Effect of non-invasive spinal cord stimulation in unmedicated adults with major depressive disorder: a pilot randomized controlled trial and induced current flow pattern.

Converging theoretical frameworks suggest a role and a therapeutic potential for spinal interoceptive pathways in major depressive disorder (MDD). Here, we aimed to evaluate the antidepressant effects and tolerability of transcutaneous spinal direct current stimulation (tsDCS) in MDD. This was a double-blind, randomized, sham-controlled, parallel group, pilot clinical trial in unmedicated adults with moderate MDD. Twenty participants were randomly allocated (1:1 ratio) to receive "active" 2.5 mA or "sham" anodal tsDCS sessions with a thoracic (anode; T10)/right shoulder (cathode) electrode montage 3 times/week for 8 weeks. Change in depression severity (MADRS) scores (prespecified primary outcome) and secondary clinical outcomes were analyzed with ANOVA models. An E-Field model was generated using the active tsDCS parameters. Compared to sham (n = 9), the active tsDCS group (n = 10) showed a greater baseline to endpoint decrease in MADRS score with a large effect size (-14.6 ± 2.5 vs. -21.7 ± 2.3, p = 0.040, d = 0.86). Additionally, compared to sham, active tsDCS induced a greater decrease in MADRS "reported sadness" item (-1.8 ± 0.4 vs. -3.2 ± 0.4, p = 0.012), and a greater cumulative decrease in pre/post tsDCS session diastolic blood pressure change from baseline to endpoint (group difference: 7.9 ± 3.7 mmHg, p = 0.039). Statistical trends in the same direction were observed for MADRS "pessimistic thoughts" item and week-8 CGI-I scores. No group differences were observed in adverse events (AEs) and no serious AEs occurred. The current flow simulation showed electric field at strength within the neuromodulation range (max. ~0.45 V/m) reaching the thoracic spinal gray matter. The results from this pilot study suggest that tsDCS is feasible, well-tolerated, and shows therapeutic potential in MDD. This work also provides the initial framework for the cautious exploration of non-invasive spinal cord neuromodulation in the context of mental health research and therapeutics. The underlying mechanisms warrant further investigation. Clinicaltrials.gov registration: NCT03433339 URL: https://clinicaltrials.gov/ct2/show/NCT03433339 .

Disentangling the effects of racism-related stress on opioid use disorder and chronic pain outcomes.

In recent years, Black people in the U.S. have had one of the highest increases in opioid overdose mortality rates, despite being less likely to be prescribed opioids for pain. This population is also less likely to receive medications for opioid use disorder (MOUD). Chronic pain is a central factor in understanding this crisis, as minoritized people are more likely to live with undertreated pain, a major risk factor for developing opioid use disorder (OUD). Current practices fail to effectively treat pain among persons with OUD, a missed opportunity that is worse in minoritized populations and further producing disparities. In this perspective, we discuss how racism-related stress and disparities in addiction treatments may impact the pain experience, diagnosis, treatment, contribute to developing OUD, and perpetuate stigma. This high-level perspective invites clinicians and researchers to reflect on the biopsychosocial burden imposed upon historically minoritized people with pain and OUD. To address such complex issues, multidisciplinary efforts and methodological improvements are required, imbued by antiracist values. Collaboration across disciplines is necessary toward the common goal of improving pain management and mitigating opioid mortality among minoritized populations. As antiracist perspectives inform research practices and cultural humility principles guide care, we will be better equipped to close current gaps in knowledge and address widening healthcare disparities.

Chronic use of benzodiazepines: The problem that persists.

Though clinical guidelines and policies discourage the chronic prescribing of benzodiazepines, rates of prescribing have continued to rise in the United States with an estimated 65.9 million office visits per year made for this purpose. Quietly, we have become a nation on benzodiazepines. There are numerous reasons for this discrepancy between official recommendations on the one hand, and actual clinical practice on the other. Drawing from the literature, we argue that while patients and providers both shoulder some of the responsibility, they cannot be solely blamed. Rather, policies and guidelines regarding benzodiazepine prescribing have become out of touch with the clinical reality that benzodiazepines are now deeply entrenched in modern medicine. We propose that guidelines regarding benzodiazepines need to reconsider how to apply concepts such as harm reduction and other lessons learned in the opioid epidemic in order to help physicians manage this increasingly pressing problem affecting millions of Americans.

Outcome of Patients with Common Endocrine Diseases Who Had COVID-19 in two Centers in Lagos, Nigeria: A Cross-Sectional Study.

BACKGROUND: Endocrine diseases are ubiquitous. In our environment, diabetes mellitus (DM), obesity and thyroid disorders represent the most common examples. Diabetes mellitus is a global health problem with a myriad of complications. We sought to evaluate outcome in terms of fatality in those with common endocrine diseases who were infected with COVID-19. AIMS AND OBJECTIVES: To determine outcome in terms of mortality in patients with common endocrine diseases who contracted COVID-19. MATERIALS AND METHODS: We conducted an observational, descriptive, cross-sectional study with 120 participants drawn from the endocrinology/DM clinic at the Lagos University Teaching Hospital and Serenity Hospital, Surulere (a private medical clinic). Data collected included age, gender, type of endocrine disease, comorbid diseases, and COVID-19 status. Through charts from the medical records department, outcome of participants in terms of mortality was determined. RESULTS: Data of 120 subjects were analyzed. There were 61males and 59 females, yielding a male:female ratio of 1:1. Mean age was 58 years and the mode was 46 years. Over half (88) of the patients had diabetes mellitus, 22 had obesity, and 17 had thyroid disorders. The case fatality rate of patients with endocrine diseases who had COVID-19 was 11%, with about 85% of these deaths occurring in the elderly (those aged above 60 years). Ninety-two percent of the patients who died had type 2 DM. Approximately 80% of patients who were infected with COVID-19 had at least one co-morbid disease. CONCLUSION: Older age, type 2 diabetes mellitus, and the presence of at least one comorbidity were associated with increased mortality in patients with endocrine diseases who were infected with COVID-19 in our study.

CONTEXTE: Les maladies endocriniennes sont omniprésentes. Dans notre environnement, le diabète sucré, l'obésité et les troubles thyroïdiens en sont les exemples les plus courants. Le diabète est un problème de santé mondial qui s'accompagne d'une myriade de complications. Nous avons cherché à évaluer l'issue en termes de mortalité chez les personnes atteintes de maladies endocriniennes courantes qui ont été infectées par COVID-19. BUTS ET OBJECTIFS: Déterminer l'issue en termes de mortalité chez les patients atteints de maladies endocriniennes courantes qui ont contracté COVID 19. MATÉRIEL ET MÉTHODOLOGIES: Nous avons mené une étude observationnelle, descriptive et transversale auprès de 120 participants provenant de la clinique d'endocrinologie/DM de l'hôpital universitaire de Lagos et de l'hôpital Serenity, Surulere (clinique médicale privée). Les données recueillies comprenaient l'âge, le sexe, le type de maladie endocrinienne, les maladies concomitantes et le statut COVID-19. Les résultats des participants en termes de mortalité ont été déterminés à partir des dossiers médicaux. RÉSULTATS: Les données de 120 sujets ont été analysées. Il y avait 61 hommes et 59 femmes, avec un ratio homme/femme de 1:1. L'âge moyen était de 58 ans, le mode de 46 ans. Plus de la moitié [88] des patients souffraient de diabète sucré. 22 patients souffraient d'obésité et 17 de troubles thyroïdiens. Le taux de létalité des patients souffrant de maladiesendocriniennes et atteints de COVID-19 était de 11 %, 85 % de ces décès survenant chez des personnes âgées, c'est-à-dire de plus de 60 ans. 92 % des patients décédés souffraient de diabète de type 2. Environ 80 % des patients infectés par COVID-19 présentaient au moins une maladie concomitante. CONCLUSION: L'âge avancé, le diabète de type 2, la présence d'au moins une comorbidité sont associés à une mortalité accrue chez les patients atteints de maladies endocriniennes et infectés par COVID-19 dans notre étude. Mots-clés: Maladies endocriniennes, COVID-19, comorbidités, syndrome métabolique.

Mapping the corticoreticular pathway from cortex-wide anterograde axonal tracing in the mouse.

The corticoreticular pathway (CRP) has been implicated as an important mediator of motor recovery and rehabilitation after central nervous system damage. However, its origins, trajectory and laterality are not well understood. This study mapped the mouse CRP in comparison with the corticospinal tract (CST). We systematically searched the Allen Mouse Brain Connectivity Atlas (© 2011 Allen Institute for Brain Science) for experiments that used anterograde tracer injections into the right isocortex in mice. For each eligible experiment (N = 607), CRP and CST projection strength were quantified by the tracer volume reaching the reticular formation motor nuclei (RFmotor ) and pyramids, respectively. Tracer density in each brain voxel was also correlated with RFmotor versus pyramids projection strength to explore the relative trajectories of the CRP and CST. We found significant CRP projections originating from the primary and secondary motor cortices, anterior cingulate, primary somatosensory cortex, and medial prefrontal cortex. Compared with the CST, the CRP had stronger projections from each region except the primary somatosensory cortex. Ipsilateral projections were stronger than contralateral for both tracts (above the pyramidal decussation), but the CRP projected more bilaterally than the CST. The estimated CRP trajectory was anteromedial to the CST in the internal capsule and dorsal to the CST in the brainstem. Our findings reveal a widespread distribution of CRP origins and confirm strong bilateral CRP projections, theoretically increasing the potential for partial sparing after brain lesions and contralesional compensation after unilateral injury.

Relationship between ocular surface disease and patient's satisfaction among cataract surgical patients in Nigeria.

PURPOSE: To determine the effect of clinical and cytological features of ocular surface disease on patient's satisfaction following small incision cataract surgery at a tertiary eye care centre. METHOD: This is a prospective observational study of 70 consecutive consenting patients who underwent manual small incision cataract surgery(MSICS) at a tertiary eye care centre. All participants underwent ocular surface profile assessment using Schirmer I test (ST1), tear film break-up time (TBUT), conjunctival impression cytology (CIC) and ocular surface disease index (OSDI) at pre-operative visit, 1-week and 4-week post-operative visit. Patient's satisfaction with surgical outcome was evaluated at 6-week post-operative visit using a rating scale of 1 to 10. Data were analysed using IBM Statistical Package for the Social Sciences (SPSS) version 20.0 (IBM Corp., Armonk, NY USA). RESULTS: The mean age was 68 ± 9.4 years with a male/female ratio of 1:1.1. The mean OSDI score decreased significantly (p < 0.001) from 33.1 ± 8.4 pre-operatively to 20.8 ± 7.4 four weeks after surgery. The TBUT was 12 ± 4.1 s pre-operatively, but significantly reduced to 11.2 ± 3.9 s (p < 0.001) at 4-week post-operative period. At 6 weeks, patients with normal CIC reduced from 53 (75.8%) pre-operatively to 8 (11.4%) (p < 0.001, z = - 7.24). Fifty percent of patients with severe post-operative ocular surface disease reported dissatisfaction with their surgical outcome (p = 0.024). CONCLUSION: Manual small incision cataract surgery can significantly impair the ocular surface health profile of patients. The presence of ocular surface disease in patients pre-operatively can negatively impact their level of satisfaction with surgical outcome.

Extended Motor Evoked Potentials Monitoring Helps Prevent Delayed Paraplegia After Aortic Surgery.

OBJECTIVE: Motor evoked potentials (MEPs) monitoring can promptly detect spinal cord ischemia (SCI) from aortic clamping during open thoracoabdominal aneurysm repair (OTAAR) with distal aortic perfusion (DAP) and thus help decrease the risk of immediate postoperative SCI (IP-SCI). However, neither stable MEPs during aortic clamp interval (ACI) nor absence of IP-SCI eliminate the possibility of delayed postoperative SCI (DP-SCI). We hypothesized that extension of MEPs monitoring beyond ACI can also help decrease the risk of DP-SCI. METHODS: We identified 150 consecutive patients at our institution between April 2005 and October 2014 who underwent OTAAR with DAP and MEPs monitoring and had no IP-SCI. Using logistic regression analysis, we studied the independent effect of extended MEPs monitoring on the risk of developing DP-SCI. We used a propensity score analysis to adjust for potential confounders, such as poorly controlled hypertension, previous aneurysm surgery, splenectomy, acute aortic dissection, aneurysm type, older age, and history of diabetes and smoking. RESULTS: From the 150 patients, 129 (86%) remained neurologically intact whereas 21 (14%) developed DP-SCI. Nineteen of these twenty-one patients (90%) had no extended monitoring. Fifty-seven of fifty-nine (97%) patients who benefited from extended monitoring had no DP-SCI (p = 0.003). Extended MEPs monitoring was independently associated with decreased risk of DP-SCI (odds ratio = 0.14; 95% confidence interval: 0.03, 0.65; p = 0.01). INTERPRETATION: MEPs detect the lowest systemic blood pressure that ensures appropriate spinal cord perfusion in the postoperative period. Thus, they inform the hemodynamic management of patients post-OTAAR, particularly in the absence of a reliable neurological exam.

Early Rehabilitation After Stroke: a Narrative Review.

PURPOSE OF REVIEW: Despite current rehabilitative strategies, stroke remains a leading cause of disability in the USA. There is a window of enhanced neuroplasticity early after stroke, during which the brain's dynamic response to injury is heightened and rehabilitation might be particularly effective. This review summarizes the evidence of the existence of this plastic window, and the evidence regarding safety and efficacy of early rehabilitative strategies for several stroke domain-specific deficits. RECENT FINDINGS: Overall, trials of rehabilitation in the first 2 weeks after stroke are scarce. In the realm of very early mobilization, one large and one small trial found potential harm from mobilizing patients within the first 24 h after stroke, and only one small trial found benefit in doing so. For the upper extremity, constraint-induced movement therapy appears to have benefit when started within 2 weeks of stroke. Evidence for non-invasive brain stimulation in the acute period remains scant and inconclusive. For aphasia, the evidence is mixed, but intensive early therapy might be of benefit for patients with severe aphasia. Mirror therapy begun early after stroke shows promise for the alleviation of neglect. Novel approaches to treating dysphagia early after stroke appear promising, but the high rate of spontaneous improvement makes their benefit difficult to gauge. The optimal time to begin rehabilitation after a stroke remains unsettled, though the evidence is mounting that for at least some deficits, initiation of rehabilitative strategies within the first 2 weeks of stroke is beneficial. Commencing intensive therapy in the first 24 h may be harmful.

Molecular epidemiology of Avian Rotaviruses Group A and D shed by different bird species in Nigeria.

BACKGROUND: Avian rotaviruses (RVs) cause gastrointestinal diseases of birds worldwide. However, prevalence, diversity, epidemiology and phylogeny of RVs remain largely under-investigated in Africa. METHODS: Fecal samples from 349 birds (158 symptomatic, 107 asymptomatic and 84 birds without recorded health status) were screened by reverse transcription PCR to detect RV groups A and D (RVA and RVD). Partial gene sequences of VP4, VP6, VP7 and NSP4 for RVA, and of VP6 and VP7 for RVD were obtained and analyzed to infer phylogenetic relationship. Fisher's exact test and logistic regression were applied to identify factors potentially influencing virus shedding in chickens. RESULTS: A high prevalence of RVA (36.1%; 126/349) and RVD (31.8%; 111/349) shedding was revealed in birds. In chickens, RV shedding was age-dependent and highest RVD shedding rates were found in commercial farms. No negative health effect could be shown, and RVA and RVD shedding was significantly more likely in asymptomatic chickens: RVA/RVD were detected in 51.9/48.1% of the asymptomatic chickens, compared to 18.9/29.7% of the symptomatic chickens (p < 0.001/p = 0.01). First RVA sequences were obtained from mallard ducks (Anas platyrhynchos) and guinea fowls (Numida meleagris). Phylogenetic analyses illustrated the high genetic diversity of RVA and RVD in Nigerian birds and suggested cross-species transmission of RVA, especially at live bird markets. Indeed, RVA strains highly similar to a recently published fox rotavirus (RVA/Fox-tc/ITA/288356/2011/G18P[17]) and distantly related to other avian RVs were detected in different bird species, including pigeons, ducks, guinea fowls, quails and chickens. CONCLUSION: This study provides new insights into epidemiology, diversity and classification of avian RVA and RVD in Nigeria. We show that cross-species transmission of host permissive RV strains occurs when different bird species are mixed.

Indoor mold levels and current asthma among school-aged children in Saskatchewan, Canada.

Current knowledge regarding the association between indoor mold exposures and asthma is still limited. The objective of this case-control study was to investigate the relationship between objectively measured indoor mold levels and current asthma among school-aged children. Parents completed a questionnaire survey of health history and home environmental conditions. Asthma cases had a history of doctor-diagnosed asthma or current wheeze without a cold in the past 12 months. Controls were age- and sex-matched to cases. Vacuumed dust samples were collected from the child's indoor play area and mattress. Samples were assessed for mold levels and quantified in colony-forming units (CFU). Sensitization to mold allergens was also determined by skin testing. Being a case was associated with family history of asthma, pet ownership, and mold allergy. Mold levels (CFU/m2 ) in the dust samples of children's mattress and play area floors were moderately correlated (r = 0.56; P < 0.05). High mold levels (≥30 000 CFU/m2 ) in dust samples from play [adjusted odds ratio (aOR) = 2.6; 95% CI: 1.03-6.43] and mattress (aOR) = 3.0; 95% CI: 1.11-8.00) areas were significantly associated with current asthma. In this study high levels of mold are a risk factor for asthma in children.

Metal uptake, oxidative stress and histopathological alterations in gills and hepatopancreas of Callinectes amnicola exposed to industrial effluent.

Metal uptake by biota due to elevated environmental concentrations elicits oxidative stress and could lead to pathological outcomes. The relationship between the histopathological profile of hepatopancreas and gills and altered biochemical features (antioxidant enzymes i.e. GSH, GPx, CAT, SOD, lipid peroxidation (MDA) and serum protein) in the blue crab, Callinectes amnicola from contaminated parts of the Lagos Lagoon was investigated. Monthly crab, sediment and surface water samples were taken from effluent receiving areas of the Lagos lagoon i.e. Makoko, Okobaba, Iddo, Ikoyi and Mid-lagoon (control site) over an 18-month period and analyzed for metal levels (Pb, Cd, Zn and Cu). Significantly higher levels of GPx and lower levels of Pb, Zn and Cu was recorded in gills and hepatopancreas of crabs from the mid-lagoon compared to crabs from other sites. Reaction patterns of gills across the different sites of the lagoon included regressive (ranging from epithelial lifting, disruption of pilaster cells, detached cuticle to focal necrosis) and circulatory disruptions (oedema); increased activity of GSH and GPx in gills were positively correlated with lesions of lower importance factor. Reaction patterns in hepatopancreas were more regressive including vacuolation/infiltration of fatty lobules, necrosis, granuloma, disintegrated lumen, atrophied tubules and loss of lobular hepatocyte structure; increased activity of GSH, GPx and CAT were positively correlated with lesions of low importance factor in the hepatopancreas. Findings show that lesions in both gills and hepatopancreas of the blue crab could be associated with uptake of metals, depleted antioxidant activity and incidence of lipid peroxidation in tissue.

Effect of resilient lining of obturator bulbs on patients with maxillectomies.

STATEMENT OF PROBLEM: Poly(methyl methacrylate) (PMMA) obturator bulbs are hard and nonresilient. The relief for these obturators limits the support available for the bulbs and may limit mastication on the side with the resection. Resilient liners may improve mastication by gaining greater support from closer contact with tissues within the defects. PURPOSE: The purpose of this crossover clinical trial was to compare masticatory function scores of individuals with maxillectomies rehabilitated by using all-PMMA and PMMA obturator bulbs lined with resilient silicone. MATERIAL AND METHODS: Twelve participants with maxillectomies were provided with 2 definitive obturator dentures after initial rehabilitation. One of the obturator dentures had a hollow obturator bulb in all-PMMA, while the other had a hollow-core PMMA with an outer layer of silicone-resilient liner. Participants wore each obturator for a 2-week period without washout. Masticatory function on the rehabilitated sides was assessed by using an adapted Sato questionnaire. Statistical analysis was performed by using paired t test results of mean masticatory function scores (α=.05). RESULTS: Participants found 98.35% of the foodstuffs easy to masticate on the dentate sides. An average of 60.40% of the participants found the foodstuffs easy to masticate on the rehabilitated sides with the silicone-lined obturators. 18.35% of participants found the foodstuffs easy to masticate with the all-PMMA obturators (P<.05). CONCLUSIONS: Resilient lining of PMMA resin obturator bulbs significantly improved masticatory ability in rehabilitated areas of the mouth.

Positron emission tomography in the evaluation of pulmonary nodules among patients living in a coccidioidal endemic region.

BACKGROUND: Within a coccidioidal endemic region, pulmonary nodules due to coccidioidomycosis are common. Uptake of (18)fluorodeoxyglucose ((18)FDG) by positron emission tomography with computed axial tomography (PET/CT) has been used to assess whether pulmonary nodules are malignant but inflammatory lesions can be positive. The purpose of this study was to compare by PET/CT the (18)FDG uptake in pulmonary nodules likely due to coccidioidomycosis to that of nodules shown to be malignant among patients living in a coccidioidal endemic region. METHODS: We retrospectively reviewed patients who underwent a PET/CT at the Southern Arizona Veterans Affairs Health Care System between January 2008 and March 2012 who were subsequently found on biopsy to have pulmonary nodules that were coccidioidal or granulomatous or were due to malignancy. RESULTS: Among 245 diagnostic biopsies where the subject had a previous PET/CT, 15 (6.1 %) were either coccidioidal (n = 12) or granulomatous without an identified organism (n = 3). The median maximum standard unit of uptake (SUV(max)) on PET/CT of coccidioidal or granulomatous lesions was 2.0 compared to 9.8 for malignant lesions (P < 0.001). The maximum diameter of the coccidioidal or granulomatous nodules was 2.1 cm compared to 3.0 cm for the malignant lesions (P = 0.009). On multivariable analysis, an elevated SUV(max) was the only distinguishing feature between the malignant and the granulomatous lesions (OR 1.28, 95 % CI 1.05-1.55; P = 0.013). CONCLUSIONS: Coccidioidal pulmonary nodules take up significantly less (18)FDG than those due to malignancies, but there is considerable overlap between granulomatous and malignant lesions at lower SUV(max).

Production and characterization of low-density silicon nitride reinforced zinc nanocomposite coatings on mild steel for applications in marine and automotive industries.

In today's automotive, marine and petrochemical industries, the desire for lightweight materials has increased. Hence, necessitating the production of components with low density. In this work, lightweight Zn-Si3N4 coatings were developed by including Si3N4 in the zinc matrix. The optimal coatings were produced on steel samples at 45 °C and varied Si3N4 particles and voltages following ASTM A53/A53M standard. The deterioration (corrosion) property i.e. corrosion rate (CR) and current density (jocorr) of the uncoated (control) and coated samples were examined in 0.5 M of sulphuric acid using a potentiodynamic polarization technique following ASTM G3/G102 standard. The microstructure of the samples was studied via the SEM micrographs and XRD patterns, while the wear performance resistance (following ASTM G99 standard) and electrical conductivity of the samples were examined with a pin-on-disc tribometer and ammeter-voltmeter. The corrosion experiment indicated that the uncoated mild steel specimen possessed a CR of 12.345 mm year-1 and jocorr of 1060 µA/cm2, while the CR and jcorr of the coated samples ranged from 2.6793 to 4.7975 mm year-1 and 231-413 µA/cm2, respectively. The lower CR and jcorr values of the coated specimens, relative to the coated sample showed that the coatings possessed superior passivation ability in the test medium. The SEM micrographs of the samples showed refined morphology, while the XRD patterns revealed high peak intensity crystals such as Zn4SiN, ZnNSi, Zn4N and Zn2NSi, which could be beneficial to the mechanical properties and corrosion resistance of the steel. Moreover, the wear resistance study indicated that the COF of the uncoated sample ranged from 0.1 to 0.5, while those for coated specimens ranged from 0.05 to 0.35. Similarly, the uncoated steel exhibited a wear volume (WV) of 0.00508 mm3, while the WV of the coated specimens ranged from 0.00266 to 0.0028 mm3, indicating the existence of high strengthening mechanisms between the interface of the protecting device and the steel. Also, the electrical conductivity of the mild steel sample reduced from 12.97 Ω-1cm-1 to 0.64 Ω-1cm-1, indicating that the electrical resistivity of the steel was enhanced by the coatings.

Evaluating the Neural Underpinnings of Motivation for Walking Exercise.

OBJECTIVE: Motivation is critically important for rehabilitation, exercise, and motor performance, but its neural basis is poorly understood. Recent correlational research suggests that the dorsomedial prefrontal cortex (dmPFC) may be involved in motivation for walking activity and/or descending motor output. This study experimentally evaluated brain activity changes in periods of additional motivation during walking exercise and tested how these brain activity changes relate to self-reported exercise motivation and walking speed. METHODS: Adults without disability (N = 26; 65% women; 25 [standard deviation = 5] years old) performed a vigorous exercise experiment involving 20 trials of maximal speed overground walking. Half of the trials were randomized to include "extra-motivation" stimuli (lap timer, tracked best lap time, and verbal encouragement). Wearable near-infrared spectroscopy measured oxygenated hemoglobin responses from frontal lobe regions, including the dmPFC, primary sensorimotor, dorsolateral prefrontal, anterior prefrontal, supplementary motor, and dorsal premotor cortices. RESULTS: Compared with standard trials, participants walked faster during extra-motivation trials (2.43 vs 2.67 m/s; P < .0001) and had higher oxygenated hemoglobin responses in all tested brain regions, including dmPFC (+842 vs +1694 µM; P < .0001). Greater dmPFC activity was correlated with more self-determined motivation for exercise between individuals (r = 0.55; P = .004) and faster walking speed between trials (r = 0.18; P = .0002). dmPFC was the only tested brain region that showed both of these associations. CONCLUSION: Simple motivational stimuli during walking exercise seem to upregulate widespread brain regions. Results suggest that dmPFC may be a key brain region linking affective signaling to motor output. IMPACT: These findings provide a potential biologic basis for the benefits of motivational stimuli, elicited with clinically feasible methods during walking exercise. Future clinical studies could build on this information to develop prognostic biomarkers and test novel brain stimulation targets for enhancing exercise motivation (eg, dmPFC).

Characterizing the Longitudinal Impact of Backward Locomotor Treadmill Training on Walking and Balance Outcomes in Chronic Stroke Survivors: A Randomized Single Center Clinical Trial.

Background and Purpose: Walking and balance impairments after stroke are a global health concern, causing significant morbidity and mortality. However, effective strategies for achieving meaningful recovery in the chronic stages are limited. Backward locomotor treadmill training (BLTT) is a novel walking rehabilitation protocol that is safe, feasible, and likely beneficial in stroke survivors; however, its efficacy has not been tested. This single-center, randomized, assessor-blind clinical trial aims to test the preliminary efficacy of BLTT compared to forward locomotor treadmill training (FLTT) on walking speed, symmetry, and postural stability. Methods: Forty stroke survivors [BLTT (N=19), FLTT (N=21); mean age= 56.3 ± 8.6 years; 53% Female; 30% Non-Hispanic Black] with mild-moderate walking impairment were enrolled. Participants underwent nine 30-minute BLTT or FLTT sessions over three weeks. The primary outcome was the mean change in the 10-meter walk test (10 MWT) at 24 hours post-training (24 hr POST). Secondary outcome measures were changes in spatiotemporal walking symmetry and postural stability during quiet standing at 24 hr POST. Retention was explored at Days 30- and 90 POST. Results: We report clinically meaningful (≥ 0.16 m/s) improvements in overground walking speed at 24 hr POST, with retention up to Day 90 POST with BLTT and FLTT. However, contrary to our working hypothesis, no between-group differences in walking speed were observed. Nonetheless, we found that BLTT resulted in offline improvements in spatial symmetry and retention of subcomponents of the modified clinical test of sensory interaction on balance (mCTSIB), including the testing of proprio-vestibular integration up to Day 30 POST. Conclusion: Among chronic stroke patients with mild-moderate walking impairment, BLTT and FLTT both resulted in long-lasting and clinically meaningful improvement in walking speed. However, preliminary findings suggest that BLTT may better comprehensively target walking asymmetry and sensory systems processing and integration.

Normative concentrations of urine thiocyanate in cassava eating communities in Nigeria.

Exposure to cyanide is a major public health problem where highly cyanogenic cassava foods are consumed. Thiocyanate (SCN), the biomarker of exposure to cyanide is present in several foods, and produced endogenously. Concentrations of urine SCN were measured in endemic and non-endemic areas of ataxic polyneuropathy in Nigeria. Cassava food consumption in the endemic area was twice that of non-endemic areas. Geometrical mean (95% CI) urine SCN was 20 µmol/l (18-24) for no consumption of cassava foods, 56 µmol/l (49-64) for daily consumption, 56 µmol/l (48-65) for twice daily consumption and 85 µmol/l (62-117) for thrice daily consumption. 95th percentile reference limit was 125 µmol/l for no consumption of cassava food, but 360 µmol/l for thrice daily consumption. Urine SCN is a useful biomarker of exposure to cyanide from cassava foods. There is strong ecological association of exposure to cyanide and endemicity of ataxic polyneuropathy.

Insufficiencies in sensory systems reweighting is associated with walking impairment severity in chronic stroke: an observational cohort study.

Background: Walking and balance impairment are common sequelae of stroke and significantly impact functional independence, morbidity, and mortality. Adequate postural stability is needed for walking, which requires sufficient integration of sensory information between the visual, somatosensory, and vestibular centers. "Sensory reweighting" describes the normal physiologic response needed to maintain postural stability in the absence of sufficient visual or somatosensory information and is believed to play a critical role in preserving postural stability after stroke. However, the extent to which sensory reweighting successfully maintains postural stability in the chronic stages of stroke and its potential impact on walking function remains understudied. Methods: In this cross-sectional study, fifty-eight community-dwelling ambulatory chronic stroke survivors underwent baseline postural stability testing during quiet stance using the modified Clinical test of Sensory Interaction in Balance (mCTSIB) and assessment of spatiotemporal gait parameters. Results: Seventy-six percent (45/58) of participants showed sufficient sensory reweighting with visual and somatosensory deprivation for maintaining postural stability, albeit with greater postural sway velocity indices than normative data. In contrast, survivors with insufficient reweighting demonstrated markedly slower overground walking speeds, greater spatiotemporal asymmetry, and limited acceleration potential. Conclusion: Adequate sensory system reweighting is essential for chronic stroke survivors' postural stability and walking independence. Greater emphasis should be placed on rehabilitation strategies incorporating multisensory system integration testing and strengthening as part of walking rehabilitation protocols. Given its potential impact on outcomes, walking rehabilitation trials may benefit from incorporating formal postural stability testing in design and group stratification.

Optimal Intensity and Duration of Walking Rehabilitation in Patients With Chronic Stroke: A Randomized Clinical Trial.

Importance: For walking rehabilitation after stroke, training intensity and duration are critical dosing parameters that lack optimization. Objective: To assess the optimal training intensity (vigorous vs moderate) and minimum training duration (4, 8, or 12 weeks) needed to maximize immediate improvement in walking capacity in patients with chronic stroke. Design, Setting, and Participants: This multicenter randomized clinical trial using an intent-to-treat analysis was conducted from January 2019 to April 2022 at rehabilitation and exercise research laboratories. Survivors of a single stroke who were aged 40 to 80 years and had persistent walking limitations 6 months or more after the stroke were enrolled. Interventions: Participants were randomized 1:1 to high-intensity interval training (HIIT) or moderate-intensity aerobic training (MAT), each involving 45 minutes of walking practice 3 times per week for 12 weeks. The HIIT protocol used repeated 30-second bursts of walking at maximum safe speed, alternated with 30- to 60-second rest periods, targeting a mean aerobic intensity above 60% of the heart rate reserve (HRR). The MAT protocol used continuous walking with speed adjusted to maintain an initial target of 40% of the HRR, progressing up to 60% of the HRR as tolerated. Main Outcomes and Measures: The main outcome was 6-minute walk test distance. Outcomes were assessed by blinded raters after 4, 8, and 12 weeks of training. Results: Of 55 participants (mean [SD] age, 63 [10] years; 36 male [65.5%]), 27 were randomized to HIIT and 28 to MAT. The mean (SD) time since stroke was 2.5 (1.3) years, and mean (SD) 6-minute walk test distance at baseline was 239 (132) m. Participants attended 1675 of 1980 planned treatment visits (84.6%) and 197 of 220 planned testing visits (89.5%). No serious adverse events related to study procedures occurred. Groups had similar 6-minute walk test distance changes after 4 weeks (HIIT, 27 m [95% CI, 6-48 m]; MAT, 12 m [95% CI, -9 to 33 m]; mean difference, 15 m [95% CI, -13 to 42 m]; P = .28), but HIIT elicited greater gains after 8 weeks (58 m [95% CI, 39-76 m] vs 29 m [95% CI, 9-48 m]; mean difference, 29 m [95% CI, 5-54 m]; P = .02) and 12 weeks (71 m [95% CI, 49-94 m] vs 27 m [95% CI, 3-50 m]; mean difference, 44 m [95% CI, 14-74 m]; P = .005) of training; HIIT also showed greater improvements than MAT on some secondary measures of gait speed and fatigue. Conclusions and Relevance: These findings show proof of concept that vigorous training intensity is a critical dosing parameter for walking rehabilitation. In patients with chronic stroke, vigorous walking exercise produced significant and meaningful gains in walking capacity with only 4 weeks of training, but at least 12 weeks were needed to maximize immediate gains. Trial Registration: ClinicalTrials.gov Identifier: NCT03760016.