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Background Oxaliplatin-induced peripheral neuropathy (OIPN) is prevalent among gastrointestinal cancer survivors and often impairs quality of life (QOL). Objective This pilot randomized controlled trial aimed to explore the effect of an 8-week home-based brisk walking (the "MI-Walk") intervention on (1) OIPN severity and (2) QOL at 8 weeks, compared with physical activity (PA) education alone in oxaliplatin-receiving adults with gastrointestinal cancer. Interventions/methods Participants (N = 57) recruited from 5 infusion sites received PA education at their second oxaliplatin visit, followed by phone assessments of adverse events over 8 weeks. Half (n = 29) received additional MI-Walk intervention motivational supports (eg, a Fitbit Charge 2 and motivational enhancement therapy sessions). Self-reported OIPN, QOL, and PA were measured before and after intervention. Results The intervention compared with the control condition had no effect on sensory OIPN (mean difference [X¯[INCREMENT]] = -0.01; P > .99), motor OIPN (X¯[INCREMENT] = 2.39; P = .17), and QOL (X¯[INCREMENT] = -1.43; P > .99). Eight-week sensory (X¯ =11.48 ± 0.38) and motor OIPN severities (X¯ = 7.48 ± 0.36) were mild but higher than baseline (P ≤ .01). Self-reported PA level increased over time in both groups (X¯[INCREMENT] = 44.85; P = .01). Averaging ≥225 moderate to vigorous PA minutes per week led to less sensory OIPN, particularly finger/hand tingling (X¯[INCREMENT] = -26.35; P = .01). Conclusions This study failed to detect beneficial effects of the MI-Walk intervention; however, the findings suggest that aerobic walking may blunt but not completely prevent OIPN. Further research is necessary. Implications for practice Although the effectiveness of brisk walking in reducing OIPN is unclear, this study supports prior evidence that moderate to vigorous PA is beneficial and safe during chemotherapy treatment.

Background/Objectives Spaceflight associated neuro-ocular syndrome (SANS), a health risk related to long-duration spaceflight, is hypothesized to result from a headward fluid shift that occurs with the loss of hydrostatic pressure gradients in weightlessness. Shifts in the vascular and cerebrospinal fluid compartments alter the mechanical forces at the posterior eye and lead to flattening of the posterior ocular globe. The goal of the present study was to develop a method to quantify globe flattening observed by magnetic resonance imaging after spaceflight. Subjects/Methods Volumetric displacement of the posterior globe was quantified in 10 astronauts at 5 time points after spaceflight missions of ~6 months. Results Mean globe volumetric displacement was 9.88 mm3 (95% CI 4.56–15.19 mm3, p 3 (95% CI 3.73–14.27 mm3, p = 0.001) at R + 30 days; 6.53 mm3 (95% CI 1.24–11.83 mm3, p 3 (95% CI −0.96 to 9.86 mm3, p = 0.12) at R + 180 days; and 7.21 mm3 (95% CI 1.82–12.60 mm3, p Conclusions There was a consistent inward displacement of the globe at the optic nerve, which had only partially resolved 1 year after landing. More pronounced globe flattening has been observed in previous studies of astronauts; however, those observations lacked quantitative measures and were subjective in nature. The novel automated method described here allows for detailed quantification of structural changes in the posterior globe that may lead to an improved understanding of SANS.

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.

Highlights • This literature review found that adults ≥ 80 years are sedentary 10.6 h/day. • Five personal factors were associated with sedentary behavior in adults ≥ 80 years. • Factors influencing sedentary behavior in adults ≥ 80 years are understudied., Sedentary behavior contributes to health decline and frailty in older adults, especially the oldest old. The purpose of this systematic review was to synthesize evidence describing the volume of device-measured sedentary behavior and factors that influence sedentary behavior in community-dwelling adults aged 80 and older. Four electronic databases were searched in August 2018; the search was updated in September 2019 and December 2020. Twenty-one articles representing 16 unique datasets from six countries met inclusion criteria. Various devices and data processing methods were used to measure sedentary behavior; the most common device was the ActiGraph accelerometer. Sedentary time during the waking day ranged from 7.6 to 13.4 h/day. Studies using similar measurement methods (hip-worn ActiGraph with uniaxial cut-point

Summary Loss of muscle mass is a major concern for long duration spaceflight. However, due to the need for specialized equipment, muscle size has only been assessed before and after spaceflight where ~20% loss is observed. Here, we demonstrate the utility of teleguided self-ultrasound scanning (Tele-SUS) to accurately monitor leg muscle size in astronauts during spaceflight. Over an average of 168 ± 57 days of spaceflight, 74 Tele-SUS sessions were performed. There were no significant differences between panoramic ultrasound images obtained by astronauts seven days prior to landing and expert sonographer after flight or between change in muscle size assessed by ultrasound and magnetic resonance imaging. These findings extend the current capabilities of ultrasound imaging to allow self-monitoring of muscle size with remote guidance., Graphical abstract, Highlights • We examined teleguided self-ultrasound to monitor leg muscle size on the ISS • Muscle thickness ultrasound does not detect change in muscle size during spaceflight • Panoramic ultrasound accurately monitors change in muscle size compared to MRI • Teleguided self-ultrasound reveals upper and lower leg muscle loss during spaceflight, Medicine; Medical Imaging; Biological Sciences

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.

A subset of long-duration spaceflight astronauts have experienced ophthalmic abnormalities, collectively termed spaceflight-associated neuro-ocular syndrome (SANS). Little is understood about the pathophysiology of SANS; however, microgravity-induced alterations in intracranial pressure (ICP) due to headward fluid shifts is the primary hypothesized contributor. In particular, potential changes in optic nerve (ON) tortuosity and ON sheath (ONS) distension may indicate altered cerebrospinal fluid dynamics during weightlessness. The present longitudinal study aims to provide a quantitative analysis of ON and ONS cross-sectional areas, and ON deviation, an indication of tortuosity, before and after spaceflight. Ten astronauts undergoing ~6-month missions on the International Space Station (ISS) underwent high-resolution magnetic resonance imaging (MRI) preflight and at five recovery time points extending to 1 year after return from the ISS. The mean changes in ON deviation, ON cross-sectional area, and ONS cross-sectional area immediately post flight were −0.14 mm (95% CI: −0.36 to 0.08, Bonferroni-adjusted P = 1.00), 0.13 mm2 (95% CI −0.66 to 0.91, Bonferroni-adjusted P = 1.00), and −0.22 mm2 (95% CI: −1.78 to 1.34, Bonferroni-adjusted P = 1.00), respectively, and remained consistent during the recovery period. Terrestrially, ONS distension is associated with increased ICP; therefore, these results suggest that, on average, ICP was not pathologically elevated immediately after spaceflight. However, a subject diagnosed with optic disc edema (Frisen Grade 1, right eye) displayed increased ONS area post flight, although this increase is relatively small compared to clinical populations with increased ICP. Advanced quantitative MRI-based assessment of the ON and ONS could help our understanding of SANS and the role of ICP.

Historically, International Space Station (ISS) exercise countermeasures have not fully protected astronauts’ musculoskeletal and cardiorespiratory fitness. Although these losses have been reduced on more recent missions, decreasing the time required to perform in-flight exercise would permit reallocation of that time to other tasks. To evaluate the effectiveness of a new training prescription, ISS crewmembers performed either the high intensity/lower volume integrated Sprint resistance (3 d wk−1) and aerobic (interval and continuous workouts, each 3 d wk−1 in alternating fashion) exercise program (n = 9: 8M/1F, 48 ± 7 y, 178 ± 5 cm, 77.7 ± 12.0 kg) or the standard ISS countermeasure consisting of daily resistance and aerobic exercise (n = 17: 14M/3F, 46 ± 6 y, 176 ± 6 cm, 80.6 ± 10.5 kg) during long-duration spaceflight. Bone mineral density (dual energy X-ray absorptiometry (DXA)), muscle strength (isokinetic dynamometry), muscle function (cone agility test), and cardiorespiratory fitness (VO2peak) were assessed pre- and postflight. Mixed-effects modeling was used to analyze dependent measures with alpha set at P 2peak (−6.1%) were decreased in both groups (simple main effects of time, all P

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 (

BACKGROUND: Whether the unique environment of space affects astronaut risk of venous thromboembolism (VTE) is not known. On Earth, it is known that use of combined oral contraceptives (COCs) doubles the risk of VTE. Since some female astronauts choose to use COCs, this retrospective study examined known risk factors associated with VTE risk to determine whether the available data suggested elevated VTE risk in female astronauts.METHODS: Longitudinal health data were requested for female astronauts who flew short and long duration missions between 2000 and 2014. Pre- and postflight hematological and biochemical blood markers were available and evaluated. Astronauts’ postflight measurements were compared to clinically relevant terrestrial high risk levels to determine any trend toward increased risk for VTE following spaceflight. Secondarily, a comparison of pre- and postflight changes was made, as well as an assessment of COC impact.RESULTS: A total of 38 astronaut-flights were included in this study and no VTE events were found. Analysis of potential VTE risk factors showed no evidence suggesting elevated VTE risk in female astronauts associated with spaceflight, regardless of contraceptive use.DISCUSSION: Arguably, all astronauts encounter many physiological stressors during spaceflight missions, but women using the combined contraceptive pill add a known risk factor for VTE. The risk factors analyzed within this study showed no trend toward an increased risk of VTE for female astronauts. This study provides an evidence base supporting the safety of COC use by female astronauts and also reinforces the importance of healthy lifestyle on VTE risk reduction.Jain V, Ploutz-Snyder R, Young M, Charvat JM, Wotring VE. Potential venous thromboembolism risk in female astronauts. Aerosp Med Hum Perform. 2020; 91(5):432–439.

Importance Long-duration spaceflight induces structural changes in the brain and eye. Identification of an association between cerebral and ocular changes could help determine if there are common or independent causes and inform targeted prevention strategies or treatments. Objective To determine if there is an association between quantitative changes in intracranial compartment volumes and peripapillary total retinal thickness after spaceflight. Design, Setting, and Participants This cohort study included healthy International Space Station crew members before and immediately after long-duration spaceflight. Data on race were not collected. Analysis was conducted from September to November 2020. Exposures Long-duration spaceflight (mean [SD], 191 [55] days). Main Outcomes and Measures Optical coherence tomography–derived peripapillary total retinal thickness as a quantitative assessment and early sign of optic disc edema and magnetic resonance imaging–derived measures of lateral ventricle volume, white matter volume, and whole brain plus cerebrospinal fluid volume. Results In 19 healthy crew members included in this study (5 women [26.3%], 14 men [73.7%]; mean [SD] age, 45.2 [6.4] years), analyses revealed a positive, although not definitive, association between spaceflight-induced changes in total retinal thickness and lateral ventricle volume (4.7-μm increase in postflight total retinal thickness [95% CI, −1.5 to 10.8 μm;P = .13] per 1-mL postflight increase in lateral ventricle volume). Adjustments for mission duration improved the strength of association (5.1 μm; 95% CI, −0.4 to 10.5 μm;P = .07). No associations were detected between spaceflight-induced changes in total retinal thickness and white matter volume (0.02 μm; 95% CI, −0.5 to 0.5 μm;P = .94) or brain tissue plus cerebrospinal fluid volume, an estimate of intracranial volume (0.02 μm; 95% CI, −0.6 to 0.6 μm;P = .95). Conclusions and Relevance These results help characterize spaceflight-associated neuro-ocular syndrome and the physiologic associations of headward fluid shifts with outcomes during spaceflight on the central nervous system. The possibly weak association between increased total retinal thickness and lateral ventricle volume suggest that while weightlessness-induced fluid redistribution during spaceflight may be a common stressor to the brain and retina, the development of optic disc edema appears to be uncoupled with changes occurring in the intracranial compartment.

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.

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

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

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.

OBJECTIVES: The time course and magnitude of atrophic remodeling and the effects of an acute rehabilitation program on muscle atrophy are unclear. We sought to characterize bed rest–induced leg muscle atrophy and evaluate the safety and efficacy of an acute rehabilitation program. DESIGN: Prespecified analysis of a randomized controlled trial. SETTING: Single-center urban hospital. PATIENTS: Adults (24–55 yr) randomized to 70 days of sedentary bed rest. INTERVENTIONS: The 11-day post-bed rest rehabilitation program consisted of low intensity exercise and progressed to increased aerobic exercise duration, plyometric exercises, and higher intensity resistance exercise. MEASUREMENTS AND MAIN RESULTS: Upper (rectus femoris, vastus lateralis, quadriceps, hamstrings, adductors) and lower leg (medial gastrocnemius, lateral gastrocnemius, and soleus) MRI scans were obtained once before, nine times during, and three times after bed rest to assess muscle cross-sectional area. The magnitude and rate of muscle atrophy and recovery were determined for each muscle. Nine participants completed 70 days of sedentary bed rest and an 11-day rehabilitation program. A total of 11,588 muscle cross-sectional area images were quantified. Across all muscles except the rectus femoris (no change), there was a linear decline during bed rest, with the highest atrophic rate occurring in the soleus (–0.33%/d). Following rehabilitation, there was rapid recovery in all muscles; however, the quadriceps (–3.74 cm(2); 95% CI, –7.36 to –0.12; p = 0.04), hamstrings (–2.30 cm(2); 95% CI, –4.07 to –0.54; p = 0.01), medial gastrocnemius (–0.62 cm(2); 95% CI, –1.10 to –0.14; p = 0.01), and soleus (–1.85 cm(2); 95% CI, –2.90 to –0.81; p < 0.01) remained significantly lower than baseline. CONCLUSIONS: Bed rest results in upper and lower leg muscle atrophy in a linear pattern, and an 11-day rehabilitation program was safe and effective in initiating a rapid trajectory of muscle recovery. These findings provide important information regarding the design and refinement of rehabilitation programs following bed rest.

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

e24151 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common intractable side effect of oxaliplatin treatment that presents with numbness, tingling, and nerve pain in both hands and feet; and sometimes, weakness and impaired balance and quality of life. Moderate-vigorous (MV) physical activity (PA) may reduce CIPN by improving blood circulation, chemotherapy distribution, inflammation, oxidative stress, and neuroplasticity. This dose-response analysis aimed to explore the effect of different MVPA and total PA doses on CIPN severity among oxaliplatin-receiving gastrointestinal cancer survivors. Methods: The original pilot RCT tested an 8-week home-based brisk walking intervention versus PA education alone to reduce CIPN. This analysis focuses on the intervention group ( n = 29), which received MVPA motivational supports (e.g., a Fitbit Charge 2, walking plan, motivational interviewing). Participants completed self-report CIPN severity surveys at baseline (2nd oxaliplatin infusion) and 8 weeks. Fitbit-classified minutes of weekly MV and daily total (light-vigorous) PA were averaged over the 8 weeks. MVPA was dichotomized: met 225 weekly MVPA minutes ( n = 17) or not ( n = 19). Linear regression was used to analyze the effect of MVPA/total PA changes and effects on 8-week CIPN severity, controlling for oxaliplatin dose received and baseline CIPN levels. Results: Increases over the 8 weeks were observed in patients’ MVPA (mean difference [ MD] = 17.39 min/week; 95% CI 1.38, 33.40; p = .03) and total PA ( MD = 7.80 min/week; 95% CI 2.31, 13.29; p = .01). Total PA had no effect on the outcomes. However, averaging at least 225 MVPA minutes per week led to less severe sensory CIPN ( MD = -7.28; 95% CI -13.53, -1.03; p = .03), particularly tingling in the hands ( MD = -26.35; 95% CI -44.03, -8.68; p = .01). The models accounted for 37% and 44% of the variance in sensory CIPN ( p = .02) and tingling at 8 weeks ( p = .01), respectively. Conclusions: This pilot study provides preliminary evidence that increasing weekly MVPA, specifically, may lead to reduced CIPN severity among gastrointestinal cancer survivors receiving oxaliplatin. A larger study that utilizes stronger MVPA measurement and biomarker evaluation is needed. Clinical trial information: NCT03515356 .

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.

Background Although a state of anemia is perceived to be associated with spaceflight, to date a peripheral blood hematologic assessment of red blood cell (RBC) indices has not been performed during long-duration space missions. Methods This investigation collected whole blood samples from astronauts participating in up to 6-months orbital spaceflight, and returned those samples (ambient storage) to Earth for analysis. As samples were always collected near undock of a returning vehicle, the delay from collection to analysis never exceeded 48 h. As a subset of a larger immunologic investigation, a complete blood count was performed. A parallel stability study of the effect of a 48 h delay on these parameters assisted interpretation of the in-flight data. Results We report that the RBC and hemoglobin were significantly elevated during flight, both parameters deemed stable through the delay of sample return. Although the stability data showed hematocrit to be mildly elevated at +48 h, there was an in-flight increase in hematocrit that was ~3-fold higher in magnitude than the anticipated increase due to the delay in processing. Conclusions While susceptible to the possible influence of dehydration or plasma volume alterations, these results suggest astronauts do not develop persistent anemia during spaceflight.

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.

Background: Type 2 diabetes is a prevalent, chronic disease for which diet is an integral aspect of treatment. In our previous trial, we found that recommendations to follow a very low-carbohydrate ketogenic diet and to change lifestyle factors (physical activity, sleep, positive affect, mindfulness) helped overweight people with type 2 diabetes or prediabetes improve glycemic control and lose weight. This was an in-person intervention, which could be a barrier for people without the time, flexibility, transportation, social support, and/or financial resources to attend. Objective: The aim was to determine whether an online intervention based on our previous recommendations (an ad libitum very low-carbohydrate ketogenic diet with lifestyle factors; “intervention”) or an online diet program based on the American Diabetes Associations’ “Create Your Plate” diet (“control”) would improve glycemic control and other health outcomes among overweight individuals with type 2 diabetes. Methods: In this pilot feasibility study, we randomized overweight adults (body mass index ≥25) with type 2 diabetes (glycated hemoglobin [HbA1c] 6.5%-9.0%) to a 32-week online intervention based on our previous recommendations (n=12) or an online diet program based around a plate method diet (n=13) to assess the impact of each intervention on glycemic control and other health outcomes. Primary and secondary outcomes were analyzed by mixed-effects linear regression to compare outcomes by group. Results: At 32 weeks, participants in the intervention group reduced their HbA1c levels more (estimated marginal mean [EMM] –0.8%, 95% CI –1.1% to –0.6%) than participants in the control group (EMM –0.3%, 95% CI –0.6% to 0.0%; P=.002). More than half of the participants in the intervention group (6/11, 55%) lowered their HbA1c to less than 6.5% versus 0% (0/8) in the control group (P=.02). Participants in the intervention group lost more weight (EMM –12.7 kg, 95% CI –16.1 to –9.2 kg) than participants in the control group (EMM –3.0 kg, 95% CI –7.3 to 1.3 kg; P

Importance Exposure to a weightless environment during spaceflight results in a chronic headward blood and tissue fluid shift compared with the upright posture on Earth, with unknown consequences to cerebral venous outflow. Objectives To assess internal jugular vein (IJV) flow and morphology during spaceflight and to investigate if lower body negative pressure is associated with reversing the headward fluid shift experienced during spaceflight. Design, Setting, and Participants This prospective cohort study included 11 International Space Station crew members participating in long-duration spaceflight missions . Internal jugular vein measurements from before launch and approximately 40 days after landing were acquired in 3 positions: seated, supine, and 15° head-down tilt. In-flight IJV measurements were acquired at approximately 50 days and 150 days into spaceflight during normal spaceflight conditions as well as during use of lower body negative pressure. Data were analyzed in June 2019. Exposures Posture changes on Earth, spaceflight, and lower body negative pressure. Main Outcomes and Measures Ultrasonographic assessments of IJV cross-sectional area, pressure, blood flow, and thrombus formation. Results The 11 healthy crew members included in the study (mean [SD] age, 46.9 [6.3] years, 9 [82%] men) spent a mean (SD) of 210 (76) days in space. Mean IJV area increased from 9.8 (95% CI, −1.2 to 20.7) mm2in the preflight seated position to 70.3 (95% CI, 59.3-81.2) mm2during spaceflight (P Conclusions and Relevance This cohort study found stagnant and retrograde blood flow associated with spaceflight in the IJVs of astronauts and IJV thrombosis in at least 1 astronaut, a newly discovered risk associated with spaceflight. Lower body negative pressure may be a promising countermeasure to enhance venous blood flow in the upper body during spaceflight.

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.

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.

How can humans live and work in space? Ask one of NASA's biostatisticians. With the International Space Station, the prospect of a return to the moon and – who knows?– perhaps a manned voyage to Mars, ever-longer space missions must be planned for. Robert Ploutz-Snyder describes some of NASA's work to reduce the risk to astronauts.

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.

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, P < 0.001). Participants with a greater BMI (participant BMI range = 19–43 g/m2) had a smaller increase in 25-hydroxyvitamin D after 6-mo supplementation (P < 0.05). Participants with high serum cortisol and higher serum 25-hydroxyvitamin D were less likely to shed Epstein-Barr virus in saliva (P < 0.05). 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.

Mechanical loading during childhood and adolescence may yield skeletal benefits that persist beyond activity cessation and menarche. At 1 year pre- and 2 years post-menarche, nondominant forearm areal bone mineral density (aBMD), bone mineral content (BMC) and projected area (area) were compared in gymnasts (n = 9), ex-gymnasts (n = 8) and nongymnasts (n = 13). At both observations, gymnasts and ex-gymnasts had higher forearm aBMD, BMC and area than nongymnasts. gymnasts had higher postmenarcheal means than ex-gymnasts for all three parameters. Childhood mechanical loading yields skeletal advantages that persist at least 24 months after loading cessation and menarche. Continued postmenarcheal loading yields additional benefit.

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.

Although quantitative computed tomography (QCT) is considered the gold standard for in vivo densitometry, dual-energy X-ray absorptiometry (DXA) scans assess larger bone regions and are more appropriate for pediatric longitudinal studies. Unfortunately, DXA does not yield specific bone architectural output. To address this issue in healthy, postmenarcheal girls, Sievänen's distal radius formulae [1996] were applied to derive indices of bone geometry, volumetric bone mineral density (vBMD), and strength from DXA data; results were compared to peripheral quantitative computed tomography (pQCT) output. Contemporaneous scans were performed on the left, distal radii of 35 gymnasts, ex-gymnasts, and nongymnasts (aged 13.3-20.4 yr, mean 16.6 yr). For 4% and 33% regions, pQCT measured cross-sectional areas (CSAs) and vBMD; comparable DXA indices were generated at ultradistal and 1/3 regions. Index of structural strength in axial compression was calculated from 4% pQCT and DXA output for comparison; 33% pQCT strength-strain index was compared to 1/3 DXA section modulus. Sievänen DXA indices were significantly, positively correlated with pQCT output (R=+0.61 to +0.98; p0.0001). At the distal radius, in healthy postmenarcheal girls, Sievänen's method yielded potentially useful DXA indices of diaphyseal cortical CSA and bone strength at both the diaphysis (section modulus) and the metaphysis (index of structural strength in axial compression).

To compare autonomic function, measured during handgrip (HG) and cold pressor (CP), between obese with and without type 2 diabetes and non-obese women in fasting and post-glucose load states. Twelve obese women with type 2 diabetes (50 ± 1 years), 15 obese women without type 2 diabetes (48 ± 2 years), and 12 non-obese women (49 ± 2 years) participated in this study. Heart rate variability (HRV) was determined during autonomic function tests, conducted in both the fasting state and after a glucose challenge (oral glucose tolerance test-OGTT). Obese women with and without diabetes and non-obese women responded similarly fasted and post-glucose challenge, such that in the fasted state low frequency power normalized (LF(nu)) to total power (TP), log transformed (Ln) low frequency to high frequency ratio (LnLF/HF) and heart rate (HR) significantly increased with the autonomic functional tasks (P < 0.05), whereas HF(nu) significantly decreased with the tasks (P < 0.05). Handgrip elicited a lower LnTP and a higher HR (P < 0.05) when compared to CP in the fasted state. In the glucose challenged state LF(nu), LnLF/HF and HR increased (P < 0.05) and HF(nu) significantly decreased (P < 0.05). Results of autonomic testing did not differ between obese women, with and without diabetes, and non-obese women. The HG test elicited a greater reduction in HRV total power compared to the CP. This suggests that HG may be more useful when examining autonomic function in women with complicated diabetes.

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.

In preparation for an electronic mail (e-mail) and web-based health promotion intervention across multiple worksites, secure, regulatory-compliant, user-friendly e-mail and Internet applications were used to recruit potential participants across worksites, to enroll participants, and to collect baseline health assessment data. Specific hardware and software information technology environments were required of the 19 participating worksites. Sequential e-mails introduced the study and invited participation. Twenty-four percent of all employees (1106 of approximately 4600) provided consent. E-mail delivered a web link for the baseline study assessment, and reminder e-mails were sent to prompt completion. Of those who consented, 888 (80%) completed baseline health and behavior data surveys. An HTML-native web survey software was more stable across computing environments. Using e-mail and web assessment, this research recruited, enrolled, and collected data from more than 850 participants. Technical and operational challenges emerged at each step. Solutions and recommendations are discussed. Overall, this experience suggests that the use of e-mail and web software can facilitate recruitment, enrollment, and data acquisition through direct contact with study participants. This experience yields a series of lessons learned for using e-mail and the Internet to support multi-site trials.

In 1996 we initiated a retrospective-prospective study in 184 untreated women infected in 1977 with chronic hepatitis C virus (HCV). To provide insight into the natural history of HCV, we determined liver fibrosis outcomes and any predictors of such.Baseline 1994 biopsy specimens (size,or=15 mm; portal areas,or=5) and sequential biopsy specimens were assessed by Ishak score for grade change (increase or decrease ofor=2 points) and stage progression or regression (increase or reduction ofor=1 point), the latter correlated with digital quantification of fibrosis percentage.No baseline biopsy specimens had cirrhosis, therefore all could potentially progress. Grade and stage scores decreased or increased significantly in 28% and 18% and 24% and 27% of patients, respectively. There was a positive correlation between baseline and sequential grade/stage scores (r = .39, P.001), and between semiquantitative Ishak scores and fibrosis percentage (Spearman rho = .85; P.01). Baseline alanine transaminase values (mean, 49 U/L; range, 23-363 U/L) correlated positively with changes in grade (r = .41, P.01) and stage (r = .39, P.01), and regression analyses indicated that baseline alanine transaminase value was a good predictor of such changes. Confounding variables (alcohol, smoking, and herbal and paracetamol [acetaminophen] use) did not correlate with histologic outcomes.In a follow-up study, 49% of patients showed no change in fibrosis, 24% showed regression, and only 27% showed progression, including 4 patients (2.1%) who developed stage 6 cirrhosis. Unidirectional sequential grade/stage concordance attested to biopsy sample reliability. Given the current age of these women in their fifth decade, some still may have a risk for more advanced liver disease, but for most of these patients it appears unlikely.

Background and Aims: The necessity of liver biopsy for staging fibrosis and its quantification in patients with chronic hepatitis C (CHC) remains controversial. Semiquantitative scoring of fibrosis is considered more subjective and less objective than digital quantification by image analysis. However, measurement of fibrosis using digital image analysis is thought to be less reliable in determining early stage fibrosis as compared with advanced fibrosis or cirrhosis. Our aims were to correlate all Ishak stages of fibrosis (0–6) with fibrosis percentage (%) using computerized digital image analysis, and thereby seek to improve discrimination between varying levels of liver fibrosis. Methods: Fibrosis % data were obtained by image analysis on 164 trichrome-stained liver biopsies from untreated patients with CHC, representing all Ishak stages of fibrosis. Results: Digital analysis of fibrosis % was highly correlated with Ishak scores of fibrosis (Kendall's τ–β=0.86, P

The authors’ class structure incorporates individual meal and exercise planning in the group setting. This study was conducted to (1) determine if class participants can create their own meal and exercise plans, (2) determine if class participants feel they will be able to adhere to their meal and exercise plans, and (3) assess adherence to the plans over time. Subjects were recruited from the classes offered at the Joslin Diabetes Center. Following completion of class, patients completed the evaluation questionnaire. Two and 6 months later, study participants received follow-up questionnaires by phone or mail. Among respondents, 63% were able to determine their own carbohydrate goals, with 95.9% indicating they could adhere to the plan, and 82.8% felt the plan would be easier than previous ones. At 2 and 6 months, respectively, 89% and 92% of the participants felt they were following the meal plan either some or most of the time. One hundred percent of the respondents were able to determine their own exercise plan, with 98% indicating they could adhere to the plan, and 85.7% felt the new plan would be easier than previous ones. At 2 and 6 months, respectively, 70% and 73% felt they were following their exercise plan either some or most of the time. Individualized meal and exercise plans can be successfully created in a group setting.

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.

In this study, 107 primary total joint replacement (TJR) patients were assessed preoperatively using the SF-36 (Mental Component Score [MCS] and Physical Component Score [PCS]), Beck Depression Inventory (BDI), Spielberger Trait Anxiety Inventory, Interpersonal Support Evaluation List, and the Coping Strategies Questionnaire. Patients with preoperative MCS or = 50. Low MCS patients used more catastrophizing coping techniques (P

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.

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