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Background Stroke survivors experience chronic gait impairments, so rehabilitation has focused on restoring ambulatory capacity. High-intensity speed-based treadmill training (HISTT) is one form of walking rehabilitation that can improve walking, but its effectiveness has not been thoroughly investigated. Additionally, cortical priming with transcranial direct current stimulation (tDCS) and movement may enhance HISTT-induced improvements in walking, but there have been no systematic investigations. The objective of this study was to determine if motor priming can augment the effects of HISTT on walking in chronic stroke survivors. Methods Eighty-one chronic stroke survivors participated in a controlled trial with stratification into four groups: 1) control–15 min of rest ( n  = 20), 2) tDCS–15 min of stimulation-based priming with transcranial direct current stimulation ( n  = 21), 3) ankle motor tracking (AMT)–15 min of movement-based priming with targeted movements of the ankle and sham tDCS ( n  = 20), and 4) tDCS+AMT–15 min of concurrent tDCS and AMT (n = 20). Participants performed 12 sessions of HISTT (40 min/day, 3 days/week, 4 weeks). Primary outcome measure was walking speed. Secondary outcome measures included corticomotor excitability (CME). Outcomes were measured at pre, post, and 3-month follow-up assessments. Results HISTT improved walking speed for all groups, which was partially maintained 3 months after training. No significant difference in walking speed was seen between groups. The tDCS+AMT group demonstrated greater changes in CME than other groups. Individuals who demonstrated up-regulation of CME after tDCS increased walking speed more than down-regulators. Conclusions Our results support the effectiveness of HISTT to improve walking; however, motor priming did not lead to additional improvements. Upregulation of CME in the tDCS+AMT group supports a potential role for priming in enhancing neural plasticity. Greater changes in walking were seen in tDCS up-regulators, suggesting that responsiveness to tDCS might play an important role in determining the capacity to respond to priming and HISTT. Trial registration ClinicalTrials.gov , NCT03492229. Registered 10 April 2018 – retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03492229 .

Objective Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with limited treatment options. Transcranial direct current stimulation (tDCS) shows promise as a neuromodulatory intervention in various neurological disorders, but its application in ALS, particularly in a remote, home‐based format, remains underexplored. This study investigates the feasibility, safety, and preliminary efficacy of remotely supervised tele‐tDCS in ALS patients. Methods This double‐blinded pilot study included 14 spinal‐onset ALS participants randomized into two groups: the intervention group received 72 tele‐tDCS sessions over 24 weeks, and the delayed‐start group received 36 sham sessions followed by 36 tele‐tDCS sessions. Stimulation was delivered at 2 mA for 20 min 3 times a week. Primary outcomes included feasibility, safety, and disease progression measured by the ALS Functional Rating Scale‐Revised (ALSFRS‐R). Adherence and adverse effects were monitored throughout. Results Ten participants completed the study, with an overall compliance rate of 98.3%. No serious adverse events were reported, and mild side effects, like itching and tingling, were consistent with tDCS literature. The intervention group demonstrated a significantly slower decline in ALSFRS‐R scores than the delayed‐start group. At 24 weeks, the intervention group had a mean ALSFRS‐R change of −1.7, compared to −13.6 in the delayed‐start group (p = 0.0018). Additionally, the change in ALSFRS‐R between pre‐ and mid‐intervention significantly differed between groups (p = 0.0071). Interpretation Tele‐tDCS was feasible, safe, and well‐tolerated in individuals with ALS. Preliminary efficacy results suggest that tele‐tDCS may slow disease progression, underscoring the potential of tele‐tDCS as a promising home‐based neuromodulatory intervention in ALS management. Trial Registration: Clinical trial registration: NCT04866771

Abstract Introduction The inflammatory response of critical illness is accompanied by nonthyroidal illness syndrome (NTIS). Feeding has been shown to attenuate this process, but this has not been explored prospectively over time in critically ill patients. Objective To explore the impact of calorie exposure on NTIS over time in critically ill patients. Methods Mechanically ventilated patients with systemic inflammatory response syndrome (SIRS) were randomized to receive either 100% or 40% of their estimated caloric needs (ECN). Thyroid hormones were measured daily for 7 days or until intensive care unit discharge or death. Mixed level regression modeling was used to explore the effect of randomization group on plasma triiodothyronine (T3), reverse triiodothyronine (rT3), thyroxine (T4), and thyroid stimulating hormone (TSH), as well as the T3/rT3 ratio. Results Thirty-five participants (n=19 in 100% ECN; n=16 in 40% ECN) were recruited. Adjusting for group differences in baseline T3/rT3 ratio, the parameters defining the fitted curves (intercept, linear effect of study day, and quadratic effect of study day) differed by randomization group (P = 0.001, P = 0.01, and P = 0.02 respectively). Plots of the fitted curves revealed that participants in the 100% ECN group had a 54% higher T3/rT3 ratio on postintervention day 1 compared with the 40% ECN group, a difference which attenuated over time. This was driven by a 23% higher plasma T3 and 10% lower plasma rT3 levels on postintervention 1. Conclusions Higher caloric exposure in NTIS patients transiently attenuates the drop of the plasma T3/rT3 ratio, an effect that is minimized and finally lost over the following 3 days of continued higher caloric exposure.

Background Alternate day modified fasting (ADMF) is an effective strategy for weight loss in obese adults. Objective The objective of this study was to examine the dietary and physical activity adaptations that occur during short-term ADMF, and to determine how these modulations affect rate of weight loss. Methods Sixteen obese subjects (12 women/4 men) completed a 10-week trial consisting of 3 phases: 1) 2-week control phase, 2) 4-week ADMF controlled feeding phase, and 3) 4-week ADMF self-selected feeding phase. Results Body weight decreased ( P < 0.001) by 5.6 ± 1.0 kg post-treatment. Energy intake on the fast day was 26 ± 3% of baseline needs (501 ± 28 kcal/d). No hyperphagic response occurred on the feed day (95 ± 6% of baseline needs consumed, 1801 ± 226 kcal/d). Daily energy restriction (37 ± 7%) was correlated to rate of weight loss ( r = 0.42, P = 0.01). Dietary fat intake decreased (36% to 33% of kcal, P < 0.05) with dietary counseling, and was related to rate of weight loss ( r = 0.38, P = 0.03). Hunger on the fast day decreased ( P < 0.05) by week 2, and remained low. Habitual physical activity was maintained throughout the study (fast day: 6416 ± 851 steps/d; feed day: 6569 ± 910 steps/d). Conclusion These findings indicate that obese subjects quickly adapt to ADMF, and that changes in energy/macronutrient intake, hunger, and maintenance of physical activity play a role in influencing rate of weight loss by ADMF.

Background: Transcranial direct current stimulation (tDCS) is emerging as a promising adjuvant to enhance motor function. However, there has been increasing reservations about the reliability and variability of the neuromodulatory effects evoked by tDCS. Objective/Hypothesis: The main purpose of this study was to explore the test-retest reliability and inter-individual variability of tDCS of the lower limb M1 and the relationship between transcranial magnetic stimulation (TMS)-related measures and tDCS-induced changes. Methods: Fifteen healthy participants received anodal tDCS of the lower limb M1 either when performing a lower limb motor task or when the limb was at rest. Each condition was tested twice. tDCS induced changes in corticomotor excitability of the tibialis anterior muscle were measured using TMS. A repeated measures ANOVA was performed to examine efficacy of tDCS between the two task conditions. Intraclass correlation coefficients (ICC) and variance component analyses were performed to examine reliability and variability respectively. Results: A significant increase in in corticomotor excitability was noted for the tDCS-task condition at 140% active motor threshold (AMT) and when comparing recruitment curve slopes, but not at 120% and 130% AMT. Overall, ICC values between testing days for each stimulation condition ranged from 0.6–0.9. Higher ICCs were seen for higher TMS intensities (140% AMT) and recruitment curve slopes. Inter-individual variability contributed to 34% of the exhibited variance. Conclusions: Our data suggest that the TMS-related measure used to assess neuromodulation after tDCS has an effect on its perceived test-retest reliability and inter-individual variability. Importantly, we noticed that a high reliability and low variability does not necessarily indicate clinical efficacy of tDCS as some participants showed little to no modulation of corticomotor excitability consistently.

Mothers who identify as Black or African American are more likely to report depressed moods in late pregnancy and early postpartum and have the lowest rates of human milk feeding compared with all other racial groups in the United States. Internet interventions offer the potential to extend preventative and supportive services as they address key barriers, particularly for those navigating the complex and vulnerable early postpartum period. However, there is limited evidence on the feasibility of such interventions for preventing perinatal mental health disorders and improving human milk feeding outcomes in Black mothers. This pilot study aimed to assess the feasibility and preliminary findings of a web-based cognitive behavioral therapy-based internet intervention, with and without human milk feeding education and support, to prevent perinatal depression and promote human milk feeding in Black mothers. Participants were Black-identifying individuals between 20 and 28 weeks of pregnancy with human milk feeding intention and mild to moderate depressive symptoms (Patient Health Questionnaire scores 5-14). Participants were randomized to either Sunnyside, a 6-week cognitive behavioral therapy-based web-based intervention, or Sunnyside Plus, which included additional education and support to promote human milk feeding. Assessments occurred at baseline, third trimester (end of antenatal treatment), 6 weeks postpartum (end of postpartum treatment), and 12 weeks postpartum. The primary focus of this randomized pilot trial was the feasibility and preliminary outcomes of mental health and human milk feeding. A total of 22 tertiary-educated participants were randomized. The mean number of log-ins was 7.3 (SD 5.3) for Sunnyside and 13.8 (SD 10.5) for Sunnyside Plus. Scores of depression and anxiety measures remained below the clinical threshold for referral to treatment in both groups. All the participants initiated human milk feeding (18/18, 100%). Most participants reported at least some human milk feeding at both 6 and 12 weeks postpartum (6/7, 86%; 11/11, 100%, or 10/10, 100%, for Sunnyside and Sunnyside Plus, respectively). The results suggest that tertiary-educated Black mothers at risk for perinatal depression and who intended to human milk feed were receptive to and satisfied with a web-based cognitive behavioral therapy-based internet intervention, with and without human milk feeding education and support. Preliminary findings indicate that both Sunnyside and Sunnyside Plus interventions have the potential to affect symptoms of depression, anxiety, and human milk feeding outcomes. ClinicalTrials.gov NCT04128202; https://www.clinicaltrials.gov/ct2/show/NCT04128202.

Background Studies have shown associations of diabetes and endogenous hormones with exposure to a wide variety of organochlorines. We have previously reported positive associations of polychlorinated biphenyls (PCBs) and inverse associations of selected steroid hormones with diabetes in postmenopausal women previously employed in a capacitor manufacturing plant. Methods This paper examines associations of PCBs with diabetes and endogenous hormones in 63 men previously employed at the same plant who in 1996 underwent surveys of their exposure and medical history and collection of bloods and urine for measurements of PCBs, lipids, liver function, hematologic markers and endogenous hormones. Results PCB exposure was positively associated with diabetes and age and inversely associated with thyroid stimulating hormone and triiodothyronine-uptake. History of diabetes was significantly related to total PCBs and all PCB functional groupings, but not to quarters worked and job score, after control for potential confounders. None of the exposures were related to insulin resistance (HOMA-IR) in non-diabetic men. Conclusions Associations of PCBs with specific endogenous hormones differ in some respects from previous findings in postmenopausal women employed at the capacitor plant. Results from this study, however, do confirm previous reports relating PCB exposure to diabetes and suggest that these associations are not mediated by measured endogenous hormones.

Background. Perineal pressure due to bicycle riding has been associated with erectile dysfunction. We developed a novel method to measure the occlusive force exerted over the perineal arteries and determined perineal artery occlusion by a variety of seat designs. Methods. Doppler ultrasonography facilitated perineal artery localization and determination of the force required for perineal artery occlusion in 20 healthy men. Flexiforce ® sensors were affixed over the proximal and distal aspects of the perineal arteries bilaterally. Individuals completed bicycle rides in the road- and stationary-settings with six distinct seat designs, including those with and without an anterior “nose.” Results. The occlusion time proportion of the total ride time was calculated for each trial. The overall occlusion time proportion was 0.59 (95% CI [0.45–0.73]) across all seats and settings. The “no-nose” bicycle seat and the stationary-setting demonstrated significantly lower occlusion proportion times than the traditional nose bicycle seat and road-setting, respectively. However, all bicycle seats yielded an occlusion time proportion of 0.41 or greater. Discussion. Our method of real-time, non-invasive force measurement localized to the perineal arteries may be used to validate future bicycle seat design. It also underscores the significant risk of perineal artery insufficiency in men who are avid bicyclists. This risk may be minimized by using newer “no-nose” bicycle seats.

Atrazine, a common water contaminant in the U.S., has been associated with adverse birth outcomes in previous studies. This study aimed to determine if atrazine concentrations in drinking water are associated with adverse birth outcomes including small for gestational age (SGA), term low birth weight (term LBW), very low birth weight (VLBW), preterm birth (PTB), and very preterm birth (VPTB). This study included 14,445 live singleton births from Ohio communities served by 22 water systems enrolled in the U.S. Environmental Protection Agency’s Atrazine Monitoring Program between 2006 and 2008. Mean gestational and trimester-specific atrazine concentrations were calculated. Significantly increased odds of term LBW birth was associated with atrazine exposure over the entire gestational period (OR 1.27, 95% CI 1.10, 1.45), as well as the first (OR 1.20, 95% CI 1.08, 1.34) and second trimesters (OR 1.13, 95% CI 1.07, 1.20) of pregnancy. We observed no evidence of an association between atrazine exposure via drinking water and SGA, VLBW, PTB, or VPTB. Our results suggest that atrazine exposure is associated with reduced birth weight among term infants and that exposure to atrazine in drinking water in early and mid-pregnancy may be most critical for its toxic effects on the fetus.

A mortality study of workers employed between 1944 and 1977 at an electrical capacitor manufacturing plant where polychlorinated biphenyh (PCBs), chlorinated naphthalenes, and other chemicals were used was undertaken. Age, gender, and calendar year-adjusted standardized mortality ratios (SMRs) were calculated for 2885 white workers. Total mortality and all-cancer mortality were similar to expected in both male and females. Females employed 10 or more years had a significantly elevated SMR of 6.2 for liver/biliary cancer. Intestinal cancer was significantly elevated in females employed 5 or more years after PCBs were introduced (SMR = 2.2). In males, stomach cancer (SMR = 2.2) and thyroid cancer (SMR = 15.2) were significantly elevated. Although individual exposure assessment was limited, PCBs alone or in combination with other chemicals could be associated with increased risks for liver/biliary, stomach, intestinal, and thyroid cancer.