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Rationale: The conducting of clinical trials in infants with cystic fibrosis (CF) has been hindered by lack of sensitive outcome measures.Objectives: To evaluate safety, feasibility, and ability to detect abnormalities in lung function of serial pulmonary function tests (PFTs) in infants with CF.Methods: Multicenter observational study using a commercial device, rigorous training, ongoing quality control, and over-reading of data by an independent panel. Raised volume rapid thoracoabdominal compression technique and plethysmography were performed at enrollment and at 6 and 12 months, with an additional 1-month reproducibility visit.Measurements and Main Results: A total of 342 procedures were performed in 100 infants with CF at 10 centers. FRC measurements were acceptable at a higher proportion of study visits (89%) than raised volume (72%) or fractional lung volume (68%) measurements. Average Z scores for many parameters differed significantly from historical control values. Mean (95% confidence interval) Z scores were: -0.52 (-0.78 to -0.25) for forced expiratory flow at 75% (FEF₇₅) for FVC; 1.92 (1.39-2.45) for FRC; 1.22 (0.68-1.76) for residual volume; 0.87 (0.60-1.13) for FRC/total lung capacity; and 0.66 (0.27-1.06) for residual volume/total lung capacity. For future multicenter clinical trials using infant PFTs as primary endpoints, minimum detectable treatment effects are presented for several sample sizes.Conclusions: In this 10-center study, key PFT measures were significantly different in infants with CF than in historical control subjects. However, infant PFTs do not yet appear ready as primary efficacy endpoints for multicenter clinical trials, particularly at inexperienced sites, based on acceptability rates, variability, and potentially large sample sizes required to detect reasonable treatment effects. [ABSTRACT FROM AUTHOR]

Monitoring body temperature and energy expenditure in freely-moving laboratory mice remains a powerful methodology used widely across a variety of disciplines-including circadian biology, sleep research, metabolic phenotyping, and the study of body temperature regulation. Some of the most pronounced changes in body temperature are observed when small heterothermic species reduce their body temperature during daily torpor. Daily torpor is an energy saving strategy characterized by dramatic reductions in body temperature employed by mice and other species when challenged to meet energetic demands. Typical measurements used to describe daily torpor are the measurement of core body temperature and energy expenditure. These approaches can have drawbacks and developing alternatives for these techniques provides options that can be beneficial both from an animal-welfare and study-complexity perspective. First, this paper presents and assesses a method to estimate core body temperature based on measurements of subcutaneous body temperature, and second, a separate approach to better estimate energy expenditure during daily torpor based on core body temperature. Third, the effects of light exposure during the habitual dark phase and sleep deprivation during the light period on body temperature dynamics were tested preliminary in fed and fasted mice. Together, the here-published approaches and datasets can be used in the future to assess body temperature and metabolism in freely-moving laboratory mice., (© 2024. The Author(s).)

Brain-related plasticity can occur at a significant rate varying on the developmental period. Adolescence in particular has been identified as a period of growth and change across the structure and function of the nervous system. Notably, research has identified migraines as common in both pediatric and adult populations, but evidence suggests that the phenotype for migraines may differ in these cohorts due to the unique needs of each developmental period. Accordingly, primary aims of this study were to define hippocampal structure in females (7-27 years of age) with and without migraine, and to determine whether this differs across developmental stages (i.e., childhood, adolescence, and young adulthood). Hippocampal volume was quantified based on high-resolution structural MRI using FMRIB's Integrated Registration and Segmentation Tool. Results indicated that migraine and age may have an interactional relationship with hippocampal volume, such that, while hippocampal volumes were lower in female migraineurs (compared to age-matched controls) during childhood and adolescence, this contrast differed during young adulthood whereby hippocampal volumes were higher in migraineurs (compared to age-matched controls). Subsequent vertex analysis localized this interaction effect in hippocampal volume to displacement of the anterior hippocampus. The transition of hippocampal volume during adolescent development in migraineurs suggests that hippocampal plasticity may dynamically reflect components of migraine that change over the lifespan, exerting possible altered responsivity to stress related to migraine attacks thus having physiological expression and psychosocial impact., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background: Adjustment disorder (AD) is the most common mental health diagnosis in the U.S. military and is more than twice as likely to be diagnosed in active duty servicewomen as compared with male servicemembers. The literature on ADs, particularly in female servicemembers, has not been reviewed yet. We conducted a scoping review of the literature to explore the degree of research activity and summarize current literature gaps., Methods: We created a PRISMA-ScR checklist and prospectively registered it in Open Science Framework. The literature search included articles (including studies and reports) published between 2000 and 2018 in either the grey literature or the following databases: Ovid Medline, CINAHL, Embase, PsycINFO, Web of Science, and Ovid Cochrane. We used DistillerSR to conduct title and abstracts screening, full-text screening, and data charting. The social ecological model for military women's health framework was used to organize the results., Results: After screening 1,304 records, 29 were included for data charting. Most frequently, studies were descriptive (cross-sectional) (25%), with no randomized controlled studies. The studies primarily focused on ADs' risk factors in servicewomen (76%), followed by military readiness (38%). Only 14% addressed recommendations for treatments based on expert opinion, although they did not directly test interventions, and 7% focused on health outcomes., Conclusions: ADs affect the health of U.S. military women and military readiness, yet little is known about their successful treatment or health outcomes. Additional research in those areas is warranted., (Published by Elsevier Inc.)

Body temperature is an important physiological parameter in many studies of laboratory mice. Continuous assessment of body temperature has traditionally required surgical implantation of a telemeter, but this invasive procedure adversely impacts animal welfare. Near-infrared thermography provides a non-invasive alternative by continuously measuring the highest temperature on the outside of the body (T skin ), but the reliability of these recordings as a proxy for continuous core body temperature (T core ) measurements has not been assessed. Here, T core (30 s resolution) and T skin (1 s resolution) were continuously measured for three days in mice exposed to ad libitum and restricted feeding conditions. We subsequently developed an algorithm that optimised the reliability of a T skin -derived estimate of T core . This identified the average of the maximum T skin per minute over a 30-min interval as the optimal way to estimate T core . Subsequent validation analyses did however demonstrate that this T skin -derived proxy did not provide a reliable estimate of the absolute T core due to the high between-animal variability in the relationship between T skin and T core . Conversely, validation showed that T skin -derived estimates of T core reliably describe temporal patterns in physiologically-relevant T core changes and provide an excellent measure to perform within-animal comparisons of relative changes in T core .

The 24-hr cycle of activity and sleep provides perhaps the most familiar example of circadian rhythms. In mammals, circadian activity rhythms are generated by a master biological clock located in the hypothalamic suprachiasmatic nuclei (SCN). This clock is synchronized (entrained) to the external light environment via light input from retinal photoreceptors. However, sleep is not a simple circadian output and also is regulated by a homeostatic process whereby extended wakefulness increases the need for subsequent sleep. As such, the amount and distribution of sleep depends upon the interaction between both circadian and homeostatic processes. Moreover, the study of circadian activity and sleep is not confined only to these specialized fields. Sleep and circadian rhythm disruption is common in many conditions, ranging from neurological and metabolic disorders to aging. Such disruption is associated with a range of negative consequences including cognitive impairment and mood disorders, as well as immune and metabolic dysfunction. As circadian activity and sleep are hallmarks of normal healthy physiology, they also provide valuable welfare indicators. However, traditional methods for the monitoring of circadian rhythms and sleep in mice can require separate specialized resources as well as significant expertise. Here, we outline a low-cost, non-invasive, and open-source method for the simultaneous assessment of circadian activity and sleep in mice. This protocol describes both the assembly of the hardware used and the capture and analysis of data without the need for expertise in electronics or data processing. © 2020 Wiley Periodicals LLC. Basic Protocol: Assembly of a PIR system for basic activity and sleep recordings Alternate Protocol: Data collection using Raspberry Pi Support Protocol: Circadian analysis using PIR sensors., (© 2020 Wiley Periodicals LLC.)

Objective: Military family caregivers (MFCGs) are a growing population with well-being and quality of life (QOL) challenges. New technologies can help meet their needs while minimizing disruption to caregiving responsibilities. Preliminary research needs to address intervention implementation challenges before larger-scale efficacy studies are conducted. This study aimed to evaluate the feasibility of implementing an avatar-based intervention and preliminarily investigate outcomes., Methods: One-hundred twenty-four MFCGs were recruited to participate in this feasibility study. Sixty-four MFCGs completed the intervention. Data were analyzed using repeated-measures analysis of variance to assess 3- and 6-month differences., Results: Meeting the a priori goal of 50 MFCGs completing the program supported feasibility. Preliminary results indicated significant reductions in depression, anxiety, and somatic symptoms, and significant improvements in physical health and overall QOL., Conclusions: Findings support for the feasibility of implementing an avatar-based intervention for MFCGs and present promising findings related to improving caregiver well-being and overall QOL., (© 2019 Wiley Periodicals, Inc.)

Objective: To determine brain magnetic resonance imaging (MRI) measures of cerebrospinal fluid (CSF) and whole brain volume of full-term and premature infants following surgical treatment for thoracic non-cardiac congenital anomalies requiring critical care. Methods: Full-term ( n = 13) and pre-term ( n = 13) patients with long-gap esophageal atresia, and full-term naïve controls ( n = 19) < 1 year corrected age, underwent non-sedated brain MRI following completion of thoracic non-cardiac surgery and critical care treatment. Qualitative MRI findings were reviewed and reported by a pediatric neuroradiologist and neurologist. Several linear brain metrics were measured using structural T1-weighted images, while T2-weighted images were required for segmentation of total CSF and whole brain tissue using the M orphologically A daptive N eonatal T issue S egmentation ( MANTiS ) tool. Group differences in absolute (mm, cm 3 ) and normalized (%) data were analyzed using a univariate general linear model with age at scan as a covariate. Mean normalized values were assessed using one-way ANOVA. Results: Qualitative brain findings suggest brain atrophy in both full-term and pre-term patients. Both linear and volumetric MRI analyses confirmed significantly greater total CSF and extra-axial space, and decreased whole brain size in both full-term and pre-term patients compared to naïve controls. Although linear analysis suggests greater ventricular volumes in all patients, volumetric analysis showed that normalized ventricular volumes were higher only in premature patients compared to controls. Discussion: Linear brain metrics paralleled volumetric MRI analysis of total CSF and extra-axial space, but not ventricular size. Full-term infants appear to demonstrate similar brain vulnerability in the context of life-saving thoracic non-cardiac surgery requiring critical care as premature infants.

Migraine is a disease that peaks in late adolescence and early adulthood. The aim of this study was to evaluate age-related brain changes in resting state functional connectivity (rs-FC) in migraineurs vs. age-sex matched healthy controls at two developmental stages: adolescence vs. young adulthood. The effect of the disease was assessed within each developmental group and age- and sex-matched healthy controls and between developmental groups (migraine-related age effects). Globally the within group comparisons indicated more widespread abnormal rs-FC in the adolescents than in the young adults and more abnormal rs-FC associated with sensory networks in the young adults. Direct comparison of the two groups showed a number of significant changes: (1) more connectivity changes in the default mode network in the adolescents than in the young adults; (2) stronger rs-FC in the cerebellum network in the adolescents in comparison to young adults; and (3) stronger rs-FC in the executive and sensorimotor network in the young adults. The duration and frequency of the disease were differently associated with baseline intrinsic connectivity in the two groups. fMRI resting state networks demonstrate significant changes in brain function at critical time point of brain development and that potentially different treatment responsivity for the disease may result.

Introduction Although migraine is a common headache complaint in children and adolescents there remains a significant gap in understanding the unique aspects of the disease in these age groups and their evolution with development. The aim of this retrospective cohort study was to identify migraine features that are influenced by age and sex. Methods The headache characteristics of 359 paediatric patients with a clinical diagnosis of migraine from a tertiary paediatric headache clinic were assessed. Patients retrospectively reported headache characteristics during a structured intake interview and clinical exam. Headache characteristics, description and associated symptoms were compared between children (age ≤ 12 years) and adolescents (age > 12 years), and between male and female migraineurs. Results Several migraine features differed significantly with age and/or sex, including: (i) a marked change from a 1:1 sex ratio in children to a 2:1 predominance of girls in adolescents; (ii) a higher frequency of headache attacks per month in adolescents and female migraineurs; (iii) a higher proportion of adolescents endorsed a 'throbbing' pain quality; (iv) a higher proportion of children reporting nausea and vomiting; and (v) a higher proportion of adolescents, particularly female migraineurs, had a diagnosis of a co-morbid anxiety. Conclusion The presentation of migraine, both in terms of its headache characteristics and associated symptoms, appear to vary as a function of age and sex. Given that migraine symptoms have a neural basis, it is not surprising that during the key period of neurodevelopment from childhood to adolescence this may impact their presentation.

Craig JC, Broxterman RM, Wilcox SL, Chen C, Barstow TJ. Effect of adipose tissue thickness, muscle site, and sex on near-infrared spectroscopy derived total-[hemoglobin + myoglobin]. J Appl Physiol 123: 1571-1578, 2017. First published September 21, 2017; doi: 10.1152/japplphysiol.00207.2017 .-Adipose tissue thickness (ATT) attenuates signals from near-infrared spectroscopy (NIRS) and diminishes the absolute quantification of underlying tissues by contemporary NIRS devices. Based on the relationship between NIRS-derived total-[hemoglobin + myoglobin] (total-[Hb + Mb]) and ATT, we tested the hypotheses that the correction factor for ATT 1) is muscle site specific; 2) does not differ between men and women; and that 3) exclusion of the shortest source-detector distance from data analysis increases total-[Hb + Mb]. Fourteen healthy subjects (7 men) rested in a neutral body position (supine or prone) while measurements of total-[Hb + Mb] and ATT were taken at four muscles common to resting and exercise studies: vastus lateralis (VL), rectus femoris (RF), gastrocnemius (GS), and flexor digitorum superficialis (FDS). ATT averaged 6.0 ± 0.4 mm across all muscles. Every muscle showed a negative slope ( r 2 : 0.6-0.94; P < 0.01) for total-[Hb + Mb] as a function of ATT: VL (-34 μM/mm), RF (-26 μM/mm), GS (-54 μM/mm), and FDS (-33 μM/mm). The projected total-[Hb + Mb] at 0 mm ATT ( y-intercept) was 452, 372, 620, and 456 μM for VL, RF, GS, and FDS, respectively. No differences were found between the sexes within VL, RF, or FDS, but men had a greater projected total-[Hb + Mb] at 0 mm for GS (688 ± 44 vs. 552 ± 40 μM; P < 0.05). Exclusion of the shortest source-detector distance increased total-[Hb + Mb] by 12 ± 1 μM ( P < 0.05). The present findings demonstrate that total-[Hb + Mb] should be corrected for ATT using muscle site-specific factors which are not sex specific, except in the case of GS. NEW & NOTEWORTHY Near-infrared spectroscopy (NIRS) is an important tool for physiologists and clinicians. However, adipose tissue greatly attenuates the signals from these devices. Correcting for this attenuation has been suggested based on the strength of the relationship between NIRS-derived measurements and the adipose tissue thickness. We show that this relationship is unique to the muscle site of interest but may not be sex specific. Accurate quantification of underlying tissue mandates researchers correct for adipose tissue thickness.

Over the past decade, human brain imaging investigations have reported altered regional cerebral blood flow (rCBF) in the interictal phase of migraine. However, there have been conflicting findings across different investigations, making the use of perfusion imaging in migraine pathophysiology more difficult to define. These inconsistencies may reflect technical constraints with traditional perfusion imaging methods such as single-photon emission computed tomography and positron emission tomography. Comparatively, pseudocontinuous arterial spin labeling (pCASL) is a recently developed magnetic resonance imaging technique that is noninvasive and offers superior spatial resolution and increased sensitivity. Using pCASL, we have previously shown increased rCBF within the primary somatosensory cortex (S1) in adult migraineurs, where blood flow was positively associated with migraine frequency. Whether these observations are present in pediatric and young adult populations remains unknown. This is an important question given the age-related variants of migraine prevalence, symptomology, and treatments. In this investigation, we used pCASL to quantitatively compare and contrast blood flow within S1 in pediatric and young adult migraineurs as compared with healthy controls. In migraine patients, we found significant resting rCBF increases within bilateral S1 as compared with healthy controls. Furthermore, within the right S1, we report a positive correlation between blood flow value with migraine attack frequency and cutaneous allodynia symptom profile. Our results reveal that pediatric and young adult migraineurs exhibit analogous rCBF changes with adult migraineurs, further supporting the possibility that these alterations within S1 are a consequence of repeated migraine attacks. Hum Brain Mapp 38:4078-4087, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Migraine is a recurring, episodic neurological disorder characterized by headache, nausea, vomiting, and sensory disturbances. These events are thought to arise from the activation and sensitization of neurons along the trigemino-vascular pathway. From animal studies, it is known that thalamocortical projections play an important role in the transmission of nociceptive signals from the meninges to the cortex. However, little is currently known about the potential involvement of cortico-cortical feedback projections from higher-order multisensory areas and/or feedforward projections from principle primary sensory areas or subcortical structures. In a large cohort of human migraine patients ( N = 40) and matched healthy control subjects ( N = 40), we used resting-state intrinsic functional connectivity to examine the cortical networks associated with the three main sensory perceptual modalities of vision, audition, and somatosensation. Specifically, we sought to explore the complexity of the sensory networks as they converge and become functionally coupled in multimodal systems. We also compared self-reported retrospective migraine symptoms in the same patients, examining the prevalence of sensory symptoms across the different phases of the migraine cycle. Our results show widespread and persistent disturbances in the perceptions of multiple sensory modalities. Consistent with this observation, we discovered that primary sensory areas maintain local functional connectivity but express impaired long-range connections to higher-order association areas (including regions of the default mode and salience network). We speculate that cortico-cortical interactions are necessary for the integration of information within and across the sensory modalities and, thus, could play an important role in the initiation of migraine and/or the development of its associated symptoms.

Objectives: Although many service members successfully cope with exposure to stress and traumatic experiences, others have symptoms of depression, posttraumatic stress disorder (PTSD), and anxiety; contextual factors may account for the variability in outcomes from these experiences. This work sought to understand mechanisms through which social support influences the mental health of service members and whether dyadic functioning mediates this relationship., Methods: We collected cross-sectional data as part of a larger study conducted in 2013; 321 military personnel who had at least 1 deployment were included in these analyses. Surveys were completed online; we collected data on demographic characteristics, social support, mental health measures (depression, PTSD, and anxiety), and dyadic functioning. We performed process modeling through mediation analysis., Results: The direct effects of social support on the mental health of military personnel were limited; however, across all types of support networks, greater social support was significantly associated with better dyadic functioning. Dyadic functioning mediated the relationships between social support and depression/PTSD only when social support came from nonmilitary friends or family; dyadic functioning mediated social support and anxiety only when support came from family. We found no indirect effects of support from military peers or military leaders., Conclusion: Findings here highlight the need to continue to explore ways in which social support, particularly from family and nonmilitary-connected peers, can bolster healthy intimate partner relationships and, in turn, improve the well-being of military service members who are deployed., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The sustainable duration of severe intensity exercise is well-predicted by critical power (CP) and the curvature constant (W'). The development of the W'BAL model allows for the pattern of W' expenditure and reconstitution to be characterized and this model has been applied to intermittent exercise protocols. The purpose of this investigation was to assess the influence of relaxation phase duration and exercise intensity on W' reconstitution during dynamic constant power severe intensity exercise. Six men (24.6 ± 0.9 years, height: 173.5 ± 1.9 cm, body mass: 78.9 ± 5.6 kg) performed severe intensity dynamic handgrip exercise to task failure using 50% and 20% duty cycles. The W'BAL model was fit to each exercise test and the time constant for W' reconstitution (τW') was determined. The τW' was significantly longer for the 50% duty cycle (1640 ± 262 sec) than the 20% duty cycle (863 ± 84 sec, P = 0.02). Additionally, the relationship between τW' and CP was well described as an exponential decay (r(2) = 0.90, P < 0.0001). In conclusion, the W'BAL model is able to characterize the expenditure and reconstitution of W' across the contraction-relaxation cycles comprising severe intensity constant power handgrip exercise. Moreover, the reconstitution of W' during constant power severe intensity exercise is influenced by the relative exercise intensity, the duration of relaxation between contractions, and CP., (© 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.)

Unlabelled: For many years, neurobiological theories have emphasized the importance of neuronal oscillations in the emergence of brain function. At the same time, clinical studies have shown that disturbances or irregularities in brain rhythms may relate to various common neurological conditions, including migraine. Increasing evidence suggests that the CNS plays a fundamental role in the predisposition to develop different forms of headache. Here, we present human imaging data that strongly support the presence of abnormal low-frequency oscillations (LFOs) in thalamocortical networks of patients in the interictal phase of migraine. Our results show that the main source of arrhythmic activity was localized to the higher-order thalamic relays of the medial dorsal nucleus. In addition, spontaneous LFOs in the thalamus were selectively associated with the headache attack frequency, meaning that the varying amplitude of dysrhythmia could predispose patients to recurrent attacks. Rhythmic cortical feedback to the thalamus is a major factor in the amplification of thalamocortical oscillations, making it a strong candidate for influencing neuronal excitability. We further speculate that the intrinsic dynamics of thalamocortical network oscillations are crucial for early sensory processing and therefore could underlie important pathophysiological processes involved in multisensory integration., Significance Statement: In many cases, migraine attacks are thought to begin centrally. A major obstacle to studying intrinsic brain activity has been the identification of the precise anatomical structures and functional networks that are involved in migraine. Here, we present imaging data that strongly support the presence of abnormal low-frequency oscillations in thalamocortical networks of patients in the interictal phase of migraine. This arrhythmic activity was localized to the higher-order thalamic relays of the medial dorsal nucleus and was selectively associated with headache attack frequency. Rhythmic cortical feedback to the thalamus is a major factor in the amplification of thalamocortical oscillations, making it a strong candidate for influencing neuronal excitability and higher-level processes involved in multisensory integration., (Copyright © 2016 the authors 0270-6474/16/368026-11$15.00/0.)

Pain is both an unpleasant sensory and emotional experience. This is highly relevant in migraine where cortical hyperexcitability in response to sensory stimuli (including pain, light, and sound) has been extensively reported. However, migraine may feature a more general enhanced response to aversive stimuli rather than being sensory-specific. To this end we used functional magnetic resonance imaging to assess neural activation in migraineurs interictaly in response to emotional visual stimuli from the International Affective Picture System. Migraineurs, compared to healthy controls, demonstrated increased neural activity in response to negative emotional stimuli. Most notably in regions overlapping in their involvement in both nociceptive and emotional processing including the posterior cingulate, caudate, amygdala, and thalamus (cluster corrected, p < 0.01). In contrast, migraineurs and healthy controls displayed no and minimal differences in response to positive and neutral emotional stimuli, respectively. These findings support the notion that migraine may feature more generalized altered cerebral processing of aversive/negative stimuli, rather than exclusively to sensory stimuli. A generalized hypersensitivity to aversive stimuli may be an inherent feature of migraine, or a consequential alteration developed over the duration of the disease. This proposed cortical-limbic hypersensitivity may form an important part of the migraine pathophysiology, including psychological comorbidity, and may represent an innate sensitivity to aversive stimuli that underpins attack triggers, attack persistence and (potentially) gradual headache chronification.

Background: This study aimed to investigate the feasibility of determining the physiological parameters associated with the ability to complete simulated exploration type tasks at metabolic rates which might be expected for lunar and Martian ambulation., Methods: Running V̇O2max and gas exchange threshold (GET) were measured in 21 volunteers. Two simulated extravehicular activity field tests were completed in 1 G in regular athletic apparel at two intensities designed to elicit metabolic rates of ∼20.0 and ∼30.0 ml · kg(-1) · min(-1), which are similar to those previously reported for ambulation in simulated lunar- and Martian-based environments, respectively., Results: All subjects were able to complete the field test at the lunar intensity, but 28% were unable to complete the field test at the Martian intensity (non-Finishers). During the Martian field test there were no differences in V̇O2 between Finishers and non-Finishers, but the non-Finishers achieved a greater %V̇O2max compared to Finishers (78.4 ± 4.6% vs. 64.9 ± 9.6%). Logistic regression analysis revealed fitness thresholds for a predicted probability of 0.5, at which Finishing and non-Finishing are equally likely, and 0.75, at which an individual has a 75% chance of Finishing, to be a V̇O2max of 38.4 ml · kg(-1) · min(-1) and 40.0 ml · kg(-1) · min(-1) or a GET of 20.1 ml · kg(-1) · min(-1) and 25.1 ml · kg(-1) · min(-1), respectively (χ(2) = 10.2). Logistic regression analysis also revealed that the expected %V̇O2max required to complete a field test could be used to successfully predict performance (χ(2) = 19.3)., Discussion: The results of the present investigation highlight the potential utility of V̇O2max, particularly as it relates to the metabolic demands of a surface ambulation, in defining successful completion of planetary-based exploration field tests.

Oxygen uptake (V̇O2) kinetics have been shown to be governed by a nonlinear control system across a range of work rates. However, the linearity of the V̇O2 response to ramp incremental exercise would appear to be the result of a linear control system. This apparent contradiction could represent a balancing of changing V̇O2 kinetics parameter values across a range of work rates. To test this, six healthy men completed bouts of ramp incremental exercise at 15, 30, and 60 W/min (15R, 30R, 60R, respectively) and four bouts of an extended-step incremental exercise. V̇O2 parameter values were derived from the step exercise using two monoexponential models: one starting at time zero and encompassing the entire stage (MONO), and the other truncated to the first 5 min and allowing a time delay (5TD). The resulting parameter values were applied to an integrative model to estimate the ramp responses. As work rate increased, gain values increased (P < 0.001 for MONO and 5TD), as did mean response time (or time constant) values (MONO: P < 0.001; 5TD: P = 0.003). Up to maximal V̇O2 (V̇O(2 max)), the gains of the estimated ramp responses from both models were not different from the gains of the actual observed V̇O2 responses for 15R and 30R (15R: 11.3 ± 1.2, 11.7 ± 0.7, 10.9 ± 0.3; 30R: 10.5 ± 0.8, 11.0 ± 0.5, 10.7 ± 0.3 ml O2·min(-1)·W(-1), for actual, MONO, 5TD, respectively) but were significantly greater for 60R (8.7 ± 1.0, 9.9 ± 0.4, 10.3 ± 0.3 ml O2·min(-1)·W(-1) for actual, MONO, 5TD, respectively). Up to 80%V̇O(2 max) gain values were not significantly different for any ramp rate (P > 0.05 for all). We conclude that the apparent linearity of the V̇O2 response to ramp incremental exercise is consequent to a balancing of increasing time constant and gain parameter values., (Copyright © 2016 the American Physiological Society.)

Background: Missions to terrestrial destinations (i.e., asteroids, the Moon, and Mars) will consist of physically challenging mission-critical tasks. These tasks, coupled with the negative physiological effects of prolonged microgravity exposure, create a plausible situation in which physical requirements may exceed an astronaut's physical capacity. Therefore, the objective of the current study was to evaluate the association of aerobic fitness and muscular strength parameters with performance during two field tests designed to simulate upper-body mission-critical activities., Methods: There were 70 subjects who completed a material transport field test requiring the loading, transport, and unloading of geological samples and a device operations field test consisting of tasks associated with equipment set-up and the operations of controls and valves. The relationships between test duration and the following measurements were determined: running Vo(2max), gas exchange threshold (GET), speed at Vo(2max) (s-Vo(2max)), highest sustainable rate of aerobic metabolism [critical speed (CS)], and the finite distance that could be covered above CS (D'); and arm cranking Vo(2peak), GET, critical power (CP), and the finite work that can be performed above CP (W')., Results: CP (r = -0.66), CS (r = -0.56), and arm cranking Vo(2peak) (r = -0.54) were most strongly correlated with the material transport field test and decision tree analysis revealed CP as the best predictor of performance. For the device operations field test, CP (r = -0.70), CS (r = -0.62), and arm cranking peak power output (r = -0.56) were significant predictors., Discussion: Arm cranking tests are strongly associated with upper-body dependent tasks, highlighting that the nature of mission tasks needs to be considered when evaluating astronaut physical capacity.

The regulation of cerebral blood flow (CBF) is a complex integrated process that is critical for supporting healthy brain function. Studies have demonstrated a high incidence of alterations in CBF in patients suffering from migraine with and without aura during different phases of attacks. However, the CBF data collected interictally has failed to show any distinguishing features or clues as to the underlying pathophysiology of the disease. In this study we used the magnetic resonance imaging (MRI) technique-arterial spin labeling (ASL)-to non-invasively and quantitatively measure regional CBF (rCBF) in a case-controlled study of interictal migraine. We examined both the regional and global CBF differences between the groups, and found a significant increase in rCBF in the primary somatosensory cortex (S1) of migraine patients. The CBF values in S1 were positively correlated with the headache attack frequency, but were unrelated to the duration of illness or age of the patients. Additionally, 82% of patients reported skin hypersensitivity (cutaneous allodynia) during migraine, suggesting atypical processing of somatosensory stimuli. Our results demonstrate the presence of a disease-specific functional deficit in a known region of the trigemino-cortical pathway, which may be driven by adaptive or maladaptive functional plasticity. These findings may in part explain the altered sensory experiences reported between migraine attacks.

It has previously been postulated that the anaerobic work capacity (W') may be utilized during resting blood flow occlusion in the absence of mechanical work. We tested the hypothesis that W' would not be utilized during an initial range of time following the onset of resting blood flow occlusion, after which W' would be utilized progressively more. Seven men completed blood flow occlusion constant power severe intensity handgrip exercise to task failure following 0, 300, 600, 900, and 1,200 s of resting blood flow occlusion. The work performed above critical power (CP) was not significantly different between the 0-, 300-, and 600-s conditions and was not significantly different from the total W' available. Significantly less work was performed above CP during the 1,200-s condition than the 900-s condition (P < 0.05), while both conditions were significantly less than the 0-, 300-, and 600-s conditions (P < 0.05). The work performed above CP during these conditions was significantly less than the total W' available (P < 0.05). The utilization of W' during resting blood flow occlusion did not begin until 751 ± 118 s, after which time W' was progressively utilized. The current findings demonstrate that W' is not utilized during the initial ∼751 s of resting blood flow occlusion, but is progressively utilized thereafter, despite no mechanical work being performed. Thus, the utilization of W' is not exclusive to exercise, and a constant amount of work that can be performed above CP is not the determining mechanism of W'., (Copyright © 2015 the American Physiological Society.)

Critical power represents an important threshold for neuromuscular fatigue development and may, therefore, dictate intensities for which exercise tolerance is determined by the magnitude of fatigue accrued. Peripheral fatigue appears to be constant across O2 delivery conditions for large muscle mass exercise, but this consistency is equivocal for smaller muscle mass exercise. We sought to determine the influence of blood flow occlusion during handgrip exercise on neuromuscular fatigue development and to examine the relationship between neuromuscular fatigue development and W '. Blood flow occlusion influenced the development of both peripheral and central fatigue, thus providing further evidence that the magnitude of peripheral fatigue is not constant across O2 delivery conditions for small muscle mass exercise. W ' appears to be related to the magnitude of fatigue accrued during exercise, which may explain the reported consistency of intramuscular metabolic perturbations and work performed for severe-intensity exercise. The influence of the muscle metabolic milieu on peripheral and central fatigue is currently unclear. Moreover, the relationships between peripheral and central fatigue and the curvature constant (W ') have not been investigated. Six men (age: 25 ± 4 years, body mass: 82 ± 10 kg, height: 179 ± 4 cm) completed four constant power handgrip tests to exhaustion under conditions of control exercise (Con), blood flow occlusion exercise (Occ), Con with 5 min post-exercise blood flow occlusion (Con + Occ), and Occ with 5 min post-exercise blood flow occlusion (Occ + Occ). Neuromuscular fatigue measurements and W ' were obtained for each subject. Each trial resulted in significant peripheral and central fatigue. Significantly greater peripheral (79.7 ± 5.1% vs. 22.7 ± 6.0%) and central (42.6 ± 3.9% vs. 4.9 ± 2.0%) fatigue occurred for Occ than for Con. In addition, significantly greater peripheral (83.0 ± 4.2% vs. 69.0 ± 6.2%) and central (65.5 ± 14.6% vs. 18.6 ± 4.1%) fatigue occurred for Occ + Occ than for Con + Occ. W ' was significantly related to the magnitude of global (r = 0.91) and peripheral (r = 0.83) fatigue. The current findings demonstrate that blood flow occlusion exacerbated the development of both peripheral and central fatigue and that post-exercise blood flow occlusion prevented the recovery of both peripheral and central fatigue. Moreover, the current findings suggest that W ' may be determined by the magnitude of fatigue accrued during exercise., (© 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.)

Accumulated evidence from experimental animal models suggests that neuroplastic changes at the dorsal horn are critical for the maintenance of various chronic musculoskeletal pain conditions. However, to date, no study has specifically investigated whether neuroplastic changes also occur at this level in humans. Using brain imaging techniques, we sought to determine whether anatomical changes were present in the medullary dorsal horn (spinal trigeminal nucleus caudalis) in subjects with the chronic musculoskeletal pain. In twenty-two subjects with painful temporomandibular disorders (TMDs) and forty pain-free controls voxel based morphometry of T1-weighted anatomical images and diffusion tensor images were used to assess regional grey matter volume and microstructural changes within the brainstem and, in addition, the integrity of ascending pain pathways. Voxel based morphometry revealed significant regional grey matter volume decreases in the medullary dorsal horn, in conjunction with alterations in diffusivity properties, namely an increase in mean diffusivity, in TMD subjects. Volumetric and mean diffusivity changes also occurred in TMD subjects in regions of the descending pain modulation system, including the midbrain periaqueductal grey matter and nucleus raphe magnus. Finally, tractography revealed altered diffusivity properties, namely decreased fractional anisotropy, in the root entry zone of the trigeminal nerve, the spinal trigeminal tract and the ventral trigeminothalamic tracts of TMD subjects. These data reveal that chronic musculoskeletal pain in humans is associated with discrete alterations in the anatomy of the medullary dorsal horn, as well as its afferent and efferent projections. These neural changes may be critical for the maintenance of pathological pain., (Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.)

Background: Aerobic exercise capacity provides information regarding cardiorespiratory health and physical capacity. However, in many populations the ability to measure whole-body or leg aerobic exercise capacity is limited due to physical disability or lack of appropriate equipment. Clinically there is a need to evaluate aerobic capacity in individuals who cannot use their legs for locomotion. In astronauts the habitable space for exercise testing in the next generation of space exploration systems may be restricted and may not support the traditional lower body testing. Therefore, the purpose was to determine if upper body physical performance could estimate lower body aerobic capacity., Methods: Maximal O₂uptake (Vo(2max)), gas exchange threshold (GET), and the highest sustainable rate of aerobic metabolism [arm cranking critical power ((A)CP) and lower body critical speed ((L)CS)] were determined in 55 conditioned men and women during arm-cranking and treadmill running., Results: Vo(2max) and GET (48.6 ± 7.6 and 29.0 ± 4.8 ml · kg⁻¹ · min⁻¹, respectively) were significantly lower during arm-cranking exercise compared to running (27.1 ± 7.6 and 13.5 ± 2.6 ml · kg⁻¹ · min⁻¹, respectively). The Vo₂at ACP was significantly lower than the Vo₂at the (L)CS (18.4 ± 5.01 vs. 39.5 ± 8.1 ml · kg⁻¹ · min⁻¹, respectively). There was a significant correlation between arm-cranking and lower body Vo2max, GET, and the Vo₂at (L)CS and ACP. Backward stepwise regression analyses revealed that arm-cranking physical fitness could explain 67%, 40%, and 49% of the variance in lower body Vo(2max), GET, and (L)CS, respectively., Discussion: Results suggest arm-cranking exercise can be used to obtain an approximation of lower body aerobic capacity.

Introduction: More than a third of young military personnel report experiencing some level of erectile dysfunction (ED). Preoccupation with body image, particularly genitals, is a distraction that can influence sexual anxiety (SA) and sexual functioning problems (SFPs), particularly ED., Aims: This study assessed the relationships between male genital self-image (MGSI), SA, and ED in a sample of male military personnel age 40 or younger., Methods: Data were from a larger study on SFPs in military populations. This sample consisted of 367 male military personnel age 40 or younger. Hierarchical regression analyses and process modeling using mediation analysis were performed to examine the effects of MGSI on ED with SA as an intermediate variable. We predicted that SA would mediate the relationship between MGSI and ED., Main Outcome Measures: ED severity was assessed with the International Index of Erectile Function. MGSI was assessed using the MGSI Scale. SA was assessed with the SA subscale of the Sexual Needs Scale., Results: As hypothesized, greater satisfaction with MGSI was predictive of significantly lower SA (F[8, 352] = 4.07, P = 0.001) and lower ED (F[8, 352] = 13.20, P = 0.001). Lower levels of SA were predictive of lower levels of ED (F[8, 354] = 21.35, P < 0.001). Additionally, results also revealed a significant indirect effect of MGSI on ED through SA (b = -0.07, standard error = 0.03, confidence interval = [-0.14,-0.02], P < 0.05), indicating mediation of MGSI on ED via SA., Conclusions: This study underscores the complex etiologic basis of SFPs, particularly ED, and highlights the importance of considering psychologic contributors to ED, such as SA and MGSI. Strategies aimed at reducing SA may be useful in improving ED in young military populations and are worth considering as complements to strategies that improve SFPs., (© 2015 International Society for Sexual Medicine.)

It was previously (Monod H, Scherrer J. Ergonomics 8: 329-338, 1965) postulated that blood flow occlusion during exercise would reduce critical power (CP) to 0 Watts (W), while not altering the curvature constant (W'). We empirically assessed the influence of blood flow occlusion on CP, W', and muscle oxygenation characteristics. Ten healthy men (age: 24.8 ± 2.6 yr; height: 180 ± 5 cm; weight: 84.6 ± 10.1 kg) completed four constant-power handgrip exercise tests during both control blood flow (control) and blood flow occlusion (occlusion) for the determination of the power-duration relationship. Occlusion CP (-0.7 ± 0.4 W) was significantly (P < 0.001) lower than control CP (4.1 ± 0.7 W) and significantly (P < 0.001) lower than 0 W. Occlusion W' (808 ± 155 J) was significantly (P < 0.001) different from control W' (558 ± 129 J), and all 10 subjects demonstrated an increased occlusion W' with a mean increase of ∼49%. The present findings support the aerobic nature of CP. The findings also demonstrate that the amount of work that can be performed above CP is constant for a given condition, but can vary across conditions. Moreover, this amount of work that can be performed above CP does not appear to be the determinant of W', but rather a consequence of the depletion of intramuscular energy stores and/or the accumulation of fatigue-inducing metabolites, which limit exercise tolerance and determine W'., (Copyright © 2015 the American Physiological Society.)

Accumulated evidence from experimental animal models suggests that neuronal loss within the dorsal horn is involved in the development and/or maintenance of peripheral neuropathic pain. However, to date, no study has specifically investigated whether such neuroanatomical changes also occur at this level in humans. Using brain imaging techniques, we sought to determine whether anatomical changes were present in the spinal trigeminal nucleus in subjects with chronic orofacial neuropathic pain. In 22 subjects with painful trigeminal neuropathy and 44 pain-free controls, voxel-based morphometry of T1-weighted anatomical images and diffusion tensor images were used to assess regional gray matter volume and microstructural changes within the brainstem. In addition, deterministic tractography was used to assess the integrity of ascending pain pathways. Orofacial neuropathic pain was associated with significant regional gray matter volume decreases, fractional anisotropy increases, and mean diffusivity decreases within the spinal trigeminal nucleus, specifically the subnucleus oralis. In addition, tractography revealed no significant differences in diffusivity properties in the root entry zone of the trigeminal nerve, the spinal trigeminal tract, or the ventral trigeminothalamic tracts in painful trigeminal neuropathy subjects compared with controls. These data reveal that chronic neuropathic pain in humans is associated with discrete alterations in the anatomy of the primary synapse. These neuroanatomical changes may be critical for the generation and/or maintenance of pathological pain., (Copyright © 2015 the authors 0270-6474/15/352508-08$15.00/0.)

Background: Military culture and workplace are areas of interest for researchers across disciplines. However, few publications on military culture exist., Objective: The purpose of this article is to introduce general concepts regarding the structure and culture of the United States Military and discuss how this creates challenges for reintegrating into the civilian world., Method: Topics that will be covered in this article include an overview of the Department of Defense (DoD) and Department of Veterans Affairs (VA), socialization to military culture, the unique features of the military as a workplace, the cultural experiences of military personnel reintegrating back into the community, and the challenges faced by military members and their spouses., Results: The provided information on military culture will expand military cultural competency so that civilian employers can enhance their ability to create supportive workplaces for veterans and military spouses during times of transition and reintegration., Discussion: The unique characteristics of the military culture should be understood by those who work with or plan to work with military populations.

It has previously been suggested that the respiratory compensation point (RCP) and critical speed (CS) parameters are equivalent and, therefore, like CS, RCP demarcates the boundary between the heavy- and severe-intensity domains. However, these findings are equivocal and therefore must be interpreted cautiously. Thus, we examined the relationship between CS and RCP across a wide range of subject fitness levels, in an attempt to determine if CS and RCP are equivalent. Forty men and 30 women (age: 23.2 ± 2.5 year, height: 174 ± 10 cm, body mass: 74.1 ± 15.7 kg) completed an incremental and four constant-speed protocols on a treadmill. RCP was determined as the point at which the minute ventilation increased disproportionately to CO2 production and the end-tidal CO2 partial pressure began to decrease. CS was determined from the constant-speed protocols using the linearized 1·time(-1) model. CS and RCP, expressed as speed or metabolic rate, were not significantly different (11.7 ± 2.3 km·h(-1) vs. 11.5 ± 2.3 km·h(-1), p = 0.208; 2.88 ± 0.80 l·min(-1) vs. 2.83 ± 0.72 l·min(-1), p = 0.293) and were significantly correlated (r(2) = 0.52, p < 0.0001; r(2) = 0.74, p < 0.0001, respectively). However, there was a high degree of variability between the parameters. The findings of the current study indicate that, while on average CS and RCP were not different, the high degree of variability between these parameters does not permit accurate estimation of one from the other variable and suggests that these parameters may not be physiologically equivalent.

Background: More Reserve and Guard members have been activated in the past few years than in any other time in history. In addition to the high rates of psychological and behavioral challenges among military personnel, there are other equally important post-deployment reintegration challenges. Post-deployment reintegration challenges are particularly important to Reserve and Guard members, who transition rapidly from civilian-military-civilian., Objective: This study aims to describe the scope of challenges that a battalion of National Guard members (NGM) report experiencing after returning from a one-year deployment to Iraq., Method: This article reports data from a sample of 126 NGM who recently returned from a one-year deployment to Iraq. The scope of post-deployment problems at baseline, 3- and 6-month post-deployment are presented., Results: Overall, the rates of post-deployment psychological and behavioral problems were elevated upon returning from deployment and remained fairly constant for up to 6 months post-deployment. Approximately 30% of respondents were unsatisfied with their relationship and upwards of 30% reported family reintegration challenges., Conclusions: Comparisons with similar research and implications for prevention and improvement of post-deployment quality of life are addressed.

The purpose was to evaluate the relationships between tests of fitness and two activities that simulate components of Lunar- and Martian-based extravehicular activities (EVA). Seventy-one subjects completed two field tests: a physical abilities test and a 10km Walkback test. The relationships between test times and the following parameters were determined: running V˙O2max, gas exchange threshold (GET), speed at V˙O2max (s-V˙O2max), highest sustainable rate of aerobic metabolism [critical speed (CS)], and the finite distance that could be covered above CS (D'): arm cranking V˙O2peak, GET, critical power (CP), and the finite work that can be performed above CP (W'). CS, running V˙O2max, s-V˙O2max, and arm cranking V˙O2peak had the highest correlations with the physical abilities field test (r=0.66-0.82, P<0.001). For the 10km Walkback, CS, s-V˙O2max, and running V˙O2max were significant predictors (r=0.64-0.85, P<0.001). CS and to a lesser extent V˙O2max are most strongly associated with tasks that simulate aspects of EVA performance, highlighting CS as a method for evaluating astronaut physical capacity., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Introduction: Although the military is a young and vigorous force, service members and veterans may experience sexual functioning problems (SFPs) as a result of military service. Sexual functioning can be impaired by physical, psychological, and social factors and can impact quality of life (QOL) and happiness., Aims: This study aims to estimate rates and correlates of SFPs in male military personnel across demographic and psychosocial characteristics, to examine the QOL concomitants, and to evaluate barriers for treatment seeking., Methods: This exploratory cross-sectional study was conducted using data from a larger nationwide study conducted between October 2013 and November 2013. This sample consists of 367 male active duty service members and recent veterans (military personnel) age 40 or younger., Main Outcome Measures: Erectile dysfunction (ED) was determined using the five-item International Index of Erectile Function, sexual dysfunction (SD) was determined using the Arizona Sexual Experiences Scale, Male, and QOL was determined using the World Health Organization Quality of Life, Brief., Results: SFPs were associated with various demographic, physical, and psychosocial risk factors. The rates of SD and ED were 8.45% and 33.24%, respectively, for male military personnel aged 21-40. Those who were 36-40, nonmarried, nonwhite, and of lower educational attainment reported the highest rates of SFPs. Male military personnel with poor physical and psychosocial health presented the greatest risk for ED and SD. SFPs were associated with reduced QOL and lower happiness, and barriers for treatment were generally related to social barriers., Conclusions: SFPs in young male military personnel are an important public health concern that can severely impact QOL and happiness., (© 2014 International Society for Sexual Medicine.)

There is increasing evidence relating thalamic changes to the generation and/or maintenance of neuropathic pain. We have recently reported that neuropathic orofacial pain is associated with altered thalamic anatomy, biochemistry, and activity, which may result in disturbed thalamocortical oscillatory circuits. Despite this evidence, it is possible that these thalamic changes are not responsible for the presence of pain per se, but result as a consequence of the injury. To clarify this subject, we compared brain activity and biochemistry in 12 people with below-level neuropathic pain after complete thoracic spinal cord injury with 11 people with similar injuries and no neuropathic pain and 21 age- and gender-matched healthy control subjects. Quantitative arterial spinal labelling was used to measure thalamic activity, and magnetic resonance spectroscopy was used to determine changes in neuronal variability quantifying N-acetylaspartate and alterations in inhibitory function quantifying gamma amino butyric acid. This study revealed that the presence of neuropathic pain is associated with significant changes in thalamic biochemistry and neuronal activity. More specifically, the presence of neuropathic pain after spinal cord injury is associated with significant reductions in thalamic N-acetylaspartate, gamma amino butyric acid content, and blood flow in the region of the thalamic reticular nucleus. Spinal cord injury on its own did not account for these changes. These findings support the hypothesis that neuropathic pain is associated with altered thalamic structure and function, which may disturb central processing and play a key role in the experience of neuropathic pain., (Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

The highest sustainable rate of aerobic metabolism [critical power (CP)] and the finite amount of work that can be performed above CP (W' [curvature constant]) were determined under two muscle contraction duty cycles. Eight men completed at least three constant-power handgrip tests to exhaustion to determine CP and W' for 50% and 20% duty cycles, while brachial artery blood flow (Q̇BA) and deoxygenated-[hemoglobin + myoglobin] (deoxy-[Hb+Mb]) were measured. CP was lower for the 50% duty cycle (3.9 ± 0.9 W) than the 20% duty cycle (5.1 ± 0.8 W; p < 0.001), while W' was not significantly different (50% duty cycle: 452 ± 141 J vs. 20% duty cycle: 432 ± 130 J; p > 0.05). At the same power output, Q̇BA and deoxy-[Hb + Mb] achieved higher end-exercise values for the 20% duty cycle (9.87 ± 1.73 ml·s(-1); 51.7 ± 4.7 μM) than the 50% duty cycle (7.37 ± 1.76 ml·s(-1), p < 0.001; 44.3 ± 2.4 μM, p < 0.03). These findings indicate that blood flow influences CP, but not W'., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Rationale: Lung function in children with neuroendocrine cell hyperplasia of infancy (NEHI) and correlations with future clinical outcomes are needed to guide clinical management., Objective: To compare results of infant pulmonary function tests (IPFTs) in children with NEHI to disease control (DC) subjects and to correlate NEHI IPFTs with future outcomes., Methods: We performed a retrospective, single center study of IPFT in subjects diagnosed by lung biopsy (NEHI) or clinically (NEHI syndrome) and in DC subjects evaluated for cancer or pre-hematopoietic stem cell transplantation (HSCT). Raised volume rapid thoracoabdominal compression (RVRTC) and plethysmography were performed on all infants and evaluated for quality. Standard spirometry measures, room air oxygen saturations (RA O2 sat), and weight percentiles were collected during follow up., Measurements and Main Results: Fifty-seven IPFTs were performed in 15 NEHI, 22 NEHI syndrome, and 20 DC subjects. RVRTC and FRC measurements were obtained in 85% or more of subjects in all groups. Significant airflow limitation (FEV0.5 P-value ≤ 0.01) and air trapping (FRC P-value ≤ 0.01) were seen in NEHI and NEHI syndrome subjects compared to DCs. No significant correlations were found between IPFT, oxygen use, RA O2 sat, and weight at the time of the IPFTs. Initial FEV0.5 and FRC z-scores correlated with RA O2 sat (r = 0.60 and -0.49) at short-term follow up (6-12 months). Most measurements of RVRTC correlated with FEV1 (n = 5) measured 4-5 years later (r > 0.50)., Conclusions: IPFTs in NEHI subjects are feasible, demonstrate significant obstruction and air trapping, and correlate with future RA O2 sat and FEV1 . IPFTs may provide valuable clinical information when caring for NEHI patients. Pediatr Pulmonol. 2013; 48:1008-1015. © 2012 Wiley Periodicals, Inc., (© 2012 Wiley Periodicals, Inc.)

Unlabelled: Trigeminal neuralgia, painful trigeminal neuropathy, and painful temporomandibular disorders (TMDs) are chronic orofacial pain conditions that are thought to have fundamentally different etiologies. Trigeminal neuralgia and neuropathy are thought to arise from damage to or pressure on the trigeminal nerve, whereas TMD results primarily from peripheral nociceptor activation. This study sought to assess the volume and microstructure of the trigeminal nerve in these 3 conditions. In 9 neuralgia, 18 neuropathy, 20 TMD, and 26 healthy controls, the trigeminal root entry zone was selected on high-resolution T1-weighted magnetic resonance images and the volume (mm(3)) calculated. Additionally, using diffusion-tensor images (DTIs), the mean diffusivity and fractional anisotropy values of the trigeminal nerve root were calculated. Trigeminal neuralgia patients displayed a significant (47%) decrease in nerve volume but no change in DTI values. Conversely, trigeminal neuropathy subjects displayed a significant (40%) increase in nerve volume but again no change in DTI values. In contrast, TMD subjects displayed no change in volume or DTI values. The data suggest that the changes occurring within the trigeminal nerve are not uniform in all orofacial pain conditions. These structural and volume changes may have implications in diagnosis and management of different forms of chronic orofacial pain., Perspective: This study reveals that neuropathic orofacial pain conditions are associated with changes in trigeminal nerve volume, whereas non-neuropathic orofacial pain is not associated with any change in nerve volume., (Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.)

Human brain imaging has revealed that acute pain results from activation of a network of brain regions, including the somatosensory, insular, prefrontal, and cingulate cortices. In contrast, many investigations report little or no alteration in brain activity associated with chronic pain, particularly neuropathic pain. It has been hypothesized that neuropathic pain results from misinterpretation of thalamocortical activity, and recent evidence has revealed altered thalamocortical rhythm in individuals with neuropathic pain. Indeed, it was suggested nearly four decades ago that neuropathic pain may be maintained by a discrete central generator, possibly within the thalamus. In this investigation, we used multiple brain imaging techniques to explore central changes in subjects with neuropathic pain of the trigeminal nerve resulting in most cases (20 of 23) from a surgical event. Individuals with chronic neuropathic pain displayed significant somatosensory thalamus volume loss (voxel-based morphometry) which was associated with decreased thalamic reticular nucleus and primary somatosensory cortex activity (quantitative arterial spin labeling). Furthermore, thalamic inhibitory neurotransmitter content was significantly reduced (magnetic resonance spectroscopy), which was significantly correlated to the degree of functional connectivity between the somatosensory thalamus and cortical regions including the primary and secondary somatosensory cortices, anterior insula, and cerebellar cortex. These data suggest that chronic neuropathic pain is associated with altered thalamic anatomy and activity, which may result in disturbed thalamocortical circuits. This disturbed thalamocortical activity may result in the constant perception of pain.

Glyceraldehyde-3-phosphate dehydrogenase gene (GAPDH) and its paralogs were implicated in late-onset Alzheimer's disease (LOAD), although the strength and direction of association have not been consistent. We genotyped 3 previously reported single nucleotide polymorphisms (SNPs; rs3741916-GAPDH 5' UTR, rs2029721-pGAPD, and rs4806173-GAPDHS) in 3 case-control series (2112 cases and 3808 controls). Rs3741916 showed the strongest LOAD association (p = 0.003). The minor allele of rs3741916 showed a protective effect in our combined series (odds ratio [OR] = 0.87%, 95% confidence interval [CI] = 0.79-0.96). This is consistent with results from the 2 published follow-up studies and in opposite direction of the original report. Meta-analysis of the published series with ours suggests presence of heterogeneity (Breslow-Day p < 0.0001). Meta-analysis of only the follow-up series including ours revealed a significant protective effect for the minor allele of rs3741916 (OR = 0.85%, 95% CI = 0.76-0.96, p = 0.009). Our results support the presence of LOAD variants and heterogeneity at the GAPDH locus. The most promising rs3741916 variant is unlikely to be functional given opposing effects in different series. Identification of functional variant(s) in this region likely awaits deep sequencing., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Trigeminal neuropathic pain (TNP) and temporomandibular disorders (TMD) are thought to have fundamentally different etiologies. It has been proposed that TNP arises through damage to, or pressure on, somatosensory afferents in the trigeminal nerve, whereas TMD results primarily from peripheral nociceptor activation. Because some reports suggest that neuropathic pain is associated with changes in brain anatomy, it is possible that TNP is maintained by changes in higher brain structures, whereas TMD is not. The aim of this investigation is to determine whether changes in regional brain anatomy and biochemistry occur in both conditions. Twenty-one TNP subjects, 20 TMD subjects, and 36 healthy controls were recruited. Voxel-based morphometry of T1-weighted anatomical images revealed no significant regional gray matter volume change in TMD patients. In contrast, gray matter volume of TNP patients was reduced in the primary somatosensory cortex, anterior insula, putamen, nucleus accumbens, and the thalamus, whereas gray matter volume was increased in the posterior insula. The thalamic volume decrease was only seen in the TNP patients classified as having trigeminal neuropathy but not those with trigeminal neuralgia. Furthermore, in trigeminal neuropathy patients, magnetic resonance spectroscopy revealed a significant reduction in the N-acetylaspartate/creatine ratio, a biochemical marker of neural viability, in the region of thalamic volume loss. The data suggest that the pathogenesis underlying neuropathic and non-neuropathic pain conditions are fundamentally different and that neuropathic pain conditions that result from peripheral injuries may be generated and/or maintained by structural changes in regions such as the thalamus.

The degree to which neuropathic and non-neuropathic pain conditions differ in psychological and psychosocial status remains largely unexplored. A better understanding of these aspects would be of considerable benefit in helping to define whether similar psychological treatment strategies (eg, cognitive-behavioural therapy) can be adopted in the management of neuropathic pain as in non-neuropathic pain conditions. Chronic orofacial pain disorders present a unique opportunity to compare nociceptive and neuropathic pain in the same body region. Twenty-four patients with trigeminal neuropathic pain, 21 patients with temporomandibular disorder, and 38 healthy controls were assessed with a psychological/psychosocial battery encompassing the 4 dimensions of the pain experience; sensory-discriminative, affective-motivational, cognitive-evaluative, and psychosocial. Although patients with trigeminal neuropathic pain (neuropathic pain) and temporomandibular disorder (non-neuropathic pain) described the sensory aspects of their pain differently, they exhibited comparable negative affective-motivational, cognitive-evaluative, and psychosocial states, although these were significantly different compared to healthy controls. These findings support growing evidence that the negative affective, cognitive, and psychosocial state of chronic pain is universal, regardless of a neuropathic or nociceptive nature. Further characterisation of these 4 dimensions of the pain experience in different chronic pain subtypes may improve the efficacy of cognitive-behavioural therapy., (Copyright © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

Background: The insulin-degrading enzyme gene (IDE) is a strong functional and positional candidate for late onset Alzheimer's disease (LOAD)., Methodology/principal Findings: We examined conserved regions of IDE and its 10 kb flanks in 269 AD cases and 252 controls thereby identifying 17 putative functional polymorphisms. These variants formed eleven haplotypes that were tagged with ten variants. Four of these showed significant association with IDE transcript levels in samples from 194 LOAD cerebella. The strongest, rs6583817, which has not previously been reported, showed unequivocal association (p = 1.5x10(-8), fold-increase = 2.12,); the eleven haplotypes were also significantly associated with transcript levels (global p = 0.003). Using an in vitro dual luciferase reporter assay, we found that rs6583817 increases reporter gene expression in Be(2)-C (p = 0.006) and HepG2 (p = 0.02) cell lines. Furthermore, using data from a recent genome-wide association study of two Croatian isolated populations (n = 1,879), we identified a proxy for rs6583817 that associated significantly with decreased plasma Abeta40 levels (ss = -0.124, p = 0.011) and total measured plasma Abeta levels (b = -0.130, p = 0.009). Finally, rs6583817 was associated with decreased risk of LOAD in 3,891 AD cases and 3,605 controls. (OR = 0.87, p = 0.03), and the eleven IDE haplotypes (global p = 0.02) also showed significant association., Conclusions: Thus, a previously unreported variant unequivocally associated with increased IDE expression was also associated with reduced plasma Abeta40 and decreased LOAD susceptibility. Genetic association between LOAD and IDE has been difficult to replicate. Our findings suggest that targeted testing of expression SNPs (eSNPs) strongly associated with altered transcript levels in autopsy brain samples may be a powerful way to identify genetic associations with LOAD that would otherwise be difficult to detect.

By analyzing late-onset Alzheimer's disease (LOAD) in a genome-wide association study (313,504 SNPs, three series, 844 cases and 1,255 controls) and evaluating the 25 SNPs with the most significant allelic association in four additional series (1,547 cases and 1,209 controls), we identified a SNP (rs5984894) on Xq21.3 in PCDH11X that is strongly associated with LOAD in individuals of European descent from the United States. Analysis of rs5984894 by multivariable logistic regression adjusted for sex gave global P values of 5.7 x 10(-5) in stage 1, 4.8 x 10(-6) in stage 2 and 3.9 x 10(-12) in the combined data. Odds ratios were 1.75 (95% CI = 1.42-2.16) for female homozygotes (P = 2.0 x 10(-7)) and 1.26 (95% CI = 1.05-1.51) for female heterozygotes (P = 0.01) compared to female noncarriers. For male hemizygotes (P = 0.07) compared to male noncarriers, the odds ratio was 1.18 (95% CI = 0.99-1.41).