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Addressing climate change risks requires collaboration and engagement across all sectors of society. In particular, effective partnerships are needed between research scientists producing new knowledge, policy-makers and practitioners who apply conservation actions on the ground. We describe the implementation of a model for increasing the application and useability of biodiversity research in climate adaptation policy and practice. The focus of the program was to increase the ability of a state government agency and natural resource practitioners in Australia to manage and protect biodiversity in a changing climate. The model comprised a five-stage process for enhancing impact (i) initiation of research projects that addressed priority conservation policy and management issues; (ii) co-design of the research using a collaborative approach involving multiple stakeholders; (iii) implementation of the research and design of decision tools and web-based resources; (iv) collaborative dissemination of the tools and resources via government and community working groups; and (v) evaluation of research impact. We report on the model development and implementation, and critically reflect on the model's impact. We share the lessons learnt from the challenges of operating within a stakeholder group with diverse objectives and criteria for success, and provide a template for creating an environmental research program with real world impact., (© 2021 John Wiley & Sons Ltd.)

Competing Interests: Financial & competing interests disclosure This study was made possible with the financial support of Fonds de Recherche du Québec – Santé. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

Acute respiratory distress syndrome remains the main cause of death among people with COVID-19. Although many immunomodulatory and antiviral drug therapies have been tested, the only effective therapy against severe COVID-19 pneumonia among the general population is a regimen of high-dose corticosteroids for cases of severe associated inflammation. In solid-organ transplant recipients with long-term immunosuppression, data on disease presentation and evolution are scarce, and the benefit of high-dose corticosteroids remains uncertain for cases of severe COVID-19 pneumonia. Here, we report 2 cases of COVID-19-related acute respiratory distress syndrome that occurred in lung transplant recipients in March and April 2020, respectively. Both cases of acute respiratory distress syndrome occurred in patients with long-term azithromycin treatment prescribed to prevent chronic allograft dysfunction. Acute respiratory distress syndrome was associated with severe inflammation and was cured after early administration of high-dose corticosteroids in both cases, with progressive and complete resolution of lung lesions evidenced on thoracic computed tomography scan. Our findings support the benefit of early high-dose corticosteroids in COVID-19-related acute respiratory distress syndrome with hyperinflammation in patients with long-term immunosuppression such as lung transplant recipients.

Traumatic brain injury is one of the leading causes of morbidity and mortality throughout the world. Its increasing incidence, in addition to its fundamental role in the development of neurodegenerative disease, proves especially concerning. Despite extensive preclinical and clinical studies, researchers have yet to identify a safe and effective neuroprotective strategy. Following brain trauma, secondary injury from molecular, metabolic, and cellular changes causes progressive cerebral tissue damage. Chronic neuroinflammation following traumatic brain injuries is a key player in the development of secondary injury. Targeting this phenomenon for development of effective neuroprotective therapies holds promise. This strategy warrants a concrete understanding of complex neuroinflammatory mechanisms. In this review, we discuss pathophysiological mechanisms such as the innate immune response, glial activation, blood-brain barrier disruption, activation of immune mediators, as well as biological markers of traumatic brain injury. We then review existing and emerging pharmacological therapies that target neuroinflammation to improve functional outcome.

We studied the effects of mild traumatic brain injury (mTBI) in an aging population. We examined visual search with event-related potentials (ERPs) and event-related fields (ERF) for a lateral color singleton focusing on the P1 and N1 in each hemisphere. Forty participants (19 mTBI and 21 controls) aged 50 to 72 performed a visual search task, while we recorded their magnetoencephalogram (MEG) with simultaneous electroencephalogram (EEG). We compared visual ERPs and ERFs and associated cortical activity estimated using MEG source localization. Relative to matched controls, participants with an mTBI had a smaller P1 in the left hemisphere and a smaller N1 in the right hemisphere. Also, mTBI participants showed inversed activation patterns across the hemispheres during the N1 in MEG compared with controls. This is the first study to investigate the impact of mTBI on neuronal source activations during early visual processing in an aging population. Results showed that when aging individuals suffer from an mTBI, there are perturbations in the amplitude and hemispheric dominance patterns in the visual P1 and N1 responses that are visible for months to years following the injury. Our findings indicate that mTBI can lead to modifications of sensory and/or perceptual responses, suggesting possible adaptive functional reorganization following mTBI., (© 2020 Society for Psychophysiological Research.)

Subconcussive hits to the head and physical fitness both have been associated with alterations in white matter (WM) microstructure in partly overlapping areas of the brain. The aim of the present study was to determine whether WM damage associated with repeated exposure to subconcussive hits to the head in university level contact sports athletes is modulated by high levels of fitness. To this end, 72 students were recruited: 24 athletes practicing a varsity contact sport (A-CS), 24 athletes practicing a varsity non-contact sport (A-NCS), and 24 healthy non-athletes (NA). Participants underwent a magnetic resonance imaging session that included diffusion-weighted imaging. Between-groups, statistical analyses were performed with diffusion tensor imaging measures extracted by tractometry of sections of the corpus callosum and the corticospinal tract. Most significant effects were found in A-NCS who exhibited higher fractional anisotropy (FA) values than A-CS in almost all segments of the corpus callosum and in the corticospinal tract. The A-NCS also showed higher FA compared with NA in the anterior regions of the corpus callosum and the corticospinal tracts. No group difference was found between the A-CS and the NA groups. These data suggest that repeated subconcussive hits to the head lead to anisotropic changes in the WM that may counteract the beneficial effects associated with high levels of fitness.

Transcranial alternating current stimulation, a non-invasive brain stimulation technique, has been used to increase alpha (8-12 Hz) power, the latter being associated with various brain functions and states. Heterogeneity among stimulation parameters across studies makes it difficult to implement reliable transcranial alternating current stimulation protocols, explaining the absence of consensus on optimal stimulation parameters to modulate the alpha rhythm. This project documents the differential impact of controlling for key transcranial alternating current stimulation parameters, namely the intensity, the frequency and the stimulation site (anterior versus posterior). Phase 1:20 healthy participants underwent 4 different stimulation conditions. In each experimental condition, stimulation via 2 electrodes was delivered for 20 min. Stimulation conditions were administered at PO7-PO8 or F3-F4 at individual's alpha frequency, or at individual's theta frequency or sham. Stimulation intensity was set according to each participant's comfort following a standardized unpleasantness scale (≤ 40 out of 100) and could not exceed 6 mA. All conditions were counterbalanced. Phase 2: participants who tolerated higher intensity of stimulation (4-6 mA) underwent alpha-frequency stimulation applied over PO7-PO8 at 1 mA to investigate within-subject modulation of stimulation response according to stimulation intensity. Whether set over posterior or anterior cortical sites, alpha-frequency stimulation showed greater increase in alpha power relative to stimulation at theta frequency and sham stimulation. Posterior alpha-frequency stimulation showed a greater increase in alpha power relative to the adjacent frequency bands over frontal and occipito-parietal brain areas. Low intensity (1 mA) posterior alpha stimulation showed a similar increase in alpha power than at high (4-6 mA) intensity when measured immediately after stimulation. However, when tested at 60 min or 120 min, low intensity stimulation was associated with significantly superior alpha power increase relative to high intensity stimulation. This study shows that posterior individual's alpha frequency stimulation at higher intensities is well tolerated but fails to increase stimulation aftereffects recorded within 2 h of stimulation on brain oscillations of the corresponding frequency band. In sharp contrast, stimulating at 1 mA (regardless of phosphene generation or sensory perception) effectively and selectively modulates alpha power within that 2-h time window, thus validating that it as a reliable stimulus intensity for future studies. This study also shows that posterior alpha-frequency stimulation preferentially modulates endogenous brain oscillations of the corresponding frequency band. Moreover, our data suggest that posterior alpha-frequency transcranial alternating current stimulation is a reliable and precise non-invasive brain stimulation technique for persistent modulation of both frontal and occipito-parietal alpha power., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Introduction : The neurocognitive outcomes of sustaining a mild traumatic brain injury (mTBI) during late adulthood are vastly understudied. In young, asymptomatic adults, mTBI-related synaptic plasticity alterations have been associated with persistent implicit motor sequence learning impairments outlasting the usual cognitive recovery period. The current study examined whether uncomplicated mTBI sustained during late adulthood could exert persistent deleterious consequences on implicit motor sequence learning. Method : Thirty participants (aged 50-70 years) who experienced an uncomplicated mTBI within 3 to 24 months of testing, and 40 age-, sex- and education-equivalent healthy controls performed an implicit serial reaction time task (SRT task). The SRT task consisted of 10 blocks of a repeating sequence embedded among 4 random blocks. Participants also completed a battery of standardized neuropsychological tests of attention, memory and executive functioning. Results : While both mTBI participants and controls showed significant implicit motor sequence learning effects, the mTBI group achieved a lower level of competence at performing the SRT task as evidenced by smaller gains in reaction times across the 10 training blocks of the repeating sequence. The time elapsed since the injury was unrelated to implicit motor learning effects. There was no evidence of a persistent effect of mTBI on any neuropsychological domain compared to controls. Conclusions : Findings from this study suggest that a single mTBI sustained during older age may have persistent repercussions on training-dependent motor sequence learning capacity outlasting the recovery of mTBI symptoms and gold-standard neuropsychological tests performance.

Sleep disturbances (e.g., difficulty to initiate or maintain sleep) and poor sleep quality are major health concerns that accompany several neurological and neuropsychiatric clinical conditions where different brain circuitries are affected (e.g., chronic pain, Parkinson's disease or depression), having a great impact in the individual's well-being, quality of life, and the socioeconomic system. Sleep disturbances in absence of breathing or neurological disorders are mainly treated with medications (e.g., benzodiazepines, hypnotics, etc.) and cognitive behavioral therapy, which are associated with side-effects and adherence issues, respectively. Moreover, these therapies do not seem to work effectively for some individuals. Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are non-invasive stimulation techniques used to treat several conditions and symptoms. Results from this systematic review indicate that rTMS and tDCS are safe and have potential to improve insomnia symptoms and sleep disturbances across different types of neurological and neuropsychiatric diseases. However, uncontrolled and quasi experimental studies with high risk of bias were included. Thus, although these results can help developing the field, caution in interpreting them is advised. Additional research efforts are needed to reduce bias, improve quality, and characterize optimal brain stimulation parameters to promote their efficacy on sleep related outcomes., Competing Interests: Conflicts of interest The authors have no conflict of interest to declare., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Pediatric traumatic brain injury (TBI) can lead to adverse emotional, social, and behavioral consequences. However, outcome is difficult to predict due to significant individual variability, likely reflecting a complex interaction between injury- and child-related variables. Among these variables are genetically determined individual differences, which can modulate TBI outcome through their influence on neuroplasticity mechanisms. In this study, we examined the effect of Val66Met, a common polymorphism of the brain-derived neurotrophic factor gene known to be involved in neuroplasticity mechanisms, on behavioral symptoms of mild TBI (mTBI) sustained in early childhood. This work is part of a prospective, longitudinal cohort study of early TBI. The current sample consisted of 145 children between ages 18 and 60 months assigned to one of three participant groups: mild TBI, orthopedic injury, or typically developing children. Participants provided a saliva sample to detect the presence of the Val66Met polymorphism, and the Child Behavior Checklist was used to document the presence of behavioral symptoms at 6- and 18-months post-injury. Contrary to our initial hypothesis, at 6 months post-injury, non-carriers of the Val66Met polymorphism in the mTBI group presented significantly more internalizing symptoms (e.g., anxiety/depression and somatic complaints) than Val66Met carriers, who were similar to orthopedically injured and typically developing children. However, at 18 months post-injury, all children with mTBI presented more internalizing symptoms, independent of genotype. The results of the study provide evidence for a protective effect of the Val66Met polymorphism on internalizing behavior symptoms 6 months after early childhood mTBI.

Background: A concern about the susceptibility of immunocompromised patients to the worldwide pandemic of coronavirus disease 2019 (COVID-19) has been raised. We aimed at describing COVID-19 infections in the French cohort of lung transplant (LT) patients., Methods: Multicenter nationwide cohort study of all LT recipients with COVID-19 diagnosed from March 1 to May 19, 2020. Recipient main characteristics and their management were retrieved. Hospitalization characteristics, occurrence of complications and survival were analyzed., Results: Thirty-five LT patients with a COVID-19 infection were included. Median age was 50.4 (40.6-62.9) years, 16 (45.7%) were female, and 80% were double-LT recipients. Infection was community-acquired in 25 (71.4%). Thirty-one (88.6%) required hospitalization, including 13 (41.9%) in the intensive care unit. The main symptoms of COVID-19 were fever, cough, and diarrhea, present in 71.4%, 54.3%, and 31.4% of cases, respectively. Extension of pneumonia on chest CT was moderate to severe in 51.4% of cases. Among the 13 critically ill patients, 7 (53.9%) received invasive mechanical ventilation. Thrombotic events occurred in 4 patients. Overall survival rate was 85.7% after a median follow-up of 50 days (41.0-56.5). Four of 5 nonsurvivors had had bronchial complications or intensification of immunosuppression in the previous weeks. On univariate analysis, overweight was significantly associated with risk of death (odds ratio, 16.0; 95% confidence interval, 1.5-170.6; P = 0.02)., Conclusions: For the 35 LT recipients with COVID-19, the presentation was severe, requiring hospitalization in most cases, with a survival rate of 85.7%., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Although there is a growing body of literature on the impact of multiple concussions on cognitive function with aging, less is known about the long-term impact of sustaining a single mild traumatic brain injury (mTBI). Additionally, very few interventions exist to treat mTBI patients and prevent a possible accelerated cognitive decline. This study aimed to: 1) examine the long-term effects of a single mTBI on cognition in patients aged between 55 and 70 years old; and 2) evaluate the cognitive effects of an aerobic exercise program for these patients., Methods: Thirty-five participants (average age: 58.89, SD=4.14) were assessed using neuropsychological tests. Among them, 18 hadsustained a mTBI two to seven years earlier. Significant differences in information processing speed, executive function and visual memory were found between controls and mTBI patients. Sixteen of the mTBI patients then engaged in a 12-week physical exercise program. They were divided into equivalent groups: 1) aerobic training (cycle ergometers); or 2) stretching exercises. The participants' cardiopulmonary fitness (VO2max) was evaluated pre- and postintervention and neuropsychological tests were re-administered postintervention., Results: Participants from the aerobic group significantly improved their fitness compared to the stretching group. However, no between-group difference was found on neuropsychological measures postintervention., Conclusions: In summary, this study shows long-term cognitive effects of mTBI in late adulthood patients. Moreover, the controlled, 12-week aerobic exercise program did not lead to cognitive improvements in our small mTBI sample. Lastly, future directions in optimizing mTBI intervention are discussed.

Mild traumatic brain injury (mTBI) in early childhood is prevalent, and some children may be at risk for short- and long-term difficulties that could affect quality of life (QoL). Despite growing efforts to understand associations between potential risk factors and outcomes after injury, prognosis is elusive and lacks the inclusion of genetic variables which may convey additional predictive power. This study assessed which factors contribute to pediatric QoL 6 and 18 months post-recruitment in 159 participants (mTBI = 52; orthopedic injury [OI] = 43; typically developing controls [TDC] = 64) aged 18 to 60 months at the time of injury (M = 37.50, SD = 11.69). Family environment, injury characteristics, and child cognitive-behavioral functioning were assessed at 6 months via parent questionnaires and socio-cognitive assessment. QoL was determined using the Pediatric Quality of Life Inventory at both time points. Genetic information (Brain-derived neurotrophic factor [BDNF] genotype) was collected using saliva samples. Hierarchical regression analyses testing biological, family-environmental, injury and cognitive-behavioral factors revealed that the BDNF Val66Met polymorphism was a significant independent predictor of better QoL 6 months post-injury in the mTBI group. Lower parental distress significantly and independently predicted higher QoL 18 months after mTBI, and 6 months post-recruitment in the TDC group. At 18 months, models were non-significant for both control groups. Genetic factors involved in neuroplasticity may play an important role in recovery 6 months after mTBI and contribute to outcome via their interplay with environmental factors. Over time, family factors appear to become the primary determinants of post-mTBI outcome., Competing Interests: Declaration of Competing Interest 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., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: Mild traumatic brain injury (mTBI) is highly prevalent, especially in children under 6 years. However, little research focuses on the consequences of mTBI early in development. The objective of the Kids' Outcomes And Long-term Abilities (KOALA) study is to document the impact of early mTBI on children's motor, cognitive, social and behavioural functioning, as well as on quality of life, stress, sleep and brain integrity., Methods and Analyses: KOALA is a prospective, multicentre, longitudinal cohort study of children aged 6 months to 6 years at the time of injury/recruitment. Children who sustain mTBI (n=150) or an orthopaedic injury (n=75) will be recruited from three paediatric emergency departments (PEDs), and compared with typically developing children (community controls, n=75). A comprehensive battery of prognostic and outcome measures will be collected in the PED, at 10 days, 1, 3 and 12 months postinjury. Biological measures, including measures of brain structure and function (magnetic resonance imaging, MRI), stress (hair cortisol), sleep (actigraphy) and genetics (saliva), will complement direct testing of function using developmental and neuropsychological measures and parent questionnaires. Group comparisons and predictive models will test the a priori hypotheses that, compared with children from the community or with orthopaedic injuries, children with mTBI will (1) display more postconcussive symptoms and exhibit poorer motor, cognitive, social and behavioural functioning; (2) show evidence of altered brain structure and function, poorer sleep and higher levels of stress hormones. A combination of child, injury, socioenvironmental and psychobiological factors are expected to predict behaviour and quality of life at 1, 3 and 12 months postinjury., Ethics and Dissemination: The KOALA study is approved by the Sainte-Justine University Hospital, McGill University Health Centre and University of Calgary Conjoint Health Research Ethics Boards. Parents of participants will provide written consent. Dissemination will occur through peer-reviewed journals and an integrated knowledge translation plan., Competing Interests: Competing interests: CL’s spouse is an employee of General Electric Healthcare. The other authors report no biomedical financial interests or potential conflicts of interest., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Characterizing the effects of obstructive sleep apnea (OSA) on the aging brain could be key in our understanding of neurodegeneration in this population. Our objective was to assess white matter properties in newly diagnosed and untreated adults with mild to severe OSA. Sixty-five adults aged 55 to 85 were recruited and divided into three groups: control (apnea-hypopnea index ≤5/hr; n = 18; 65.2 ± 7.2 years old), mild (>5 to ≤15 hr; n = 27; 64.2 ± 5.3 years old) and moderate to severe OSA (>15/hr; n = 20; 65.2 ± 5.5 years old). Diffusion tensor imaging metrics (fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity, and mean diffusivity) were compared between groups with Tract-Based Spatial Statistics within the white matter skeleton created by the technique. Groups were also compared for white matter hyperintensities volume and the free-water (FW) fraction. Compared with controls, mild OSA participants showed widespread areas of lower diffusivity (p < .05 corrected) and lower FW fraction (p < .05). Participants with moderate to severe OSA showed lower AD in the corpus callosum compared with controls (p < .05 corrected). No between-group differences were observed for FA or white matter hyperintensities. Lower white matter diffusivity metrics is especially marked in mild OSA, suggesting that even the milder form may lead to detrimental outcomes. In moderate to severe OSA, competing pathological responses might have led to partial normalization of diffusion metrics., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.)

This longitudinal study aimed to evaluate qualitative (parosmia) and quantitative (hyposmia/anosmia) olfaction 2-4 weeks (baseline) and six months (follow-up) after a mild traumatic brain injury (mTBI). We further evaluated the predictive value of baseline depression, anxiety and olfaction scores on depression and anxiety at follow-up. At baseline, olfactory function and affective state were assessed in 107 participants (53 patients with mild TBI; 54 healthy controls). At follow-up, data were collected on 71 participants (32 patients, 39 controls). Both at baseline and follow-up, patients with mild TBI showed more signs of parosmia, depression and anxiety, compared to controls. However, patients did not, neither at baseline nor follow-up, show quantitative olfactory impairment. Moreover, while baseline scores of depression and anxiety helped predict the development of symptoms of depression and anxiety at follow up, adding parosmia scores to the prediction model significantly increased the amount of explained variances. Clinicians should implement affective and olfactory evaluation to predict patients' affective outcome., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Sleep disturbances and chronic pain are considered public health concerns. They are frequently associated, and the direction of its relationship and possible mechanisms underlying it are frequently debated. The exploration of the sleep-pain association is of great clinical interest to explore in order to steer potential therapeutic avenues, accommodate the patient's experience, and adapt the common practice of health professionals. In this review, the direction between sleep-pain in adult and pediatric populations will be discussed. Moreover, the possible mechanisms contributing to this relationship as endogenous pain modulation, inflammation, affect, mood and other states, the role of different endogenous substances (dopamine, orexin, melatonin, vitamin D) as well as other lesser known such as cyclic alternating pattern among others, will be explored. Finally, directions for future studies on this area will be discussed, opening up to the addition of tools such as brain imaging (e.g., fMRI), electrophysiology and non-invasive brain stimulation techniques. Such resources paired with artificial intelligence are key to personalized medicine management for patients facing pain and sleep interacting conditions.

Objective: Primary motor (M1) cortical excitability alterations are involved in the development and maintenance of chronic pain. Less is known about M1-cortical excitability implications in the acute phase of an orthopedic trauma. This study aims to assess acute M1-cortical excitability in patients with an isolated upper limb fracture (IULF) in relation to pain intensity., Methods: Eighty-four (56 IULF patients <14 days post-trauma and 28 healthy controls). IULF patients were divided into two subgroups according to pain intensity (mild versus moderate to severe pain). A single transcranial magnetic stimulation (TMS) session was performed over M1 to compare groups on resting motor threshold (rMT), short-intracortical inhibition (SICI), intracortical facilitation (ICF), and long-interval cortical inhibition (LICI)., Results: Reduced SICI and ICF were found in IULF patients with moderate to severe pain, whereas mild pain was not associated with M1 alterations. Age, sex, and time since the accident had no influence on TMS measures., Discussion: These findings show altered M1 in the context of acute moderate to severe pain, suggesting early signs of altered GABAergic inhibitory and glutamatergic facilitatory activities., Competing Interests: The authors have declared that no competing interests exist.

Belatacept (BTC) is indicated for prophylaxis of graft rejection in adults receiving a renal transplant (Tx). This retrospective observational study (three centers) included all heart transplant recipients receiving BTC between January 2014 and October 2018. Forty EBV+ patients mean GFR 35 ± 20 mL/min/m 2 were identified, among whom belatacept was initiated during the first 3 months after transplantation in 12 patients, and later in 28 patients. Several patients were multiorgan transplant recipients. Study outcomes were GFR, safety, and changes in immunosuppressive therapy. The main reason for switching to BTC was to preserve renal function, resulting in discontinuation of CNI and changes in immunosuppressive therapy in 76% of cases. At study closeout, 24/40 patients were still on BTC therapy. GFR was improved (+59%, P = .0002*) within 1 month, particularly in the early group. More episodes of rejection were observed among "late" patients (1 death). Sixteen treatment discontinuations were recorded: GFR recovery (n = 4), DSA no longer detectable (n = 1), compliance issues (n = 3), poor venous access (n = 2), multiple infections (n = 1), 1 death (fungal lung infection), and treatment failure (n = 4). Median follow-up was 24 months. Four patients developed de novo DSA (MFI<1500). BTC is an effective alternative immunosuppressive for postoperative transient kidney failure, stabilizing delayed renal function, with acceptable safety profile under careful monitoring., (© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Stress exposure over the lifespan is robustly associated with accelerated cognitive decline in later life. Brain-derived neurotrophic factor (BDNF) is shown to regulate activity of the hypothalamic-pituitary-adrenal axis. The objective of this study was to evaluate the association betweenthe BDNF polymorphism and indices of stress among adults aged 50+. Community-dwelling middle-aged and older adults provided a blood sample for BDNF genotyping. Participants also sampled their saliva 5 times/day for 3 consecutive days for the measurement of diurnal cortisol and underwent the Trier Social Stress Test (TSST) for the measurement of stress reactivity. Among 121 adults aged 50-67 years (78% female; 89% Caucasian), 74 participants were Val/Val carriers and 47 carried 1 copy of the Met allele. Repeated-measures analyses did not reveal an association between BDNF genotype and diurnal salivary cortisol (p = 0.63); however, analyses revealed that Met+ carriers displayed lower levels of cortisol secretion in response to the TSST compared with Val/Val carriers; F(4.43, 496.238) = 2.57, p = 0.032. This is the first study to evaluate the role of the BDNF polymorphism in stress physiology among older adults. Future studies are needed to evaluate the lifespan interconnections between BDNF and stress physiology., (© 2019 S. Karger AG, Basel.)

Objectives: This study seeks to evaluate the incidence rate of heterotopic ossification (HO) formation in patients afflicted by an isolated limb fracture (ILF) and a concomitant mild traumatic brain injury (mTBI)., Methods: The current study is an observational study including ILF patients with or without a concomitant mTBI recruited from an orthopedic clinic of a Level 1 Trauma Hospital. Patients were diagnosed with a mTBI according to the American Congress of Rehabilitation Medicine (ACRM) criteria. Radiographs taken on average 3 months post-trauma were analyzed separately by two distinct specialists for the presence of HO proximally to the fracture site (joints or extra joints). Both raters referred to Brooker's and Della's Valle's classification to establish signs of HO. First, analyses were conducted for the full sample. Secondly, a matched cohort was used in order to control for specific factors, namely age, sex, type of injury, and time elapsed between the accident and the analyzed radiograph., Results: The full sample included a total of 183 patients with an ILF (94 females; 47.5 years old), of which 50 had a concomitant mTBI and 133 without. Radiographic evidence of HO was significantly higher in patients with an ILF and a mTBI compared to ILF patients (X 2  = 6.50; p  = 0.01). The matched cohort consisted of 94 participants (i.e.; 47 patients from the ILF + mTBI group and 47 patients from the ILF group). Again, ILF + mTBI patients presented significantly higher rates of HO signs in comparison to ILF patients (X 2  = 3.69; p  = 0.04). Presence of HO was associated with prolonged delays to return to work (RTW) only in ILF + mTBI patients (F = 4.055; p  = 0.05) but not in ILF patients (F = 0.823; p  = 0.37)., Conclusions: Study findings suggest that rates of HO are significantly higher proximally to fracture sites when ILF patients sustain a concomitant mTBI, even after controlling for factors known to influence HO. Moreover, results show that HO is associated with a prolonged RTW only in ILF patients with a concomitant mTBI but not in ILF-only patients. The impact of mTBI on HO formation warrants further attention to detect early signs of HO, to identify shared physiopathological mechanisms and, ultimately, to design targeted therapies.

Persistent cognitive and motor symptoms are known consequences of concussions/mild traumatic brain injury (mTBIs) that can be partly attributable to altered neurotransmission. Indeed, cerebral microdialysis studies in rodents have demonstrated an excessive extracellular glutamate release in the hippocampus within the first 10 min following trauma. Microdialysis offers the clear advantage of in vivo neurotransmitter continuous sampling while not having to sacrifice the animal. In addition to the aforementioned technique, a closed head injury model that exerts rapid acceleration and deceleration of the head and torso is needed, as such a factor is not available in many other animal models. The Wayne State weight-drop model mimics this essential component of human craniocerebral trauma, allowing the induction of an impact on the head of an unrestrained rodent with a falling weight. Our novel and translational rat model combines cerebral microdialysis with the Wayne State weight-drop model to study, in lightly anesthetized and unrestrained adult rats, the acute changes in extracellular neurotransmitter levels following concussion. In this protocol, the microdialysis probe was inserted inside the hippocampus as region of interest, and was left inserted in the brain at impact. There is a high density of terminals and receptors in the hippocampus, making it a relevant region to document altered neurotransmission following concussion. When applied to adult Sprague-Dawley rats, our combined model induced increases in hippocampal extracellular glutamate concentrations within the first 10 min, consistent with the previously reported post-concussion symptomology. This combined weight-drop model provides a reliable tool for researchers to study early therapeutic responses to concussions in addition to repetitive brain injury, since this protocol induces a closed-head mild trauma.

Static magnetic fields (SMFs) are known to alter neural activity, but evidence of their ability to modify learning-related neuroplasticity is lacking. The present study tested the hypothesis that application of static magnetic stimulation (SMS), an SMF applied transcranially via a neodymium magnet, over the primary motor cortex (M1) would alter learning of a serial reaction time task (SRTT). Thirty-nine participants took part in two experimental sessions separated by 24 h where they had to learn the SRTT with their right hand. During the first session, two groups received SMS either over contralateral (i.e., left) or ipsilateral (i.e., right) M1 while a third group received sham stimulation. SMS was not applied during the second session. Results of the first session showed that application of SMS over contralateral M1 impaired online learning as compared to both ipsilateral and sham groups, which did not differ. Results further revealed that application of SMS did not impair offline learning or relearning. Overall, these results are in line with those obtained using other neuromodulatory techniques believed to reduce cortical excitability in the context of motor learning and suggest that the ability of SMS to alter learning-related neuroplasticity is temporally circumscribed to the duration of its application.

Study Objectives: Recent studies show that obstructive sleep apnea (OSA) is a possible contributor to abnormal cognitive decline in older adults. These new observations create the need to identify older adults with OSA who are at risk of the developing dementia if not treated. This study's goal was to verify whether self-reported cognitive complaints could become a useful tool to screen for objective cognitive deficits in late middle-aged and older adults with OSA., Methods: Fifty-seven participants with OSA with an apnea-hypopnea index (AHI) ≥ 15 events/h (3% or arousal) and aged between 55 and 85 years were compared to 54 participants in a mild/non-OSA group on their ability to evaluate their objective cognitive functioning. They underwent overnight polysomnography followed by a comprehensive neuropsychological assessment. We recruited a similar proportion of participants with mild cognitive impairment (MCI) in both groups (OSA: 36.8%; mild/non-OSA: 35.2%). They filled out questionnaires assessing mood, sleep, and cognition. Group (OSA versus mild/non-OSA) × cognitive status (MCI versus non-MCI) analyses of variance were performed on cognitive complaint questionnaires., Results: We found that among participants without objective cognitive deficits, participants in the OSA group reported more cognitive complaints compared to those in the mild/non-OSA group. Among participants with objective cognitive deficits, those in the OSA group reported less cognitive complaints compared to those in the mild/non-OSA group., Conclusions: Participants with OSA and MCI were less aware of their deficits compared to those in the mild/non-OSA group, possibly reflecting a distinctive OSA-associated cognitive impairment. Our results underscore the importance of referring patients with OSA for a comprehensive neuropsychological assessment when an abnormal cognitive decline is suspected., (© 2019 American Academy of Sleep Medicine.)

Mounting evidence suggests that mild traumatic brain injuries (mTBI) have long-term effects that interact with the aging process to precipitate cognitive decline. This line of research predicts that early exposure to brain trauma is particularly detrimental to long-term brain integrity. However, a second line of research into the effects of age at trauma onset predict that older brains are more vulnerable to the effects of mTBI than younger brains. We sought to determine whether patients who sustain a mTBI earlier in life fare better than patients who sustain a mTBI at an older age. We conducted a multi-cohort, case-control study, with participants randomly sampled from a population of patients with a history of mTBI. We recruited two cohorts of aging participants (N = 74, mean [SD] = 61.16 [6.41]) matched in age and education levels that differed in only one respect: age at mTBI onset. One cohort sustained their concussion in their early twenties (24.60 [6.34] y/o), the other in their early sixties (61.05 [4.90] y/o). Each mTBI cohort had its own matched control group. Participants underwent high-resolution MRI at 3 Tesla for T 1 and diffusion-weighted images (DWI) acquisition. Images were processed and analyzed using Deformation-Based Morphometry and DWI Tract-Based Spatial Statistics to identify group differences in a 2 × 2 ANOVA design. Results showed a significant interaction on DWI measures of white matter integrity indicating larger anomalies in participants who sustained a mTBI at a younger age (F 1,70 , P < .05, FDR corrected). These findings suggest that mTBI initiates a lifelong neurodegeneration process that outweighs the risks associated with sustaining a mTBI at an older age. Implications are important for young athletes' populations exposed to the risk of mTBI in the practice of their sports and for retired athletes aging with a history of concussions sustained at a younger age., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Pain is a multifaceted condition and a major ongoing challenge for healthcare professionals having to treat patients in whom pain put them at risk of developing other conditions. Significant efforts have been invested in both clinical and research settings in an attempt to demystify the mechanisms at stake and develop optimal treatments as well as to reduce individual and societal costs. It is now universally accepted that neuroinflammation and central sensitization are two key underlying factors causing pain chronification as they result from maladaptive central nervous system plasticity. Recent research has shown that the mechanisms of action of repetitive transcranial magnetic stimulation (rTMS) make it a particularly promising avenue in treating various pain conditions. This review will first discuss the contribution of neuroinflammation and central sensitization in the transition from acute to chronic pain in traumatically injured patients. A detailed discussion on how rTMS may allow the restoration from maladaptive plasticity in addition to breaking down the chain of events leading to pain chronification will follow. Lastly, this review will provide a theoretical framework of what might constitute optimal rTMS modalities in dealing with pain symptoms in traumatically injured patients based on an integrated perspective of the physiopathological mechanisms underlying pain., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The aim of this article is to introduce transcranial magnetic stimulation (TMS) to dental practitioners and to explain its use in obstructive sleep apnea (OSA) and sleep bruxism (SB). In these 2 sleep disorders, TMS has proven to be a useful tool to explore pathophysiological pathways and disease mechanisms, and in a more limited way, to recruit upper airway muscles in OSA and reduce muscle activity and pain intensity in SB. Although promising, research using TMS in these conditions is still very limited and future investigations should be conducted before its clinical application can be considered., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Healthy aging is associated with decline of motor function that can generate serious consequences on the quality of life and safety. Our studies aim to explore the 3-month effects of a 5-day multisession anodal transcranial direct current stimulation (a-tDCS) protocol applied over the primary motor cortex (M1) during motor sequence learning in elderly. The present sham-controlled aging study investigated whether tDCS-induced motor improvements previously observed 1 day after the intervention persist beyond 3 months. A total of 37 cognitively-intact aging participants performed five consecutive daily 20-min sessions of the serial-reaction time task (SRTT) concomitant with either anodal ( n = 18) or sham ( n = 19) tDCS over M1. All participants performed the Purdue Pegboard Test and transcranial magnetic stimulation (TMS) measures of cortical excitability were collected before, 1 day after and 3 months after the intervention. The last follow-up session also included the execution of the trained SRTT. The main findings are the demonstration of durable effects of a 5-day anodal tDCS intervention at the trained skill, while the active intervention did not differ from the sham intervention at both the untrained task and on measures of M1-disinhibition. Thus, the current article revealed for the first time the durability of functional effects of a-tDCS combined with motor training after only 5 days of intervention in an aging population. This finding provides evidence that the latter treatment alternative is effective in achieving our primary motor rehabilitation goal, that is to allow durable motor training effects in an aging population.

Background: Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) are non-invasive brain stimulation techniques that are being explored as therapeutic alternatives for the management of various chronic pain conditions., Objective: The primary objective of this systematic review is to assess the efficacy of TMS and tDCS in reducing clinical pain intensity in chronic orofacial pain (OFP) disorders. The secondary objectives are to describe adverse effects, duration of relief, and TMS/tDCS methodologies used in chronic OFP disorders., Methods: A search was performed in MEDLINE, Embase, Web of Science, Scopus, and Google Scholar. Inclusion criteria were 1) population: adults diagnosed with chronic OFP including neuropathic and non-neuropathic disorders; 2) intervention: active TMS or tDCS stimulation regardless of the used protocol; 3) comparison: sham TMS or tDCS stimulation; and 4) outcome: primary outcome was patient reported pain intensity. Secondary outcomes were duration of pain relief, adverse effects, and methodological parameters. Risk of bias and quality of study reporting were also assessed., Results: A total of 556 individual citations were identified by the search strategy, with 14 articles meeting selection criteria (TMS=11; tDCS=3). Data were obtained for a total of 228 patients. Included OFP disorders were trigeminal neuralgia, trigeminal neuropathy, burning mouth syndrome, atypical facial pain, and temporomandibular disorders. Significant pain reductions were obtained in both techniques. More number of sessions yielded to more durable effects. Overall, high risk of bias and poor study quality were found., Conclusion: TMS and tDCS appear to be safe and promising alternatives to reduce pain intensity in different chronic OFP disorders. Additional research effort is needed to reduce bias, improve quality, and characterize optimal brain stimulation parameters to promote their efficacy., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Objectives: Concussions affect the processing of emotional stimuli. This study aimed to investigate how sex interacts with concussion effects on early event-related brain potentials (ERP) measures (P1, N1) of emotional facial expressions (EFE) processing in asymptomatic, multi-concussion athletes during an EFE identification task., Methods: Forty control athletes (20 females and 20 males) and 43 multi-concussed athletes (22 females and 21 males), recruited more than 3 months after their last concussion, were tested. Participants completed the Beck Depression Inventory II, the Beck Anxiety Inventory, the Post-Concussion Symptom Scale, and an Emotional Facial Expression Identification Task. Pictures of male and female faces expressing neutral, angry, and happy emotions were randomly presented and the emotion depicted had to be identified as fast as possible during EEG acquisition., Results: Relative to controls, concussed athletes of both sex exhibited a significant suppression of P1 amplitude recorded from the dominant right hemisphere while performing the emotional face expression identification task. The present study also highlighted a sex-specific suppression of the N1 component amplitude after concussion which affected male athletes., Conclusions: These findings suggest that repeated concussions alter the typical pattern of right-hemisphere response dominance to EFE in early stages of EFE processing and that the neurophysiological mechanisms underlying the processing of emotional stimuli are distinctively affected across sex. (JINS, 2018, 24, 673-683).

Appropriate exposure to posaconazole (PSZ) has been limited until the recent approval of the delayed-release oral tablet formulation. Our goal was to determine the exposure obtained by using the standard dose of 300 mg once a day in lung transplant (LT) patients, including patients with cystic fibrosis (CF). PSZ trough concentrations ( C 0 ) were determined using a liquid chromatography-tandem mass spectrometry assay. Indicative thresholds of interest were <0.7 mg/liter for prophylaxis and 1 to 3 mg/liter for cure. The tacrolimus (TRL) and everolimus (ERL) C 0 measured during PSZ exposure were also collected. The interaction with proton-pump inhibitors (PPI) was evaluated. We recorded the results for 21 CF patients with LT (CFLT patients), 11 non-CF patients with LT (NCFLT patients), and 27 nontransplant (NT) patients in pneumology departments. The weights of the NCFLT, CFLT, and NT patients were 59.2 ± 8.4, 48.8 ± 8.4, and 63.7 ± 16.6 kg, respectively ( P = 0.001* [asterisk means that statistical test is significant]), and the PSZ C 0 exposures for these patients were 1.9 ± 1.5, 1.1 ± 0.8, and 2.4 ± 1.8 mg/liter, respectively ( P < 0.00001*). More than 60% of the concentrations were in the therapeutic range. In CFLT patients, the administration of one 300-mg PSZ tablet quickly achieved an exposure similar to that achieved with the PSZ oral suspension formulation (OSF) administered 3 or 4 times a day for several months. The TRL C 0 /dose ratio ( C 0 / D ) was 7.4 ± 4.4 mg/liter with PSZ tablets, whereas it was 4.6 ± 0.8 mg/liter with the PSZ oral solution ( P = 0.034*). The ERL C 0 / D was similar with both formulations. PPI had no impact on the PSZ concentration (1.49 ± 1.07 mg/liter without PPI versus 1.33 ± 1.17 mg/liter with PPI; P = 0.4134*). Despite the high levels of exposure, PSZ remained well tolerated (one case of diarrhea and one case of fatigue were reported). PSZ tablet administration allows satisfactory exposure, even in CFLT patients, with a dosage lower than that of the PSZ OSF. This once-a-day formulation was not impacted by PPI, which are extensively used in CF patients., (Copyright © 2018 American Society for Microbiology.)

Objectives: The present aging study investigated the impact of a multisession anodal-tDCS protocol applied over the primary motor cortex (M1) during motor sequence learning on generalization of motor learning and plasticity-dependent measures of cortical excitability., Methods: A total of 32 cognitively-intact aging participants performed five consecutive daily 20-min sessions of the serial-reaction time task (SRTT) concomitant with either anodal (n = 16) or sham (n = 16) tDCS over M1. Before and after the intervention, all participants performed the Purdue Pegboard Test (PPT) and Transcranial Magnetic Stimulation (TMS) measures of cortical excitability were collected., Results: Relative to sham, participants assigned to the anodal-tDCS intervention revealed significantly greater performance gains on both the trained SRTT and the untrained PPT as well as a greater disinhibition of long-interval cortical inhibition (LICI). Generalization effects of anodal-tDCS significantly correlated with LICI disinhibition., Conclusion: Anodal-tDCS facilitates motor learning generalisation in an aging population through intracortical disinhibition effects., Significance: The current findings demonstrate the potential clinical utility of a multisession anodal-tDCS over M1 protocol as an adjuvant to motor training in alleviating age-associated motor function decline. This study also reveals the pertinence of implementing brain stimulation techniques to modulate age-associated intracortical inhibition changes in order to facilitate motor function gains., (Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Most EEG studies used event-related potentials to assess long-term and cumulative effects of sport-related concussions on brain activity. Time-frequency methods provide another approach that allows the detection of subtle shifts in types and patterns of brain oscillations. We sought to discover whether event-related alpha activity would be significantly affected in asymptomatic multi-concussed athletes. We measured the amplitude of alpha activity (8-12Hz) from the EEG recorded during a visual-spatial attention task to compare event-related alpha perturbations in 13 multi-concussed athletes and 14 age-equivalent, non-concussed teammates. Relative to non-concussed athletes, multi-concussed athletes showed significantly less event-related perturbations time-locked to stimulus presentation. Alpha activity alterations were closely related to the number of concussions sustained. Event-related alpha activity differed in asymptomatic multi-concussed athletes when compared to controls. Our study suggests that low-level neurophysiological underpinnings of the deployment of visual-spatial attention are affected in multi-concussed athletes even though their last concussion occurred on average 30 months prior to testing., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Little is known of the long-term effects of sports-related concussion. Within the scientific literature, conclusions vary substantially where some work suggests there are no long-term consequences at all and other studies show rampant neurodegeneration thought to be caused by sometimes even a single concussive blow to the head. There is growing evidence that supports multiple long-term outcomes, showing both subclinical and clinically relevant changes in the brains of athletes, young and old alike. This article reviews the pathohistology of cerebral concussions and examines the extant literature with a focus on electrophysiological and neuroimaging findings. Neurobehavioral and neurocognitive changes are also reviewed, particularly as they are related to chronic traumatic encephalopathy. Lacunae within the literature are explored, and future research directions are proposed.

Aims: To explore whether traumatic brain injury (TBI) patients have a higher prevalence of sleep bruxism (SB) and a higher level of orofacial muscle activity than healthy controls and whether orofacial muscle activity in the context of mild TBI (mTBI) increases the risk for headache disability., Methods: Sleep laboratory recordings of 24 mTBI patients (15 males, 9 females; mean age ± standard deviation [SD]: 38 ± 11 years) and 20 healthy controls (8 males, 12 females; 31 ± 9 years) were analyzed. The primary variables included degree of headache disability, rhythmic masticatory muscle activity (RMMA) index (as a biomarker of SB), and masseter and mentalis muscle activity during quiet sleep periods., Results: A significantly higher prevalence of moderate to severe headache disability was observed in mTBI patients than in controls (50% vs 5%; P = .001). Although 50% and 25% of mTBI patients had a respective RMMA index of ≥ 2 episodes/hour and ≥ 4 episodes/hour, they did not present more evidence of SB than controls. No between-group differences were found in the amplitude of RMMA or muscle tone. Logistic regression analyses suggested that while mTBI is a strong predictor of moderate to severe headache disability, RMMA frequency is a modest but significant mediator of moderate to severe headache disability in both groups (odds ratios = 21 and 2, respectively)., Conclusion: Clinicians caring for mTBI patients with poorly controlled headaches should screen for SB, as it may contribute to their condition.

Objectives: This study seeks to evaluate the effects of a mild traumatic brain injury (mTBI) on pain in patients with an isolated limb fracture (ILF) when compared to a matched cohort group with no mTBI (control group)., Patients and Methods: All subjects included in this observational study suffered from an ILF. Groups were matched according to the type of injury, sex, age, and time since the accident. Main outcome measurements were: Standardized semi-structured interviews at follow-up of a Level I Trauma Center, and a questionnaire on fracture-related pain symptoms. Factors susceptible to influence the perception of pain, such as age, sex, severity of post-concussive symptoms, and worker compensation were also assessed., Results: A total of 68 subjects (36 females; 45 years old) with an ILF were selected, 34 with a comorbid mTBI and 34 without (24/34 with an upper limb fracture per group, 71% of total sample). Patients with mTBI and an ILF reported significantly higher pain scores at the time of assessment (mean: 49days, SD: 34.9), compared to the control group (p<0.0001; mean difference 2.8, 95% confidence interval 1.8-4.0). Correlational analyses show no significant association between the level of pain and factors such as age, sex, severity of post-concussive symptoms, and worker compensation., Conclusions: Results suggest that mTBI exacerbate perception of pain in the acute phase when occurring with an ILF, and were not explained by age, sex, post-concussive symptoms, or worker compensation. Rather, it appears possible that neurological sequelae induced by mTBI may interfere with the normal recovery of pain following trauma., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Sports-related concussions lead to persistent anomalies of the brain structure and function that interact with the effects of normal ageing. Although post-mortem investigations have proposed a bio-signature of remote concussions, there is still no clear in vivo signature. In the current study, we characterized white matter integrity in retired athletes with a history of remote concussions by conducting a full-brain, diffusion-based connectivity analysis. Next, we combined MRI diffusion markers with MR spectroscopic, MRI volumetric, neurobehavioral and genetic markers to identify a multidimensional in vivo signature of remote concussions. Machine learning classifiers trained to detect remote concussions using this signature achieved detection accuracies up to 90% (sensitivity: 93%, specificity: 87%). These automated classifiers identified white matter integrity as the hallmark of remote concussions and could provide, following further validation, a preliminary unbiased detection tool to help medical and legal experts rule out concussion history in patients presenting or complaining about late-life abnormal cognitive decline., (© 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

It is well established that blindness induces changes in cerebral function and structure, namely affecting the somatomotor regions. However, the behavioural significance of these changes on the motor system, and on motor learning in particular, remains elusive. In this study, we used a modified version of the serial reaction time task (SRTT) with auditory cues to assess sequence specific and non-specific motor learning in blind adults and sighted controls, and compare them with sighted controls performing the classic visual SRTT. Our results show that the auditory SRTT faithfully replicates the typical learning pattern obtained with the visual SRTT. On the auditory SRTT, blind individuals consistently showed faster reaction times than sighted controls, being at par with sighted individuals performing the visual SRTT. On the other hand, blind participants displayed a particular pattern of motor learning in comparison to both sighted groups; while controls improved prominently on sequence specific learning, blind individuals displayed comparable performance on both specific and non-specific learning, markedly outperforming the control groups on non-specific learning. These results show that blindness, in addition to causing long-term changes in cortical organisation, can also influence dynamic neuroplastic mechanisms in systems beyond those typically associated with compensatory sensory processing.

Purpose: Body mass index (BMI) is an inadequate measure of nutritional status in children and adolescents with cancer as it does not distinguish muscle from adipose tissue. However, arm anthropometry offers simple assessments of fat mass and lean body mass; especially valuable in low- and middle-income countries where the great majority of young people with cancer live and access to sophisticated expensive measures of body composition is markedly limited., Methods: The nutritional status of 75 long-term survivors of acute lymphoblastic leukemia was assessed by arm anthropometry, in addition to BMI, in a cross-sectional cohort study. Normal ranges for triceps skin fold thickness (TSFT, a surrogate for fat mass) and mid-upper arm circumference (MUAC, a surrogate for lean body mass) were between the 15th and 85th percentiles for age and sex. Overweight/obesity was classified as a TSFT >85th percentile and sarcopenia as an MUAC <15th percentile. Height normalized indices for TSFT and MUAC were also calculated., Results: Overweight/obesity was identified in 1/3 of subjects by a BMI >25 and by TSFT; and 20% of the subjects had a TSFT >95th percentile. Only two subjects were sarcopenic. None met the combined criteria for sarcopenic obesity. TSFT and MUAC/height indices did not add sensitivity to identification of sarcopenia or obesity., Conclusions: TSFT is a useful measure of overweight/obesity in this population, but MUAC does not identify a notable proportion with sarcopenia. Further resolution may be provided by more sophisticated measures of body composition.

Rationale: Obstructive sleep apnea causes intermittent hypoxemia, hemodynamic fluctuations, and sleep fragmentation, all of which could damage cerebral gray matter that can be indirectly assessed by neuroimaging., Objectives: To investigate whether markers of obstructive sleep apnea severity are associated with gray matter changes among middle-aged and older individuals., Methods: Seventy-one subjects (ages, 55-76 yr; apnea-hypopnea index, 0.2-96.6 events/h) were evaluated by magnetic resonance imaging. Two techniques were used: (1) voxel-based morphometry, which measures gray matter volume and concentration; and (2) FreeSurfer (an open source software suite) automated segmentation, which estimates the volume of predefined cortical/subcortical regions and cortical thickness. Regression analyses were performed between gray matter characteristics and markers of obstructive sleep apnea severity (hypoxemia, respiratory disturbances, and sleep fragmentation)., Measurements and Main Results: Subjects had few symptoms, that is, sleepiness, depression, anxiety, and cognitive deficits. Although no association was found with voxel-based morphometry, FreeSurfer revealed increased gray matter with obstructive sleep apnea. Higher levels of hypoxemia correlated with increased volume and thickness of the left lateral prefrontal cortex as well as increased thickness of the right frontal pole, the right lateral parietal lobules, and the left posterior cingulate cortex. Respiratory disturbances positively correlated with right amygdala volume, and more severe sleep fragmentation was associated with increased thickness of the right inferior frontal gyrus., Conclusions: Gray matter hypertrophy and thickening were associated with hypoxemia, respiratory disturbances, and sleep fragmentation. These structural changes in a group of middle-aged and older individuals may represent adaptive/reactive brain mechanisms attributed to a presymptomatic stage of obstructive sleep apnea.

Objective: To investigate whether the progressive recuperation of consciousness was associated with the reconsolidation of sleep and wake states in hospitalized patients with acute traumatic brain injury (TBI)., Methods: This study comprised 30 hospitalized patients (age 29.1 ± 13.5 years) in the acute phase of moderate or severe TBI. Testing started 21.0 ± 13.7 days postinjury. Consciousness level and cognitive functioning were assessed daily with the Rancho Los Amigos scale of cognitive functioning (RLA). Sleep and wake cycle characteristics were estimated with continuous wrist actigraphy. Mixed model analyses were performed on 233 days with the RLA (fixed effect) and sleep-wake variables (random effects). Linear contrast analyses were performed in order to verify if consolidation of the sleep and wake states improved linearly with increasing RLA score., Results: Associations were found between scores on the consciousness/cognitive functioning scale and measures of sleep-wake cycle consolidation (p < 0.001), nighttime sleep duration (p = 0.018), and nighttime fragmentation index (p < 0.001). These associations showed strong linear relationships (p < 0.01 for all), revealing that consciousness and cognition improved in parallel with sleep-wake quality. Consolidated 24-hour sleep-wake cycle occurred when patients were able to give context-appropriate, goal-directed responses., Conclusions: Our results showed that when the brain has not sufficiently recovered a certain level of consciousness, it is also unable to generate a 24-hour sleep-wake cycle and consolidated nighttime sleep. This study contributes to elucidating the pathophysiology of severe sleep-wake cycle alterations in the acute phase of moderate to severe TBI., (© 2016 American Academy of Neurology.)

Background: The objective is to explore the effects of concomitant mild traumatic brain injury (mTBI) on return to work (RTW), among patients suffering from an isolated limb fracture. This follow-up study included a total of 170 working age subjects with an isolated limb fracture, and was conducted in a phone interview approximately 1-year post trauma. 41 had experienced an mTBI and 129 did not., Methods: Data were obtained through a phone interview conducted on average 20.7 months (SD = 9.6 months) post-accident. The main outcome measure was the number of days taken to RTW after the injury. Demographic information was also gathered during the phone interview. Workers' compensation status was obtained through the hospitals' orthopaedic clinic data., Results: The mTBI group took on average 329.7 days (SD = 298.0) to RTW after the injury, as opposed to 150.3 days (SD = 171.3) for the control group (p < 0.001). After excluding patients who received workers' compensation, the mTBI group still missed significantly more days of work (M = 299.4 days; SD = 333.0) than the control group (M = 105.2 days; SD = 121.6) (p < 0.0001)., Conclusion: This study shows that mTBI increases work disability by preventing working-age individuals from rapidly returning to work.

Aim: Plant invasions often follow initial introduction with a considerable delay. The current non-native flora of a region may hence contain species that are not yet naturalized but may become so in the future, especially if climate change lifts limitations on species spread. In Europe, non-native garden plants represent a huge pool of potential future invaders. Here, we evaluate the naturalization risk from this species pool and how it may change under a warmer climate., Location: Europe., Methods: We selected all species naturalized anywhere in the world but not yet in Europe from the set of non-native European garden plants. For this subset of 783 species, we used species distribution models to assess their potential European ranges under different scenarios of climate change. Moreover, we defined geographical hotspots of naturalization risk from those species by combining projections of climatic suitability with maps of the area available for ornamental plant cultivation., Results: Under current climate, 165 species would already find suitable conditions in > 5% of Europe. Although climate change substantially increases the potential range of many species, there are also some that are predicted to lose climatically suitable area under a changing climate, particularly species native to boreal and Mediterranean biomes. Overall, hotspots of naturalization risk defined by climatic suitability alone, or by a combination of climatic suitability and appropriate land cover, are projected to increase by up to 102% or 64%, respectively., Main Conclusions: Our results suggest that the risk of naturalization of European garden plants will increase with warming climate, and thus it is very likely that the risk of negative impacts from invasion by these plants will also grow. It is therefore crucial to increase awareness of the possibility of biological invasions among horticulturalists, particularly in the face of a warming climate.

Objectives: Concussion is defined as a complex pathophysiological process affecting the brain. Although the cumulative and long-term effects of multiple concussions are now well documented on cognitive and motor function, little is known about their effects on emotion recognition. Recent studies have suggested that concussion can result in emotional sequelae, particularly in females and multi-concussed athletes. The objective of this study was to investigate sex-related differences in emotion recognition in asymptomatic male and female multi-concussed athletes., Methods: We tested 28 control athletes (15 males) and 22 multi-concussed athletes (10 males) more than a year since the last concussion. Participants completed the Post-Concussion Symptom Scale, the Beck Depression Inventory-II, the Beck Anxiety Inventory, a neuropsychological test battery and a morphed emotion recognition task. Pictures of a male face expressing basic emotions (anger, disgust, fear, happiness, sadness, surprise) morphed with another emotion were randomly presented. After each face presentation, participants were asked to indicate the emotion expressed by the face., Results: Results revealed significant sex by group interactions in accuracy and intensity threshold for negative emotions, together with significant main effects of emotion and group., Conclusions: Male concussed athletes were significantly impaired in recognizing negative emotions and needed more emotional intensity to correctly identify these emotions, compared to same-sex controls. In contrast, female concussed athletes performed similarly to same-sex controls. These findings suggest that sex significantly modulates concussion effects on emotional facial expression recognition. (JINS, 2017, 23, 65-77).

While most studies have been interested in the distinct, predisposing roles of the common BDNF Val66Met variant and extraversion personality traits on episodic memory, very few studies have looked at the synergistic effects of genetic and personality factors to account for cognitive variance. This is surprising considering recent reports challenging the long-held belief that the BDNF Met variant negatively impacts cognitive function. A total of 75 young healthy adults (26 of them carried at least one copy of the BDNF Met allele) took part in this study consisting of genetic profiling from saliva, personality assessment using the Revised NEO Personality Inventory (NEO PI-R) and a short battery of neuropsychological tests. An ANOVA revealed that BDNF Met carriers were significantly less extraverted than BDNF Val carriers ( F 1,73 = 9.54; p < 0.01; η p ² = 0.126). Moreover, extraversion was found to significantly moderate the relationship between the BDNF genotype and episodic memory performance ( p = 0.03). Subsequent correlational analyses yielded a strong and significant correlation ( r = 0.542; p < 0.005) between introversion and delayed episodic memory specific to BDNF Met individuals. The present study suggests that introversion and the BDNF Met variant synergistically interact to reduce episodic memory performance in healthy, young adults. These findings reaffirm that a more accurate explanation of cognitive variance can be achieved by looking at the synergistic effects of genotype and phenotype factors., Competing Interests: The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

Motor representations in the human mirror neuron system are tuned to respond to specific observed actions. This ability is widely believed to be influenced by genetic factors, but no study has reported a genetic variant affecting this system so far. One possibility is that genetic variants might interact with visuomotor associative learning to configure the system to respond to novel observed actions. In this perspective, we conducted a candidate gene study on the Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism, a genetic variant linked to motor learning in regions of the mirror neuron system, and tested the effect of this polymorphism on motor facilitation and visuomotor associative learning. In a single-pulse TMS study carried on 16 Met (Val/Met and Met/Met) and 16 Val/Val participants selected from a large pool of healthy volunteers, Met participants showed significantly less muscle-specific corticospinal sensitivity during action observation, as well as reduced visuomotor associative learning, compared to Val homozygotes. These results are the first evidence of a genetic variant tuning sensitivity to action observation and bring to light the importance of considering the intricate relation between genetics and associative learning in order to further understand the origin and function of the human mirror neuron system.

Background: Genetic heterogeneity in amnestic mild cognitively impaired (aMCI) subjects could lead to variations in progression rates and response to cholinomimetic agents. Together with the apolipoprotein E4 (APOE-ɛ4) gene, butyrylcholinesterase (BCHE) has become recently one of the few Alzheimer's disease (AD) susceptibility genes with distinct pharmacogenomic properties., Objective: To validate candidate genes (APOE/BCHE) which display associations with age of onset of AD and donepezil efficacy in aMCI subjects., Methods: Using the Petersen et al. (2005) study on vitamin E and donepezil efficacy in aMCI, we contrasted the effects of BCHE and APOE variants on donepezil drug response using the Alzheimer's Disease Assessment Score-Cognition (ADAS-Cog) scale. Independently, we assessed the effects of APOE/BCHE genotypes on age of onset and cortical choline acetyltransferase activity in autopsy-confirmed AD and age-matched control subjects., Results: Statistical analyses revealed a significant earlier age of onset in AD for APOE-ɛ4, BCHE-K*, and APOE-ɛ4/BCHE-K* carriers. Among the carriers of APOE-ɛ4 and BCHE-K*, the benefit of donepezil was evident at the end of the three-year follow-up. The responder's pharmacogenomic profile is consistent with reduced brain cholinergic activity measured in APOE-ɛ4 and BCHE-K* positive subjects., Conclusions: APOE-ɛ4 and BCHE-K* positive subjects display an earlier age of onset of AD, an accelerated cognitive decline and a greater cognitive benefits to donepezil therapy. These results clearly emphasize the necessity of monitoring potential pharmacogenomic effects in this population of subjects, and suggest enrichment strategies for secondary prevention trials involving prodromal AD subjects.

Unlabelled: It is hypothesized that a fundamental function of sleep is to restore an individual's day-to-day ability to learn and to constantly adapt to a changing environment through brain plasticity. Brain-derived neurotrophic factor (BDNF) is among the key regulators that shape brain plasticity. However, advancing age and carrying the BDNF Met allele were both identified as factors that potentially reduce BDNF secretion, brain plasticity, and memory. Here, we investigated the moderating role of BDNF polymorphism on sleep and next-morning learning ability in 107 nondemented individuals who were between 55 and 84 years of age. All subjects were tested with 1 night of in-laboratory polysomnography followed by a cognitive evaluation the next morning. We found that in subjects carrying the BDNF Val66Val polymorphism, consolidated sleep was associated with significantly better performance on hippocampus-dependent episodic memory tasks the next morning (β-values from 0.290 to 0.434, p ≤ 0.01). In subjects carrying at least one copy of the BDNF Met allele, a more consolidated sleep was not associated with better memory performance in most memory tests (β-values from -0.309 to -0.392, p values from 0.06 to 0.15). Strikingly, increased sleep consolidation was associated with poorer performance in learning a short story presented verbally in Met allele carriers (β = -0.585, p = 0.005). This study provides new evidence regarding the interacting roles of consolidated sleep and BDNF polymorphism in the ability to learn and stresses the importance of considering BDNF polymorphism when studying how sleep affects cognition., Significance Statement: Individuals with the BDNF Val/Val (valine allele) polymorphism showed better memory performance after a night of consolidated sleep. However, we observed that middle-aged and older individuals who are carriers of the BDNF Met allele displayed no positive association between sleep quality and their ability to learn the next morning. This interaction between sleep and BDNF polymorphism was more salient for hippocampus-dependent tasks than for other cognitive tasks. Our results support the hypothesis that reduced activity-dependent secretion of BDNF impairs the benefits of sleep on synaptic plasticity and next-day memory. Our work advances the field by revealing new evidence of a clear genetic heterogeneity in how sleep consolidation contributes to the ability to learn., (Copyright © 2016 the authors 0270-6474/16/368391-09$15.00/0.)