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Presents a letter to the editor regarding cognitive fatigue in multiple sclerosis.

Background: Older adults who sustain a traumatic brain injury (TBI) have been shown to have reduced functional independence and life satisfaction relative to younger individuals with TBI. The purpose of this study was to examine the covarying patterns of functional independence and life satisfaction over the 10 years after TBI in adults who were 60 years of age or older upon injury., Method: Participants were 1841 individuals aged 60 or older at the time of TBI, were enrolled in the longitudinal TBI Model Systems database, and had Functional Independence Measure and Satisfaction with Life Scale scores during at least one time point at 1, 2, 5, and 10 years after TBI., Results: A k -means cluster analysis identified four distinct group-based longitudinal patterns of these two variables. Three cluster groups suggested that functional independence and life satisfaction generally traveled together over time, with one group showing relatively high functional independence and life satisfaction over time (Cluster 2), one group showing relatively moderate functional independence and life satisfaction (Cluster 4), and one group showing relatively low functional independence and life satisfaction (Cluster 1). Cluster 3 had relatively high functional independence over time but, nonetheless, relatively low life satisfaction; they were also the youngest group upon injury. Participants in Cluster 2 generally had the highest number of weeks of paid competitive employment but lower percentages of underrepresented racial/ethnic minority participants, particularly Black and Hispanic individuals. Women were more likely to be in the cluster with the lowest life satisfaction and functional independence (Cluster 1)., Conclusion: Functional independence and life satisfaction generally accompany one another over time in older adults, although this does not always occur, as life satisfaction can still be low in a subgroup of older individuals after TBI with higher functioning. These findings contribute to a better understanding of post-TBI recovery patterns in older adults over time that may inform treatment considerations to improve age-related discrepancies in rehabilitation outcomes.

The COVID-19 pandemic transformed the delivery of psychological services as many psychologists adopted telepsychology for the first time or dramatically increased their use of it. The current study examined qualitative and quantitative data provided by 2619 practicing psychologists to identify variables facilitating and impeding the adoption of telepsychology in the U.S. at the beginning of the COVID-19 pandemic. The top five reported barriers were: inadequate access to technology, diminished therapeutic alliance, technological issues, diminished quality of delivered care or effectiveness, and privacy concerns. The top five reported facilitators were: increased safety, better access to patient care, patient demand, efficient use of time, and adequate technology for telepsychology use. Psychologists' demographic and practice characteristics robustly predicted their endorsement of telepsychology barriers and facilitators. These findings provide important context into the implementation of telepsychology at the beginning of the pandemic and may serve future implementation strategies in clinics and healthcare organizations attempting to increase telepsychology utilization.

Background: Older adults have the highest traumatic brain injury (TBI)-related morbidity and mortality, and rates in older adults are increasing, chiefly due to falls., Objective: This study used hierarchical linear modeling (HLM) to examine baseline predictors of functional independence trajectories across 1, 2, 5, and 10 years after TBI in older adults., Methods: Participants comprised 2,459 individuals aged 60 or older at the time of TBI, enrolled in the longitudinal TBI Model Systems database, and had Functional Independence Measure Motor and Cognitive subscale scores and Glasgow Outcome Scale-Extended scores during at least 1 time point., Results: Functional independence trajectories generally declined over the 10 years after TBI. Individuals who were older, male, underrepresented minorities, had lower education, were unemployed at time of injury, had no history of substance use disorder, or had difficulties with learning, dressing, and going out of the home prior to the TBI, or longer time in posttraumatic amnesia had lower functional independence trajectories across at least one of the functional independence outcomes., Conclusion: These predictors of functional independence in older adults with TBI may heighten awareness of these factors in treatment planning and long-term health monitoring and ultimately as a way to decrease morbidity and mortality.

The COVID-19 pandemic has altered life globally like no other event in modern history, and psychological service changes to meet the resultant impacts on families have not been assessed in the empirical literature. The purpose of the current study was to examine whether family systems therapists increased their teletherapy use during the pandemic relative to prepandemic usage, and whether projected postpandemic rates would remain at the same level; further, environmental and demographic predictors of these changes were examined. In May 2020, a sample of 626 family systems therapists (58.6% women, 40.6% men; M = 57.4 years old; M years in practice = 25.5) completed a national online study assessing these variables. Results suggested that family systems therapists performed 7.92% of their clinical work using teletherapy before the pandemic and 88.17% during the pandemic. They also projected that they would perform 36.57% of their clinical work using teletherapy after the pandemic. Teletherapy uptake was unrelated to primary practice setting, provider age, gender, race/ethnicity, and practice location (urban/suburban vs. rural) but was higher for family systems therapists who reported increased supportive teletherapy policies and training in their practice setting. Organizational infrastructure and availability of training played an important role in influencing teletherapy uptake during the pandemic. Family systems therapists have a unique opportunity to deploy teletherapy modalities to meet the needs of families during the COVID-19 pandemic, and infrastructure and training to do so may facilitate that work., (© 2021 Family Process Institute. This article is a U.S. Government work and is in the public domain in the USA.)

Study Design: Pre-post study., Objective: To evaluate the efficiency of a series of recruitment strategies in a longitudinal study of individuals with SCI and their informal caregivers. Primary strategies included (a) rapport building in advance, (b) warm handoffs from another healthcare provider who already had a relationship with the potential participant, (c) ensuring the potential participant had information about the study prior to the initial contact by the research coordinator (RC), (d) attempting informed consent only when both the patient and informal caregiver were present, and (e) ensuring the RC had at least 30 minutes to explain the study when attempting recruitment., Summary of Background Data: While a fairly large body of research has been conducted on general recruitment strategies for clinical trials, very little has examined the efficacy of these strategies within neurological conditions and almost none within SCI., Methods: Individuals with an acute SCI and their informal caregivers were recruited from acute spinal cord rehabilitation units with a Veteran's Affairs medical center and an academic medical center in the same urban area. Of 49 eligible dyads, 41 were approached for consent, with 27 consenting to join the study (9 from the academic medical center; 18 from the VA)., Results: There was a significant difference in enrollment rates after implementing the recruitment strategies, χ2(1) = 7.572, P = 0.006, with the per month participant enrollment rate nearly doubling after implementation., Conclusion: Using a multiteam and multidisciplinary approach to recruitment may increase the likelihood that individuals with an acute SCI and their caregivers enroll in research.Level of Evidence: 3., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Despite older adults' extremely high vulnerability to COVID-19 complications and death, few studies have examined how personal characteristics and the COVID-19 pandemic have impacted the mental health of older adults at the global level. The purpose of this study was to examine the relationships among demographics, COVID-19 life impacts, and depression and anxiety in adults aged 60 and older from 33 countries. A sample of 823 older adults aged 60-94 and residing in 33 countries completed a 10-min online survey following recruitment from mailing lists and social media. Being separated from and having conflicts with loved ones predicted both anxiety and depression, as did residing in a country with higher income. Getting medical treatment for severe symptoms of COVID-19 and having decreased work responsibilities predicted depression, but adjustment to working from home and younger age predicted both depression and anxiety. Participants from Europe and Central Asia reported higher depression than those from all other regions and higher anxiety than those from Latin America and the Caribbean. The COVID-19 pandemic has had serious deleterious effects on the mental health of older adults worldwide. The current findings have direct implications for mental health services that may be delivered to older adults to help facilitate healthy psychological adjustment.

Purpose/Objective: Despite the increasingly high number of individuals who survive burns and the documented impairments in functioning across psychological, work, sexual, and interpersonal domains, there has been a dearth of research investigating connections between pain and functioning in these domains after burn injury. The purpose of the current study was to investigate the relationships among pain, mental health, and functioning of individuals with burn injury. It was hypothesized that pain after burn would yield direct effects on functioning (work, sexual, and interpersonal), as well as indirect effects on functioning through depression and anxiety. Research Method/Design: Eighty-seven individuals with burn injury completed a questionnaire assessing study constructs in an outpatient burn center setting. Results: Pain was positively related to depression and anxiety and inversely related to all three forms of functioning. In a series of mediational models, depression and anxiety simultaneously and partially mediated the relationship between pain and work functioning. Depression fully mediated the relationship between pain and sexual functioning, as well as partially mediated the relationship between pain and interpersonal functioning. The models explained 39.2% of the variance in work functioning, 28.4% in sexual functioning, and 35.6% in interpersonal functioning. Conclusions/Implications: Although the cross-sectional findings are unable to conclude causality, individuals with burn injury experiencing pain may benefit from a biopsychosocial treatment approach while also addressing symptoms of depression and anxiety. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The COVID-19 pandemic has altered mental health care delivery like no other event in modern history. The purpose of this study was to document the magnitude of that effect by examining (a) the amount of psychologists' telepsychology use before the COVID-19 pandemic, during the pandemic, and anticipated use after the pandemic; as well as (b) the demographic, training, policy, and clinical practice predictors of these changes. This study used a cross-sectional, national online design to recruit 2,619 licensed psychologists practicing in the United States. Prior to the COVID-19 pandemic, psychologists performed 7.07% of their clinical work with telepsychology, which increased 12-fold to 85.53% during the pandemic, with 67.32% of psychologists conducting all of their clinical work with telepsychology. Psychologists projected that they would perform 34.96% of their clinical work via telepsychology after the pandemic. Psychologists working in outpatient treatment facilities reported over a 26-fold increase in telepsychology use during the pandemic, while those in Veterans Affairs medical centers only reported a sevenfold increase. A larger increase in percentage telepsychology use occurred in women, in psychologists who reported an increase in telepsychology training and supportive organizational telepsychology policies, and in psychologists who treated relationship issues, anxiety, and women's issues. The lowest increases in percentage telepsychology use were reported by psychologists working in rural areas, treating antisocial personality disorder, performing testing and evaluation, and treating rehabilitation populations. Although there was a remarkable increase in telepsychology use during the COVID-19 pandemic, individual and practice characteristics affected psychologists' ability to adopt telepsychology. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The Richmond Health and Wellness Program (RHWP) is an innovative interprofessional care coordination program that seeks to support the health and wellness of independent-living older adults and educate future practitioners. Since 2012, RHWP has provided community-based interprofessional training to students at Virginia Commonwealth University. The sudden suspension of clinical and community-based training due to the COVID-19 pandemic created the need to transform the traditional ways students received clinical education and support the vulnerable communities served by RHWP. This paper describes RHWP's rapid transition to a hybrid telephone-based program with a virtual learning component for students which allowed RHWP to continue serving its participants and provide interprofessional training experiences. Since the transition, RHWP has served 111 participants through over 400 telephonic visits, and 12 nurse practitioner and pharmacy students completed clinical hours to fulfill graduation requirements. To meet the needs of learners, interprofessional education models can be adapted to changing circumstances posed by COVID-19.

Introduction: Given the rapidly aging population in both the United States and Mexico, rates of Parkinson's disease (PD) are likely to rise in both countries, suggesting that the number of individuals providing informal care will also increase, and the healthcare system will have to consider the burden this places upon caregivers. Therefore, the purpose of the current study was to examine differences in PD caregiving and burden between the United States and Mexico., Methods: Data were collected from PD caregivers in the Parkinson's Clinic at the Hospital Civil Fray Antonio Alcalde in Guadalajara, Mexico (N = 148) and the Parkinson's and Movement Disorders Center at Virginia Commonwealth University in Richmond, Virginia (N = 105) regarding caregiver demographics and self-reported burden., Results: Despite considerably more time spent in caregiving duties, higher rates in unemployment or underemployment, and lower education levels, Mexican PD caregivers reported significantly less personal strain and role strain than did their United States counterparts. Even after controlling for these and other demographic differences between the two sites, the differences in caregiver burden remained., Conclusions: Latino cultural values in Mexico encouraging the importance of caring for family members with PD and respecting elders may promote caregiving and even make it a point of cultural pride, helping to overcome potential negative effects on caregivers seen in the United States. The scientific and medical communities should view caregiving as a culturally embedded and potentially positive role, rather than predominantly as burdensome as frequently conceptualized in Western or Eurocentric cultures., (© 2020 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Only scant literature has focused on social support in Parkinson's disease (PD) caregivers, and no studies to date have examined resilience in this population, despite both variables having been shown to be important in other caregiving populations. As a result, the purpose of the current study was to construct and validate a theoretical structural equation model whereby social support is associated with higher levels of resilience in PD caregivers and increased resilience is related to decreased mental health symptoms. Two hundred fifty three PD caregivers from two clinics in the United States and Mexico completed self-report measures of these constructs. Results suggested that the hypothesized pattern was robustly supported with the structural equation model showing generally good fit indices. Higher levels of social support were associated with increased resilience, which in turn was associated with reduced mental health symptoms. Resilience partially mediated social support's effect on mitigating mental health symptoms. The model explained 11% of the variance in resilience and 35% in mental health symptoms. These findings have implications for future research on the development and tailoring of interventions to improve social support, resilience, and mental health in PD caregivers., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 Carmen M. Tyler et al.)

Informal caregivers are critical in the care of individuals with Parkinson's disease (PD) and spend substantial time providing care, which may be associated with negative caregiver outcomes such as burden and mental health issues. Although research in the United States and Europe has generally supported these relations, there is very limited research on PD caregiving in Latin America. The current study examined the following connections in a sample of PD caregivers from the United States ( N = 105) and Mexico ( N = 148): (a) PD-related impairments (motor and nonmotor symptoms) and caregiver burden, (b) caregiver burden and caregiver mental health, and (c) PD-related impairments and mental health through caregiver burden. Study results uncovered significant relations among PD-related impairments, caregiver burden, and caregiver mental health. Further, caregiver burden fully mediated the relation between PD-related impairments and caregiver mental health at both study sites. Findings highlight a number of important intervention targets for caregivers and families, including caregiver burden and mental health., Competing Interests: The authors report no conflicts of interest., (Copyright © 2019 Erin R. Smith et al.)

Background: Major histocompatibility complex class I (MHCI) proteins present antigenic peptides for immune surveillance and play critical roles in nervous system development and plasticity. Most MHCI are transmembrane proteins. The extracellular domain of MHCI interacts with immunoreceptors, peptides, and co-receptors to mediate immune signaling. While the cytoplasmic domain also plays important roles in endocytic trafficking, cross-presentation of extracellularly derived antigens, and CTL priming, the molecular mediators of cytoplasmic signaling by MHCI remain largely unknown., Results: Here we show that the cytoplasmic domain of MHCI contains putative protein-protein interaction domains known as PDZ (PSD95/disc large/zonula occludens-1) ligands. PDZ ligands are motifs that bind to PDZ domains to organize and mediate signaling at cell-cell contacts. PDZ ligands are short, degenerate motifs, and are therefore difficult to identify via sequence homology alone, but several lines of evidence suggest that putative PDZ ligand motifs in MHCI are under positive selective pressure. Putative PDZ ligands are found in all of the 99 MHCI proteins examined from diverse species, and are enriched in the cytoplasmic domain, where PDZ interactions occur. Both the position of the PDZ ligand and the class of ligand motif are conserved across species, as well as among genes within a species. Non-synonymous substitutions, when they occur, frequently preserve the motif. Of the many specific possible PDZ ligand motifs, a handful are strikingly and selectively overrepresented in MHCI's cytoplasmic domain, but not elsewhere in the same proteins. Putative PDZ ligands in MHCI encompass conserved serine and tyrosine residues that are targets of phosphorylation, a post-translational modification that can regulate PDZ interactions. Finally, proof-of-principle in vitro interaction assays demonstrate that the cytoplasmic domains of particular MHCI proteins can bind directly and specifically to PDZ1 and PDZ4&5 of MAGI-1, and identify a conserved PDZ ligand motif in the classical MHCI H2-K that is required for this interaction., Conclusions: These results identify cryptic protein interaction motifs in the cytoplasmic domain of MHCI. In so doing, they suggest that the cytoplasmic domain of MHCI could participate in previously unsuspected PDZ mediated protein-protein interactions at neuronal as well as immunological synapses.

Proteins of the major histocompatibility complex class I (MHCI) negatively regulate synapse density in the developing vertebrate brain (Glynn et al., 2011; Elmer et al., 2013; Lee et al., 2014), but the underlying mechanisms remain largely unknown. Here we identify a novel MHCI signaling pathway that involves the inhibition of a known synapse-promoting factor, the insulin receptor. Dominant-negative insulin receptor constructs decrease synapse density in the developing Xenopus visual system (Chiu et al., 2008), and insulin receptor activation increases dendritic spine density in mouse hippocampal neurons in vitro (Lee et al., 2011). We find that genetically reducing cell surface MHCI levels increases synapse density selectively in regions of the hippocampus where insulin receptors are expressed, and occludes the neuronal insulin response by de-repressing insulin receptor signaling. Pharmacologically inhibiting insulin receptor signaling in MHCI-deficient animals rescues synapse density, identifying insulin receptor signaling as a critical mediator of the tonic inhibitory effects of endogenous MHCI on synapse number. Insulin receptors co-immunoprecipitate MHCI from hippocampal lysates, and MHCI unmasks a cytoplasmic epitope of the insulin receptor that mediates downstream signaling. These results identify an important role for an MHCI-insulin receptor signaling pathway in circuit patterning in the developing brain, and suggest that changes in MHCI expression could unexpectedly regulate neuronal insulin sensitivity in the aging and diseased brain., (Copyright © 2014 the authors 0270-6474/14/3411844-13$15.00/0.)

In many parts of the developing vertebrate nervous system, axons are pruned to establish mature patterns of connectivity. In this issue of Neuron, Schafer et al. (2012) show that microglia may play a role in developmental axon pruning in the thalamus by engulfing presynaptic retinal ganglion cell terminals via a C3- and CR3-dependent mechanism., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Proteins of the major histocompatibility complex class I (MHCI) are known for their role in immunity and have recently been implicated in long-term plasticity of excitatory synaptic transmission. However, the mechanisms by which MHCI influences synaptic plasticity remain unknown. Here we show that endogenous MHCI regulates synaptic responses mediated by NMDA-type glutamate receptors (NMDARs) in the mammalian central nervous system (CNS). The AMPA/NMDA ratio is decreased at MHCI-deficient hippocampal synapses, reflecting an increase in NMDAR-mediated currents. This enhanced NMDAR response is not associated with changes in the levels, subunit composition, or gross subcellular distribution of NMDARs. Increased NMDAR-mediated currents in MHCI-deficient neurons are associated with characteristic changes in AMPA receptor trafficking in response to NMDAR activation. Thus, endogenous MHCI tonically inhibits NMDAR function and controls downstream NMDAR-induced AMPA receptor trafficking during the expression of plasticity.

Natural recruitment of oaks appears to be declining throughout the northern hemisphere. Summer drought poses a potentially important barrier to oak recruitment in southern California. To evaluate this barrier, we grew evergreen Quercus agrifolia and deciduous Q. lobata from seeds near parental trees. We measured water relations, chlorophyll fluorescence, and gas exchange during these seedlings' fourth and fifth summers and compared them to neighboring adults. Most seedlings had substantially lower values for predawn xylem pressure potential (Ψ(pd)), minimum photosystem II (PSII) quantum efficiency (Φ(PSIIMIN)), maximum quantum efficiency for PSII under dark-adapted leaf conditions (Fv/Fm), and maximum photosynthetic assimilation (Amax), and higher values for maximum nonphotochemical quenching (NPQmax) than did conspecific adults. The high, unvarying Ψ(pd) values of the adults suggest they use perennially available groundwater. Quercus lobata seedlings commonly had lower values for Ψ(pd) than did Q. agrifolia, and values for Ψ(pd) and Φ(PSIIMIN) were significantly related to size in Q. lobata but not in Q. agrifolia. These data suggest important interspecific differences in root architecture. Lower values for Φ(PSIIMIN), Fv/Fm, and higher NPQmax in Q. agrifolia indicate that Q. agrifolia seedlings were usually under more stress than Q. lobata, which typically had higher Amax rates than did Q. agrifolia seedlings. Diurnal photosynthesis curves were quite flat for Q. agrifolia, but they peaked in the morning for Q. lobata. Established seedlings appeared to be under more stress than adults, but this stress did not appear severe enough to cause death. Access to perennially available groundwater may be crucial for the seedling to sapling transition.

This preliminary study explored the cultural socialization processes of 227 African American and European American parents of elementary schoolchildren. The Cultural Value Socialization Scales (K. M. Tyler, A. W. Boykin, C. M. Boelter, & M. L. Dillihunt, 2005) were used to garner parents' reports of their cultural value socialization activities at home. The scales contained written vignettes depicting persons involved in activity that reflected a specific cultural value. Ethnocultural values examined were communalism, verve, movement, and affect, and mainstream cultural values included individualism, competition, bureaucracy, and materialism. Regression analyses reveal that being an African American parent was predictive of competition and materialism scores. Race was not a significant predictor of the remaining cultural value socialization scores. Limitations to the study are discussed., (Copyright (c) 2008 APA, all rights reserved.)

Nerve growth factor mediates neuronal survival, synaptogenesis, and synaptic remodeling. We utilized primary hippocampal cultures to investigate the intrinsic motifs of proNGF that might contribute to its processing and subsequent allocation to a regulated versus constitutive secretory pathway. The addition of a carboxypeptidase E motif to proNGF did not alter the secretion of NGF. However, mutagenesis of proNGF proteolytic processing sites had significant effects on the final NGF product and its secretion. The furin recognition site (R118-S-K-R121) is essential for the proper processing of proNGF to its 13.5kDa mature product and mutating the furin site exposed an alternative processing site resulting in an intermediate NGF product of approximately 22kDa. Finally, inhibiting the processing of proNGF abolished regulated secretion of the resulting NGF product. These experiments demonstrate that hippocampal neurons harbor multiple pathways to process proNGF of which the furin consensus sequence is the preferred processing site.

Strategies that employ HSV amplicon vectors in the prevention and/or amelioration of pathogenic states afflicting the central nervous system (CNS) have been extensively documented in preclinical disease models. The versatility of the HSV amplicon platform allows for the implementation of therapeutic approaches that require expression of genes exhibiting neuroprotective or neuroplastic activities, or even applications that necessitate the elaboration of antigen-specific immune responses to pathogenic proteins/structures harbored within the CNS. This discourse highlights the successes and challenges encountered using HSV amplicon vectors as tools for the dissection of neural network function and as therapeutics directed against a variety of neurologic disorders.

We review published studies on the demography and recruitment of California oak trees and focus on the widespread dominant species of the foothill woodlands, Quercus douglasii, Q. lobata, and Q. agrifolia, to ascertain the nature and strength of evidence for a decline in populations of these species. The vast majority of studies have been of short duration (less than three years), focused on the acorn and seedling life stages, and conducted at few locations within each species geographic range. We summarize the extensive body of research that has been conducted on the biological and physical factors that limit natural seedling recruitment of oaks. The oak "regeneration problem" has largely been inferred from current stand structure rather than by demographic analyses, which in part reflects the short-term nature of most oak research. When viewed over longer periods of time usingfield surveys or historical photos, the evidence for a regeneration problem in foothill oaks is mixed. Q. douglasii shows very limited seedling or sapling recruitment at present, but longer term studies do not suggest a decline in tree density, presumably because rare recruitment is sufficient to offset low rates of mortality of overstory individuals. Q. agrifolia appears to be stable or increasing in some areas, but decreasing in areas recently impacted by the disease Phytophthora ramorum. Evidence from the few available studies is more consistent in suggesting long-term declines in foothill populations of Q. lobata. Long-term monitoring, age structure analysis, and population models are needed to resolve the current uncertainty over the sustainability of oak woodlands in California.

Gene therapy is a potentially promising new treatment for neurodegenerative disorders such as Alzheimer's disease (AD), which has been difficult to treat with conventional therapeutics. Viral vector-mediated somatic gene therapy is a rapidly developing methodology for providing never before achieved capability to deliver specific genes to the CNS in a highly localized and controlled manner. With the advent and refinements of this technology one focus is directed to which genes are the most appropriate to select for specific disease indications. Nerve growth factor (NGF), a potent survival factor for critical cell populations that degenerate in AD, has been chosen already for clinical gene therapy trials in human AD patients. Much knowledge about the pathophysiological underpinnings of AD is still lacking to make clear which patients may benefit from a gene therapy approach. Moreover, a detailed understanding of sustained NGF action in the normal and diseased CNS needs to be resolved before conclusions can be drawn regarding the utility of NGF gene therapy. Systematic efforts to acquire this new knowledge should compel clinically and biologically sophisticated efforts to advance gene therapy for neurodegenerative diseases.

Background: Fatigue is common in multiple sclerosis (MS), but difficulty quantifying fatigue severity has impeded studies of its characteristics, mechanisms, and therapeutics. Motor fatigue can be objectively measured as the decline in strength occurring during sustained contractions. Analogous declines in cognitive performance occur during tasks requiring sustained attention., Objective: To objectively measure cognitive fatigue as a decline in performance during tests requiring sustained attention., Design/methods: Patients with clinically stable MS (n = 20) and healthy controls (n = 21) with comparable age, gender, and education completed the Paced Auditory Serial Addition Test (PASAT) and the Digit Ordering Test (DOT) at two identical test sessions separated by 4-10 days, within a month after two practice sessions. Cognitive fatigue was quantified with two pre-specified methods for each test. The reliability of cognitive fatigue assessments was evaluated with intraclass correlation coefficients (ICCs) and construct validity was evaluated using correlations with measures of self-reported fatigue, cognition, and overall impairment/disability., Results: MS patients had an average of 18.7 items correct on the first 20 items of the PASATand 17.8 correct on the last 20 items, quantified as 5.3-5.8% declines in performance using the different measurement methods (P = 0.01, rejecting the null hypothesis of zero mean decline). Although MS patients as a group demonstrated a similar decline at both sessions, ICCs were relatively low. Control patients did not demonstrate significant declines in performance during PASAT administration, but tests comparing declines in MS patients and controls did not demonstrate significant differences. Fatigue was not demonstrated using the DOT, and test-retest reliability was very poor., Conclusions: MS patients have objectively measurable cognitive fatigue during administration of the PASAT.

Thirteen standard-bred horses were trained intensively for 34 weeks and detrained for 6 weeks to study skeletal muscle adaptations to prolonged training, overtraining and detraining. Training included endurance (phase 1, 7 weeks), high-intensity (phase 2, 9 weeks) and overload training (OLT) (phase 3, 18 weeks). During phase 3, horses were divided into two groups, OLT and control (C), with OLT horses performing greater intensities and durations of exercise than C horses. Overtraining was evident in OLT horses after week 31 and was defined as a significant reduction in treadmill run time in response to a standardised exercise test (P<0.05). Relationships between peripheral (skeletal muscle) and whole body (maximum O2 uptake, V.O2, max, treadmill run time) adaptations to training were determined. Prolonged training resulted in significant adaptations in morphological characteristics of skeletal muscle but the adaptations were limited and largely completed by 16 weeks of training. Fibre area increased in all fibres while the number of capillaries per fibre increased and the diffusional index (area per capillary) decreased. Mitochondrial volume density continued to increase throughout 34 weeks of training and paralleled increases in V.O2,max and treadmill run time. Significant correlations were noted between mitochondrial volume and V.O2,max (R=0.71), run time and V.O2,max (R=0.83) and mitochondrial volume and run time (R=0.57). We conclude that many of adaptive responses of muscle fibre area and capillarity occur in the initial training period but that markers of oxidative capacity of muscle indicate progressive increases in aerobic capacity with increases in training load. The lack of differences between C and OLT groups indicated that there may be an upper limit to the ability of training stimulus to evoke skeletal muscle adaptive responses. There was no effect of overtraining or detraining on any of the adaptive responses measured.

Thirteen standardbred horses were trained as follows: phase 1 (endurance training, 7 wk), phase 2 (high-intensity training, 9 wk), phase 3 (overload training, 18 wk), and phase 4 (detraining, 12 wk). In phase 3, the horses were divided into two groups: overload training (OLT) and control (C). The OLT group exercised at greater intensities, frequencies, and durations than group C. Overtraining occurred after 31 wk of training and was defined as a significant decrease in treadmill run time in response to a standardized exercise test. In the OLT group, there was a significant decrease in body weight (P < 0.05). From pretraining values of 117 +/- 2 (SE) ml.kg-1.min-1, maximal O2 uptake (VO2max) increased by 15% at the end of phase 1, and when signs of overtraining were first seen in the OLT group, VO2max was 29% higher (151 +/- 2 ml.kg-1.min-1 in both C and OLT groups) than pretraining values. There was no significant reduction in VO2max until after 6 wk detraining when VO2max was 137 +/- 2 ml.kg-1.min-1. By 12 wk detraining, mean VO2max was 134 +/- 2 ml.kg-1.min-1, still 15% above pretraining values. When overtraining developed, VO2max was not different between C and OLT groups, but maximal values for CO2 production (147 vs. 159 ml.kg-1.min-1) and respiratory exchange ratio (1.04 vs. 1.11) were lower in the OLT group. Overtraining was not associated with a decrease in VO2max and, after prolonged training, decreases in VO2max occurred slowly during detraining.

The VO2(max) in racehorses is approximately double that of elite human athletes and the rate of increase in VO2 at the onset of high intensity exercise is much greater than in man. The kinetics of gas exchange are affected by a warm-up prior to exercise in humans, there being a greater aerobic contribution to high intensity exercise after warm-up. Our hypothesis was that a warm-up would increase aerobic energy delivery in racehorses during high intensity exercise. Thirteen fit Standardbred racehorses ran to fatigue at 115% of VO2(max) on a treadmill at 10% slope. Prior to acceleration, horses were exercised either for 5 min at 50% VO2(max) followed by 5 min walk, or walked for 2 min. Samples of expired gas were collected every 10 s during the run for determination of VO2 and VCO2 and measurement of maximal accumulated oxygen deficit (MAOD). Blood lactate concentration was measured 5 min post exercise. We found that with a warm-up, horses had faster kinetics of gas exchange and a greater proportion of their total energy requirement was supplied by aerobic sources. The aerobic contribution to total energy requirement with and without warm-up was, respectively, 79.3 +/- 1.0% and 72.4 +/- 1.7% (P < 0.01). There was also a higher MAOD (P < 0.01) in horses that had not been given a warm-up (mean +/- s.e.m. 34.7 +/- 2.6 and 47.3 +/- 2.6 mLO2eq/kg bwt with and without a warm-up respectively). However, there were no significant differences in total run time or estimated total energy expenditure between the 2 protocols. We concluded that during high intensity exercise to fatigue lasting 1 to 2 min, more than 70% of energy supply is from aerobic energy sources and that this contribution is even greater when the horses have received a warm-up.

Where plant species vie for limited resources, disturbances might preclude competition by releasing a flush of nutrients, or by reducing biomass and thereby diminishing the consumption of resources. However, if new seedlings colonize in clumps, they may still deplete resources within the local aggregations, which may then reduce their growth and survivorship. We investigated competition among seedlings in a burned area by examining the relationship between the performance of newly established shrub seedlings of Ceanothus impressus and (1) the proximity and (2) the identity of their near neighbors. We also investigated the relationship between neighbor proximity and the availability of water. Both survivorship and growth of C. impressus were positively associated with increasing distance to near neighbors, in a manner consistent with resource competition. The availability of water (as determined by pre-dawn xylem pressure potentials) tended to be greater when neighbors were farther away, providing evidence that water was a resource for which plants were competing. This conclusion is reinforced by the finding that the effects of neighbors were stronger in drought years, suggesting that yearly variation in the availability of an important resource (water) can affect the strength of competitive interactions. This suggests that after disturbances, when some resources are apparently abundant on a large scale, competition may be important in determining the small scale patterns of seedling growth and survival.

Aims: To develop a fluorimetric method for the estimation of urinary aldosterone; to establish a normal range in 24 hour and overnight urine samples; and to investigate the use of overnight urines for detecting hyperaldosteronism., Methods: Essential steps include hydrolysis of the 18 conjugate to release aldosterone and its oxidation with Benedict's solution, followed by thin-layer chromatography on silica gel and development of fluorescence on the plate with sulphuric acid., Results: There was a linear correlation between the amount of aldosterone and the area under the peak on the chromatogram. The mean intra-assay and interassay coefficients of variation were 4.4% and 6.8%, respectively. The mean aldosterone excretion in 67 adults was 15.7 (SD 8.1) nmol/24 hours. The mean overnight excretion in 65 adults was 2.6 (1.4) nmol/8 hours. The method detected raised concentrations in patients with primary and secondary aldosteronism., Conclusions: This technique provides an accurate means of assaying urinary aldosterone. Overnight estimations seem to be as effective as 24 hour assays for identifying patients with hyperaldosteronism.

Invasion by the alien succulent,Carpobrotus edulis, has become a common occurrence after fire in maritime chaparral in coastal California, USA. We studied post-burnCarpobrotus establishment in chaparral that lackedCarpobrotus plants before the fire and compared seedbank and field populations in adjacent burned and unburned stands.Carpobrotus seeds were abundant in deer scat and in the soil before burning. Burning did not enhance germination: many seeds were apparently killed by fire and seed bank cores taken after fire revealed no germinable seeds. Laboratory tests showed that temperatures over 105°C for five minutes killedCarpobrotus seeds. In a field experiment involving use of herbivore exclosures, we found that herbivory was an important source of mortality for seedlings in both burned and unburned chaparral. All seedlings, however, died outside of the burn regardless of the presence of cages. Establishment there is apparently limited by factors affecting plant physiology. In the burned area, seedlings that escaped herbivory grew very rapidly. Overall, it appears that herbivory limited seedling establishment in both burned and unburned sites but that the post-burn soil environment supportedCarpobrotus growth in excess of herbivore use, thus promoting establishment.