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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 Foodborne bacteria like Escherichia coli threaten global food security, necessitating affordable, on-site detection methods, especially in resource-limited settings. This study optimized loop-mediated isothermal amplification (LAMP) integrated with peroxidase-mimicking G-quadruplex DNA structures (DNAzyme), termed DNAzyme-LAMP which was designed to incorporate two different catalytic DNAzymes per amplification unit, enabling colorimetric detection of E. coli in leafy vegetables and milk samples. Additionally, we introduce a novel electrochemical method that enhances analytical sensitivity. The optimized DNAzyme-LAMP achieved a detection limit below 6.3 CFU per reaction or 0.1 aM gene copies. This system lays the groundwork for the development of on-site biosensors and can be adapted for detecting other foodborne pathogens.

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.

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.

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.

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.

This study examined the responses of force alterations, relative to critical force (CF), neuromuscular parameters, and muscle oxygenation (SmO2) for isometric handgrip holds to failure (HTF) anchored to ratings of perceived exertion (RPE) of 3 and 7. Twelve men completed pre-maximal voluntary isometric contractions (pre-MVIC), submaximal HTF at 4 percentages of pre-MVIC, HTF at RPE = 3 and 7, and post-MVIC. Mechanomyograpic (MMG) signals and SmO2 were recorded during the RPE HTF. Analyses included paired-samples t-tests and repeated-measures ANOVAsatan alpha level of p ≤ 0.05. Time to task failure was not different between RPE 3 (478.7 ± 196.6 s) and RPE 7 (495.8 ± 173.8 s). Performance fatigability (PF) and MMG amplitude (AMP) were greater for RPE 7 (PF: 37.9 ± 12.9%; MMG AMP: 15.7 ± 7.4% MVIC) than RPE 3 (PF: 30.0 ± 14.5%; MMG AMP: 10.2 ± 6.5% MVIC), but MMG mean power frequency (MPF) was greater for RPE 3 (146.2 ± 31.1% MVIC) than RPE 7 (128.8 ± 23.0% MVIC). There were RPE-dependent decreases in force (p ≤ 0.01) across 3 discernable phases during the HTF. There were decreases in MMG AMP across time for both RPEs, but there were no significant changes in MMG MPF or SmO2. There were overall similar motor unit control strategies and local metabolic demand between RPEs. The majority of the HTF performed below CF at RPE 3 and 7 indicated CF did not reflect the highest sustainable force. When prescribing isometric exercise anchored to RPE, practitioners should be aware of the magnitude of force loss and relative intensity of the task to be sure desired training loads are met. [ABSTRACT FROM AUTHOR]

To determine the effects of blood flow restriction (BFR) on the mean firing rate (MFR) and motor unit action potential amplitude (MUAPAMP) VS. recruitment threshold (RT) relationships during fatiguing isometric elbow flexions. Ten men (24.5 ± 4.0 years) performed isometric trapezoidal contractions at 50% maximum voluntary contraction to task failure with or without BFR, on 2 separate days. For BFR, a cuff was inflated to 60% of the pressure required for full brachial artery occlusion at rest. During both visits, surface electromyography was recorded from the biceps brachii of the dominant limb and the signal was decomposed. A paired-samples t test was used to determine the number of repetitions completed between BFR and CON. ANOVAS (repetition [first, last] × condition [BFR, CON]) were used to determine differences in MFR vs. RT and MUAPAMP VS. RT relationships. Subjects completed more repetitions during CON (12 ± 4) than BFR (9 ± 2; p = 0.012). There was no significant interaction (p > 0.05) between the slopes and y-intercepts during the repetition X condition interaction for MUAPAMP VS. MFR. However, there was a main effect of repetition for the slopes of the MUAPAMP VS. RT (p = 0.041) but not the y-intercept (p = 0.964). Post hoc analysis (collapsed across condition) indicated that the slopes of the MUAPAMP VS. RT during the first repetition was less than the last repetition (first: 0.022 ± 0.003 mv/%MVC; last: 0.028 ± 0.004 mv/%MVC; p = 0.041). Blood flow restriction resulted in the same amount of higher threshold MU recruitment in approximately 75% of the repetitions. Furthermore, there was no change in MFR for either condition, even when taken to task failure. Thus, BFR training may create similar MU responses with less total work completed than training without BFR. [ABSTRACT FROM AUTHOR]

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. Author summary: Gram-negative bacteria possess a highly impermeable outer membrane, which protects against environmental stress and antibiotics. Outer membrane phospholipid transport remained mysterious until YhdP, TamB, and YdbH were recently implicated in phospholipid transport between the inner and outer membranes of E. coli. Similar roles for YhdP and/or TamB have been suggested in both closely and distantly related gram-negative bacteria. Here, given the transporters' apparent partial redundancy, we investigated functional differentiation between YhdP and TamB and its potential link to phospholipid metabolism. Our data demonstrate YhdP and TamB have differential involvement with fatty acid and phospholipid metabolism. Transport of increased levels of cardiolipin and saturated phospholipids in the absence of YhdP and presence of TamB at a non-permissive temperature is lethal. These data clearly demonstrate that the diversification of function between YhdP and TamB is related to phospholipid metabolism. One possible mechanism for this differentiation would be differential phospholipid transport preference between YhdP and TamB. Diversification of function between YhdP and TamB roles in phospholipid metabolism provides a potential mechanism for regulation of phospholipid composition, and possibly the mechanical strength and permeability of the outer membrane, and so the cell's intrinsic antibiotic resistance, in changing environmental conditions. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]