Association of Chemotherapy-Induced Peripheral Neuropathy with Diet Quality Among Post-Treatment Cancer Survivors.

Nutrition is essential for peripheral nerve function, yet dietary factors associated with chronic chemotherapy-induced peripheral neuropathy (CIPN) remain poorly characterized. The purpose of this cross-sectional study was to determine differences in diet quality and macronutrients for cancer survivors with and without CIPN. Cancer survivors (e.g., ≥3 months post platinum and/or taxane-based neurotoxic chemotherapy) with (i.e., ≥1/4 PRO-CTACE™ Numbness and Tingling Severity) and without CIPN completed the VioScreen Research Graphical Food Frequency Questionnaire. The association among diet (Healthy Eating Index [HEI]), macronutrient intake (average percent caloric intake), and CIPN severity were analyzed using generalized linear regression models, adjusting for caloric intake, body mass index, age, and sex. Results revealed that for each one-point increase in diet quality, PRO-CTCAE severity decreased by -0.06 (95% CI: -0.10, -0.02, P < 0.01). Participants without CIPN reported higher diet quality than those with CIPN (HEI mean: 70.11 vs 68.45) (OR = 0.94, P = 0.03, 95% CI: 0.89, 0.99). Participants with CIPN had significantly higher carbohydrate consumption than participants without CIPN (OR = 1.11, P = 0.04, 95% CI: 1.01, 1.22). There were no significant differences in consumption of proteins or fats between groups. Further research should be pursued to discover the potential benefits of dietary interventions for CIPN management among cancers survivors.

Reaching Populations to Address Disparities in Cancer Care Delivery: Results From a Six-Site Initiative.

BACKGROUND: Large segments of the US population do not receive quality cancer care due to pervasive and systemic inequities, which can increase morbidity and mortality. Multicomponent, multilevel interventions can address inequities and improve care, but only if they reach communities with suboptimal access. Intervention studies often underenroll individuals from historically excluded groups. METHODS: The Alliance to Advance Patient-Centered Cancer Care includes 6 grantees across the United States who implemented unique multicomponent, multilevel intervention programs with common goals of reducing disparities, increasing engagement, and improving the quality of care for targeted populations. The Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework informed the evaluation efforts across sites. Each Alliance site identified their intended populations, which included underrepresented minorities (eg, Black and Latinx persons), individuals who prefer a language other than English, and rural residents. We evaluated the demographic characteristics of participants to determine program reach. RESULTS: Between 2018 and 2020, a total of 2,390 of 5,309 potentially eligible participants were enrolled across the 6 sites. The proportion of enrolled individuals with selected characteristics included 38% (n=908) Black adults, 24% (n=574) Latinx adults, 19% (n=454) preferring a language other than English, and 30% (n=717) rural residents. The proportion of those enrolled who were the intended population was commensurate to the proportion with desired characteristics in those identified as potentially eligible. CONCLUSIONS: The grantees met or exceeded enrollments from their intended populations who have been underserved by quality cancer care into patient-centered intervention programs. Intentional application of recruitment/engagement strategies is needed to reach individuals from historically underserved communities.

Psychometric Evaluation of the Modes of Health Information Acquisition, Sharing, and Use Questionnaire: Prospective Cross-Sectional Observational Study.

BACKGROUND: Health information is a critical resource for individuals with health concerns and conditions, such as hypertension. Enhancing health information behaviors may help individuals to better manage chronic illness. The Modes of Health Information Acquisition, Sharing, and Use (MHIASU) is a 23-item questionnaire that measures how individuals with health risks or chronic illness acquire, share, and use health information. Yet this measure has not been psychometrically evaluated in a large national sample. OBJECTIVE: The objective of this study was to evaluate the psychometric properties of the self-administered MHIASU in a large, diverse cohort of individuals living with a chronic illness. METHODS: Sharing Information, a prospective, observational study, was launched in August 2018 and used social media campaigns to advertise to Black women. Individuals who were interested in participating clicked on the advertisements and were redirected to a Qualtrics eligibility screener. To meet eligibility criteria individuals had to self-identify as a Black woman, be diagnosed with hypertension by a health care provider, and live in the United States. A total of 320 Black women with hypertension successfully completed the eligibility screener and then completed a web-based version of the MHIASU questionnaire. We conducted a psychometric evaluation of the MHIASU using exploratory factor analysis. The evaluation included item review, construct validity, and reliability. RESULTS: Construct validity was established using exploratory factor analysis with principal axis factoring. The analysis was constricted to the expected domains. Interitem correlations were examined for possible item extraction. There were no improvements in factor structure with the removal of items with high interitem correlation (n=3), so all items of the MHIASU were retained. As anticipated, the instrument was found to have 3 subscales: acquisition, sharing, and use. Reliability was high for all 3 subscales, as evidenced by Cronbach α scores of .81 (acquisition), .81 (sharing), and .93 (use). Factor 3 (use of health information) explained the maximum variance (74%). CONCLUSIONS: Construct validity and reliability of the web-based, self-administered MHIASU was demonstrated in a large national cohort of Black women with hypertension. Although this sample was highly educated and may have had higher digital literacy compared to other samples not recruited via social media, the population captured (Black women living with hypertension) are often underrepresented in research and are particularly vulnerable to this chronic condition. Future studies can use the MHIASU to examine health information behavior in other diverse populations managing health concerns and conditions.

Toward rational use of cognitive training in those with mild cognitive impairment.

The term cognitive training includes a range of techniques that hold potential for treating cognitive impairment caused by neurologic injury and disease. Our central premise is that these techniques differ in their mechanisms of action and therefore engage distinct brain regions (or neural networks). We support this premise using data from a single-blind randomized-controlled trial in which patients with mild cognitive impairment were randomized to either mnemonic strategy training (MST) or spaced retrieval training (SRT) as they learned ecologically relevant object-location associations. Both training approaches were highly effective in the short term, but MST demonstrated a clear advantage after days to weeks. MST also increased activation in and functional connectivity between frontal, temporal, and parietal regions as well as the hippocampus. In contrast, patterns of reduced activation and functional connectivity were evident following SRT. These findings support the rational development of cognitive training techniques.

Trauma History as a Significant Predictor of Posttraumatic Growth Beyond Mental Health Symptoms in Women-Identifying Survivors of Undergraduate Non-Consensual Sexual Experiences.

There is little data on what influences posttraumatic growth for women who experienced non-consensual sexual contact (NCSC) as an undergraduate college student. The purpose of this study is to garner a better understanding of posttraumatic growth among women-identifying survivors of undergraduate NCSC by addressing the following aims: 1) evaluate the mediating role of NCSC-related shame on the relationship between perceived peer rape myth acceptance and posttraumatic growth (n = 174); and 2) evaluate the shared and independent variance contributions of mental health symptoms and trauma history clusters on posttraumatic growth (n = 151).NCSC-related shame did not mediate the relationship between perceived peer rape myth acceptance and posttraumatic growth. Mental health symptoms and trauma history significantly contributed to 35.27% of posttraumatic growth variance, with the trauma history cluster significantly influencing posttraumatic growth scores beyond mental health symptoms. Based on these findings, it is important that clinicians assess for a history of trauma and the impact of that trauma in addition to mental health symptoms when trying to understand posttraumatic growth after campus sexual violence.

Recovery opioid overdose team (ROOT) pilot program evaluation: A community-wide post-overdose response strategy.

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.

Intracranial Effects of Microgravity: A Prospective Longitudinal MRI Study.

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.

Skeletal muscle fiber type-selective effects of acute exercise on insulin-stimulated glucose uptake in insulin-resistant, high-fat-fed rats.

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.

Interactive Computer Simulation for Adolescent Screening, Brief Intervention, and Referral to Treatment (SBIRT) for Substance Use in an Undergraduate Nursing Program.

PURPOSE: 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. DESIGN AND METHOD: 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. RESULTS: 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. CONCLUSIONS: 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. PRACTICAL IMPLICATION: This project provided further support for the potential benefits of an interactive computer-based simulation in an undergraduate nursing curriculum.

Genotype, B-vitamin status, and androgens affect spaceflight-induced ophthalmic changes.

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 ß-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.

An Online Intervention Comparing a Very Low-Carbohydrate Ketogenic Diet and Lifestyle Recommendations Versus a Plate Method Diet in Overweight Individuals With Type 2 Diabetes: A Randomized Controlled Trial.

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<.001). A greater percentage of participants lost at least 5% of their body weight in the intervention (10/11, 90%) versus the control group (2/8, 29%; P=.01). Participants in the intervention group lowered their triglyceride levels (EMM -60.1 mg/dL, 95% CI -91.3 to -28.9 mg/dL) more than participants in the control group (EMM -6.2 mg/dL, 95% CI -46.0 to 33.6 mg/dL; P=.01). Dropout was 8% (1/12) and 46% (6/13) for the intervention and control groups, respectively (P=.07). CONCLUSIONS: Individuals with type 2 diabetes improved their glycemic control and lost more weight after being randomized to a very low-carbohydrate ketogenic diet and lifestyle online program rather than a conventional, low-fat diabetes diet online program. Thus, the online delivery of these very low-carbohydrate ketogenic diet and lifestyle recommendations may allow them to have a wider reach in the successful self-management of type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT01967992; https://clinicaltrials.gov/ct2/show/NCT01967992 (Archived by WebCite at http://www.webcitation.org/6o0fI9Mkq).

Breast Milk as a Potential Source of Epstein-Barr Virus Transmission Among Infants Living in a Malaria-Endemic Region of Kenya.

BACKGROUND: We previously reported that infants in Kenya were infected with Epstein-Barr virus (EBV) at <6 months of age, suggesting that mothers were the likely source of transmissible virus to the infant. In this study, we investigated whether breast milk contained infectious EBV and the role of malaria in EBV shedding in breast milk. METHODS: Breast milk samples were obtained from Kenyan mothers at postpartum weeks 6, 10, 14, and 18 and analyzed for presence of infectious EBV. RESULTS: We found that the prevalence of EBV DNA and the mean EBV load were significantly higher at 6 weeks and decreased through postpartum week 18 (P < .0001). High EBV load in breast milk correlated with mothers who had Plasmodium falciparum malaria at delivery. To determine whether viral DNA was encapsidated, breast milk samples were treated with DNAse before DNA extraction. Sixty percent of samples were DNAse resistant, suggesting that the viral DNA in breast milk was encapsidated. Next, we exposed peripheral blood mononuclear cells to breast milk supernatant, which resulted in the generation of EBV-positive lymphoblastoid cell lines, indicating that the virus in breast milk was infectious. CONCLUSIONS: Our data suggest that breast milk contains infectious EBV and is a potential source of viral transmission to infants living in malaria-endemic regions.

Plasmodium falciparum infection is associated with Epstein-Barr virus reactivation in pregnant women living in malaria holoendemic area of Western Kenya.

The role of Plasmodium falciparum malaria in Epstein-Barr virus (EBV) transmission among infants early in life remain elusive. We hypothesized that infection with malaria during pregnancy could cause EBV reactivation leading to high EBV load in circulation, which could subsequently enhance early age of EBV infection. Pregnant women in Kisumu, where P. falciparum malaria is holoendemic, were actively followed monthly through antenatal visits (up to 4 per mother) and delivery. Using real-time quantitative (Q)-PCR, we quantified and compared EBV and P. falciparum DNA levels in the blood of pregnant women with and without P. falciparum malaria. Pregnant women that had malaria detected during pregnancy were more likely to have detectable EBV DNA than pregnant women who had no evidence of malaria infection during pregnancy (64 vs. 36 %, p = 0.01). EBV load as analyzed by quantifying area under the longitudinal observation curve (AUC) was significantly higher in pregnant women with P. falciparum malaria than in women without evidence of malaria infection (p = 0.01) regardless of gestational age of pregnancy. Increase in malaria load correlated with increase in EBV load (p < 0.0001). EBV load was higher in third trimester (p = 0.04) than first and second trimester of pregnancy independent of known infections. Significantly higher frequency and elevated EBV loads were found in pregnant women with malaria than in women without evidence of P. falciparum infection during pregnancy. The loss of control of EBV latency following P. falciparum infection during pregnancy and subsequent increase in EBV load in circulation could contribute to enhanced shedding of EBV in maternal saliva and breast milk postpartum, but further studies are needed.

Gradient compression garments protect against orthostatic intolerance during recovery from bed rest.

INTRODUCTION: 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. PURPOSE: 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. METHODS: 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. RESULTS: 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/m(2)), 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. CONCLUSIONS: 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.

The metabolic cost of an integrated exercise program performed during 14 days of bed rest.

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.

Ocular outcomes evaluation in a 14-day head-down bed rest study.

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.

Salience Network Segregation Mediates the Effect of Tau Pathology on Mild Behavioral Impairment.

INTRODUCTION: A recently developed mild behavioral impairment (MBI) diagnostic framework standardizes the early characterization of neuropsychiatric symptoms in older adults. However, the links between MBI, brain function, and Alzheimer's disease (AD) biomarkers are unclear. METHODS: Using data from 128 participants with diagnosis of amnestic mild cognitive impairment and mild dementia - Alzheimer's type, we test a novel model assessing direct relationships between AD biomarker status and MBI symptoms, as well as mediated effects through segregation of the salience and default-mode networks. RESULTS: We identified a mediated effect of tau positivity on MBI through functional segregation of the salience network from the other high-level, association networks. There were no direct effects of AD biomarkers status on MBI. DISCUSSION: Our findings suggest an indirect role of tau pathology in MBI through brain network dysfunction and emphasize the role of the salience network in mediating relationships between neuropathological changes and behavioral manifestations.

Home-based aerobic exercise feasibility in oxaliplatin-receiving newly-diagnosed cancer survivors.

PURPOSE: Physical activity (PA) is beneficial but difficult to maintain during chemotherapy. This pilot RCT explored the feasibility of the MI-Walk intervention-an 8-week motivational enhancement therapy- and home-based brisk walking intervention-among gastrointestinal (GI) cancer survivors receiving chemotherapy. METHODS: Sixty stage II-IV GI cancer survivors were recruited from 5 sites at their second infusion visit. Participants were randomized to receive PA education alone or the MI-Walk intervention: motivational enhancement therapy consisting of 3 motivational interviewing and self-efficacy-enhancing counseling sessions, a Fitbit Charge 2, exercise diaries, telephone follow-up, scripted motivational email messages, and optional weekly walking groups. RESULTS: The enrollment and completion rates were 62% and 90%, respectively. The MI-Walk participants (n = 29; mean age = 56.79, SD = 11.72; 97% white; 79% male) reported a baseline moderate-vigorous PA duration of 250.93 (SD = 636.52) min/wk. The mean MI-Walk Intervention acceptability score was 50.32 (SD = 12.02) on a scale of 14-70. Mean Fitbit and counseling helpfulness scores on a 5-point scale were 3.67 (SD = 1.43) and 3.44 (SD = 1.36), respectively. Participants' Fitbit moderate-vigorous PA 8-week averages ranged from 0 to 716.88 min/wk; 64% of participants adhered to ≥127 min/wk. Several characteristics (e.g., age, comorbidity, PA level, employment status, BMI, education level, gender, symptoms) were associated with enrollment, attrition, and intervention acceptability and adherence (p < 0.05). CONCLUSION: Enrollment and retention were adequate. The Fitbit and counseling were the most helpful. Acceptability and adherence varied based on participant characteristics; therefore, intervention tailoring and further research among cancer survivors less physically active at baseline and most in need of complex exercise intervention are needed. CLINICALTRIALS: gov NCT03515356.

Resilience, mental health, sleep, and smoking mediate pathways between lifetime stressors and Multiple Sclerosis severity.

Intro: Lifetime stressors (e.g., poverty, violence, discrimination) have been linked to Multiple Sclerosis (MS) features; yet mechanistic pathways and relationships with cumulative disease severity remain nebulous. Further, protective factors like resilience, that may attenuate the effects of stressors on outcomes, are seldom evaluated. Aim: To deconstruct pathways between lifetime stressors and cumulative severity on MS outcomes, accounting for resilience. Methods: Adults with MS (N=924) participated in an online survey through the National MS Society listserv. Structural Equation Modeling was used to examine the direct and indirect effect of lifetime stressors (count/severity) on MS severity (self-reported disability, relapse burden, fatigue, pain intensity and interference), via resilience, mental health (anxiety and depression), sleep disturbance, and smoking. Results: The final analytic model had excellent fit (GFI=0.998). Lifetime stressors had a direct relationship with MS severity (ß=0.27, p<.001). Resilience, mental health, sleep disturbance, and smoking significantly mediated the relationship between lifetime stressors and MS severity. The total effect of mediation was significant (ß=0.45). Conclusions: This work provides foundational evidence to inform conceptualization of pathways by which stress could influence MS disease burden. Resilience may attenuate effects of stressors, while poor mental health, smoking, and sleep disturbances may exacerbate their impact. Parallel with usual care, these mediators could be targets for early multimodal therapies to improve disease course.