Unveiling the connection between gut microbiome and metabolic health in individuals with chronic spinal cord injury.

Accumulating evidence has revealed that alterations in the gut microbiome following spinal cord injury (SCI) exhibit similarities to those observed in metabolic syndrome. Considering the causal role of gut dysbiosis in metabolic syndrome development, SCI-induced gut dysbiosis may be a previously unidentified contributor to the increased risk of cardiometabolic diseases, which has garnered attention. With a cross-sectional design, we evaluated the correlation between gut microbiome composition and functional potential with indicators of metabolic health among 46 individuals with chronic SCI. Gut microbiome communities were profiled using next-generation sequencing techniques. Indices of metabolic health, including fasting lipid profile, glucose tolerance, insulin resistance, and inflammatory markers, were assessed through fasting blood tests and an oral glucose tolerance test. We used multivariate statistical techniques (i.e., regularized canonical correlation analysis) to identify correlations between gut bacterial communities, functional pathways, and metabolic health indicators. Our findings spotlight bacterial species and functional pathways associated with complex carbohydrate degradation and maintenance of gut barrier integrity as potential contributors to improved metabolic health. Conversely, those correlated with detrimental microbial metabolites and gut inflammatory pathways demonstrated associations with poorer metabolic health outcomes. This cross-sectional investigation represents a pivotal initial step toward comprehending the intricate interplay between the gut microbiome and metabolic health in SCI. Furthermore, our results identified potential targets for future research endeavors to elucidate the role of the gut microbiome in metabolic syndrome in this population.NEW & NOTEWORTHY Spinal cord injury (SCI) is accompanied by gut dysbiosis and the impact of this on the development of metabolic syndrome in this population remains to be investigated. Our study used next-generation sequencing and multivariate statistical analyses to explore the correlations between gut microbiome composition, function, and metabolic health indices in individuals with chronic SCI. Our results point to potential gut microbial species and functional pathways that may be implicated in the development of metabolic syndrome.

Racial differences in serological markers across the first year of injury in spinal cord injury: a retrospective analysis of a multi-center interventional study.

STUDY DESIGN: Secondary analysis of a randomized, multi-center, placebo-controlled study(Sygen®). OBJECTIVES: To evaluate racial differences in serological markers in individuals with spinal cord injury(SCI) across the first year of injury. SETTING: Hospitals in North America. METHODS: Serological markers (e.g.,cell count, liver, kidney, and pancreatic function, metabolism, and muscle damage) were assessed among 316 participants (247 White, 69 Black) at admission, weeks 1, 2, 4, 8, and 52 post-injury. Linear mixed models were employed to explore the main effects of time, race (Black vs. White), and their interaction, with adjustment of covariates such as study center, polytrauma, injury (level, completeness), treatment group, and sex. RESULTS: A main effect of race was observed where White individuals had higher alanine transaminase, blood urea nitrogen(BUN), BUN/Creatinine ratio, sodium, and chloride, while Black individuals had higher calcium, total serum protein, and platelets. For markers with interaction effects, post-hoc comparisons showed that at week 52, White individuals had higher mature neutrophils, hematocrit, hemoglobin, mean corpuscular hemoglobin, albumin, and triglycerides, and Black individuals had higher amylase. Eosinophils, monocytes, red blood cells, aspartate aminotransferase, bilirubin, cholesterol, partial thromboplastin time, urine specific gravity, urine pH, CO2, and inorganic phosphorus did not differ between races. CONCLUSIONS: Our results revealed racial differences in serological markers and underscores the importance of considering race as a determinant of physiological responses. Future studies are warranted to explore the causes and implications of these racial disparities to facilitate tailored clinical management and social policy changes that can improve health equity.

Effects of a Low-Carbohydrate, High-Protein Diet on Gut Microbiome Composition in Insulin-Resistant Individuals With Chronic Spinal Cord Injury: Preliminary Results From a Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect of a low-carbohydrate, high-protein (LC/HP) diet that includes healthy dietary components (eg, lean meat, whole grains, fruits and vegetables, fiber, etc) on the gut microbiome composition in individuals with chronic spinal cord injury (SCI). DESIGN: A single-center randomized parallel controlled trial. SETTING: Research University. PARTICIPANTS: Adult participants with chronic SCI (N=19, 3 years or more after the injury, C2-L2, American Spinal Injury Association Impairment Scale A-D). Participants were insulin resistant and had not received antibiotics within 4 weeks before enrolling in the study. INTERVENTIONS: Participants were randomized to the LC/HP diet group (40% energy from carbohydrates, 30% energy from protein, and 30% energy from fat and met dietary guideline recommendations) or the control group for 8 weeks. Participants assigned to the LC/HP group were provided with all meals delivered weekly to their homes. Participants assigned to the control group were asked to continue their usual diet. MAIN OUTCOME MEASURES: Stool samples were collected at baseline and the end of week 8. The gut microbiome 16S ribosomal RNA V4 region was sequenced, and gut microbiome diversity and taxonomical abundance were computed using the QIIME2 suite. RESULTS: Participants in the LC/HP group had significant changes in alpha-diversity (reduced operational taxonomic unit and Faith's phylogenetic diversity) and beta-diversity (unweighted UniFrac), while no significant differences were observed among participants in the control group after the intervention. Moreover, several taxa changed differently over time between groups, including increased Bacteroides thetaiotaomicron, Coprococcus 3, Fusicatenibacter, Tannerellaceae, and decreased Tyzzerella, Phascolarctobacterium, Romboutsia, Clostridium sensu stricto 1, Hungatella, Ruminococcus gauvreauii, family XI, and Bacillales among participants in the diet group, while these taxa did not change in the control group. CONCLUSIONS: An LC/HP diet with healthy dietary components improved gut microbiome composition in individuals with SCI, including increased bacteria implicated in fiber metabolism and reduced bacteria communities linked to cardiometabolic disorders.

Gut Microbiome Composition and Serum Metabolome Profile Among Individuals With Spinal Cord Injury and Normal Glucose Tolerance or Prediabetes/Type 2 Diabetes.

OBJECTIVE: To compare the gut microbiome composition and serum metabolome profile among individuals with spinal cord injury (SCI) and normal glucose tolerance (NGT) or prediabetes/type 2 diabetes (preDM/T2D). DESIGN: Cross-sectional design. SETTING: Research university. PARTICIPANTS: A total of 25 adults (N=25) with SCI were included in the analysis and categorized as NGT (n=16) or preDM/T2D (n=9) based on their glucose concentration at minute 120 during a 75-g oral glucose tolerance test. The American Diabetes Association diagnosis guideline was used for grouping participants. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: A stool sample was collected and used to assess the gut microbiome composition (alpha and beta diversity, microbial abundance) via the 16s ribosomal RNA sequencing technique. A fasting serum sample was used for liquid chromatography-mass spectrometry-based untargeted metabolomics analysis, the results from which reflect the relative quantity of metabolites detected and identified. Gut microbiome and metabolomics data were analyzed by the Quantitative Insights into Microbial Ecology 2 and Metaboanalyst platforms, respectively. RESULTS: Gut microbiome alpha diversity (Pielou's evenness index, Shannon's index) and beta diversity (weighted UniFrac distances) differed between groups. Compared with participants with NGT, participants with preDM/T2D had less evenness in microbial communities. In particular, those with preDM/T2D had a lower abundance of the Clostridiales order and higher abundance of the Akkermansia genus, as well as higher serum levels of gut-derived metabolites, including indoxyl sulfate and phenylacetylglutamine (P < .05 for all). CONCLUSIONS: Our results provide evidence for altered gut microbiome composition and dysregulation of gut-derived metabolites in participants with SCI and preDM/T2D. Both indoxyl sulfate and phenylacetylglutamine have been implicated in the development of cardiovascular diseases in the able-bodied population. These findings may inform future investigations in the field of SCI and cardiometabolic health.

Differences in Glucose Metabolism Among Women With Spinal Cord Injury May Not Be Fully Explained by Variations in Body Composition.

OBJECTIVE: To investigate the differences in glucose metabolism among women with paraplegic, and tetraplegic spinal cord injury (SCI) in comparison to their able-bodied (AB) counterparts after adjusting for differences in body composition. DESIGN: Cross-sectional study. After an overnight fast, each participant consumed a 75-g glucose solution for oral glucose tolerance test (OGTT). Blood glucose, insulin, and C-peptide concentrations were analyzed before and 30, 60, 90, and 120 minutes after ingesting glucose solution. Insulin sensitivity index (ISI) was estimated using the Matsuda index. Percentage fat mass (%FM) and total body lean mass (TBLM) were estimated using data from dual-energy x-ray absorptiometry. Visceral fat (VF) was quantified using computed tomography. Outcome measures were compared among groups using analysis of covariance with %FM (or VF) and TBLM as covariates. SETTING: Research university. PARTICIPANTS: Women (N=42) with SCI (tetraplegia: n=8; paraplegia: n=14) and their race-, body mass index-, and age-matched AB counterparts (n=20). INTERVENTIONS: Not applicable. RESULTS: At fasting, there was no difference in glucose homeostasis (glucose, insulin, C-peptide concentrations) among 3 groups of women. In contrast, glucose, insulin, and C-peptide concentrations at minute 120 during OGTT were higher in women with tetraplegia versus women with paraplegia and AB women (P<.05, adjusted for TBLM and %FM). In addition, women with tetraplegia had lower ISI (P<.05, adjusted for TBLM and %FM) versus AB women. These differences remained after adjusting for VF and TBLM. CONCLUSION: Our study confirms that impaired glucose metabolism among women with tetraplegia may not be fully explained by changes in their body composition. Future studies exploring additional factors involved in glucose metabolism are warranted.

Heightened TWEAK-NF-κB signaling and inflammation-associated fibrosis in paralyzed muscles of men with chronic spinal cord injury.

Individuals with long-standing spinal cord injury (SCI) often present with extreme muscle atrophy and impaired glucose metabolism at both the skeletal muscle and whole body level. Persistent inflammation and increased levels of proinflammatory cytokines in the skeletal muscle are potential contributors to dysregulation of glucose metabolism and atrophy; however, to date no study has assessed the effects of long-standing SCI on their expression or intracellular signaling in the paralyzed muscle. In the present study, we assessed the expression of genes (TNFαR, TNFα, IL-6R, IL-6, TWEAK, TWEAK R, atrogin-1, and MuRF1) and abundance of intracellular signaling proteins (TWEAK, TWEAK R, NF-κB, and p-p65/p-50/105) that are known to mediate inflammation and atrophy in skeletal muscle. In addition, based on the effects of muscle inflammation on promotion of skeletal muscle fibrosis, we assessed the degree of fibrosis between myofibers and fascicles in both groups. For further insight into the distribution and variability of muscle fiber size, we also analyzed the frequency distribution of SCI fiber size. Resting vastus lateralis (VL) muscle biopsy samples were taken from 11 men with long-standing SCI (≈22 yr) and compared with VL samples from 11 able-bodied men of similar age. Our results demonstrated that chronic SCI muscle has heightened TNFαR and TWEAK R gene expression and NF-κB signaling (higher TWEAK R and phospho-NF-κB p65) and fibrosis, along with substantial myofiber size heterogeneity, compared with able-bodied individuals. Our data suggest that the TWEAK/TWEAK R/NF-κB signaling pathway may be an important mediator of chronic inflammation and fibrotic adaptation in SCI muscle.

Mechanosensitivity may be enhanced in skeletal muscles of spinal cord-injured versus able-bodied men.

We investigated the effects of an acute bout of neuromuscular electrical stimulation-induced resistance exercise (NMES-RE) on intracellular signaling pathways involved in translation initiation and mechanical loading-induced muscle hypertrophy in spinal cord-injured (SCI) versus able-bodied (AB) individuals. AB and SCI individuals completed 90 isometric knee extension contractions at 30% of maximum voluntary or evoked contraction, respectively. Muscle biopsies were collected before, and 10 and 60 min after NMES-RE. Protein levels of α7- and ß1-integrin, phosphorylated and total GSK-3α/ß, S6K1, RPS6, 4EBP1, and FAK were assessed by immunoblotting. SCI muscle appears to be highly sensitive to muscle contraction even several years after the injury, and in fact it may be more sensitive to mechanical stress than AB muscle. Heightened signaling associated with muscle mechanosensitivity and translation initiation in SCI muscle may be an attempted compensatory response to offset elevated protein degradation in atrophied SCI muscle. .

The Effect of Lower Limb Combined Neuromuscular Electrical Stimulation on Skeletal Muscle Signaling for Glucose Utilization, Myofiber Distribution, and Metabolic Function after Spinal Cord Injury.

Maintaining healthy myofiber type and metabolic function early after spinal cord injury (SCI) may prevent chronic metabolic disorders. This study compares the effects of a 2-5 week combined (aerobic + resistance) neuromuscular electrical stimulation (Comb-NMES) regimen versus a sham control treatment on muscle protein signaling for glucose uptake, myofiber type distribution, and metabolic function. Twenty participants (31 ± 9 years of age) with an SCI (C4-L1, AIS level A-C) within 14 days of the SCI were randomly assigned to control (N = 8) or Comb-NMES (N = 12). Sessions were given three times per week. Fasting blood samples and vastus lateralis muscle biopsies were collected 24-48 h before or after the last session. Western blots were performed to quantify proteins, immunohistochemical analyses determined muscle myofiber distribution, and enzymatic assays were performed to measure serum glucose, insulin, and lipids. Our main findings include a decrease in fasting glucose (p < 0.05) and LDL-C (p < 0.05) levels, an upregulation of CamKII and Hexokinase (p < 0.05), and an increase in type I (+9%) and a decrease in type IIx (-36%) myofiber distribution in response to Comb-NMES. Our findings suggest that maintaining healthy myofiber type and metabolic function may be achieved via early utilization of Comb-NMES.

Effects of a low-carbohydrate/high-protein diet on metabolic health in individuals with chronic spinal cord injury: An exploratory analysis of results from a randomized controlled trial.

We explored the impact of a low-carbohydrate/high-protein diet (LC/HP, ~30% energy from protein, 40% energy from carbohydrate) on indices of metabolic function and body composition in individuals with chronic spinal cord injury (SCI). Adults with SCI (≥3 years post-injury, C4-L2, AIS A-D) and insulin resistance or pre-diabetes were randomly assigned to an 8-week iso-caloric LC/HP diet group (n = 11) or control group (n = 14). All LC/HP meals were delivered weekly to participants' homes, and participants in the control group consumed their habitual diet. Each participant underwent an oral glucose tolerance test (OGTT) to assess glucose tolerance, insulin, area under the curve (AUC) for glucose and insulin, Matsuda Index, glucose-stimulated insulin secretion (GSIS), disposition index, and hepatic insulin extraction (HIE). Fasting blood lipid and inflammation were assessed, and body composition was estimated using dual-energy x-ray absorptiometry. A linear mixed model was used to evaluate the main effect of diet, time, and their interaction. Compared to the control group, participants in the LC/HP group had reduced total body fat mass (LC/HP: -5.9%, Control: 0.7%), visceral fat mass (LC/HP: -16.2%, Control: 5.2%), total- (LC/HP: -20.1, Control: 3.7 mg/dl), and LDL-cholesterol (LC/HP: -13.9, Control: 3.1 mg/dl) (pdiet*time < 0.05 for all). Regardless of group, AUCinsulin and peak insulin during the OGTT decreased, and HIE increased over time (ptime < 0.05). A trend for diet*time interaction was observed for glucoseOGTT120min (LC/HP: -20.7, Control: 3.0 mg/dl, pdiet*time  = 0.09) and peak C-peptide (LC/HP: -2.1, Control: 0.0 ng/ml, pdiet*time  = 0.07). HDL-cholesterol, lean body mass, Matsuda Index, fasting glucose, insulin, insulinOGTT120min , AUCglucose , pancreatic beta cell function (GSIS, disposition index), and inflammation (C-reactive protein, IL-6, IL-8, IL-10, TNF-α) did not change over time. In conclusion, our results suggest that individuals with SCI and insulin resistance may adopt an LC/HP diet to improve body composition and lipid profiles. Its impact on glucose metabolism and inflammation remains inconclusive and warrants future investigations.

Telehealth high-intensity interval exercise and cardiometabolic health in spinal cord injury.

BACKGROUND: The number of exercise trials examining cardiometabolic outcomes in spinal cord injury (SCI) is low, and prescribed exercise is often inconvenient for individuals with SCI to perform within their community. Individuals with SCI experience a myriad of barriers to exercise participation, which can include a lack of time, accessible or usable equipment and facilities, and transportation. Thus, it is imperative to identify effective modes of exercise that provide the greatest overall health benefits but do not require a significant time commitment. Low-volume high intensity interval training (HIIT) has demonstrated the same improvements in cardiometabolic health as moderate intensity exercise training (MIT), despite only requiring 20% of the total time commitment in adults without disabilities and more recently in individuals with SCI. OBJECTIVES: The primary purpose of this study is to integrate a 16 week home-based telehealth HIIT arm crank exercise training program in individuals with SCI and assess changes in cardiometabolic health. METHODS: Men and women between the ages of 19 and 60 with a confirmed diagnosis of SCI between C7 and T12 will be recruited for this study. Participants will be randomized to 16 weeks of telehealth HIIT exercise two days per week or a no-exercise control group. Aerobic capacity, muscular strength, blood lipids, glucose tolerance, resting energy expenditure, blood pressure, and body composition will be assessed at baseline and 16 weeks post-training. DISCUSSION: Inactivity associated with SCI leads to chronic cardiometabolic health conditions. The majority of exercise interventions to date show that exercise is capable of increasing physical function, aerobic capacity, and muscle mass, and strength. Additionally, we have recently shown the ability of HIIT to improve blood lipid and glucose concentrations. Advances in telehealth exercise approaches have improved the capability to prescribe home-based exercise programs. Therefore, we hypothesize that the utilization of a home-based telehealth HIIT program will improve cardiometabolic health markers, yield high adherence (> 75%), and will be more enjoyable in individuals with SCI. TRIAL REGISTRATION: Telehealth High-Intensity Interval Exercise and Cardiometabolic Health in Spinal Cord Injury NCT04940598.

Comparison of the gut microbiome composition among individuals with acute or long-standing spinal cord injury vs. able-bodied controls.

Objective: Compare the gut microbiome composition among individuals with acute spinal cord injury (A-SCI), long-standing SCI (L-SCI), vs. able-bodied (AB) controls.Design: Cross-sectional study.Setting: The University of Alabama at Birmingham.Participants: Seven adults with A-SCI (36 ± 12 years, 2F/5M, C4-T10, and American Spinal Injury Association Impairment Scale [AIS] A-D), 25 with L-SCI (46 ± 13 years, 6F/19M, C4-L1, and AIS A-D), and 25 AB controls (42 ± 13 years, 9F/16M).Methods: Stool samples were collected after a median of 7 days and 18 years after injury in the A-SCI and L-SCI groups, respectively. Gut microbiome composition was analyzed using the 16S rRNA sequencing technique and QIIME software. The abundances of bacteria communities among groups were compared using the Kruskal-Wallis test adjusted for age.Results: Several alpha diversity indices were different among groups (Chao1, Observed species, and Phylogenetic Diversity), but not others (Shannon and Simpson). Beta diversity differed among each pair of groups (P < 0.05). A number of microbial communities were differentially abundant among the groups (P < 0.05).Conclusion: Our results revealed differences in the gut microbiome composition among groups. Compared to the AB controls, the SCI groups demonstrated microbiome profiles that shared features linked to metabolic syndrome, inflammation-related bowel disorders, depressive disorders, or antibiotics use, whereas the L-SCI group's microbiome included features linked to reduced physical activity compared to the A-SCI and AB controls. Our results provided preliminary data and a scientific foundation for future studies investigating the impact of the gut microbiome composition on long-term health in individuals with SCI.

Ketogenic regimens for acute neurotraumatic events.

Dietary modification would be the most translatable, cost-efficient, and, likely, the safest approach available that can reduce the reliance on pharmaceutical treatments for treating acute or chronic neurological disorders. A wide variety of evidence suggests that the ketogenic diet (KD) could have beneficial effects in acute traumatic events, such as spinal cord injury and traumatic brain injury. Review of existing human and animal studies revealed that KD can improve motor neuro-recovery, gray matter sparing, pain thresholds, and neuroinflammation and decrease depression. Although the exact mechanism by which the KD provides neuroprotection is not fully understood, its effects on cellular energetics, mitochondria function and inflammation are likely to have a role.

Limited Association between the Total Healthy Eating Index-2015 Score and Cardiovascular Risk Factors in Individuals with Long-Standing Spinal Cord Injury: An Exploratory Study: An Exploratory Study.

BACKGROUND: The healthy eating index-2015 (HEI-2015) reflects diet quality in reference to the 2015-2020 Dietary Guidelines for Americans (DGA). Little is known regarding its application in individuals with chronic spinal cord injury (SCI). OBJECTIVE: To explore the relationship between diet quality as assessed by the HEI-2015 and cardiovascular risk factors among individuals with chronic SCI. DESIGN: This is a cross-sectional analysis of baseline data collected from August 2017 through November 2019 for an interventional study that evaluates the effects of a high-protein/low-carbohydrate diet on cardiovascular risk factors in individuals with chronic SCI at the University of Alabama at Birmingham. PARTICIPANTS/SETTING: Twenty-four free-living adults with SCI (mean age, 45 ± 12 y; 8F/16M, level of injury: nine cervical, 15 thoracic; mean duration of injury: 20 ± 13 y) were included. MAIN OUTCOME MEASURES: Participants underwent a 2-hour oral glucose tolerance test (OGTT) and a dual-energy x-ray absorptiometry scan. Dietary intake was assessed by three, 24-hour multiple-pass dietary recalls to calculate the HEI-2015 using the simple HEI scoring algorithm method. DATA ANALYSIS: Multiple linear regression analyses were performed to predict indices of lipid metabolism and glucose homeostasis and C-reactive protein (CRP) from the HEI-2015. Principal component analysis was used to reduce the number of covariates (level of injury, sex, and body fat percentage). RESULTS: On average, participants' diets were of low quality (HEI-2015, 47.2 ± 10.8). The regression models for fasting glucose (FG), cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and CRP had moderate to large effect sizes (adjusted R2 ≥ 13%), suggesting good explanatory abilities of the predictors. Small or limited effect sizes were observed for glucose tolerance, fasting insulin, triglycerides, and Matsuda index (adjusted R2 < 13%). The HEI-2015 accounted for a moderate amount of variation in FG (partial omega-squared, ωP2 = 13%). Each 10-point HEI-2015 score increase was associated with a 3.3-mg/dL decrease in FG concentrations. The HEI-2015 accounted for a limited amount of variation in other indices (ωP2 < 5%). CONCLUSIONS: Among participants with SCI, higher conformance to the 2015-2020 DGA was 1) moderately associated with better FG homeostasis; and 2) trivially associated with other cardiovascular risk factors. Because of the small sample size, these conclusions cannot be extrapolated beyond the study sample. Future larger studies are warranted to better understand the relationship between diet quality and cardiovascular disease risks in this population.

Sex and race contribute to variation in mitochondrial function and insulin sensitivity.

OBJECTIVE: Insulin sensitivity is lower in African American (AA) versus Caucasian American (CA). We tested the hypothesis that lower insulin sensitivity in AA could be explained by mitochondrial respiratory rates, coupling efficiency, myofiber composition, or H2 O2 emission. A secondary aim was to determine whether sex affected the results. METHODS: AA and CA men and women, 19-45 years, BMI 17-43 kg m2 , were assessed for insulin sensitivity (SIClamp ) using a euglycemic clamp at 120 mU/m2 /min, muscle mitochondrial function using high-resolution respirometry, H2 O2 emission using amplex red, and % myofiber composition. RESULTS: SIClamp was greater in CA (p < 0.01) and women (p < 0.01). Proportion of type I myofibers was lower in AA (p < 0.01). Mitochondrial respiratory rates, coupling efficiency, and H2 O2 production did not differ with race. Mitochondrial function was positively associated with insulin sensitivity in women but not men. Statistical adjustment for mitochondrial function, H2 O2 production, or fiber composition did not eliminate the race difference in SIClamp . CONCLUSION: Neither mitochondrial respiratory rates, coupling efficiency, myofiber composition, nor mitochondrial reactive oxygen species production explained lower SIClamp in AA compared to CA. The source of lower insulin sensitivity in AA may be due to other aspects of skeletal muscle that have yet to be identified.

Evaluation of a ketogenic diet for improvement of neurological recovery in individuals with acute spinal cord injury: study protocol for a randomized controlled trial.

BACKGROUND: Therapies that significantly improve the neurological and functional recovery of individuals with spinal cord injury (SCI) are still urgently needed. The ketogenic diet (KD) has been shown to improve forelimb motor function in an SCI rat model, likely by reducing inflammation and cell death in the spinal cord. Furthermore, our recent pilot study in patients with SCI showed that, compared with a standard hospital diet (SD), 5 weeks of KD started during acute care improved upper extremity motor function and reduced serum levels of a neuroinflammatory blood protein. The primary goals of the current study are to: 1) show the safety and feasibility of administering a KD during acute care for SCI; 2) determine if consuming 5 weeks of a KD significantly improves motor and sensory functions, functional independence and glycemic control; and 3) quantify serum biomarkers that are linked to improvements in neurological recovery and functional independence via targeted proteomics. METHODS/DESIGN: In a single-masked, longitudinal, randomized, parallel-controlled study, a total of 60 eligible, acutely traumatic spinal cord injured (cervical 5 to thoracic 12) participants ranging in age from 18 to 60 years with American Spinal Injury Association impairment scale (AIS) grades A-C (AIS-A, sensorimotor complete; AIS-B, sensory incomplete/motor complete; and AIS-C, nonfunctional motor incomplete) are being enrolled. Neurological and functional examinations, resting energy expenditure, blood, urine, and stool collections, and protein analyses related to neurological recovery will be performed within 72 h of injury (baseline measure) and repeated after 5 weeks of KD or SD (discharge measure). We anticipate a completion rate of 80% with a total of 48 participants. DISCUSSION: Intervention with a more neuroprotective diet during acute care of SCI can be implemented anywhere in the world at low cost and without major regulatory hurdles. Better functional recovery will lead to a better quality of life and long-term health outcomes in individuals with SCI. While this study targets SCI, if successful it has the potential to improve neurological outcomes for individuals with various traumatic injuries. TRIAL REGISTRATION: NCT03509571 Registered on April 28, 2018.

Spinal Mobilization Prevents NGF-Induced Trunk Mechanical Hyperalgesia and Attenuates Expression of CGRP.

INTRODUCTION: Low back pain (LBP) is a complex and growing global health problem in need of more effective pain management strategies. Spinal mobilization (SM) is a non-pharmacological approach recommended by most clinical guidelines for LBP, but greater utilization and treatment optimization are hampered by a lack of mechanistic knowledge underlying its hypoalgesic clinical effects. METHODS: Groups of female Sprague-Dawley rats received unilateral trunk (L5 vertebral level) injections (50 µl) of either vehicle (phosphate-buffer solution, PBS; VEH) or nerve growth factor (NGF; 0.8 µM) on Days 0 and 5 with or without daily L5 SM (VEH, NGF, VEH + SM, VEH + SM). Daily passive SM (10 min) was delivered by a feedback motor (1.2 Hz, 0.9N) from Days 1 to 12. Changes in pain assays were determined for mechanical and thermal reflexive behavior, exploratory behavior (open field events) and spontaneous pain behavior (rat grimace scale). On Day 12, lumbar (L1-L6) dorsal root ganglia (DRG) were harvested bilaterally and calcitonin gene-related peptide (CGRP) positive immunoreactive neurons were quantified from 3 animals (1 DRG tissue section per segmental level) per experimental group. RESULTS: NGF induced bilateral trunk (left P = 0.006, right P = 0.001) mechanical hyperalgesia and unilateral hindpaw allodynia (P = 0.006) compared to the vehicle group by Day 12. Additionally, we found for the first time that NGF animals demonstrated decreased exploratory behaviors (total distance traveled) and increased grimace scale scoring compared to the VEH group. Passive SM prevented this development of local (trunk) mechanical hyperalgesia and distant (hindpaw) allodynia, and normalized grimace scale scores. NGF increased CGRP positive immunoreactive neurons in ipsilateral lumbar DRGs compared to the VEH group ([L1]P = 0.02; [L2]P = 0.007) and SM effectively negated this increase in pain-related neuropeptide CGRP expression. CONCLUSION: SM prevents the development of local (trunk) NGF-induced mechanical hyperalgesia and distant (hindpaw) allodynia, in part, through attenuation of CGRP expression in lumbar DRG sensory neurons. NGF decreases rat exploratory behavior and increases spontaneous pain for which passive SM acts to mitigate these pain-related behavioral changes. These initial study findings suggest that beginning daily SM soon after injury onset might act to minimize or prevent the development of LBP by reducing production of pain-related neuropeptides.

Turning Chutes into Ladders for Women Faculty: A Review and Roadmap for Equity in Academia.

Despite significant progress in recent decades, the recruitment, advancement, and promotion of women in academia remain low. Women represent a large portion of the talent pool in academia, and receive >50% of all PhDs, but this has not yet translated into sustained representation in faculty and leadership positions. Research indicates that women encounter numerous "chutes" that remove them from academia or provide setbacks to promotion at all stages of their careers. These include the perception that women are less competent and their outputs of lesser quality, implicit bias in teaching evaluations and grant funding decisions, and lower citation rates. This review aims to (1) synthesize the "chutes" that impede the careers of women faculty, and (2) provide feasible recommendations, or "ladders" for addressing these issues at all career levels. Enacting policies that function as "ladders" rather than "chutes" for academic women is essential to even the playing field, achieve gender equity, and foster economic, societal, and cultural benefits of academia.

Utilizing a low-carbohydrate/high-protein diet to improve metabolic health in individuals with spinal cord injury (DISH): study protocol for a randomized controlled trial.

BACKGROUND: Metabolic disorders (e.g., impaired glucose tolerance, insulin resistance, and type 2 diabetes) are more prevalent in people with spinal cord injury (SCI) than able-bodied individuals. Dietary modification is a more cost-effective treatment option than pharmacological therapies for reducing the risk of metabolic dysfunction. Lowering carbohydrate, increasing protein, and maintaining a proper dietary fat intake are expected to induce favorable adaptations in glucose control, body fat distribution, and the composition of the gut microbiome. However, dietary modification has not been rigorously investigated in people with SCI. The purpose of this study is to determine if an 8-week low-carbohydrate/high-protein (LC/HP) dietary intervention will show improvements in clinically important metrics of metabolic function, body composition, the composition of gut bacteria, and quality of life. METHODS/DESIGN: We intend to recruit 100 participants with chronic traumatic SCI (3 years postinjury, C5-L2, American Spinal Injury Association impairment scale A-D, and aged 18-65 years) and insulin resistance, impaired glucose tolerance or untreated type 2 diabetes and randomly assign them to an 8-week LC/HP dietary intervention group or a control group. The daily LC/HP dietary intervention includes ~ 30% total energy as protein (1.6 g/kg per day) with a carbohydrate-to-protein ratio < 1.5 and fat intake set at ~ 30% of the total energy intake. The control group does not receive any dietary intervention and are continuing with their regular daily diets. Glucose tolerance, insulin sensitivity, ß-cell function, body composition, gut microbiome composition, and quality of life measures are assessed at week 1, before starting the LC/HP dietary intervention, and at week 8, after completion of the LC/HP dietary intervention. DISCUSSION: New information derived from this project will result in the development of a low-cost, simple, self-administered LC/HP dietary intervention for improving metabolic function in individuals with chronic SCI, improved understanding of the composition of gut bacteria in SCI, and how a LC/HP dietary intervention alters gut bacteria composition. In addition, this project will improve our understanding of the relationship between metabolic function and quality of life in individuals with long-standing SCI. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03207841. Registered on 5 June 2017.

Effects of High-Intensity Interval Training Versus Moderate-Intensity Training on Cardiometabolic Health Markers in Individuals With Spinal Cord Injury: A Pilot Study.

Background: Recent studies in nondisabled individuals have demonstrated that low-volume high-intensity interval training (HIIT) can improve cardiometabolic health similar to moderate-intensity training (MIT) despite requiring 20% of the overall time commitment. To date, there have been no studies assessing the effects of HIIT for improving cardiometabolic health in individuals with SCI. Objectives: The primary purpose of this pilot study was to compare the effects of 6 weeks of low-volume HIIT vs MIT using arm crank ergometer exercise to improve body composition, cardiovascular fitness, glucose tolerance, blood lipids, and blood pressure in a cohort of individuals with longstanding SCI. Methods: Participants were randomized to 6 weeks of HIIT or MIT arm crank exercise training. Aerobic capacity, muscular strength, blood lipids, glucose tolerance, blood pressure, and body composition were assessed at baseline and 6 weeks post training. Results: Seven individuals (6 male, 1 female; n = 3 in MIT and n = 4 in HIIT; mean age 51.3 ± 10.5 years) with longstanding SCI completed the study. The preliminary findings from this pilot study demonstrated that individuals with SCI randomized to either 6 weeks of HIIT or MIT displayed improvements in (a) insulin sensitivity, (b) cardiovascular fitness, and (c) muscular strength (p < .05). However, MIT led to greater improvements in arm fat percent and chest press strength compared to HIIT (p < .05). Conclusion: No differences between MIT and HIIT were observed. Both conditions led to improvements in insulin sensitivity, aerobic capacity, muscle strength, and blood lipids in individuals with SCI. Future larger cohort studies are needed to determine if the shorter amount of time required from HIIT is preferable to current MIT exercise recommendations.