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Recommendations for endurance exercise prescription are often based on percentages of heart rate (HR) or the volume of oxygen consumption (V˙O2) maximum or reserve that is extrapolated to a power output (P) or velocity. Previous work has demonstrated dissociations of the expected responses to exercise anchored to the critical heart rate (CHR) compared with the P associated with CHR. However, it is unclear if similar dissociations due to reductions in P to maintain the designated intensity would be present during exercise anchored to the V˙O2 associated with CHR (V˙O2CHR). The purpose of this study was to examine the patterns in physiological (V˙O2, HR, P, respiration rate [RR], muscle oxygen saturation [%SmO2]), neuromuscular (electromyographic and mechanomyographic amplitude [EMG AMP, MMG AMP], mean power frequency [EMG MPF, MMG MPF]), and perceptual (rating of perceived exertion [RPE]) responses during exercise at V˙O2CHR (V˙O2-clamp). On separate days, ten participants (age: 25 ± 4 yr) performed a graded exercise test and four constant P trials at 85–100% of peak P (PP) to derive CHR and V˙O2CHR. Responses were recorded during a trial to exhaustion at V˙O2CHR (32.86 ± 7.12 mL·kg−1·min−1; TLim = 31.31 ± 21.37 min) and normalized in 10% intervals of TLim to their respective values at PP. The one-way repeated-measures ANOVA with post hoc, Bonferroni-corrected, pairwise comparisons indicated differences (p < 0.001) from baseline for HR (mean ± SD %change = 8 ± 3%), RR (43 ± 38%), P (−15 ± 5%), EMG MPF (10 ± 8%), and RPE (65 ± 38%), but no differences (p = 0.077–0.955) for %SmO2 (−17 ± 53%), EMG AMP (−3 ± 16%), MMG AMP (40 ± 61%), and MMG MPF (1 ± 7%). The loss in performance observed during V˙O2-Clamp exercise may provide a quantification of the inefficiency associated with the V˙O2 slow component phenomenon. The neuromuscular responses suggested constant muscle excitation despite the reductions in P, but the metabolic and perceptual responses suggested a combination of feedforward and feedback mechanisms regulating TLim. Future studies should further examine responses to the V˙O2-Clamp exercise at a uniform threshold.

The outer membrane of gram-negative bacteria is a barrier to chemical and physical stress. Phospholipid transport between the inner and outer membranes has been an area of intense investigation and, in E. coli K-12, it has recently been shown to be mediated by YhdP, TamB, and YdbH, which are suggested to provide hydrophobic channels for phospholipid diffusion, with YhdP and TamB playing the major roles. However, YhdP and TamB have different phenotypes suggesting distinct functions. It remains unclear whether these functions are related to phospholipid metabolism. We investigated a synthetic cold sensitivity caused by deletion of fadR, a transcriptional regulator controlling fatty acid degradation and unsaturated fatty acid production, and yhdP, but not by ΔtamB ΔfadR or ΔydbH ΔfadR. Deletion of tamB recuses the ΔyhdP ΔfadR cold sensitivity further demonstrating the phenotype is related to functional diversification between these genes. The ΔyhdP ΔfadR strain shows a greater increase in cardiolipin upon transfer to the non-permissive temperature and genetically lowering cardiolipin levels can suppress cold sensitivity. These data also reveal a qualitative difference between cardiolipin synthases in E. coli, as deletion of clsA and clsC suppresses cold sensitivity but deletion of clsB does not. Moreover, increased fatty acid saturation is necessary for cold sensitivity and lowering this level genetically or through supplementation of oleic acid suppresses the cold sensitivity of the ΔyhdP ΔfadR strain. Together, our data clearly demonstrate that the diversification of function between YhdP and TamB is related to phospholipid metabolism. Although indirect regulatory effects are possible, we favor the parsimonious hypothesis that YhdP and TamB have differential phospholipid-substrate transport preferences. Thus, our data provide a potential mechanism for independent control of the phospholipid composition of the inner and outer membranes in response to changing conditions based on regulation of abundance or activity of YhdP and TamB.

Purpose: This work evaluates clinical-standard semantic memory assessments in monolingual Spanish-speaking Colombian adults with and without aphasia, addressing 2 aims: (1) to examine whether event semantic memory is related to object and action semantic memory performance; and (2) to explore whether clinical-standard semantic memory assessments can distinguish between Colombian adults with and without aphasia. Methods: Object, action, and event semantic memory clinical assessments were used evaluate 16 adults with aphasia and 16 matched controls from Colombia. Bayesian linear mixed-effects models were used to examine the 2 specific aims. Results: First, results replicated and extended findings that object and action deficits may contribute to event semantic memory impairments in aphasia. Second, results suggested that clinical-standard semantic memory assessments may distinguish between people with and without post-stroke aphasia in a Colombian sample. Conclusion: This work identifies the need to continue developing sociolinguistically sensitive neuropsychological assessments, which are critical for establishing valid cognitive models and improving clinical diagnostics and treatments in diverse populations of stroke survivors. Resumen: Propósito: Este trabajo busca examinar evaluaciones clínicas de memoria semántica en adultos monolingües hispanohablantes colombianos con y sin afasia. Se describen dos objetivos: (1) examinar si la memoria semántica de eventos se relaciona con la memoria semántica de objetos y acciones; y (2) explorar si las evaluaciones clínicas de memoria semántica pueden distinguir entre adultos colombianos con y sin afasia. Métodos: Se utilizaron evaluaciones clínicas de memoria semántica de objetos, acciones y eventos en 16 adultos con afasia y 16 controles de Colombia. Se utilizaron modelos bayesianos lineales de efectos mixtos para examinar los dos objetivos específicos. Resultados: Primero, nuestros resultados replican y amplían hallazgos previos que indican que los déficits de memoria semantica de objetos y acciones contribuyen a las alteraciones de la memoria semántica de eventos en personas con afasia. Segundo, nuestros resultados sugirieren que las evaluaciones de memoria semántica clínica pueden distinguir entre personas con y sin afasia en una muestra colombiana. Conclusión: Este trabajo resalta la necesidad de desarrollar evaluaciones neuropsicológicas que sean sociolingüísticamente apropiadas. Estas evaluaciones son críticas para establecer modelos cognitivos válidos para cada población, y para mejorar el diagnóstico y tratamiento de poblaciones diversas con afasia, sobrevivientes de accidentes cerebrovasculares.

Valproic acid (VPA) is a common anti-epileptic drug and known neurodevelopmental toxicant. Although the exact mechanism of VPA toxicity remains unknown, recent findings show that VPA disrupts redox signaling in undifferentiated cells but has little effect on fully differentiated neurons. Redox imbalances often alter oxidative post-translational protein modifications and could affect embryogenesis if developmentally critical proteins are targeted. We hypothesize that VPA causes redox-sensitive post-translational protein modifications that are dependent upon cellular differentiation states. Undifferentiated P19 cells and P19-derived neurons were treated with VPA alone or pretreated with D3T, an inducer of the nuclear factor erythroid 2-related factor 2 (NRF2) antioxidant pathway, prior to VPA exposure. Undifferentiated cells treated with VPA alone exhibited an oxidized glutathione redox couple and increased overall protein oxidation, whereas differentiated neurons were protected from protein oxidation via increased S-glutathionylation. Pretreatment with D3T prevented the effects of VPA exposure in undifferentiated cells. Taken together, our findings support redox-sensitive post-translational protein alterations in undifferentiated cells as a mechanism of VPA-induced developmental toxicity and propose NRF2 activation as a means to preserve proper neurogenesis.

Summary: Opioids prescribed for pain and migraine can produce opioid-induced hyperalgesia (OIH) or medication overuse headache (MOH). We previously demonstrated that pituitary adenylate cyclase activating polypeptide (PACAP) is upregulated in OIH and chronic migraine models. Here we determined if PACAP acts as a bridge between opioids and pain chronification. We tested PACAP-PAC1 receptor inhibition in novel models of opioid-exacerbated trigeminovascular pain. The PAC1 antagonist, M65, reversed chronic allodynia in a model which combines morphine with the migraine trigger, nitroglycerin. Chronic opioids also exacerbated cortical spreading depression, a correlate of migraine aura; and M65 inhibited this augmentation. In situ hybridization showed MOR and PACAP co-expression in trigeminal ganglia, and near complete overlap between MOR and PAC1 in the trigeminal nucleus caudalis and periaqueductal gray. PACAPergic mechanisms appear to facilitate the transition to chronic headache following opioid use, and strategies targeting this system may be particularly beneficial for OIH and MOH.

This study aimed to investigate the test–retest reliability, mean, and individual responses in the measurement of maximal oxygen consumption (V˙O2max) during a cardiopulmonary exercise test (CPET) and the verification phase during cycle ergometry in women. Nine women (22 ± 2 yrs, 166.0 ± 4.5 cm, 58.6 ± 7.7 kg) completed a CPET, passively rested for 5 min, and then completed a verification phase at 90% of peak power output to determine the highest V˙O2 from the CPET (V˙O2CPET) and verification phase (V˙O2verification) on 2 separate days. Analyses included a two-way repeated measures ANOVA, intraclass correlation coefficients (ICC2,1), standard errors of the measurement (SEM), minimal differences (MD), and coefficients of variation (CoV). There was no test (test 1 versus test 2) × method (CPET vs. verification phase) interaction (p = 0.896) and no main effect for method (p = 0.459). However, test 1 (39.2 mL·kg−1·min−1) was significantly higher than test 2 (38.3 mL·kg−1·min−1) (p = 0.043). The V˙O2CPET (ICC = 0.984; CoV = 1.98%; SEM = 0.77 mL·kg−1·min−1; MD = 2.14 mL·kg−1·min−1) and V˙O2verification (ICC = 0.964; CoV = 3.30%; SEM = 1.27 mL·kg−1·min−1; MD = 3.52 mL·kg−1·min−1) demonstrated “excellent” reliability. Two subjects demonstrated a test 1 V˙O2CPET that exceeded the test 2 V˙O2CPET, and one subject demonstrated a test 1 V˙O2verification that exceeded the test 2 V˙O2verification by more than the respective CPET and verification phase MD. One subject demonstrated a V˙O2CPET that exceeded the V˙O2verification, and one subject demonstrated a V˙O2verification that exceeded the V˙O2CPET by more than the MD. These results demonstrate the importance of examining the individual responses in the measurement of the V˙O2max and suggest that the MD may be a useful threshold to quantify real individual changes in V˙O2.

This study investigated the effects of fatiguing unilateral exercise on the ipsilateral, exercised, and contralateral, non-exercised limb’s post-exercise performance in males and females. Ten males and ten females performed a fatiguing, unilateral isometric leg extension at 50% maximal voluntary isometric contraction (MVIC) force. Prior to and immediately after the fatiguing tasks, MVICs were performed for the exercised and non-exercised limb, with surface electromyographic (sEMG) and mechanomyography (sMMG) amplitude (AMP) and mean power frequency (MPF) recorded from each limb’s vastus lateralis. There were no fatigue-induced, sex-dependent, differences in time to task failure (p = 0.265) or ipsilateral performance fatigability (p = 0.437). However, there was a limb by time interaction (p < 0.001) which indicated decreases in MVIC force of the ipsilateral, exercised (p < 0.001), but not the contralateral, non-exercised limb (p = 0.962). There were no sex-dependent, fatigue-induced differences in neurophysiological outcomes between the limbs (p > 0.05), but there was a fatigue-induced difference in sEMG MPF (p = 0.005). To summarize, there were no differences in fatigability between males and females. Moreover, there was insufficient evidence to support the presence of a general crossover effect following submaximal unilateral isometric exercise. However, independent of sex, the neurophysiological outcomes suggested that competing inputs from the nervous system may influence the performance of both limbs following unilateral fatigue.

Prenatal stress can alter postnatal performance and temperament of cattle. These phenotypic effects may result from changes in gene expression caused by stress-induced epigenetic alterations. Specifically, shifts in gene expression caused by DNA methylation within the brain’s amygdala can result in altered behavior because it regulates fear, stress response and aggression in mammals Thus, the objective of this experiment was to identify DNA methylation and gene expression differences in the amygdala tissue of 5-year-old prenatally stressed (PNS) Brahman cows compared to control cows. Pregnant Brahman cows (n = 48) were transported for 2-h periods at 60 ± 5, 80 ± 5, 100 ± 5, 120 ± 5, and 140 ± 5 days of gestation. A non-transported group (n = 48) were controls (Control). Amygdala tissue was harvested from 6 PNS and 8 Control cows at 5 years of age. Overall methylation of gene body regions, promoter regions, and cytosine-phosphate-guanine (CpG) islands were compared between the two groups. In total, 202 genes, 134 promoter regions, and 133 CpG islands exhibited differential methylation (FDR ≤ 0.15). Following comparison of gene expression in the amygdala between the PNS and Control cows, 2 differentially expressed genes were identified (FDR ≤ 0.15). The minimal differences observed could be the result of natural changes of DNA methylation and gene expression as an animal ages, or because this degree of transportation stress was not severe enough to cause lasting effects on the offspring. A younger age may be a more appropriate time to assess methylation and gene expression differences produced by prenatal stress.

Anxiety, depression, and suicidality are major concerns among college students, though less is known about these constructs in autistic college students. Given the rising number of autistic individuals entering post-secondary education, adequate measurement and diagnosis of anxiety, depression, and suicidality is necessary to provide clinical care to this population. While the Generalized Anxiety Disorder--7 (GAD-7) and Patient Health Questionnaire--9 (PHQ-9) are commonly used in university settings, these instruments have not been psychometrically evaluated in autistic college students. The current study examines the differential psychometric properties of the GAD-7 and PHQ-9 utilizing invariance testing via structural equation modeling in a sample of self-identified autistic (n = 477) and non-autistic (n = 429) university students. Results showed that although the GAD-7 is invariant, the PHQ-9 was mostly invariant, with one item displaying non-invariance. Specifically, the PHQ-9 item assessing suicidality was found to be non-invariant at the metric level, indicating that autistic and non-autistic college students interpret this question differently. Future investigators should continue to assess the appropriateness of using common screening measures, originally created for non-autistic people, in autistic populations.

Caregivers of children with autism spectrum disorder (ASD) often report higher rates of depression and the related negative thought patterns that may precede a clinical diagnosis. These negative thought patterns are referred to as depressive cognitions. Depressive cognitions are exacerbated by child problem behaviors (CPB) but may be impacted by parental resilience. The current study examines relations between CPB and depressive cognitions and the role of resilience as a moderator among caregivers of children with ASD (n = 287) and a sample of caregivers of children who are typically developing (n = 207). Significant positive associations were found between CPB and depressive cognitions for caregivers of children with ASD and who are typically developing. A moderation analysis revealed that, among the ASD sample, the model accounted for 33% of the variance in caregiver depressive cognitions (R2 = 0.33, SE = 35.52, p < 0.001). The interaction of child problem behaviors and caregiver resilience on caregiver depressive cognitions was statistically significant (B = - 0.016, SE = 0.007, p = 0.037), thus resilience was a significant moderator, for caregivers of children with ASD. Resilience serves as a protective factor in the relationship between child problem behavior and caregiver depressive cognitions for caregivers of children with ASD only. This finding highlights the importance of assessing and supporting resilience among caregivers of children with ASD. Interventions addressing child behavior would benefit from additional components to bolster caregiver resilience to enhance caregiver mental health and protect against depressive cognitions.

Abstract Background B cells play a central role in multiple sclerosis (MS) through production of injurious antibodies, secretion of pro-inflammatory cytokines, and antigen presentation. The therapeutic success of monoclonal antibodies (mAbs) targeting B cells in some but not all individuals suffering from MS highlights the need for a method to stratify patients and monitor response to treatments in real-time. Herein, we describe the development of the first CD19 positron emission tomography (PET) tracer, and its evaluation in a rodent model of MS, experimental autoimmune encephalomyelitis (EAE). Methods Female C57BL/6 J mice were induced with EAE through immunization with myelin oligodendrocyte glycoprotein (MOG1–125). PET imaging of naïve and EAE mice was performed 19 h after administration of [64Cu]CD19-mAb. Thereafter, radioactivity in organs of interest was determined by gamma counting, followed by ex vivo autoradiography of central nervous system (CNS) tissues. Anti-CD45R (B220) immunostaining of brain tissue from EAE and naïve mice was also conducted. Results Radiolabelling of DOTA-conjugated CD19-mAb with 64Cu was achieved with a radiochemical purity of 99% and molar activity of 2 GBq/μmol. Quantitation of CD19 PET images revealed significantly higher tracer binding in whole brain of EAE compared to naïve mice (2.02 ± 0.092 vs. 1.68 ± 0.06 percentage of injected dose per gram, % ID/g, p = 0.0173). PET findings were confirmed by ex vivo gamma counting of perfused brain tissue (0.22 ± 0.020 vs. 0.12 ± 0.003 % ID/g, p = 0.0010). Moreover, ex vivo autoradiography of brain sections corresponded with PET imaging results and the spatial distribution of B cells observed in B220 immunohistochemistry—providing further evidence that [64Cu]CD19-mAb enables visualization of B cell infiltration into the CNS of EAE mice. Conclusion CD19-PET imaging can be used to detect elevated levels of B cells in the CNS of EAE mice, and has the potential to impact the way we study, monitor, and treat clinical MS.

The information theoretic principle of rational adaptation predicts that individuals with aphasia adapt to their language impairments by relying more heavily on comparatively unimpaired non-linguistic knowledge to communicate. This prediction was examined by assessing the extent to which adults with chronic aphasia due to left-hemisphere stroke rely more on conceptual rather than lexical information during verb retrieval, as compared to age-matched neurotypical controls. A primed verb naming task examined the degree of facilitation each participant group received from either conceptual event-related or lexical collocate cues, compared to unrelated baseline cues. The results provide evidence that adults with aphasia received amplified facilitation from conceptual cues compared to controls, whereas healthy controls received greater facilitation from lexical cues. This indicates that adaptation to alternative and relatively unimpaired information may facilitate successful word retrieval in aphasia. Implications for models of rational adaptation and clinical neurorehabilitation are discussed.

Abstract The purpose of this study was to assess the maturity‐related differences in the aerobic and anaerobic adaptations to sprint interval training (SIT) among youth male athletes. Twenty‐seven youth male athletes were assessed for years from peak height velocity (PHV) and classified into prepubescent (PRE, n = 7, years from PHV = −2.21 ± 0.47 years), peripubescent (PERI, n = 10, years from PHV = 0.25 ± 0.88 years), and postpubescent (POST, n = 10, years from PHV = 2.81 ± 0.50 years) groups based on their years from estimated peak height velocity. Participants completed a ramp exercise protocol on a cycle ergometer to determine maximal aerobic power, maximal oxygen consumption (VO2peak), and fatigue thresholds. Following baseline, all participants completed a 4‐week SIT program that consisted of eight total training sessions. During each session, participants completed repeated 20‐s sprints on a cycle ergometer against a resistance of 7.5% of body mass. The number of sprints per sessions increased from four in session 1 to seven in session 7, with four sprints in session 8. Peak and mean power from sessions 1 and 8 were recorded. All participants completed a post‐testing ramp exercise protocol that mirrored baseline. Maximal aerobic power increased (p

Chronic inflammation promotes prostate cancer (PCa) initiation and progression. We previously reported that acute intereluekin-1 (IL-1) exposure represses androgen receptor (AR) accumulation and activity, providing a possible mechanism for IL-1-mediated development of androgen- and AR-independent PCa. Given that acute inflammation is quickly resolved, and chronic inflammation is, instead, co-opted by cancer cells to promote tumorigenicity, we set out to determine if chronic IL-1 exposure leads to similar repression of AR and AR activity observed for acute IL-1 exposure and to determine if chronic IL-1 exposure selects for androgen- and AR-independent PCa cells. We generated isogenic sublines from LNCaP cells chronically exposed to IL-1α or IL-1β. Cells were treated with IL-1α, IL-1β, TNFα or HS-5 bone marrow stromal cells conditioned medium to assess cell viability in the presence of cytotoxic inflammatory cytokines. Cell viability was also assessed following serum starvation, AR siRNA silencing and enzalutamide treatment. Finally, RNA sequencing was performed for the IL-1 sublines. MTT, RT-qPCR and western blot analysis show that the sublines evolved resistance to inflammation-induced cytotoxicity and intracellular signaling and evolved reduced sensitivity to siRNA-mediated loss of AR, serum deprivation and enzalutamide. Differential gene expression reveals that canonical AR signaling is aberrant in the IL-1 sublines, where the cells show constitutive PSA repression and basally high KLK2 and NKX3.1 mRNA levels and bioinformatics analysis predicts that pro-survival and pro-tumorigenic pathways are activated in the sublines. Our data provide evidence that chronic IL-1 exposure promotes PCa cell androgen and AR independence and, thus, supports CRPCa development.

Abstract Background The cystine/glutamate antiporter (xc-) has been implicated in several neurological disorders and, specifically, in multiple sclerosis (MS) as a mediator of glutamate excitotoxicity and proinflammatory immune responses. We aimed to evaluate an xc-specific positron emission tomography (PET) radiotracer, (4S)-4-(3-[18F]fluoropropyl)-l-glutamate ([18F]FSPG), for its ability to allow non-invasive monitoring of xc- activity in a mouse model of MS. Methods Experimental autoimmune encephalomyelitis (EAE) was induced in C57BL/6 mice by subcutaneous injection of myelin oligodendrocyte glycoprotein (MOG35–55) peptide in complete Freund’s adjuvant (CFA) followed by pertussis toxin. Control mice received CFA emulsion and pertussis toxin without MOG peptide, while a separate cohort of naïve mice received no treatment. PET studies were performed to investigate the kinetics and distribution of [18F]FSPG in naïve, control, pre-symptomatic, and symptomatic EAE mice, compared to 18F-fluorodeoxyglucose ([18F]FDG). After final PET scans, each mouse was perfused and radioactivity in dissected tissues was measured using a gamma counter. Central nervous system (CNS) tissues were further analyzed using ex vivo autoradiography or western blot. [18F]FSPG uptake in human monocytes, and T cells pre- and post-activation was investigated in vitro. Results [18F]FSPG was found to be more sensitive than [18F]FDG at detecting pathological changes in the spinal cord and brain of EAE mice. Even before clinical signs of disease, a small but significant increase in [18F]FSPG signal was observed in the spinal cord of EAE mice compared to controls. This increase in PET signal became more pronounced in symptomatic EAE mice and was confirmed by ex vivo biodistribution and autoradiography. Likewise, in the brain of symptomatic EAE mice, [18F]FSPG uptake was significantly higher than controls, with the largest changes observed in the cerebellum. Western blot analyses of CNS tissues revealed a significant correlation between light chain of xc- (xCT) protein levels, the subunit of xc- credited with its transporter activity, and [18F]FSPG-PET signal. In vitro [18F]FSPG uptake studies suggest that both activated monocytes and T cells contribute to the observed in vivo PET signal. Conclusion These data highlight the promise of [18F]FSPG-PET as a technique to provide insights into neuroimmune interactions in MS and the in vivo role of xc- in the development and progression of this disease, thus warranting further investigation.

Michael W Bartoszek,1 Amy McCoart,2 Kyung-soo Jason Hong,3 Chelsey Haley,2 Krista Beth Highland,4 Anthony R Plunkett1 1Department of Anesthesiology, Womack Army Medical Center, Fort Bragg, NC, 2Clinical Investigations, Defense and Veterans Center for Integrative Pain Management, Henry M. Jackson Foundation, Womack Army Medical Center, Fort Bragg, NC, 3Research Department, The Center for Clinical Research, Sceptor Pain Foundation, Winston Salem, NC, 4Defense and Veterans Center for Integrative Pain Management, Henry M. Jackson Foundation, Uniformed Services University, Bethesda, MD, USA Purpose: The purpose of the present observational, feasibility study is to assess the preliminary safety and effectiveness of intranasal fentanyl for lumbar facet radiofrequency ablation procedures.Patients and methods: This cohort observational study included 23 adult patients. Systolic and diastolic blood pressures, heart rate, oxygen saturation percent, Pasero Opioid-Induced Sedation Scale score, and the Defense and Veterans Pain Rating Scale pain score were assessed prior to the procedure and intranasal fentanyl (100 μg) administration and every 15 minutes after administration, up to 60 minutes post administration. Follow-up of patient satisfaction with pain control and treatment was assessed 24 hours after discharge. The primary outcome was safety as evidenced by adverse events. Secondary outcomes included the above-mentioned vital signs and pain ratings.Results: No adverse events occurred in the present study and all participants maintained an acceptable level of awareness throughout the assessment period. One-way repeated measures analyses of covariance tests with Bonferroni-adjusted means indicated that oxygen saturation, blood pressure, and heart rate changed from baseline, whereas pain scores were lower at post-administration levels compared with baseline. Finally, the majority of participants reported being satisfied with pain control and treatment.Conclusion: Preliminary evidence indicates that intranasal fentanyl is safe and effective for lumbar facet radiofrequency ablation procedures. Future rigorous randomized control trials are needed to confirm the present results and to examine the effects of intranasal fentanyl on intraoperative and postoperative opioid use. Keywords: analgesia, spinal procedures, chronic pain, sedation

The study and application of the critical power (CP) concept has spanned many decades. The CP test provides estimates of two distinct parameters, CP and W′, that describe aerobic and anaerobic metabolic capacities, respectively. Various mathematical models have been used to estimate the CP and W′ parameters across exercise modalities. Recently, the CP model has been applied to dynamic constant external resistance (DCER) exercises. The same hyperbolic relationship that has been established across various continuous, whole-body, dynamic movements has also been demonstrated for upper-, lower-, and whole-body DCER exercises. The asymptote of the load versus repetition relationship is defined as the critical load (CL) and the curvature constant is L′. The CL and L′ can be estimated from the same linear and non-linear mathematical models used to derive the CP. The aims of this review are to (1) provide an overview of the CP concept across continuous, dynamic exercise modalities; (2) describe the recent applications of the model to DCER exercise; (3) demonstrate how the mathematical modeling of DCER exercise can be applied to further our understanding of fatigue and individual performance capabilities; and (4) make initial recommendations regarding the methodology for estimating the parameters of the CL test.

An evolving understanding of disease pathogenesis has compelled the development of new drug delivery approaches. Recently, bioinspired microrobots have gained traction as drug delivery systems. By leveraging the microscale phenomena found in physiological systems, these microrobots can be designed with greater maneuverability, which enables more precise, controlled drug release. Their function could be further improved by testing their efficacy in physiologically relevant model systems as part of their development. In parallel with the emergence of microscale robots, organ-on-a-chip technologies have become important in drug discovery and physiological modeling. These systems reproduce organ-level functions in microfluidic devices, and can also incorporate specific biological, chemical, and physical aspects of a disease. This review highlights recent developments in both microrobotics and organ-on-a-chip technologies and envisions their combined use for developing future drug delivery systems.

This study examined the effects of curcumin and fenugreek soluble fiber supplementation on the ventilatory threshold (VT) and peak oxygen consumption ( V ˙ O2 peak). Methods: Forty-five untrained men and women were randomly assigned to one of three supplementation groups: placebo (PLA, n = 13), 500 mg·day−1 CurQfen® (CUR, n = 14), or 300 mg·day−1 fenugreek soluble fiber (FEN, n = 18). Participants completed a maximal graded exercise test on a cycle ergometer to determine the VT and V ˙ O2 peak before (PRE) and after (POST) 28 days of daily supplementation. Separate, one-way analyses of covariance (ANCOVAs) were used to examine the between-group differences for adjusted POST VT and V ˙ O2 peak values, covaried for the respective PRE-test values. Results: The adjusted POST VT V ˙ O2 values for the CUR (mean ± SD = 1.593 ± 0.157 L·min−1) and FEN (1.597 ± 0.157 L·min−1) groups were greater than (p = 0.039 and p = 0.025, respectively) the PLA (1.465 ± 0.155 L·min−1) group, but the FEN and CUR groups were not different (p = 0.943). There were no differences in the adjusted V ˙ O2 peak values (F = 0.613, p = 0.547) among groups. Conclusion: These findings indicated that fenugreek soluble fiber was responsible for the improvements in the submaximal performance index for both CUR and FEN groups.

This study compared electromyographic (EMG) amplitude, the number of repetitions completed, and exercise volume during three sets to failure of high- (80% 1RM) versus low-load (30% 1RM) forearm flexion resistance exercise on a subject-by-subject basis. Fifteen men were familiarized, completed forearm flexion 1RM testing. Forty-eight to 72 h later, the subjects completed three sets to failure of dumbbell forearm flexion resistance exercise with 80% (n = 8) or 30% (n = 7) 1RM. EMG amplitude was calculated for every repetition, and the number of repetitions performed and exercise volume were recorded. During sets 1, 2, and 3, one of eight subjects in the 80% 1RM group demonstrated a significant linear relationship for EMG amplitude versus repetition. For the 30% 1RM group, seven, five, and four of seven subjects demonstrated significant linear relationships during sets 1, 2, and 3, respectively. The mean EMG amplitude responses show that the fatigue-induced increases in EMG amplitude for the 30% 1RM group and no change in EMG amplitude for the 80% 1RM group resulted in similar levels of muscle activation in both groups. The numbers of repetitions completed were comparatively greater, while exercise volumes were similar in the 30% versus 80% 1RM group. Our results, in conjunction with those of previous studies in the leg extensors, suggest that there may be muscle specific differences in the responses to high- versus low-load exercise.

Female caregivers of children with autism spectrum disorder (ASD) often report higher levels of psychological distress related to increased levels of caregiver strain, as well as frequency and severity of child problem behaviors (CPB). However, despite reported distress, caregivers have also reported benefits. A sample of n = 259 female caregivers of children with ASD completed online surveys assessing CPB, caregiver strain, psychological distress, and benefit finding. Results suggest that objective caregiver strain is a significant mediator between CPB and caregiver distress. Benefit finding, however, was not found to be a significant moderator. These findings inform theoretical applications and provide implications for future research in the development of interventions to enhance functioning in female caregivers.

Chile peppers, native to the Americas, have spread around the world and have been integrated into the diets of many cultures. Much like their heat content, nutritional content can vary dramatically between different pepper types. In this study, a diverse set of chile pepper types were examined for nutrient content. Some pepper types were found to have high levels of vitamin A, vitamin C, or folate. Correlations between nutrient content, species, cultivation status, or geographic region were limited. Varietal selection or plant breeding offer tools to augment nutrient content in peppers. Integration of nutrient rich pepper types into diets that already include peppers could help combat nutrient deficiencies by providing a significant portion of recommended daily nutrients.

This study compared sex responses for strength and barbell velocity from very short-term resistance training (VST, consisting of 2–3 training sessions) for an upper body dynamic constant external resistance (DCER) exercise (bench press [BP]). Ten females (mean ± standard deviation (SD) age: 21.3 ± 3 years, height: 166.2 ± 6 cm, body mass: 71.4 ± 10.7 kg) and 10 males (mean ± SD age: 24.6 ± 4 years, height: 179.5 ± 8 cm, body mass: 88.6 ± 11 kg) completed a pre-test visit to determine the BP 1 repetition maximum (1RM) as well as the mean (BPMV) and peak (BPPV) barbell velocities from the BP 1RM. The VST involved three training visits where the participants performed 5 sets of 6 repetitions, at 65% of the 1RM. The post-test followed the same procedures as the pre-test visit. There were significant increases in 1RM strength for both the males (5.1%) and females (5.4%) between pre-test and post-test. There were no significance differences between sex for mean (BPMV) and peak (BPPV); however, overall there was a 32.7% increase in BPMV and a 29.8% increase in BPPV. These findings indicated an increase in strength and barbell velocity for both males and females as a result of VST upper body DCER exercise in untrained subjects.

The vascular interface of the brain, known as the blood-brain barrier (BBB), is understood to maintain brain function in part via its low transcellular permeability1-3. Yet, recent studies have demonstrated that brain ageing is sensitive to circulatory proteins4,5. Thus, it is unclear whether permeability to individually injected exogenous tracers-as is standard in BBB studies-fully represents blood-to-brain transport. Here we label hundreds of proteins constituting the mouse blood plasma proteome, and upon their systemic administration, study the BBB with its physiological ligand. We find that plasma proteins readily permeate the healthy brain parenchyma, with transport maintained by BBB-specific transcriptional programmes. Unlike IgG antibody, plasma protein uptake diminishes in the aged brain, driven by an age-related shift in transport from ligand-specific receptor-mediated to non-specific caveolar transcytosis. This age-related shift occurs alongside a specific loss of pericyte coverage. Pharmacological inhibition of the age-upregulated phosphatase ALPL, a predicted negative regulator of transport, enhances brain uptake of therapeutically relevant transferrin, transferrin receptor antibody and plasma. These findings reveal the extent of physiological protein transcytosis to the healthy brain, a mechanism of widespread BBB dysfunction with age and a strategy for enhanced drug delivery.

These findings indicate that firefighters may enhance air consumption efficiency through training interventions focused on improving body composition the metabolic tolerance to work. Firefighters should also be mindful of excessive and unnecessary load carriage, as increasing gear mass was also associated with poorer air consumption efficiency. Objective: This study examines variability in air consumption (AC) between firefighters (FF) working at a standardized pace, evaluates the relationship between air consumption efficiency (ACE) and work economy, identifies parameters associated with ACE, and explores the relationship between ACE and self-paced work rate. Methods: FF completed randomized trials of an air consumption drill at a standardized pace while breathing through a self-contained breathing apparatus and a gas analyzer. A subsample completed another trial at a self-selected pace. Results: The average AC variability (±1 standard deviation) was ~3.1 min of cylinder usage (13.7%). AC was positively associated with work economy and numerous physiological and anthropometric outcomes. No relationship was found between ACE and self-paced air consumption drill time. Conclusions: FF working at higher internal strain demonstrated poorer ACE. Improving metabolic tolerance may extend the self-contained breathing apparatus' functional duration to enhance productivity and safety. [ABSTRACT FROM AUTHOR]

Background: Primary progressive aphasia (PPA) is a neurodegenerative syndrome characterized by progressive language deficits. The main variants of PPA – semantic (svPPA), logopenic (lvPPA), and nonfluent (nfvPPA) – can be challenging to distinguish. Limb apraxia often co-occurs with PPA, but it is unclear whether PPA variants are associated with different gesture deficits. Prior evidence from stroke indicates that temporal lobe lesions are associated with reduced benefit from meaning in gesture performance. Temporal lesions are also associated with greater deficits in hand postures compared to arm kinematics in gesture imitation. Aims: We tested the hypothesis that svPPA, who primarily exhibit temporal lobe atrophy, would differentially show this pattern. In addition, we predicted that as a group, individuals with PPA would more accurately produce meaningful than meaningless gestures and kinematic components than hand postures, as found in neurotypical adults and individuals with stroke. Methods & Procedures: Participants with PPA completed meaningful and meaningless gesture imitation tasks. Performance was scored for hand posture and arm kinematic components. Bayesian mixed-effect models examined trial-level gesture imitation accuracy, while controlling for dementia severity and random effects of subjects and items. Fixed effects included an interaction between PPA variant, task condition/meaning, and gesture component. Outcomes & Results: We found a critical interaction between PPA variant, meaning, and gesture component. In particular, unlike lvPPA and nfvPPA, svPPA subjects' hand postures failed to benefit from gesture meaning. This preliminary research extends prior findings on the role of the temporal lobe in action representations associated with manipulable objects, and is among the first to demonstrate distinct gesture imitation patterns between PPA variants. Conclusions: Characterizing gesture deficits in PPA may help inform diagnostics, compensatory communication strategies, and models of praxis. [ABSTRACT FROM AUTHOR]

Anxiety, depression, and suicidality are major concerns among college students, though less is known about these constructs in autistic college students. Given the rising number of autistic individuals entering post-secondary education, adequate measurement and diagnosis of anxiety, depression, and suicidality is necessary to provide clinical care to this population. While the Generalized Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) are commonly used in university settings, these instruments have not been psychometrically evaluated in autistic college students. The current study examines the differential psychometric properties of the GAD-7 and PHQ-9 utilizing invariance testing via structural equation modeling in a sample of self-identified autistic (n = 477) and non-autistic (n = 429) university students. Results showed that although the GAD-7 is invariant, the PHQ-9 was mostly invariant, with one item displaying non-invariance. Specifically, the PHQ-9 item assessing suicidality was found to be non-invariant at the metric level, indicating that autistic and non-autistic college students interpret this question differently. Future investigators should continue to assess the appropriateness of using common screening measures, originally created for non-autistic people, in autistic populations. Anxiety, depression, and suicidality are major concerns among college students, though less is known about these constructs in autistic college students. Given the rising number of autistic individuals entering college, adequate screening and diagnosis of mental health difficulties is necessary to provide care to this population. For example, despite widespread usage of the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7), it is unknown if the two instruments accurately measure depression and anxiety the same way between non-autistic and autistic individuals. Thus, the current study was the first to examine how these instruments measure depression and anxiety symptoms in autistic versus non-autistic college students. Utilizing tests of construct measurement in a sample of autistic (n = 477) and non-autistic (n = 429) university students aged 18–29, results showed that while the GAD-7 and PHQ-9 appear to be accurately capturing anxiety and depression in autistic college students, the PHQ-9 item assessing suicidality was found to be measuring different things. This indicates that autistic college students are not interpreting this question the way non-autistic students are, and thus, the measure is failing to capture suicidality in autistic people. Future investigators should continue to assess the appropriateness of using common screening measures, originally created by non-autistic people, in autistic populations. [ABSTRACT FROM AUTHOR]

This study examined the effects of blood flow restriction (BFR) on motor unit (MU) behaviour of the biceps brachii (BB) during a single non-exhausting submaximal muscle action. Twenty adults performed maximal voluntary contractions (MVCs) of the elbow flexors, followed by an isometric trapezoidal muscle action at 40% MVC during BFR and control (CON) visits. Surface electromyographic signals recorded from the BB during the 40% MVCs were decomposed. Recruitment thresholds (RTs), MU action potential amplitudes (MUAPAMPS), initial firing rates (IFRs), mean firing rates (MFRs) at steady force, and normalized EMG amplitude (N-EMGRMS) were analysed. Y-intercepts and slopes were calculated for the MUAPAMP, IFR, and MFR vs. RT relationships. Y-intercepts for the IFR and MFR vs. RT relationships and N-EMGRMS increased during BFR (p < 0.05) collapsed across sex. The slopes for the IFR and MFR vs. RT relationships decreased during BFR (p < 0.05) collapsed across sex. The y-intercepts and slopes for the MUAPAMP vs. RT relationships were not different (p > 0.05) between treatments or sex. BFR during the 40% MVC increased IFRs, MFRs, and N-EMGRMS. However, the similar MUAPAMPS observed between treatments may suggest that a greater load is necessary to recruit additional MUs when performing a single submaximal short-duration muscle action with BFR. [ABSTRACT FROM AUTHOR]

Mycobacterium abscessus (Mab) is highly drug resistant, and understanding regulation of antibiotic resistance is critical to future antibiotic development. Regulatory mechanisms controlling Mab's β‐lactamase (BlaMab) that mediates β‐lactam resistance remain unknown. S. aureus encodes a prototypical protease‐mediated two‐component system BlaRI regulating the β‐lactamase BlaZ. BlaR binds extracellular β‐lactams, activating an intracellular peptidase domain which cleaves BlaI to derepress blaZ. Mycobacterium tuberculosis (Mtb) encodes homologs of BlaRI (which we will denote as BlaIR to reflect the inverted gene order in mycobacteria) that regulate not only the Mtb β‐lactamase, blaC, but also additional genes related to respiration. We identified orthologs of blaIRMtb in Mab and hypothesized that they regulate blaMab. Surprisingly, neither deletion of blaIRMab nor overexpression of only blaIMab altered blaMab expression or β‐lactam susceptibility. However, BlaIMab did bind to conserved motifs upstream of several Mab genes involved in respiration, yielding a putative regulon that partially overlapped with BlaIMtb. Prompted by evidence that respiration inhibitors including clofazimine induce the BlaI regulon in Mtb, we found that clofazimine triggers induction of blaIRMab and its downstream regulon. Highlighting an important role for BlaIRMab in adapting to disruptions in energy metabolism, constitutive repression of the BlaIMab regulon rendered Mab highly susceptible to clofazimine. In addition to our unexpected findings that BlaIRMab does not regulate β−lactam resistance, this study highlights the novel role of mycobacterial BlaRI‐type regulators in regulating electron transport and respiration. [ABSTRACT FROM AUTHOR]

Objective. This study examined sex-related differences in fatigability and neuromuscular responses using surface electromyographic (sEMG) and mechanomyographic (sMMG) amplitude (AMP) and frequency (MPF) during fatiguing, maximal, bilateral isometric leg extensions. Approach. Twenty recreationally active males and females with resistance training experience performed continuous, maximal effort, bilateral isometric leg extensions until their force reduced by 50%. Linear mixed effect models analyzed patterns of force, sEMG, and sMMG AMP and MPF responses in the dominant limb. An independent samples t-test compared time-to-task failure (TTF) between sexes. Main Results. There were no significant differences in TTF between males and females. However, males experienced a greater rate of force loss compared to females. Furthermore, sEMG AMP and MPF and sMMG AMP responses followed similar linear trends for both sexes, while sMMG MPF showed non-linear responses with sex-dependent differences. Significance. These data suggest that although TTF was similar, males had a higher rate of force reduction, likely due to greater absolute strength. Furthermore, despite parallel changes in sEMG AMP and MPF, as well as sMMG AMP, the divergent responses observed in sMMG MPF highlight sex-dependent differences in how males and females experience changes in the firing rates of active motor units during sustained maximal contractions. [ABSTRACT FROM AUTHOR]

Objective: Our aim was to survey astrocyte and microglial activation across four brain regions in a mouse model of chronic migraine. Background: Chronic migraine is a leading cause of disability, with higher rates in females. The role of central nervous system neurons and glia in migraine pathophysiology is not fully elucidated. Preclinical studies have shown abnormal glial activation in the trigeminal nucleus caudalis of male rodents. No current reports have investigated glial activation in both sexes in other important brain regions involved with the nociceptive and emotional processing of pain. Methods: The mouse nitroglycerin model of migraine was used, and nitroglycerin (10 mg/kg) or vehicle was administered every other day for 9 days. Prior to injections on days 1, 5, and 9, cephalic allodynia was determined by periorbital von Frey hair testing. Immunofluorescent staining of astrocyte marker, glial fibrillary protein (GFAP), and microglial marker, ionized calcium binding adaptor molecule 1 (Iba1), in male and female trigeminal nucleus caudalis, periaqueductal gray, somatosensory cortex, and nucleus accumbens was completed. Results: Behavioral testing demonstrated increased cephalic allodynia in nitroglycerin‐ versus vehicle‐treated mice. An increase in the percent area covered by GFAP+ cells in the trigeminal nucleus caudalis and nucleus accumbens, but not the periaqueductal gray or somatosensory cortex, was observed in response to nitroglycerin. No significant differences were observed for Iba1 staining across brain regions. We did not detect significant sex differences in GFAP or Iba1 quantification. Conclusions: Immunohistochemical analysis suggests that, at the time point tested, immunoreactivity of GFAP+ astrocytes, but not Iba1+ microglia, changes in response to chronic migraine‐associated pain. Additionally, there do not appear to be significant differences between males and females in GFAP+ or Iba1+ cells across the four brain regions analyzed. Plain Language Summary: The aim of this study was to determine if supportive immune cells in the brains of males and females are altered in an animal model of chronic migraine. Mice in the chronic migraine group showed significant activation of astrocytes, but not microglia, in male and female mice in pain and emotion‐processing brain regions. These results suggest that some supportive cells in the brain may play a role in regulating chronic migraine. [ABSTRACT FROM AUTHOR]

Race-based traumatic stress, also called racial trauma, refers to "mental and emotional injury caused by encounters with racial bias and ethnic discrimination, racism, and hate crimes" (Mental Health America, n.d.). While much research on racism-based stress in schools focuses on teachers, school psychologists can just as easily cause this type of harm if they are not educated and aware of their impact on their students. One way that Black students may experience racism-based stress through a school psychologist is during the special education evaluation process. Although school psychologists provide myriad services within a school, assessment continues to account for a large portion of service delivery. Additionally, school psychology continues to be a predominantly White field; as of the 2015 NASP member survey, 87% of school psychologists identified as White (Walcott et al., 2016). This means that Black students being evaluated for special education are often working with a White psychologist whom they may not know or trust. The onus is on the school psychologist, not the student, to build trust and reduce racism-based stress throughout the evaluation process. Reducing racism-based stress that Black students may experience during the assessment process is vital to ensuring equity for Black youth in the special education evaluation process. This article describes some of the common agents of racism at school and offers action steps for white school psychologists.