigating adverse metabolic changes. SUBJECTS/METHODS: Healthy young (

OBJECTIVE: The ActiGraph is commonly used for measuring sedentary behavior, but the best data processing technique is not established for sedentary adults with chronic illness. The purpose of this study was to process ActiGraph vertical axis and vector magnitude data with multiple combinations of filters, non-wear algorithm lengths, and cut-points and to compare ActiGraph estimates to activPAL-measured sedentary time in sedentary adults with chronic obstructive pulmonary disease. APPROACH: This study was a secondary analysis of adults ≥50 years (N=59; Mean age: 69.4 years; N= 31 males) with chronic obstructive pulmonary disease. Participants wore ActiGraph GT9X and activPAL3 for 7 days. ActiGraph vertical axis and vector magnitude data were processed using combinations of filters (normal, low frequency extension), non-wear algorithm lengths (60, 90, 120 minutes), and cut-points for sedentary behavior previously validated in older adults (two for vertical axis and three for vector magnitude data). The Bland-Altman method was used to assess concordance between sedentary time measured with 30 ActiGraph techniques and activPAL-measured sedentary time. MAIN RESULTS: Agreement between the two devices was moderate to strong for all techniques; concordance correlations ranged from 0.614–0.838. Limits of agreement were wide. The best overall technique was vector magnitude data with low frequency extension filter, 120-minute non-wear algorithm, and

Importance While 6-month data are available regarding spaceflight-associated neuro-ocular syndrome, manned missions for 1 year and beyond are planned, warranting evaluation for spaceflight-associated neuro-ocular syndrome beyond 6 months. Objective To determine if the manifestation of spaceflight-associated neuro-ocular syndrome worsens during International Space Station missions exceeding the present 4- to 6-month duration. Design, Setting, and Participants The One-Year Mission Study used quantitative imaging modalities to investigate changes in ocular structure in 2 crew members who completed a 1-year–long spaceflight mission. This study investigated the ocular structure of crew members before, during, and after their mission on the International Space Station. Two crew members participated in this study from March 2015 to September 2016. Analysis began in March 2015 and ended in May 2020. Exposures Crew members were tested before, during, and up to 1 year after spaceflight. Main Outcomes and Measures This study compares ocular changes (peripapillary retinal edema, axial length, anterior chamber depth, and refraction) in two 1-year spaceflight mission crew members with cohort crew members from a 6-month mission (n = 11). Minimum rim width (the shortest distance between Bruch membrane opening and the internal limiting membrane) and peripapillary total retinal thickness were measured using optical coherence tomography. Results Both crew members were men. Minimum rim width and total retinal thickness increased in both participants throughout the duration of spaceflight exposure to the maximal observed change from preflight (minimum rim width: participant 1, 561 [+149 from preflight] μm at flight day 270; participant 2, 539 [+56 from preflight] μm at flight day 270; total retinal thickness: participant 1, 547 [+135 from preflight] μm at flight day 90; participant 2, 528 [+45 from preflight] μm at flight day 210). Changes in peripapillary choroid engorgement, axial length, and anterior chamber depth appeared similar between the 1-year mission participants and a 6-month mission cohort. Conclusions and Relevance This report documents the late development of mild optic disc edema in 1 crew member and the progressive development of choroidal folds and optic disc edema in another crew member over the duration of 1 year in low Earth orbit aboard the International Space Station. Previous reports characterized the ocular risk associated with 4 to 6 months of spaceflight. As future spaceflight missions are planned to increase in duration and extend beyond low Earth orbit, further observation of astronaut ocular health on spaceflight missions longer than 6 months in duration may be warranted.

The purpose of this study was to develop and evaluate the validity and reliability of an instrument to measure nurse manager competencies regarding evidence-based practice (EBP). The Nurse Manager EBP Competency Scale consists of 16 items for respondents to indicate their perceived level of competency on a 0 to 3 Likert-type scale. Content validity was demonstrated through expert panel review and pilot testing. Principal axis factoring and Cronbach's alpha evaluated construct validity and internal consistency reliability, respectively. Eighty-three nurse managers completed the scale. Exploratory factor analysis resulted in a 16-item scale with two subscales, EBP Knowledge ( n = 6 items, α = .90) and EBP Activity ( n = 10 items, α = .94). Cronbach's alpha for the entire scale was .95. The Nurse Manager EBP Competency Scale is a brief measure of nurse manager EBP competency with evidence of validity and reliability. The scale can enhance our understanding in future studies regarding how nurse manager EBP competency affects implementation.

Introduction We evaluated ophthalmic changes in healthy individuals who underwent integrated resistance and aerobic training (iRAT) during 70-d 6° head-down tilt (HDT) bed rest (BR). Methods Participants were selected using NASA standard screening procedures. Standardized NASA BR conditions were implemented. Subjects were randomly assigned to the iRAT protocol or no exercise during HDTBR. Weekly ophthalmic examinations were performed in the sitting (pre/post-BR only) and HDT (BR only) positions. Mixed-effects linear models compared pre- and post-HDTBR intraocular pressure (IOP), Spectralis OCT circumpapillary retinal nerve fiber layer (cpRNFL) thickness, and peripapillary retinal thickness observations between groups. Results Six controls and nine exercisers completed the study. There was an overall effect of BR on our outcomes. Except Goldmann IOP (mean pre/post difference in controls and exercisers: -0.47 mmHg vs. +1.14 mmHg), the magnitude of changes from baseline was not significantly different between groups. There was a +1.38 mmHg and a +1.63 mmHg iCare IOP increase during BR in controls and exercisers, respectively. Spectralis OCT detected a +1.33 μm average cpRNFL thickness increase in both groups, and a +9.77 μm and a +6.65 μm peripapillary retinal thickening post-BR in controls and exercisers, respectively. Modified Amsler grid, red dot test, confrontational visual field, color vision, and stereoscopic fundus photography were unremarkable. Conclusions HDTBR for 70 d induced peripapillary retinal thickening and cpRNFL thickening without visible signs of optic disc edema. The magnitude of such changes was not different between controls and exercisers. A slight IOP increase during BR subsided post-BR. Further study should evaluate whether different physical exercise paradigms may prevent/mitigate the risk of space-related visual impairment.Taibbi G, Cromwell RL, Zanello SB, Yarbough PO, Ploutz-Snyder RJ, Godley BF, Vizzeri G. Ophthalmological evaluation of integrated resistance and aerobic training during 70-day bed rest. Aerosp Med Hum Perform. 2017; 88(7):633-640.

IMPORTANCE: Astronauts on International Space Station missions demonstrate adverse neuro-ocular changes. Reversing a negative translaminar pressure gradient (TLPG) by modulating cerebral blood flow, decreasing intracranial pressure, or increasing intraocular pressure (IOP) has been proposed as potential intervention for spaceflight-associated neuro-ocular syndrome (SANS). OBJECTIVE: To examine whether exercise (resistance, moderate-intensity aerobic, and high-intensity aerobic) or artificially increasing IOP is associated with modulated cerebro-ocular hemodynamic and pressure changes during head-down tilt (HDT), an analogue of spaceflight, in healthy adults. DESIGN, SETTING, AND PARTICIPANTS: A single-center investigation was conducted at Johnson Space Center, Houston, Texas, from January 1, 2014, to December 31, 2016, in 20 healthy men. EXPOSURE: On 3 separate days, participants rested supine, were tilted to −15° HDT, and then completed 1 of 3 experimental exercise conditions (moderate-intensity aerobic, resistance, or high-intensity interval aerobic). A subset of 10 participants wore swimming goggles on all days. MAIN OUTCOMES AND MEASURES: Applanation rebound tonometry was used to noninvasively assess IOP, and compression sonography was used to assess internal jugular venous pressure (IJVP). Estimated TLPG was calculated as the difference between IOP and IJVP. Cerebral inflow and outflow were measured in extracranial arteries using color-coded duplex ultrasonography. RESULTS: Twenty men participated in the study (mean [SD] age, 36 [9] years). Compared with supine IOP (mean [SD], 19.3 [3.7] mm Hg), IJVP (mean [SD], 21.4 [6.0] mm Hg), and estimated TLPG (mean [SD], −2.1 [7.0] mm Hg), −15° HDT was associated with increased IOP (mean difference, 2.3 mm Hg; 95% CI, 1.4-3.3 mm Hg; P

Insulin-stimulated glucose uptake (GU) by skeletal muscle is enhanced several hours after acute exercise in rats with normal or reduced insulin sensitivity. Skeletal muscle is composed of multiple fiber types, but exercise’s effect on fiber type-specific insulin-stimulated GU in insulin-resistant muscle was previously unknown. Male rats were fed a high-fat diet (HFD; 2 wk) and were either sedentary (SED) or exercised (2-h exercise). Other, low-fat diet-fed (LFD) rats remained SED. Rats were studied immediately postexercise (IPEX) or 3 h postexercise (3hPEX). Epitrochlearis muscles from IPEX rats were incubated in 2-deoxy-[3H]glucose (2-[3H]DG) without insulin. Epitrochlearis muscles from 3hPEX rats were incubated with 2-[3H]DG ± 100 µU/ml insulin. After single fiber isolation, GU and fiber type were determined. Glycogen and lipid droplets (LDs) were assessed histochemically. GLUT4 abundance was determined by immunoblotting. In HFD-SED vs. LFD-SED rats, insulin-stimulated GU was decreased in type IIB, IIX, IIAX, and IIBX fibers. Insulin-independent GU IPEX was increased and glycogen content was decreased in all fiber types (types I, IIA, IIB, IIX, IIAX, and IIBX). Exercise by HFD-fed rats enhanced insulin-stimulated GU in all fiber types except type I. Single fiber analyses enabled discovery of striking fiber type-specific differences in HFD and exercise effects on insulin-stimulated GU. The fiber type-specific differences in insulin-stimulated GU postexercise in insulin-resistant muscle were not attributable to a lack of fiber recruitment, as indirectly evidenced by insulin-independent GU and glycogen IPEX, differences in multiple LD indexes, or altered GLUT4 abundance, implicating fiber type-selective differences in the cellular processes responsible for postexercise enhancement of insulin-mediated GLUT4 translocation.

Cardiovascular events are the leading cause of line-of-duty fatality for firefighters. Aspirin reduces the risk of cardiovascular events in men and may reduce fatalities in older (40 yr) firefighters. We hypothesized that both chronic and acute aspirin supplementation would improve vascular function after live firefighting but that chronic supplementation would also improve resting hemodynamics.Twenty-four firefighters (40-60 yr) were randomly assigned to acute or chronic aspirin supplementation or placebo in a balanced, crossover design. Arterial stiffness, brachial and central blood pressures, as well as forearm vasodilatory capacity and blood flow were measured at rest and immediately after live firefighting.Total hyperemic blood flow (area under the curve (AUC)) was increased (P0.001) after firefighting with no effects for aspirin supplementation or acute versus chronic administration (AUC, from 107 ± 5 to 223 ± 9 in aspirin condition and from 97 ± 5 to 216 ± 7 mL·min⁻¹ per 100-mL forearm tissue for placebo; P0.05 for main, and P0.05 for interaction). Arterial stiffness/central blood pressure increased (P0.04) with no effect of aspirin (from 0.0811 ± 0.001 to 0.0844 ± 0.003 m·s·mm⁻¹ Hg⁻¹ in aspirin condition versus 0.0802 ± 0.002 to 0.0858 ± 0.002 m·s⁻¹·mm Hg⁻¹ in placebo condition), whereas peripheral and central systolic and pulse pressures decreased after firefighting across conditions (P0.05).Live firefighting resulted in increased AUC and pressure-controlled arterial stiffness and decreased blood pressure in older firefighters, but aspirin supplementation did not affect macro- or microvascular responsiveness at rest or after firefighting.

This randomized clinical trial evaluates the effectiveness of spinal manipulation and spinal mobilization compared with a placebo at reducing pain and disability among young adults with mild to moderate chronic low back pain., Key Points Question What is the comparative effectiveness of spinal manipulation compared with spinal mobilization relative to a placebo control in reducing pain and disability in chronic low back pain? Findings In this randomized clinical trial that included 162 young adults, there was no difference in reduction of pain and disability when comparing spinal manipulation to spinal mobilization relative to the placebo control treatment. Meaning Neither spinal manipulation nor mobilization appeared to be an effective intervention for young adults with mild to moderate chronic low back pain., Importance Low back pain (LBP) is one of the most common reasons for seeking medical care. Manual therapy is a common treatment of LBP, yet few studies have directly compared the effectiveness of thrust (spinal manipulation) vs nonthrust (spinal mobilization) techniques. Objective To evaluate the comparative effectiveness of spinal manipulation and spinal mobilization at reducing pain and disability compared with a placebo control group (sham cold laser) in a cohort of young adults with chronic LBP. Design, Setting, and Participants This single-blinded (investigator-blinded), placebo-controlled randomized clinical trial with 3 treatment groups was conducted at the Ohio Musculoskeletal and Neurological Institute at Ohio University from June 1, 2013, to August 31, 2017. Of 4903 adult patients assessed for eligibility, 4741 did not meet inclusion criteria, and 162 patients with chronic LBP qualified for randomization to 1 of 3 treatment groups. Recruitment began on June 1, 2013, and the primary completion date was August 31, 2017. Data were analyzed from September 1, 2017, to January 20, 2020. Interventions Participants received 6 treatment sessions of (1) spinal manipulation, (2) spinal mobilization, or (3) sham cold laser therapy (placebo) during a 3-week period. Main Outcomes and Measures Coprimary outcome measures were the change from baseline in Numerical Pain Rating Scale (NPRS) score over the last 7 days and the change in disability assessed with the Roland-Morris Disability Questionnaire (scores range from 0 to 24, with higher scores indicating greater disability) 48 to 72 hours after completion of the 6 treatments. Results A total of 162 participants (mean [SD] age, 25.0 [6.2] years; 92 women [57%]) with chronic LBP (mean [SD] NPRS score, 4.3 [2.6] on a 1-10 scale, with higher scores indicating greater pain) were randomized. Fifty-four participants were randomized to the spinal manipulation group, 54 to the spinal mobilization group, and 54 to the placebo group. There were no significant group differences for sex, age, body mass index, duration of LBP symptoms, depression, fear avoidance, current pain, average pain over the last 7 days, and self-reported disability. At the primary end point, there was no significant difference in change in pain scores between spinal manipulation and spinal mobilization (0.24 [95% CI, −0.38 to 0.86]; P = .45), spinal manipulation and placebo (−0.03 [95% CI, −0.65 to 0.59]; P = .92), or spinal mobilization and placebo (−0.26 [95% CI, −0.38 to 0.85]; P = .39). There was no significant difference in change in self-reported disability scores between spinal manipulation and spinal mobilization (−1.00 [95% CI, −2.27 to 0.36]; P = .14), spinal manipulation and placebo (−0.07 [95% CI, −1.43 to 1.29]; P = .92) or spinal mobilization and placebo (0.93 [95% CI, −0.41 to 2.29]; P = .17). Conclusions and Relevance In this randomized clinical trial, neither spinal manipulation nor spinal mobilization appeared to be effective treatments for mild to moderate chronic LBP. Trial Registration ClinicalTrials.gov Identifier: NCT01854892

INTRODUCTION: This study investigated the safety and effectiveness of a new integrated aerobic and resistance exercise training prescription (SPRINT) using two different sets of exercise equipment: a suite of large International Space Station-like exercise equipment similar to what is found on the International Space Station and a single device with aerobic and resistance exercise capability in the spaceflight analog of bed rest (BR). METHODS: Subjects (n = 34) completed 70 d of 6° head down tilt BR: 9 were randomized to remain sedentary (CONT), 9 to exercise training using traditional equipment (EX), 8 to exercise using traditional equipment and low-dose testosterone supplementation (ExT), and 8 to exercise using a combined resistance and aerobic flywheel device. Peak aerobic capacity, ventilatory threshold, cardiac morphology and function (echocardiography), muscle mass (magnetic resonance imaging) and strength/power (isokinetic, leg press, and vertical jump), and bone health (bone mineral density, blood and urine bone markers) were assessed before and after BR. RESULTS: The SPRINT protocol mitigated BR-induced muscle and cardiac deconditioning regardless of the exercise device used. Molecular markers of bone did not change in the CONT or EX groups. Peak aerobic capacity was maintained from pre-to post-BR in all exercise groups similarly, whereas significant declines were observed in the CONT group (~10%). Significant interaction effects between the CONT group and all EX groups were observed for muscle performance including leg press total work, isokinetic upper and lower leg strength, vertical jump power, and maximal jump height as well as muscle size. CONCLUSIONS: This is the first trial to evaluate multisystem deconditioning and the role of an integrated exercise countermeasure. These findings have important implications for the design and implementation of exercise-based countermeasures on future long-duration spaceflight missions.

Background: Adolescent substance use is a significant public health problem in the United States screening, brief intervention, and referral to treatment (SBIRT) and is an evidence-based approach to assist individuals to reduce substance use before serious problems develop. Universal SBIRT is recommended for routine health care. Method: Advanced practice registered nursing (APRN) students completed a sophisticated adolescent SBIRT computer simulation, didactic content on substance use, and face-to-face simulation during laboratory. SBIRT skills were scored automatically by the computer program. Self-perceived competency and confidence were measured via pre- and postsurvey items, focused on adolescent SBIRT skills, using ordinal scales. Results: Adolescent SBIRT was successfully integrated into an advanced health assessment nursing course. Improvements in self-reported competence and confidence scores were noted across all domains at p < .001. Conclusion: APRN students demonstrated learning and reported marked increases in competency and confidence in the delivery of adolescent SBIRT. This reveals promising results for SBIRT to be implemented into APRN student coursework. [ J Nurs Educ . 2018;57(12):736–741.]

PURPOSE: Early and consistent evaluation of cardiac morphology and function throughout an atrophic stimulus is critically important for the design and optimization of interventions. This randomized, controlled trial was designed to: 1) characterize the time course of unloading-induced morpho-functional remodeling, and 2) to examine the effects of exercise with and without low dose testosterone supplementation on cardiac biomarker, structural, and functional parameters during unloading. METHODS: Twenty six subjects completed 70 days of head down tilt bed rest (BR): 9 were randomized to exercise training (Ex), 8 to EX and low dose testosterone (ExT), and 9 remained sedentary (CONT). Exercise consisted of high intensity, continuous, and resistance exercise. Cardiac morphology (left ventricular mass; LVM) and mechanics (longitudinal, radial, and circumferential strain and twist), cardiovascular biomarkers, and cardiorespiratory fitness (VO(2peak)) were assessed before, during, and following BR. RESULTS: Sedentary BR resulted in a progressive decline in LVM, longitudinal, radial, and circumferential strain in CONT, while Ex and ExT mitigated decreases in LVM and function. Twist was increased throughout bed rest in sedentary BR, while after an initial increase at BR7, there were no further changes in twist in Ex and ExT. HDL cholesterol was significantly decreased in all groups compared to pre-bed rest (p

Dietary treatment is important in management of type 2 diabetes or prediabetes, but uncertainty exists about the optimal diet. We randomized adults (n = 34) with glycated hemoglobin (HbA1c) > 6.0% and elevated body weight (BMI > 25) to a very low-carbohydrate ketogenic (LCK) diet (n = 16) or a moderate-carbohydrate, calorie-restricted, low-fat (MCCR) diet (n = 18). All participants were encouraged to be physically active, get sufficient sleep, and practice behavioral adherence strategies based on positive affect and mindful eating. At 12 months, participants in the LCK group had greater reductions in HbA1c levels (estimated marginal mean (EMM) at baseline = 6.6%, at 12 mos = 6.1%) than participants in MCCR group (EMM at baseline = 6.9%, at 12 mos = 6.7%), p = .007. Participants in the LCK group lost more weight (EMM at baseline = 99.9 kg, at 12 mos = 92.0 kg) than participants in the MCCR group (EMM at baseline = 97.5 kg, at 12 mos = 95.8 kg), p p = .005). In a 12-month trial, adults with elevated HbA1c and body weight assigned to an LCK diet had greater reductions in HbA1c, lost more weight, and reduced more medications than those instructed to follow an MCCR diet.

Ophthalmic changes have occurred in a subset of astronauts on International Space Station missions. Visual deterioration is considered the greatest human health risk of spaceflight. Affected astronauts exhibit higher concentrations of 1-carbon metabolites (e.g., homocysteine) before flight. We hypothesized that genetic variations in 1-carbon metabolism genes contribute to susceptibility to ophthalmic changes in astronauts. We investigated 5 polymorphisms in the methionine synthase reductase (MTRR), methylenetetrahydrofolate reductase (MTHFR), serine hydroxymethyltransferase (SHMT), and cystathionine β-synthase (CBS) genes and their association with ophthalmic changes after flight in 49 astronauts. The number of G alleles of MTRR 66 and C alleles of SHMT1 1420 both contributed to the odds of visual disturbances. Preflight dehydroepiandrosterone was positively associated with cotton wool spots, and serum testosterone response during flight was associated with refractive change. Block regression showed that B-vitamin status and genetics were significant predictors of many of the ophthalmic outcomes that we observed. In one example, genetics trended toward improving (P = 0.10) and B-vitamin status significantly improved (P < 0.001) the predictive model for refractive change after flight. We document an association between MTRR 66 and SHMT1 1420 polymorphisms and spaceflight-induced vision changes. This line of research could lead to therapeutic options for both space travelers and terrestrial patients.—Zwart, S. R., Gregory, J. F., Zeisel, S. H., Gibson, C. R., Mader, T. H., Kinchen, J. M., Ueland, P. M., Ploutz-Snyder, R., Heer, M. A., Smith, S. M. Genotype, B-vitamin status, and androgens affect spaceflight-induced ophthalmic changes.

Introduction The Hypobaric Decompression Sickness (DCS) Treatment Model links a decrease in computed bubble volume from increased pressure (ΔP), increased oxygen (O2) partial pressure, and passage of time during treatment to the probability of symptom resolution [P(SR)]. The decrease in offending volume is realized in two stages: 1) during compression via Boyles law; and 2) during subsequent dissolution of the gas phase via the oxygen window. Methods We established an empirical model for the P(SR) while accounting for multiple symptoms within subjects. The data consisted of 154 cases of hypobaric DCS symptoms with ancillary information from tests on 56 men and 18 women. Results Our best estimated model is P(SR)=1/(1+exp(-(ln(ΔP)-1.510+0.795×AMB-0.00308×Ts)/0.478)), where ΔP is pressure difference (psid); AMB=1 if ambulation took place during part of the altitude exposure, otherwise AMB=0; and Ts is the elapsed time in minutes from the start of altitude exposure to recognition of a DCS symptom. Discussion Values of ΔP as inputs to the model would be calculated from the Tissue Bubble Dynamics Model based on the effective treatment pressure: ΔP=P2-P1|=P1×V1/V2-P1, where V1 is the computed volume of a bubble at low pressure P1 and V2 is computed volume after a change to a higher pressure P2. If 100% ground-level oxygen was breathed in place of air, then V2 continues to decrease through time at P2 at a faster rate.

Many astronauts experience ocular structural and functional changes during long‐duration spaceflight, including choroidal folds, optic disc edema, globe flattening, optic nerve sheath diameter (ONSD) distension, retinal nerve fiber layer thickening, and decreased visual acuity. The leading hypothesis suggests that weightlessness‐induced cephalad fluid shifts increase intracranial pressure (ICP), which contributes to the ocular structural changes, but elevated ambient CO 2 levels on the International Space Station may also be a factor. We used the spaceflight analog of 6° head‐down tilt (HDT) to investigate possible mechanisms for ocular changes in eight male subjects during three 1‐h conditions: Seated, HDT, and HDT with 1% inspired CO 2 (HDT + CO 2). Noninvasive ICP, intraocular pressure (IOP), translaminar pressure difference (TLPD = IOP‐ICP), cerebral and ocular ultrasound, and optical coherence tomography (OCT) scans of the macula and the optic disc were obtained. Analysis of one‐carbon pathway genetics previously associated with spaceflight‐induced ocular changes was conducted. Relative to Seated, IOP and ICP increased and TLPD decreased during HDT. During HDT + CO 2 IOP increased relative to HDT, but there was no significant difference in TLPD between the HDT conditions. ONSD and subfoveal choroidal thickness increased during HDT relative to Seated, but there was no difference between HDT and HDT + CO 2. Visual acuity and ocular structures assessed with OCT imaging did not change across conditions. Genetic polymorphisms were associated with differences in IOP, ICP, and end‐tidal PCO 2. In conclusion, acute exposure to mild hypercapnia during HDT did not augment cardiovascular outcomes, ICP, or TLPD relative to the HDT condition.

Abdomen-high, lower body graded compression garments (GCGs) may represent the next-generation of orthostatic intolerance protection with applications for exploration missions and commercial space flight. To evaluate the efficacy of the GCG to prevent orthostatic intolerance after a 14-day 6° head-down tilt bed rest (BR) and to determine whether wearing thigh-high compression garments impairs recovery from BR. Sixteen (12 M, 4 F) subjects participated in a 15-min 80° head-up tilt test 5 day before BR (BR-5), on the last morning of BR (BR+0), and on day 1 (BR+1) and 3 after BR (BR+3). No subjects wore the GCG on BR-5, and all subjects wore the GCG during testing on BR+0. Control subjects (n = 8) wore the GCG only through testing on BR+0. Treatment subjects (n = 8) wore the GCG on BR+0 and thigh-high garments on BR+1 and BR+2. No subjects were presyncopal during tilt on BR+0 while wearing the GCG. Despite lower plasma volume index (BR-5: 1.52 ± 0.06, BR+0: 1.32 ± 0.05 l/m2), the tilt-induced increase in heart rate (ΔHR, 17 ± 2 bpm) and decrease in stroke volume (ΔSV, −28 ± 3 ml) on BR+0 were less than on BR-5 (24 ± 2 bpm, −43 ± 4 ml). On BR+1 ΔHR in the control group (33 ± 4 bpm) was higher than in the treatment group (23 ± 2 bpm) but there were no group differences on BR+3. Wearing the GCG prevented the orthostatic intolerance that is normally present after BR. Thigh-high garments provided protection after BR, and wearing these garments did not impair recovery.

Background The strong link between reduced muscle mass and morbidity and mortality highlights the urgent need for simple techniques that can monitor change in skeletal muscle cross‐sectional area (CSA). Our objective was to examine the validity of panoramic ultrasound to detect change in quadriceps and gastrocnemius size in comparison with magnetic resonance imaging (MRI) in subjects randomized to 70 days of bed rest (BR) with or without exercise. Methods Panoramic ultrasound and MRI images of the quadriceps and gastrocnemius muscles were acquired on the right leg of 27 subjects (26 male, 1 female; age: 34.6 ± 7.8 years; body mass: 77.5 ± 10.0 kg; body mass index: 24.2 ± 2.8 kg/m2; height: 179.1 ± 6.9 cm) before (BR‐6), during (BR3, 7, 11, 15, 22, 29, 36, 53, 69), and after (BR+3, +6, +10) BR. Validity of panoramic ultrasound to detect change in muscle CSA was assessed by Bland–Altman plots, Lin's concordance correlation coefficient (CCC), sensitivity, specificity, positive predictive value, and negative predictive value. Results Six hundred ninety‐eight panoramic ultrasound CSA and 698 MRI CSA measurements were assessed. Concordance between ultrasound and MRI was excellent in the quadriceps (CCC: 0.78; P

This study examined the reliability and validity of using customized templates to acquire panoramic ultrasound (US) images for determining cross-sectional area (CSA) and volume in the vastus lateralis (VL), rectus femoris (RF), medial gastrocnemius (MG) and lateral gastrocnemius (LG). Panoramic US and magnetic resonance imaging (MRI) images were analyzed by two trained investigators. The inter-experimenter reliability (coefficient of variation [CV]) of panoramic US ranged from 2.4% to 4.1% and the intraclass correlation (ICC) ranged from 0.963 to 0.991, whereas the inter-experimenter CV of MRI ranged from 2.8% to 3.8% and the ICC from 0.946 to 0.986. Bland-Altman plots demonstrated high agreement between US and MRI; however, values obtained from MRI were systematically larger than those obtained from US. The present results indicate that using a customized US template provides reliable measures of leg muscle CSA and, thus, could be used to characterize muscle CSA and volume.

Approximately 20% (7 of 38) of astronauts on International Space Station (ISS) missions have developed measurable ophthalmic changes after flight. This study was conducted to determine if the folate- and vitamin B-12-dependent 1-carbon metabolic pathway is altered in these individuals. Since 2006, we have conducted experiments on the ISS to evaluate nutritional status and related biochemical indices of astronauts before, during, and after flight. Data were modeled to evaluate differences between individuals with ophthalmic changes (n = 5) and those without them (n = 15), all of whom were on ISS missions of 48-215 d. We also determined whether mean preflight serum concentrations of the 1-carbon metabolites and changes in measured cycloplegic refraction after flight were associated. Serum homocysteine (Hcy), cystathionine, 2-methylcitric acid (2MCA), and methylmalonic acid concentrations were 25-45% higher (P < 0.001) in astronauts with ophthalmic changes than in those without them. These differences existed before, during, and after flight. Preflight serum concentrations of Hcy and cystathionine, and mean in-flight serum folate, were correlated with change (postflight relative to preflight) values in refraction (P < 0.05), and preflight serum concentrations of 2MCA tended to be associated (P = 0.06) with ophthalmic changes. The biochemical differences observed in crewmembers with vision issues strongly suggest that their folate- and vitamin B-12-dependent 1-carbon transfer metabolism was affected before and during flight. The consistent differences in markers of 1-carbon metabolism between those who did and those who did not develop changes in vision suggest that polymorphisms in enzymes of this pathway may interact with microgravity to cause these pathophysiologic changes.

Sudden cardiovascular events account for approximately 45% to 50% of all duty-related deaths among firefighters and a disproportionate number of these fatalities occur after strenuous fire suppression activities. The purpose of this study was to evaluate the effect of acute and chronic aspirin supplementation on hemostatic function before and after live firefighting activities in older firefighters. A double-blind, crossover design included 4 treatments: a 2-week aspirin/placebo treatment ("chronic") and a single prefirefighting aspirin/placebo treatment ("acute"). Hemostatic function was assessed in 24 male firefighters (mean age = 48.2 ± 5.9 years) immediately before and after 18 minutes of live-fire firefighting activity. An acute bout of firefighting activity significantly decreased platelet aggregation time and decreased activated partial thromboplastin time. Compared with placebo, acute aspirin supplementation resulted in a significant increase in epinephrine closure time, which was further augmented by chronic supplementation. Aspirin supplementation had no effect on coagulatory or fibrinolytic factors. Our findings suggest that an acute bout of firefighting leads to increased coagulatory potential in older firefighters. In conclusion, aspirin supplementation had an antiplatelet effect that decreased platelet aggregability at rest and after an acute bout of firefighting compared with placebo.

INTRODUCTION Long-duration spaceflight results in a loss of muscle strength that poses both operational and medical risks, particularly during emergency egress, upon return to Earth, and during future extraterrestrial exploration. Isokinetic testing of the knee, ankle, and trunk quantifies movement-specific strength changes following spaceflight and offers insight into the effectiveness of in-flight exercise countermeasures. METHODS We retrospectively evaluated changes in isokinetic strength for 37 ISS crewmembers (Expeditions 1-25) following 163 ± 38 d (mean ± SD) of spaceflight. Gender, in-flight resistance exercise hardware, and preflight strength were examined as potential modifiers of spaceflight-induced strength changes. RESULTS Mean isokinetic strength declined 8-17% following spaceflight. One month after return to Earth, strength had improved, but small deficits of 1-9% persisted. Spaceflight-induced strength losses were not different between men and women. Mean strength losses were as much as 7% less in crewmembers who flew after the Advanced Resistive Exercise Device (ARED) replaced the interim Resistive Exercise Device (iRED) as the primary in-flight resistance exercise hardware, although these differences were not statistically significant. Absolute and relative preflight strength were moderately correlated (r = -0.47 and -0.54, respectively) with postflight strength changes. DISCUSSION In-flight resistance exercise did not prevent decreased isokinetic strength after long-duration spaceflight. However, continued utilization of ARED, a more robust resistance exercise device providing higher loads than iRED, may result in greater benefits as exercise prescriptions are optimized. With reconditioning upon return to Earth, strength is largely recovered within 30 d.

Schizophrenia and alcohol dependence (AD) are both major risk factors for a variety of medical problems, yet little is known about the medical status of patients in whom both conditions coexist.The objectives of this study are to assess accuracy of self-reported medical problems and to compare the accuracy reports in patients with schizophrenia or schizoaffective disorder and co-occurring AD compared to patients with AD only and to controls. Our hypothesis was that medical problems are under-reported in patients with co-occurring disorders, possibly due to the combination of alcohol use and symptoms of schizophrenia.Self-reported medical diagnoses were recorded and compared to medical records obtained from all area hospitals in 42 patients with schizophrenia and AD, 44 patients with schizoaffective disorder and AD, 41 patients with AD only, and 15 control subjects. Patients underwent medical history, physical examination, and review of medical records.Patients with schizophrenia or schizoaffective disorder and co-occurring AD underreported their medical problems significantly more than patients with AD only and controls. Accuracy of self report was significantly lower in patients with schizophrenia-spectrum disorders plus co-occurring alcohol dependence than in AD alone or in controls. The most commonly underreported diagnoses included coronary artery disease, chronic renal failure, seizure disorder, hyperlipidemia, asthma and hypertension.In order to detect potentially unreported medical conditions in patients with co-occurring schizophrenia/schizoaffective disorder and alcohol dependence, the use of targeted screening questionnaires is recommended in addition to physical examination and thorough review of medical records.

Recent evidence shows that the ability to adapt to a novel discordant sensorimotor environment can be increased through prior training. We aimed to determine whether gait adaptability could be increased and then retained using a training system comprised of a treadmill placed on a motion base facing a virtual visual scene that provided a variety of sensory challenges that served as training modalities. Ten healthy adults participated in three training sessions during which they walked on a treadmill at 1.1 m/s while receiving discordant support-surface and visual manipulations. Upon completion, participants were presented with a novel sensorimotor challenge designed to test for transfer of adaptive skills. During this test, stride frequency, reaction time, and heart rate data were collected as measures of postural stability, cognitive load, and anxiety, respectively. Compared to 10 untrained controls, trained participants showed enhanced overall performance on the Novel Test, which was administered 20 min after their final training session. Subjects in both groups had greater stride frequency, reaction time, and heart rate when exposed to the new sensory environment; however, these increases were less pronounced in the trained subjects than in the controls. The Novel Test was re-administered to both groups 1 week, 1 month, 3 months, and 6 months later. Trained subjects maintained their level of performance for 6 months. Untrained subjects continued to improve in these measures at each subsequent test session, suggesting that a lasting sensorimotor adaptability training effect can be achieved with very short, repeated exposures to discordant sensory conditions.

Spectral analysis identifies localized sites of high-frequency activity during atrial fibrillation (AF).This study sought to determine the effectiveness of using real-time dominant frequency (DF) mapping for radiofrequency ablation of maximal DF (DFmax) sites and elimination of left-to-right frequency gradients in the long-term maintenance of sinus rhythm (SR) in AF patients.DF mapping was performed in 50 patients during ongoing AF (32 paroxysmal, 18 persistent), acquiring a mean of 117 +/- 38 points. Ablation was performed targeting DFmax sites, followed by circumferential pulmonary vein isolation.Ablation significantly reduced DFs (Hz) in the LA (7.9 +/- 1.4 vs. 5.7 +/- 1.3, P.001), coronary sinus (CS) (5.7 +/- 1.1 vs. 5.3 +/- 1.2, P = .006), and RA (6.3 +/- 1.4 vs. 5.4 +/- 1.3, P.001) abolishing baseline left-to-right atrial DF gradient (1.7 +/- 1.7 vs. 0.2 +/- 0.9; P.001). Only a significant reduction in DFs in all chambers with a loss of the left-to-right atrial gradient after ablation was associated with a higher probability of long-term SR maintenance in both paroxysmal and persistent AF patients. After a mean follow-up of 9.3 +/- 5.4 months, 88% of paroxysmal and 56% of persistent AF patients were free of AF (P = .02). Ablation of DFmax sites was associated with a higher probability of remaining both free of arrhythmias (78% vs. 20%; P = .001) and free of AF (88% vs. 30%; P.001).Radiofrequency ablation leading to elimination of LA-to-RA frequency gradients predicts long-term SR maintenance in AF patients.

Noninvasive serum markers of liver fibrosis are being used as an alternative to liver biopsy. Currently available tests distinguish, with accuracy, only absent/minimal fibrosis (Ishak stages 0-1) and advanced fibrosis/cirrhosis (Ishak stages 4-6), but not intermediate fibrosis (Ishak stages 2-3). Our aim was to evaluate the diagnostic accuracy of hyaluronic acid (HA), FIBROSpect II (FS-II), and YKL-40 (chondrex, human cartilage glycoprotein-39) in various clinically important categories of fibrosis, and further correlate these serum markers with digital quantification of fibrosis (DQF) and Ishak stages.Serum HA, YKL-40, and FS-II were retrospectively assessed and correlated with Ishak stages and DQF scores in 75 patients with chronic hepatitis C (HCV). Spearman's rho statistics assessed relationships among all parameters, and receiver operator characteristic curves evaluated accuracy of each parameter when compared to the Ishak stages.All three serum markers and DQF correlated highly with one another (Por = 0.01) and with Ishak stages of fibrosis. Among the serum markers, HA was effective in discriminating between Ishak stages 0-1 and Ishak stages 2-3 compared with FS-II, with an area under the curve of 0.76 versus 0.66 and a false-positive rate of 0.33 versus 0.67, respectively. All three serum markers predicted advanced fibrosis and cirrhosis. YKL-40 had the highest false-positive rates in all categories of fibrosis.HA can be utilized as a reliable surrogate marker in distinguishing three clinically relevant stages of fibrosis: absent/minimal, intermediate, and advanced/cirrhosis. HA should be considered as a cost-effective alternative to other serum markers for staging fibrosis and for determining the timing and selection of HCV treatment.

This study assessed the feasibility of voucher-based incentives for attendance for directly observed naltrexone treatment in a controlled trial for alcohol use disorders in schizophrenia.Cash-value voucher-based incentives were contingent on attendance at three research visits per week over 12 weeks for 61 participants. Vouchers increased in value based on consecutive attendance. Missed visits resulted in reduction of voucher value.Participants attended 82% of all research visits. Average value of vouchers earned was $330 (78% of the maximum possible). Psychotic symptom severity at baseline did not affect the utilization of vouchers, and 94% of participants perceived the incentive system as helpful.The incentive system was well accepted and used despite psychosis severity, and the attendance rate was high, although causality between incentives and attendance could not be examined. A voucher-based incentive system for attendance can be successfully applied in a clinical trial for alcohol dependence treatment in schizophrenia.

This clinical trial assessed the effects of monitored naltrexone treatment in 19 subjects with schizophrenia spectrum and alcohol use disorders in an eight-week prospective open pilot study. Naltrexone was directly administered to subjects in oral doses of 100 mg on Mondays and Wednesdays, and 150 mg on Fridays. Subjects received reimbursement for attending the three weekly study visits. Subjects continued to receive their usual psychiatric care with no added alcohol counseling provided. Alcohol use was assessed by self-report and biomarkers. Psychosis severity was measured by the Positive and Negative Syndrome Scale (PANSS). Subjects reported significant reductions in their number of drinks per week, drinks per drinking day, days of drinking to intoxication, and alcohol craving. Subjects also showed significant reductions in Addiction Severity Index (ASI) alcohol composite scores and in PANSS positive, negative and general psychopathology scores.

To determine how knee extensor steadiness is related to age and difficulty performing everyday tasks.In this cross-sectional study performed at a research laboratory, 50 older adults (age range, (56-95 yrs) performed steadiness testing at 50% of maximum strength and were timed and rated on four tasks of daily living: chair rise, stair ascent and descent, and walk. The independent variables of age, steadiness, and strength-to-weight ratio were entered into regression models with the ratings and time to complete the four everyday tasks as dependent variables.The strength-to-weight ratio was the only significant predictor in the multiple regression models, explaining 29%, 33%, 14%, and 14% of the variance in gait speed and time to complete a chair rise, stair ascent, and stair descent, respectively. Similar results were seen with task ratings. Age was not correlated with steadiness (r = 0.25, P = 0.07).This study suggests that knee extensor isometric steadiness performance does not carry over to tasks of everyday living, and older subjects, regardless of age, have similar steadiness values. Because the strength-to-weight ratio predicted the most variance in functional performance, it is recommended that muscle strength be improved to increase function in older adults.

OBJECTIVE—To determine whether diabetes education can be provided as effectively through telemedicine technology as through in-person encounters with diabetes nurse and nutrition educators. RESEARCH DESIGN AND METHODS—A total of 56 adults with diabetes were randomized to receive diabetes education in person (control group) or via telemedicine (telemedicine group) and were followed prospectively. The education consisted of three consultative visits with diabetes nurse and nutrition educators. The in-person and telemedicine groups were compared using measures of glycemic control (HbA1c) and questionnaires to assess patient satisfaction and psychosocial functioning as related to diabetes. Outcome measures were obtained at baseline, immediately after the completion of diabetes education, and 3 months after the third educational visit. RESULTS—Patient satisfaction was high in the telemedicine group. Problem Areas in Diabetes scale scores improved significantly with diabetes education (adjusted P < 0.05, before vs. immediately after education and 3 months after education), and the attainment of behavior-change goals did not differ between groups. With diabetes education, HbA1c improved from 8.6 ± 1.8% at baseline to 7.8 ± 1.5% immediately after education and 7.8 ± 1.8% 3 months after the third educational visit (unadjusted P < 0.001, P = 0.089 adjusted for BMI and age), with similar changes observed in the telemedicine and in-person groups. CONCLUSIONS—Diabetes education via telemedicine and in person was equally effective in improving glycemic control, and both methods were well accepted by patients. Reduced diabetes-related stress was observed in both groups. These data suggest that telemedicine can be successfully used to provide diabetes education to patients.

Considerable evidence indicates that people overattribute causality to a given stimulus when it is salient or the focus of their attention—the so-called illusory-causation phenomenon. Although illusory causation has proved to be quite robust and generalizable, a compelling explanation for it has not been empirically documented. Four social-attribution studies were conducted to test the hypothesis that illusory causation occurs because salient information is initially registered, or perceptually organized, differently than nonsalient information. The results provide considerable support for the notion that people's literal point of view affects how they initially perceive, or extract, information from an observed interaction, which in turn affects their judgments regarding the causal influence exerted by each interactant.

The purpose of this study was to identify quadriceps femoris strength thresholds below which performance on ambulatory tasks is compromised. A second purpose was to evaluate whether self-reported functioning matches evaluated performance of the activities. Subjects (N = 100; age 73 +/- 0.9 years) participated in isometric knee extension strength tests, performed three functional ambulatory tasks (chair rise, gait speed, and stair ascent and descent), and answered standard survey questions assessing physical function. Significant relationships were observed between functional performance and the ratio of isometric leg extension peak torque to body weight (STR/WT) for each activity (p

Introduction We evaluated ocular outcomes in a 14-d head-down tilt (HDT) bed rest (BR) study designed to simulate the effects of microgravity on the human body. Methods Healthy subjects were selected using NASA standard screening procedures. Standardized NASA BR conditions were implemented (e.g., strict sleep-wake cycle, standardized diet, 24-hour-a-day BR, continuous video monitoring). Subjects maintained a 6° HDT position for 14 consecutive days. Weekly ophthalmological examinations were performed in the sitting (pre/post-BR) and HDT (in-bed phase) positions. Equivalency tests with optimal-alpha techniques evaluated pre/post-BR differences in best-corrected visual acuity (BCVA), spherical equivalent, intraocular pressure (IOP), Spectral-domain OCT retinal nerve fiber layer thickness (RNFLT), optic disc and macular parameters. Results 16 subjects (12 men and 4 women) were enrolled. Nearly all ocular outcomes were within our predefined clinically relevant thresholds following HDTBR, except near BCVA (pre/post-BR mean difference: -0.06 logMAR), spherical equivalent (-0.30 D), Tonopen XL IOP (+3.03 mmHg) and Spectralis OCT average (+1.14 μm), temporal-inferior (+1.58 μm) and nasal-inferior RNFLT (+3.48 μm). Modified Amsler grid, red dot test, confrontational visual field, and color vision were within normal limits throughout. No changes were detected on stereoscopic color fundus photography. Discussion A few functional and structural changes were detected after 14-d HDTBR, notably an improved BCVA possibly due to learning effect and RNFL thickening without signs of optic disc edema. In general, 6° HDTBR determined a small nonprogressive IOP elevation, which returned to baseline levels post-BR. Further studies with different BR duration and/or tilt angle are warranted to investigate microgravity-induced ophthalmological changes.

Background Exercise countermeasures designed to mitigate muscle atrophy during long-duration spaceflight may not be as effective if crewmembers are in negative energy balance (energy output > energy input). This study determined the energy cost of supine exercise (resistance, interval, aerobic) during the spaceflight analogue of bed rest. Methods Nine subjects (eight men and one woman; 34.5 +/- 8.2 yr) completed 14 d of bed rest and concomitant exercise countermeasures. Body mass and basal metabolic rate (BMR) were assessed before and during bed rest. Exercise energy expenditure was measured during and immediately after [excess post-exercise oxygen consumption (EPOC)] each of five different exercise protocols (30-s, 2-min, and 4-min intervals, continuous aerobic, and a variety of resistance exercises) during bed rest. Results On days when resistance and continuous aerobic exercise were performed daily, energy expenditure was significantly greater (2879 +/- 280 kcal) than 2-min (2390 +/- 237 kcal), 30-s (2501 +/- 264 kcal), or 4-min (2546 +/- 264 kcal) exercise. There were no significant differences in BMR (pre-bed rest: 1649 +/- 216 kcal; week 1: 1632 +/- 174 kcal; week 2:1657 +/- 176 kcal) or body mass (pre-bed rest: 75.2 +/- 10.1 kg; post-bed rest: 75.2 +/- 9.6 kg). Discussion These findings highlight the importance of energy balance for long-duration crewmembers completing a high-intensity exercise program with multiple exercise sessions daily.

Background Locomotor instability may affect planetary extravehicular activities during the initial adaptation to the new gravitational environment. The goal of this study was to quantify the locomotor, cognitive, and metabolic effects of exposure to a discordant sensory environment. Methods A treadmill mounted on a 6-degree-of-freedom motion base was used to present 15 healthy subjects with a destabilizing support surface while they walked. Dependent measures of locomotor stability, cognitive load, and metabolic cost were stride frequency (SF), reaction time (RT), and the volume of oxygen consumed (Vo2), respectively. Subjects completed an 8-min baseline walk followed by 20 min of walking with a continuous, sinusoidal, laterally oscillating support-surface perturbation. Data for minutes 1, 7, 13, and 20 of the support-surface perturbation period were compared with the baseline. Results SF, RT, and Vo2 were significantly greater during support-surface motion than during the baseline walking condition and showed a trend toward recovery to baseline levels during the perturbation period. Results demonstrated that adaptation to walking in a discordant sensory environment has quantifiable and significant costs in SF, RT, and Vo2 as shown by mean increases of 9%, 20%, and 4%, respectively, collected during the first minute of exposure. By the fourth minute of exposure, mean Vo2 consumption had increased to 20% over its baseline. Discussion We believe that preflight sensorimotor adaptation training paradigms will impart gains in stability and the ability to multitask, and might increase productive mission time by extending work time in extravehicular activity suits where metabolic expenditure is a limiting factor.

INTRODUCTION: Ophthalmological changes, including optic disc edema with optic nerve sheath distension, posterior globe flattening with hyperopic shift, choroidal folds and cotton wool spots have been detected in some astronauts involved in long-duration spaceflights. (sup 1) It is hypothesized that elevated intracranial pressure resulting from microgravity-induced cephalad fluid shifts may be responsible for most of these findings. Head-down tilt bed rest (HTDBR) is a ground-based microgravity analog which also produces cephalad fluid shifts. It is conceivable that prolonged HDTBR exposure may induce ocular changes similar to those experienced in microgravity. Therefore, the purpose of the present study was to compare structural and functional ocular outcomes between 14- and 70-day HDTBR in healthy human subjects. It is hypothesized that 70-d HDTBR induced ocular changes of greater magnitude as compared to 14-d HDTBR. METHODS: Two HDTBR studies were conducted at the NASA Flight Analogs Research Unit, located at The University of Texas Medical Branch at Galveston, TX. Identical NASA standard screening procedures and BR conditions (e.g., strict sleep-wake cycle, standardized diet, continuous video monitoring) were implemented in both studies. Participants spent 14 and/or 70 consecutive days in a 6deg HDT position and did not engage in exercise. Subjects received weekly ocular examinations before, during, and after HDTBR. Ocular testing included: distance and near best-corrected visual acuity (BCVA), cycloplegic refraction, intraocular pressure (IOP) measurement, color vision, red dot test, modified Amsler grid test, confrontational visual field, color fundus photography and Spectral-domain OCT scans of the macula and the optic disc. Pre/post HDTBR differences between the two studies will be evaluated for BCVA, spherical equivalent, IOP, retinal nerve fiber layer (RNFL) thickness and macular OCT parameters. RESULTS: 16 (12 males and 4 females) and 6 (5 males and 1 female) subjects participated in the 14 and 70-day HDTBR studies, respectively. One subject participated in both studies. The demographic and ophthalmological characteristics of the 14-day HDTBR study have been presented elsewhere.2 In the 70- day study, subjects age averaged 39.5 +/- 7.8 years; pre- and post-HDTBR Goldmann IOP were, on average, 15.4 and 14.6 mmHg in the right eye, and 15.3 and 14.4 mmHg in the left eye, respectively; preand post-HDTBR Spectralis OCT (Heidelberg Engineering, GmbH, Heidelberg, Germany) average RNFL thickness were 103.8 and 106 m in the right eye, and 103 and 104.3 m in the left eye, respectively. In both studies, color vision, red dot test, modified Amsler grid test and confrontational visual field were within normal limits at all time points; no changes were detected on stereoscopic color optic disc photography. For the above outcomes, preliminary results of the pre/post HDTBR differences between the two studies will be presented at the 2015 Human Research Program Investigators' Workshop. CONCLUSIONS: Although 14-day HDTBR did not seem to induce clinically relevant ocular changes, (sup 2) a systematic evaluation and comparison with the 70-day HDTBR study results will elucidate whether the magnitude of ocular structural and functional changes is affected by the time spent in the recumbent position. Further research will also address the effects of integrated resistance and aerobic training during HDTBR on the ocular outcomes. REFERENCES: 1. Mader TH et al. Optic disc edema, globe flattening, choroidal folds, and hyperopic shifts observed in astronauts after long-duration space flight. Ophthalmology. 2011;118(10):2058-69. 2. Taibbi G et al. Ocular outcomes evaluation in a 14-day head-down bed rest study. Aviat Space Environ Med. 2014;85(10):983-92.

Bed rest studies provide an important tool for modeling physiological changes that occur during spaceflight. Markers of bone metabolism and nutritional status were evaluated in 12 subjects (8 men, 4 women; ages 25–49 yr) who participated in a 30-day −6° head-down-tilt diet-controlled bed rest study. Blood and urine samples were collected twice before, once a week during, and twice after bed rest. Data were analyzed using a mixed-effects linear regression with a priori contrasts comparing all days to the second week of the pre-bed rest acclimation period. During bed rest, all urinary markers of bone resorption increased ∼20% ( P < 0.001), and serum parathyroid hormone decreased ∼25% ( P < 0.001). Unlike longer (>60 days) bed rest studies, neither markers of oxidative damage nor iron status indexes changed over the 30 days of bed rest. Urinary oxalate excretion decreased ∼20% during bed rest ( P < 0.001) and correlated inversely with urinary calcium ( R = −0.18, P < 0.02). These data provide a broad overview of the biochemistry associated with short-duration bed rest studies and provide an impetus for using shorter studies to save time and costs wherever possible. For some effects related to bone biochemistry, short-duration bed rest will fulfill the scientific requirements to simulate spaceflight, but other effects (antioxidants/oxidative damage, iron status) do not manifest until subjects are in bed longer, in which case longer studies or other analogs may be needed. Regardless, maximizing research funding and opportunities will be critical to enable the next steps in space exploration.

We report the results of alendronate ingestion plus exercise in preventing the declines in bone mass and strength and elevated levels of urinary calcium and bone resorption in astronauts during 5.5 months of spaceflight. This investigation was an international collaboration between NASA and the JAXA space agencies to investigate the potential value of antiresorptive agents to mitigate the well-established bone changes associated with long-duration spaceflight. We report the results from seven International Space Station (ISS) astronauts who spent a mean of 5.5 months on the ISS and who took an oral dose of 70 mg of alendronate weekly starting 3 weeks before flight and continuing throughout the mission. All crewmembers had available for exercise a treadmill, cycle ergometer, and a resistance exercise device. Our assessment included densitometry of multiple bone regions using X-ray absorptiometry (DXA) and quantitative computed tomography (QCT) and assays of biomarkers of bone metabolism. In addition to pre- and post-flight measurements, we compared our results to 18 astronauts who flew ISS missions and who exercised using an early model resistance exercise device, called the interim resistance exercise device, and to 11 ISS astronauts who exercised using the newer advanced resistance exercise device (ARED). Our findings indicate that the ARED provided significant attenuation of bone loss compared with the older device although post-flight decreases in the femur neck and hip remained. The combination of the ARED and bisphosphonate attenuated the expected decline in essentially all indices of altered bone physiology during spaceflight including: DXA-determined losses in bone mineral density of the spine, hip, and pelvis, QCT-determined compartmental losses in trabecular and cortical bone mass in the hip, calculated measures of fall and stance computed bone strength of the hip, elevated levels of bone resorption markers, and urinary excretion of calcium. The combination of exercise plus an antiresoptive drug may be useful for protecting bone health during long-duration spaceflight.

Existing models of muscle deconditioning such as bed rest are expensive and time-consuming. We propose a new model utilizing a weighted suit to manipulate muscle strength, power, or endurance relative to body weight. The aims of the study were to determine as to which muscle measures best predict functional task performance and to determine muscle performance thresholds below which task performance is impaired. Twenty subjects performed seven occupational astronaut tasks (supine and upright seat egress and walk, rise from fall, hatch opening, ladder climb, object carry, and construction board activity), while wearing a suit weighted with 0-120 % of body weight. Models of the relationship between muscle function/body weight and task completion time were developed using fractional polynomial regression and verified with pre- and post-flight astronaut performance data. Spline regression was used to identify muscle function thresholds for each task. Upright seat egress and walk was the most difficult task according to the spline regression analysis thresholds. Thresholds normalized to body weight were 17.8 N/kg for leg press isometric force, 17.6 W/kg for leg press power, 78.8 J/kg for leg press work, 5.9 N/kg isometric knee extension and 1.9 Nm/kg isokinetic knee extension torque. Leg press maximal isometric force/body weight was the most reliable measure for modeling performance of ambulatory tasks. Laboratory-based manipulation of relative strength has promise as an analog for spaceflight-induced loss of muscle function. Muscle performance values normalized to body weight can be used to predict occupational task performance and to establish relevant strength thresholds.

Background. Infection with Epstein–Barr virus (EBV) early in life and repeated malaria exposure have been proposed as risk factors for endemic Burkitt lymphoma (eBL). Methods. Infants were enrolled from 2 rural sites in Kenya: the Kisumu District, where malaria transmission is holoendemic and risk for eBL is high, and the Nandi District, where malaria transmission is limited and the risk for eBL is low. Blood samples were taken from infants through 2 years of age to measure EBV viral load, EBV antibodies, and malaria parasitemia. Results. We observed a significantly younger age at time of primary EBV infection in children from Kisumu compared with children from Nandi (mean age, 7.28 months [60.33 SEM] in Kisumu vs 8.39 months [60.26 SEM] in Nandi), with 35.3% of children in Kisumu infected before 6 months of age. To analyze how different predictors affected EBV viral load over time, we performed multilevel mixed modeling. This modeling revealed that residence in Kisumu and younger age at first EBV infection were significant predictors for having a higher EBV viral load throughout the period of observation. Conclusions. Children from a region at high risk for eBL were infected very early in life with EBV, resulting in higher viral loads throughout infancy.

As part of a larger gait adaptability training study, we designed a program that presented combinations of visual flow and support-surface manipulations to investigate the response of healthy adults to walking on a treadmill in novel discordant sensorimotor conditions. A visual dependence score was determined for each subject, and this score was used to explore how visual dependency was linked to locomotor performance (1) during three training sessions and (2) in a new discordant environment presented at the conclusion of training. Performance measures included reaction time (RT), stride frequency (SF), and heart rate (HR), which respectively served as indicators of cognitive load, postural stability, and anxiety. We hypothesized that training would affect performance measures differently for highly visually dependent individuals than for their less visually dependent counterparts. A seemingly unrelated estimation analysis of RT, SF, and HR revealed a significant omnibus interaction of visual dependency by session (p

A pilot study was conducted to assess the feasibility and potential efficacy of a couples focused diabetes intervention in which a collaborative problem-solving approach to diabetes self-care was promoted. Couples (N = 44), in which one partner had Type 2 diabetes and was in poor blood glucose control were randomly assigned to one of three groups: a couples intervention, an individual intervention, or individual diabetes education. The intervention included goal-setting, dietary behavior change, and a focus on emotions. For those in the couples arm, this was done within the framework of promoting collaborative communication between the partners. All intervention contacts were over the telephone to increase reach. Results showed that both the individual and couples interventions yielded meaningful clinical improvements in medical outcomes. Diabetes education also resulted in improved blood glucose control. Despite the small number, mixed-model regression analyses found statistically significant treatment effects for total cholesterol. This pilot demonstrates the feasibility and potential efficacy of a telephone intervention for Type 2 diabetes patients and their partners. Information from implementing this pilot led to refinement and further development of the intervention, which is being assessed in a larger, more comprehensive trial.

We set out to describe the prevalence and severity of psychiatric and substance use disorders (SUDs) in methadone maintenance treatment (MMT) patients with chronic hepatitis C virus (HCV) infection and to measure the impact on HCV-treatment eligibility. Psychiatric disorders, SUDs, and HCV-treatment eligibility were assessed in 111 MMT patients prior to a controlled trial of HCV treatment. Lifetime and current diagnosis rates, respectively, were: any non-SUD Axis I disorder: 82% and 57%, any mood disorder: 67% and 35%, any anxiety disorder: 63% and 22%, any psychotic disorder: 11% and 9%. Antisocial personality disorder was present in 40%. A total of 56% met criteria for current SUDs. A total of 66% received psychiatric medications prior to HCV treatment; over half were receiving antidepressants. Despite psychiatric and substance use comorbidity, only 15% of patients were ineligible for HCV treatment: 10% due to failure to complete the evaluation, and 5% due to psychiatric severity. Substance use did not lead to ineligibility in any participant. Multiple logistic regression showed the Beck Depression Inventory contributed significantly to predicting HCV treatment eligibility. Most MMT patients were eligible [corrected] for HCV treatment despite current SUD and non-SUD diagnoses. Depression severity may be a more significant predictor of HCV treatment eligibility than is substance use.

Maintaining vitamin D status without sunlight exposure is difficult without supplementation. This study was designed to better understand interrelationships between periodic vitamin D supplementation and immune function in Antarctic workers. The effect of 2 oral dosing regimens of vitamin D supplementation on vitamin D status and markers of immune function was evaluated in people in Antarctica with no UV light exposure for 6 mo. Participants were given a 2000-IU (50 μg) daily (n = 15) or 10,000-IU (250 μg) weekly (n = 14) vitamin D supplement for 6 mo during a winter in Antarctica. Biological samples were collected at baseline and at 3 and 6 mo. Vitamin D intake, markers of vitamin D and bone metabolism, and latent virus reactivation were determined. After 6 mo, the serum 25-hydroxyvitamin D concentration (mean ± SD) increased from 56 ± 17 to 79 ± 16 nmol/L and from 52 ± 10 to 69 ± 9 nmol/L in the 2000-IU/d and 10,000-IU/wk groups, respectively (main effect over time, P0.001). Participants with a greater BMI (participant BMI range = 19–43 g/m2) had a smaller increase in 25-hydroxyvitamin D after 6-mo supplementation (P0.05). Participants with high serum cortisol and higher serum 25-hydroxyvitamin D were less likely to shed Epstein-Barr virus in saliva (P0.05). The doses given raised vitamin D status in participants not exposed to sunlight for 6 mo, and the efficacy was influenced by baseline vitamin D status and BMI. The data also provide evidence that vitamin D, interacting with stress, can reduce risk of latent virus reactivation during the winter in Antarctica.

Comorbid medical illness is common in patients with chronic hepatitis C (HCV) infection and in methadone treatment (MMT) patients, yet little is known about the impact of medical illness on HCV treatment eligibility. Medical illness and HCV treatment eligibility were compared in a case-control study of 80 MMT patients entering an HCV treatment trial and 80 matched non-MMT patients entering HCV treatment in a gastroenterology clinic. 91% of MMT and 85% of non-MMT patients had chronic medical conditions. Despite similar medical severity ratings, a significantly higher proportion (77%) of non-MMT patients were eligible for HCV treatment than were MMT patients (56%) (p