The presence of fear: How subjective fear, not physiological changes, shapes the experience of presence.

When we become engrossed in novels, films, games, or even our own wandering thoughts, we can feel present in a reality distinct from the real world. Although this subjective sense of presence is, presumably, a ubiquitous aspect of conscious experience, the mechanisms that produce it are unknown. Correlational studies conducted in virtual reality have shown that we feel more present when we are afraid, motivating claims that physiological changes contribute to presence; however, such causal claims remain to be evaluated. Here, we report two experiments that test the causal role of subjective and physiological components of fear (i.e., activation of the sympathetic nervous system) in generating presence. In Study 1, we validated a virtual reality simulation capable of inducing fear. Participants rated their emotions while they crossed a wooden plank that appeared to be suspended above a city street; at the same time, we recorded heart rate and skin conductance levels. Height exposure increased ratings of fear, presence, and both measures of sympathetic activation. Although presence and fear ratings were correlated during height exposure, presence and sympathetic activation were unrelated. In Study 2, we manipulated whether the plank appeared at height or at ground level. We also captured participants' movements, which revealed that alongside increases in subjective fear, presence, and sympathetic activation, participants also moved more slowly at height relative to controls. Using a mediational approach, we found that the relationship between height exposure and presence on the plank was fully mediated by self-reported fear, and not by sympathetic activation. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Emotion in motion: perceiving fear in the behaviour of individuals from minimal motion capture displays.

The ability to quickly and accurately recognise emotional states is adaptive for numerous social functions. Although body movements are a potentially crucial cue for inferring emotions, few studies have studied the perception of body movements made in naturalistic emotional states. The current research focuses on the use of body movement information in the perception of fear expressed by targets in a virtual heights paradigm. Across three studies, participants made judgments about the emotional states of others based on motion-capture body movement recordings of those individuals actively engaged in walking a virtual plank at ground-level or 80 stories above a city street. Results indicated that participants were reliably able to differentiate between height and non-height conditions (Studies 1 & 2), were more likely to spontaneously describe target behaviour in the height condition as fearful (Study 2) and their fear estimates were highly calibrated with the fear ratings from the targets (Studies 1-3). Findings show that VR height scenarios can induce fearful behaviour and that people can perceive fear in minimal representations of body movement.

Antimicrobial Peptide-Poly(ethylene glycol) Conjugates: Connecting Molecular Architecture, Solution Properties, and Functional Performance.

Antimicrobial peptides (AMPs) are promising alternatives to conventional antibiotics for treating infections caused by drug-resistant bacteria; yet, many peptides are limited by toxicity to eukaryotic cells and instability in biological environments. Conjugation to linear polymers that reduce cytotoxicity and improve stability, however, often decreases antimicrobial activity. In this work, we combine the biocompatibility advantages of poly(ethylene glycol) (PEG) with the efficacy merits of nonlinear polymer architectures that accommodate multiple AMPs per molecule. By conjugating a chemokine-derived AMP, stapled Ac-P9, to linear and star-shaped PEG with various arm numbers and lengths, we investigated the role of molecular architecture in solution properties (i.e., ζ-potential, size, and morphology) and performance (i.e., antimicrobial activity, hemolysis, and protease resistance). Linear, 4-arm, and 8-arm conjugates with 2-2.5 kDa PEG arms were found to form nanoscale structures in solution with lower ζ-potentials relative to the unconjugated AMP, suggesting that the polymer partially shields the cationic AMP. Reducing the length of the PEG arms of the 8-arm conjugate to 1.25 kDa appeared to better reveal the peptide, seen by the increased ζ-potential, and promote assembly into particles with a larger size and defined spherical morphology. The antimicrobial effects exerted by the short 8-arm conjugate rivaled that of the unconjugated peptide, and the AMP constituents of the short 8-arm conjugate were protected from proteolytic degradation. All other conjugates examined also imparted a degree of protease resistance, but exhibited some reduced level of antimicrobial activity as compared to the AMP alone. None of the conjugates caused significant cytotoxic effects, which bodes well for their future potential to treat infections. While enhancing proteolytic stability often comes with the cost of lower antimicrobial activity, we have found that presenting AMPs at high density on a neutral nonlinear polymer strikes a favorable balance, exhibiting both enhanced stability and high antimicrobial activity.

Age is positively associated with fading affect bias: A cross-sectional comparison.

Emotions elicited by personal event memories change over time such that negative affect fades more quickly than positive affect. This asymmetric fade is called the fading affect bias (FAB) and has been posited as a mechanism that helps promote a positive outlook on life. A similar bias toward positive information (i.e., the positivity effect) driven by greater emphasis on emotion regulation has been demonstrated in older adults. The current research uses two age-diverse community samples to examine the relationship between age and the strength of FAB. Participants recalled positive and negative event memories and rated the intensity of affect at the time of the event (i.e., retrospectively) and at the time of recollection. Participants of all ages exhibited a significant FAB, and crucially, the strength of the effect was positively associated with age. Age-based differences in psychological well-being and recalled event intensity had no influence on the relationship between age and FAB. The relationship was, however, related to greater personal importance placed on positive (but not negative) events. The findings are consistent with the socioemotional selectivity theory and suggest another mechanism through which emotion regulation is associated with aging to maintain a positive outlook on life. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Sex Differences in Branched-chain Amino Acid and Tryptophan Metabolism and Pathogenesis of Youth-onset Type 2 Diabetes.

OBJECTIVES: Insulin resistance is associated with elevations in plasma branched-chain amino acids (BCAAs). BCAAs compete with aromatic amino acids including tryptophan for uptake into ß cells. To explore relationships between BCAAs and tryptophan metabolism, adiposity, and glucose tolerance, we compared urine metabolites in overweight/obese youth with type 2 diabetes (T2D) with those in nondiabetic overweight/obese and lean youth. METHODS: Metabolites were measured in 24-hour and first-morning urine samples of 56 nondiabetic adolescents with overweight/obesity, 42 adolescents with T2D, and 43 lean controls, aged 12 to 21 years. Group differences were assessed by Kruskal Wallis or ANOVA. RESULTS: Groups were comparable for age, pubertal status, and ethnicity. Youth with T2D were predominantly female and had highest percent body fat. BCAAs, branched-chain ketoacids (BCKAs), tryptophan, and kynurenine were higher in urine of subjects with T2D. There were no differences between lean controls and nondiabetic youth with overweight/obesity. T2D was associated with diversion of tryptophan from the serotonin to the kynurenine pathway, with higher urinary kynurenine/serotonin ratio and lower serotonin/tryptophan and 5-HIAA/kynurenine ratios. Urinary BCAAs, BCKAs, tryptophan, and ratios reflecting diversion to the kynurenine pathway correlated positively with metrics of body fat and hemoglobin A1c. Increases in these metabolites in the obese T2D group were more pronounced and statistically significant only in adolescent girls. CONCLUSION: Increases in urinary BCAAs and BCKAs in adolescent females with T2D are accompanied by diversion of tryptophan metabolism from the serotonin to the kynurenine pathway. These adaptations associate with higher risks of T2D in obese adolescent females than adolescent males.

Caregiver Burden Associated With Pediatric Chronic Pain: A Retrospective Study Using the Pediatric Electronic Persistent Pain Outcomes Collaboration Database.

OBJECTIVES: This retrospective, cross-sectional study investigated the nature and extent of burden experienced by caregivers of children and adolescents with chronic pain, and factors associated with increased caregiver burden. METHODS: The Pediatric Electronic Persistent Pain Outcomes Collaboration database provided prospectively collected data from 1929 families attending 9 pediatric chronic pain services across Australia and New Zealand. Data included demographic information, responses to child pain and functioning measures, caregiver work impairment, and psychosocial functioning. RESULTS: Caregivers of children with chronic pain reported work impairment associated with their child's pain (mean: 15% ± SD 25 absenteeism; 38% ± SD 29 productivity lost), significantly worse than published international population norms (large-scale community survey data), most other caregiver samples of adults and children with other chronic conditions, and adult samples with various pain conditions. Caregivers reported considerable burden in multiple psychosocial functioning domains, particularly leisure functioning, pain-related catastrophizing, and adverse parenting behaviors (with greater pain-related avoidance). Caregiver psychosocial burden was significantly associated with child psychosocial functioning (ß = -0.308, P < 0.01), school absenteeism (ß = 0.161, P < 0.01), physical disability (ß = 0.096, P < 0.05), and pain duration (ß = 0.084, P < 0.05), but not pain intensity. Caregiver work productivity loss was significantly associated with school absenteeism (ß = 0.290, P < 0.01), child physical disability (ß = 0.148, P < 0.01), child health care utilization (ß = 0.118, P < 0.05), and worst pain intensity (ß = 0.101, P < 0.05). DISCUSSION: These results highlight the significant and varied impacts experienced by caregivers of children with chronic pain. This work is novel in reporting significant work impairment and confirms psychosocial burden in a larger sample than previous studies.

The pipetting Olympics: Propagating proper pipetting a priori in clinical LC-MS/MS analysis.

Introduction: Engaging pipetting events were developed to assess and challenge technicians' practical sample handling using matrices common to the clinical laboratory. As correct pipetting stands as a prerequisite for accurate clinical laboratory testing, this helped to understand sources of imprecision and bias attributed to the underlying step of aspirating and dispensing patient samples and internal standard in clinical LC-MS/MS assays while highlighting the importance for the clinical laboratory to evaluate this source of variability on an on-going basis and mitigate its impact. Methods: The events involved pipetting water, methanol, serum, and whole blood. Gravimetric analysis was used to determine the exact volumetric delivery of each matrix using two different techniques. Imprecision and bias were calculated based on the volume derived from the mass and density of each matrix, using literature values for each matrix type. Results: Low imprecision and bias were observed when pipetting water, as in common commercial pipetting assessment programs. Significantly increased imprecision and bias were observed in more applicable matrices (i.e., serum, whole blood, and methanol), indicating that water-based pipetting proficiency assessment leads to a false sense of technical ability. Additionally, the events within illuminated areas for training, leading to improved imprecision and bias. It was shown that pre-rinsing (aspirating and dispensing matrix three times to coat the tip) improved bias, particularly for delivery of methanol and whole blood. Conclusions: Precise and accurate pipetting within the clinical laboratory should not be taken for granted, nor implicitly inferred from proficiency assessment using aqueous solutions. The engaging and collegial events fostered training opportunities. Assay-specific patient sample delivery considerations (pipets and matrices) can inform the practicality of these events - the Pipetting Olympics - and drive improvements within the laboratory.

Enterobacterales draft genome sequences: 15 historical (1998-2004) and 30 contemporary (2015-2016) clinical isolates from Pakistan.

The continued emergence and spread of antimicrobial resistance among pathogenic bacteria are ever-growing threats to health and economy. Here, we report the draft genomes for 45 Enterobacterales clinical isolates, including historical and contemporary drug-resistant organisms, obtained in Pakistan between 1998 and 2016: 5 Serratia, 3 Salmonella, 3 Enterobacter, and 34 Klebsiella.

Investigation of multidrug-resistant plasmids from carbapenemase-producing Klebsiella pneumoniae clinical isolates from Pakistan.

Objectives: The study aim was to investigate multidrug-resistant (MDR) plasmids from a collection of 10 carbapenemase-producing Klebsiella pneumoniae clinical isolates identified within the same healthcare institution in Pakistan. Full characterization of the MDR plasmids including structure, typing characteristics, and AMR content as well as determination of their plasmid-based antimicrobial susceptibility profiles were carried out. Methods: Plasmids were isolated from 10 clinical isolates of Klebsiella pneumoniae, and from a corresponding set of Escherichia coli transconjugants, then sequenced using Nanopore/Illumina technology to generate plasmid hybrid assemblies. Full characterization of MDR plasmids, including determination of next generation sequencing (NGS)-based AMR profiles, plasmid incompatibility groups, and types, was carried out. The structure of MDR plasmids was analyzed using the Galileo AMR platform. For E. coli transconjugants, the NGS-based AMR profiles were compared to NGS-predicted AMR phenotypes and conventional broth microdilution (BMD) antimicrobial susceptibility testing (AST) results. Results: All carbapenemase-producing K. pneumoniae isolates (carrying either blaNDM-1, or/and blaOXA-48) carried multiple AMR plasmids encoding 34 antimicrobial resistance genes (ARGs) conferring resistance to antimicrobials from 6 different classes. The plasmid incompatibility groups and types identified were: IncC (types 1 and 3), IncFIA (type 26) IncFIB, IncFII (types K1, K2, K7, and K9), IncHI1B, and IncL. None of the blaNDM-1 and blaESBL-plasmids identified in this study were previously described. Most blaNDM-1-plasmids shared identical AMR regions suggesting potential genetic material/plasmid exchange between K. pneumoniae isolates of this collection. The majority of NGS-based AMR profiles from the E. coli transconjugants correlated well with both NGS-based predicted and conventional AST results. Conclusion: This study highlights the complexity and diversity of the plasmid-based genetic background of carbapenemase-producing clinical isolates from Pakistan. This study emphasizes the need for characterization of MDR plasmids to determine their complete molecular background and monitor AMR through plasmid transmission between multi-resistant bacterial pathogens.

Time heals all wounds? Naïve theories about the fading of affect associated with autobiographical events.

The current research examined the naïve theories that individuals hold about how affect fades over time. In three studies (with various replications), participants read about positive and negative events and estimated the emotional impact of those events on either themselves or a hypothetical other over different time frames (i.e., 1 week, 1 month, 1 year-Studies 1a-1c) or how long it would take for specific amounts of fade to occur (Studies 2a & 2b). In a final study, participants were directly asked about their beliefs regarding affect fade. Results demonstrated that people have inaccurate expectations about affect fade for positive and negative events. Specifically, participants rate that positive events fade more in the short term, but that negative events fade more in the long term. Results are discussed in terms of how these (incorrect) naïve theories of affect fade relate to metacognitive biases in memory and emotion.

Predicting the Need for Transition from Pediatric to Adult Pain Services: A Retrospective, Longitudinal Study Using the Electronic Persistent Pain Outcome Collaboration (ePPOC) Databases.

A proportion of youth with chronic pain do not respond to interdisciplinary pain management and may require transition to adult pain services. This study sought to characterize a cohort of patients referred to pediatric pain services who subsequently required referral to an adult pain service. We compared this transition group with pediatric patients eligible by age to transition but who did not transition to adult services. We sought to identify factors predicting the need to transition to adult pain services. This retrospective study utilized linkage data from the adult electronic Persistent Pain Outcomes Collaboration (ePPOC) and the pediatric (PaedePPOC) data repositories. The transition group experienced significantly higher pain intensity and disability, lower quality of life, and higher health care utilization relative to the comparison group. Parents of the transition group reported greater distress, catastrophizing, and helplessness relative to parents in the comparison group. Three factors significantly predicted transition: compensation status (OR = 4.21 (1.185-15)), daily anti-inflammatory medication use (OR = 2 (1.028-3.9)), and older age at referral (OR = 1.6 (1.3-2.17)). This study demonstrated that patients referred to pediatric pain services who subsequently need transition to adult services are a uniquely disabled and vulnerable group beyond comparative peers. Clinical applications for transition-specific care are discussed.

Large-scale physically accurate modelling of real proton exchange membrane fuel cell with deep learning.

Proton exchange membrane fuel cells, consuming hydrogen and oxygen to generate clean electricity and water, suffer acute liquid water challenges. Accurate liquid water modelling is inherently challenging due to the multi-phase, multi-component, reactive dynamics within multi-scale, multi-layered porous media. In addition, currently inadequate imaging and modelling capabilities are limiting simulations to small areas (<1 mm2) or simplified architectures. Herein, an advancement in water modelling is achieved using X-ray micro-computed tomography, deep learned super-resolution, multi-label segmentation, and direct multi-phase simulation. The resulting image is the most resolved domain (16 mm2 with 700 nm voxel resolution) and the largest direct multi-phase flow simulation of a fuel cell. This generalisable approach unveils multi-scale water clustering and transport mechanisms over large dry and flooded areas in the gas diffusion layer and flow fields, paving the way for next generation proton exchange membrane fuel cells with optimised structures and wettabilities.

Holding on & letting go: romantic attachment and fading affect bias.

The current research examined the phenomenon of fading affect bias - the tendency for affect associated with negative events to fade more than affect associated with positive events - within the context of romantic relationships. Participants recalled and evaluated positive and negative relationship-specific and non-relationship autobiographical events. Participants also completed measures of attachment avoidance and anxiety. Multi-level modeling demonstrated fading affect bias for relationship and non-relationship events, but that affect fade was shaped by attachment orientations. Specifically, higher attachment anxiety, and lower attachment avoidance predicted greater importance of relationship events which predicted lower fading of affective intensity of memories. Thus, attachment anxiety sustained, while attachment avoidance suppressed the affect of relational memories. We discuss implications of these findings for relationship maintenance.

Factors That Influence the Speed and Completion of Double Balloon Enteroscopy in Patients with Arteriovenous Malformations.

BACKGROUND: Double balloon enteroscopy remains a resource and time-intensive procedure that is not available in many endoscopy units. AIMS: We aimed to identify variables impacting the speed and completion of double balloon enteroscopy. METHODS: We retrospectively reviewed 550 patients. Using a mean time and distance for both the antegrade and retrograde approach, we determined the procedure speed and assessed factors that influenced it. In addition, we assessed the factors that contributed to a complete double balloon enteroscopy. RESULTS: A total of 386 antegrade and 164 retrograde double balloon enteroscopies were performed. Greater than 10 AVMs requiring treatment was a negative predictor (AOR 0.25, CI 0.11-0.51, p < 0.001), whereas age greater than 60 years (AOR 2.66, CI 1.18-6.65, p = 0.025) was a positive predictor of a fast antegrade enteroscopy. For retrograde, prior abdominal surgery was the only factor that trended to significance (AOR 0.38, CI 0.14-0.99, p = 0.052). A total of 120 combined procedures were performed. Female gender (AOR 2.62, CI 1.16-6.24, p = 0.02), history of prior abdominal surgery (AOR 0.31, CI 0.13-0.70, p = 0.006) and Boston bowel pre-preparation score of greater than 6 (AOR 4.50, CI 1.59-14.30, p = 0.006) were the only significant predictors of a complete procedure. CONCLUSION: By applying double balloon enteroscopy speed, a novel method of measuring procedure efficiency, we were able to more reliably identify the factors that will negatively impact the speed and success of the procedure.

Disparate Regions of the Human Chemokine CXCL10 Exhibit Broad-Spectrum Antimicrobial Activity against Biodefense and Antibiotic-Resistant Bacterial Pathogens.

CXCL10 is a pro-inflammatory chemokine produced by the host in response to microbial infection. In addition to canonical, receptor-dependent actions affecting immune-cell migration and activation, CXCL10 has also been found to directly kill a broad range of pathogenic bacteria. Prior investigations suggest that the bactericidal effects of CXCL10 occur through two distinct pathways that compromise the cell envelope. These observations raise the intriguing notion that CXCL10 features a separable pair of antimicrobial domains. Herein, we affirm this possibility through peptide-based mapping and structure/function analyses, which demonstrate that discrete peptides derived from the N- and C-terminal regions of CXCL10 mediate bacterial killing. The N-terminal derivative, peptide P1, exhibited marked antimicrobial activity against Bacillus anthracis vegetative bacilli and spores, as well as antibiotic-resistant clinical isolates of Klebsiella pneumoniae, Acinetobacter baumannii, Enterococcus faecium, and Staphylococcus aureus, among others. At bactericidal concentrations, peptide P1 had a minimal degree of chemotactic activity, but did not cause red blood cell hemolysis or cytotoxic effects against primary human cells. The C-terminal derivative, peptide P9, exhibited antimicrobial effects, but only against Gram-negative bacteria in low-salt medium─conditions under which the peptide can adopt an α-helical conformation. The introduction of a hydrocarbon staple induced and stabilized α-helicity; accordingly, stapled peptide P9 displayed significantly improved bactericidal effects against both Gram-positive and Gram-negative bacteria in media containing physiologic levels of salt. Together, our findings identify and characterize the antimicrobial regions of CXCL10 and functionalize these novel determinants as discrete peptides with potential therapeutic utility against difficult-to-treat pathogens.

Apixaban Use in Obese Patients: A Review of the Pharmacokinetic, Interventional, and Observational Study Data.

Relatively little is known about the influence of extreme body weight on the pharmacokinetics (PK), pharmacodynamics (PD), efficacy, and safety of drugs used in many disease states. While direct oral anticoagulants (DOACs) have an advantage over warfarin in that they do not require routine drug monitoring, some may regard this convenience as less compelling in obese patients. Some consensus guidelines discourage using DOACs in patients weighing > 120 kg or with a body mass index > 35-40 kg/m2, given a sparsity of available data in this population and the concern that fixed dosing in obese patients might lead to decreased drug exposure and lower efficacy. Per the prescribing information, apixaban does not require dose adjustment in patients weighing above a certain threshold (e.g., ≥ 120 kg). Data from healthy volunteers and patients with nonvalvular atrial fibrillation (NVAF) or venous thromboembolism (VTE) have shown that increased body weight has a modest effect on apixaban's PK. However, the paucity of exposure data in individuals > 120 kg and the lack of guideline consensus on DOAC use in obese patients continue to raise concerns about potential decreased drug exposure at extreme weight. This article is the first to comprehensively review the available PK data in obese individuals without NVAF or VTE, and PK, PD, efficacy, effectiveness, and safety data for apixaban in obese patients with either NVAF or VTE, including subgroup analyses across randomized controlled trials and observational (real-world) studies. These data suggest that obesity does not substantially influence the efficacy, effectiveness, or safety of apixaban in these patients. Trial Registration ARISTOTLE: NCT00412984; AVERROES: NCT00496769; AMPLIFY: NCT00643201; AMPLIFY-EXT: NCT00633893; ADVANCE-1: NCT00371683; ADVANCE-2: NCT00452530; ADVANCE-3: NCT00423319 Apixaban Use in Obese Patients: A Review of the Pharmacokinetic, Interventional, and Observational Study Data (MP4 161.22 MB).

Incidence of Injury for Professional Soccer Players in the United States: A 6-Year Prospective Study of Major League Soccer.

Background: Despite an abundance of injury research focusing on European professional soccer athletes, there are limited injury data on professional soccer players in the United States. Purpose: To describe the epidemiology of injury across multiple years in Major League Soccer (MLS) players. Study Design: Descriptive epidemiology study. Methods: A web-based health management platform was used to prospectively collect injury data from all MLS teams between 2014 and 2019. An injury was defined as an incident that required medical attention and was recorded into the health management platform anytime over the course of the 2014-2019 seasons. Injuries and exposure data were recorded in training and match settings to calculate injury incidence. Results: A total of 9713 injuries were recorded between 2014 and 2019. A mean 1.1 injuries per year per player were identified, with midfielders sustaining the largest number of injuries. The most common injuries were hamstring strains (12.3%), ankle sprains (8.5%), and adductor strains (7.6%). The mean time missed per injury was 15.8 days, with 44.2% of injuries resulting in no days missed. Overall injury incidence was 8.7 per 1000 hours of exposure, declining over the course of the investigation, with a 4.1-times greater mean incidence during matches (14.0/1000 h) than training (3.4/1000 h). Conclusion: Between 2014 and 2019, the most commonly reported injuries in MLS players were hamstring strains, ankle sprains, and adductor strains. Injury incidence during matches was 4.1 times greater when compared with training, while overall injury incidence was found to decline during the course of the study period.

The effect of acute intermittent hypoxia on human limb motoneurone output.

NEW FINDINGS: What is the central question of this study? Does a single session of repeated bouts of acute intermittent hypoxic breathing enhance the motoneuronal output of the limb muscles of healthy able-bodied participants? What is the main finding and its importance? Compared to breathing room air, there were some increases in motoneuronal output following acute intermittent hypoxia, but the increases were variable across participants and in time after the intervention and depended on which neurophysiological measure was checked. ABSTRACT: Acute intermittent hypoxia (AIH) induces persistent increases in output from rat phrenic motoneurones. Studies in people with spinal cord injury (SCI) suggest that AIH improves limb performance, perhaps via postsynaptic changes at cortico-motoneuronal synapses. We assessed whether limb motoneurone output in response to reflex and descending synaptic activation is facilitated after one session of AIH in healthy able-bodied volunteers. Fourteen participants completed two experimental days, with either AIH or a sham intervention (randomised crossover design). We measured H-reflex recruitment curves and homosynaptic post-activation depression (HPAD) of the H-reflex in soleus, and motor evoked potentials (MEPs) evoked by transcranial magnetic stimulation (TMS) and their recruitment curves in first dorsal interosseous. All measurements were performed at rest and occurred at baseline, 0, 20, 40 and 60 min post-intervention. The intervention was 30 min of either normoxia (sham, F i O 2 ${F_{{\rm{i}}{{\rm{O}}_{\rm{2}}}}}$  ≈ 0.21) or AIH (alternate 1-min hypoxia [ F i O 2 ${F_{{\rm{i}}{{\rm{O}}_{\rm{2}}}}}$  ≈ 0.09], 1-min normoxia). After AIH, the H-reflex recruitment curve shifted leftward. Lower stimulation intensities were needed to evoke 5%, 50% and 99% of the maximal H-reflex at 40 and 60 min after AIH (P < 0.04). The maximal H-reflex, recruitment slope and HPAD were unchanged after AIH. MEPs evoked by constant intensity TMS were larger 40 min after AIH (P = 0.027). There was no change in MEP recruitment or the maximal MEP. In conclusion, some measures of the evoked responses from limb motoneurones increased after a single AIH session, but only at discrete time points. It is unclear to what extent these changes alter functional performance.

Disrupted Circadian Rhythm of Epinephrine in Males With Youth-Onset Type 2 Diabetes.

Context: Blood pressure and plasma catecholamines normally decline during sleep and rapidly increase in early morning. This is blunted in adults with type 2 diabetes (T2D). Objective: We hypothesize that increased sympatho-adrenal activity during sleep differentiates youth with T2D from nondiabetic obese youth and lean youth. Methods: Fasting spot morning and 24-hour urines were collected in obese adolescents with and without T2D, and normal-weight controls. Fractionated free urine catecholamines (epinephrine, norepinephrine, and dopamine) were measured, and the ratio of fasting spot morning to 24-hour catecholamines was calculated. Results: Urinary 24-hour catecholamine levels were comparable across the 3 groups. Fasting morning epinephrine and the ratio of fasting morning/24-hour epinephrine were higher in youth with T2D (P = 0.004 and P = 0.035, respectively). In males, the ratio of fasting morning/24-hour epinephrine was also higher in youth with T2D (P = 0.005). In females, fasting morning norepinephrine and the ratio of fasting morning/24-hour dopamine were lower in obese youth with and without T2D (P = 0.013 and P = 0.005, respectively) compared with lean youth. Systolic blood pressure was higher in diabetic participants than other groups; males trended higher than females. Conclusion: Circadian rhythm in catecholamines is disrupted in youth-onset T2D, with a blunted overnight fall in urinary epinephrine in males. Conversely, fasting morning norepinephrine and dopamine levels were lower in obese females with or without T2D. Higher nocturnal catecholamines in males with T2D might associate with, or predispose to, hypertension and cardiovascular complications. Lower catecholamine excretion in females with obesity might serve an adaptive, protective role.