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Oral endotracheal intubation is a procedure performed by emergency medical services (EMS) providers-who are stationed on ground ambulances, rotor-wing air ambulances (helicopter), and fixed-wing air ambulances (airplane)-for the purpose of securing a patient's airway.Historically, intubation success rates have depended on human factors, such as provider familiarity with intubation. There has been relatively little literature examining intubation success rates as a factor of EMS transport environment, despite there being important human factors differences between the different environments.We queried a national database of EMS calls in the United States. Inclusion criteria were oral endotracheal intubations performed in 2019 where providers documented whether or not the intubation was successful and what mode of transport they were assigned to.A total of 98,048 intubations met inclusion criteria. The majority of intubations were performed by providers stationed to ground ambulances (95.38%), followed by rotor-wing air ambulances (4.35%) and fixed-wing air ambulances (0.27%). Intubation success rates were comparable between fixed-wing air ambulances (89.66%) and rotor-wing air ambulances (89.17%)-however, they were significantly lower on ground ambulances (75.69%) (p.001).Our data show that flight crew members-either on fixed-wing or rotor-wing air ambulances-are associated with significantly higher rates of intubation success than ground ambulance providers. There are a number of possible explanations for this trend, including more opportunities to intubate in the air medical setting, increased clinical education focused on airway management in the air medical setting, or assistive technologies being more commonly used in the air medical setting.

Background Gait and cognition decline with advancing age, and presage the onset of dementia. Yet, the relative trajectories of gait and cognitive decline in aging are poorly understood—particularly among those with the motoric cognitive risk (MCR) syndrome. This study compared changes in simple and complex gait performance and cognition, as a function of age and MCR. Methods We examined gait and cognitive functions of 1 095 LonGenity study participants (mean age = 75.4 ± 6.7 years) with up to 12 years of annual follow-up. Participants were of Ashkenazi Jewish descent, free of dementia, ambulatory, and had a 12.2% MCR prevalence at baseline. Gait speed was measured at usual pace walking (single-task walking, STW-speed) and walking while talking (WWT-speed). Eleven neuropsychological test scores were examined separately, and as a global cognition composite. Linear mixed-effects models adjusted for baseline sex, education, parental longevity, cognitive impairment, and global health were used to estimate changes in gait and cognition, as a function of age and MCR. Results STW-speed, WWT-speed, and cognitive tests performance declined in a nonlinear (accelerating) fashion with age. STW-speed declined faster than WWT-speed and cognitive test scores. People with MCR showed faster rates of decline on figure copy and phonemic fluency. Conclusions Gait declines at a faster rate than cognition in aging. People with MCR are susceptible to faster decline in visuospatial, executive, and language functions. This study adds important knowledge of trajectories of gait and cognitive decline in aging, and identifies MCR as a risk factor for accelerated cognitive decline.

Introduction Greater double support time (DST) variability is associated with falls and memory decline. The underlying neurophysiological mechanisms of DST variability are poorly understood. Simple reaction time (SRT) variability, a measure of attention-processing speed is associated with falls and dementia and, may underlie greater DST variability. The aims of this study were to examine the association between SRT and DST variability and if SRT variability mediates the associations between poorer cognition/brain structure and DST variability. Methods Participants (n = 408) were community-dwelling older people without dementia (mean age 72.0 ± 7.0). DST variability was the standard deviation (SD) of DST, assessed with a walkway and averaged across steps of 6 walks. SRT variability was the SD of a button pressing task in response to a visual stimulus. Executive function and processing speed were assessed with neuropsychological tests. Magnetic Resonance Imaging was used to obtain cortical thickness (total and in frontal regions) and cerebral small vessel disease (cSVD). Multivariable linear regression models were used to examine the association between SRT and DST variability and if SRT variability mediated any associations of cognition/brain structure with DST variability. Results Greater SRT variability was associated with greater DST variability (p = 0.002). SRT variability partially mediated the association between poorer executive function and greater DST variability. Smaller mean thickness in orbitofrontal regions and greater cSVD burden were only associated with DST variability (p 0.05). Conclusions Greater SRT variability, which may occur due to inefficient executive functioning, could be an underlying neurophysiological mechanism of greater DST variability.

Close to 6 million older US adults have Alzheimer's disease or related dementias, yet there is currently no cure or effective treatment. This single-blind randomized controlled trial (clinicaltrials.gov: NCT03475316) aims to establish feasibility, and explore the relative efficacy, of a 6-month social ballroom dancing intervention versus a 6-month active control intervention (treadmill walking) for improving executive function in 32 older adults at increased risk for Alzheimer's disease or related dementias. Dementia-at-risk status is determined with cut-scores on the memory impairment screen (≥3 to ≤6) and/or the AD8 Dementia Screening Interview (≥1). The primary outcome is a composite executive function score from digit-symbol substitution, flanker interference and walking-while-talking tasks. The secondary outcome is functional neuroplasticity during fMRI-adapted versions of digit-symbol substitution, flanker interference and walking-while-talking.

Helicopter emergency medical services (HEMS) frequently respond to out-of-hospital cardiac arrest (OHCA) situations. Some have speculated mechanical cardiopulmonary resuscitation (mCPR) may be able to rectify the inadequacy of human performance of cardiopulmonary resuscitation (CPR) during transport. A number of studies have examined the performance of mCPR devices in the air medical setting specifically. Many aspects of the HEMS environment seem uniquely conducive to mCPR, and a growing body of research seems to suggest mCPR holds promise for the treatment of cardiac arrest by HEMS clinicians. Simulation studies show that mCPR leads to improved CPR performance compared with manual CPR in HEMS. Case reports and the experience of several HEMS programs suggest that mCPR can be effectively integrated into HEMS care. However, further research regarding the effectiveness of mCPR in the HEMS environment and in general cardiac arrest care is needed.

Norm enforcement may be important for resolving conflicts and promoting cooperation. However, little is known about how preferred responses to norm violations vary across cultures and across domains. In a preregistered study of 57 countries (using convenience samples of 22,863 students and non-students), we measured perceptions of the appropriateness of various responses to a violation of a cooperative norm and to atypical social behaviors. Our findings highlight both cultural universals and cultural variation. We find a universal negative relation between appropriateness ratings of norm violations and appropriateness ratings of responses in the form of confrontation, social ostracism and gossip. Moreover, we find the country variation in the appropriateness of sanctions to be consistent across different norm violations but not across different sanctions. Specifically, in those countries where use of physical confrontation and social ostracism is rated as less appropriate, gossip is rated as more appropriate. Little is known about people's preferred responses to norm violations across countries. Here, in a study of 57 countries, the authors highlight cultural similarities and differences in people's perception of the appropriateness of norm violations., Swedish Foundation for Humanities and Social Sciences; Riksbankens Jubileumsfond; Czech Science Foundation; Czech Academy of Sciences; Institute of Psychology; Stockholm University

To compare optic disc perfusion, radial peripapillary capillaries (RPC) and macular vascular density, between normal subjects and subjects with obstructive sleep apnea syndrome (OSAS) using spectral-domain OCT angiography (OCTA). Sixteen eyes of patients with mild OSAS, 17 eyes with moderate OSAS, 20 eyes with severe OSAS on polygraphy and 28 controls were evaluated with OCTA RT XR Avanti (AngioVue software, Optovue Inc., Fremont, CA). Optic nerve head (ONH), RPC and macular vessel density were measured. Clinical data, visual field parameters, and Spectral Domain OCT evaluation (retinal nerve fiber layer (RNFL) thickness and ganglion cell complex (GCC) thickness) were recorded for all patients. ONH vascular flow (p = 0,396), RPC vascular density (automatized data “whole” p = 0,913, “peripapillary” p = 0,539, and segmented analysis with a topographic grid) and macular vascular density (foveal p = 0,484, parafoveal p = 0,491) were not significantly different between the four groups. FDT-Matrix™ and Humphrey 24/2 mean deviation were significantly lower in eyes with severe OSAS and were correlated to the apnea-hypopnea index. Retinal nerve fiber layer (RNFL) thickness, Cup/Disc ratio, rim area, and ganglion cell complex (GCC) were not significantly modified. OCTA did not detect reduced ONH, RPC, neither macular blood vessel density in eyes with OSAS. The precise mechanisms that link OSAS with optic nerve pathologies remain unclear: our study was not able to demonstrate a vascular impact by OCTA examination.

Background falls share risk factors with cognitive decline but whether falls predict cognitive decline, pre-dementia syndromes and dementia is poorly understood. Objectives this study aimed to examine if falls are associated with cognitive decline in specific domains and the risk of Motoric Cognitive Risk (MCR) syndrome and dementia. Design cross-sectional study. Methods in older people (age 80.6 ± 5.3 years) free of dementia at baseline, the number of falls (none, one or multiple) during the year before enrolment and the first year of follow-up (exposure) were recorded. Decline in specific cognitive functions (global cognition, episodic verbal memory, verbal fluency, working memory, response inhibition and processing speed-attention), incident MCR and incident dementia were outcome measures. Linear mixed effects models were used to examine the associations between falls and cognitive decline, adjusting for confounders. Cox proportional hazards models were used to determine if falls predicted risk of incident MCR or dementia. Results of 522 eligible participants, 140 had a single fall and 70 had multiple falls. Multiple falls were associated with a greater decline in global cognition, episodic memory, verbal fluency and processing speed-attention compared to those with no falls (P Conclusions multiple falls may be an important marker to identify older people at greater risk of future cognitive decline and incident MCR.

Previous studies have assessed drug-induced sleep endoscopy (DISE) as an interobserver reliable exam, with a learning curve effect. The objective was to check its assumed interobserver agreement and variability of between two groups of experienced and inexperienced French ENT physicians. Prospective study. Seventy-six French ENT physicians (69 inexperienced in DISE and seven experienced) observed seven DISE videos. They were asked to determine the level(s), the configuration, and the degree of collapse, according to the VOTE classification. Specific and global agreements using the Fleiss’ Kappa coefficient (k) were calculated. The interobserver agreement varied from poor to good in determining the level; the best agreement being found for the oropharynx (global agreement = 0.82 and k = 0.6 in the experienced group, global agreement = 0.87 and k = 0.7 in the inexperienced group), followed by the soft palate and the larynx; the worst agreement being found for the tongue base (k = 0.29 in the experienced group and k = 0.38 in the inexperienced group). The agreement for the configuration and the degree of collapse was moderate except for the tongue base where the concordance was poor. In both groups, agreement was at best good without any statistically significant difference between the two levels of experience groups. Even in a French ENT Sleep Experts group, DISE appears to be a technique with a limited interobserver agreement in the detection of obstructive sites, without any learning curve effect. In its current state, DISE interpretation may not be totally reliable.

Objective We examined the neural substrates of social support in older adults. Social support is associated with better outcomes in many facets of aging—including cognitive and functional health—but the underlying neural substrates remain largely unexplored. Methods Voxel-based morphometry and multivariate statistics were used to identify gray matter volume covariance networks associated with social support in 112 older adults without dementia (M age = 74.6 years, 50% female), using the Medical Outcomes Study Social Support Survey. Results A gray matter network associated with overall social support was identified and included prefrontal, hippocampal, amygdala, cingulate, and thalamic regions. A gray matter network specifically associated with tangible social support (e.g., someone to help you if you were confined to bed) was also identified, included prefrontal, hippocampal, cingulate, insular, and thalamic regions, and correlated with memory and executive function. Discussion Gray matter networks associated with overall and tangible social support in this study were composed of regions previously associated with memory, executive function, aging, and dementia. Longitudinal research of the interrelationships between social support, brain structure, and cognition is needed, but strengthening social support may represent a new path toward improving cognition in aging that should be explored.

New therapies for symptoms in Alzheimer’s disease (AD) are urgently needed. Prior studies suggest that transcranial direct current stimulation (tDCS), a noninvasive neuromodulatory method, may be a safe and potentially effective treatment, but conclusions have been limited by small-sample sizes and brief stimulation protocols. This double-blind randomized trial involving 100 older adults with mild-to-moderate AD examines effects of 6 months of at-home active tDCS or sham delivered over the dorsolateral prefrontal cortex. The primary outcome is global cognitive performance. Secondary outcomes include executive-control/spatial selective attention, functional neuroplasticity, depressive symptoms, quality of life and the durability of effects 3 months after the stimulation period. The results will provide evidence on the efficacy of multimonth at-home tDCS in the AD treatment. =Clinical trial identifier NCT 04404153 (Clinicaltrials.gov) .

International audience; We investigated safety and efficacy of transoral robotic surgery (TORS) for base of tongue (BOT) reduction in obstructive sleep apnea syndrome (OSAS) patients. PubMed, Cochrane Library, and Scopus were searched. A meta-analysis was performed. Random effects models were used. Thirty-one cohorts met our criteria (1693 patients). The analysis was based mostly on retrospective studies. The summary estimate of the reduction of Apnea–Hypoxia Index (AHI) was 24.25 abnormal events per hour (95% CI: 21.69–26.81) and reduction of Epworth Sleepiness Scale (ESS) was 7.92 (95% CI: 6.50–9.34). The summary estimate of increase in lowest O2 saturation was 6.04% (95% CI: 3.05–9.03). The success rate of TORS BOT reduction, either alone or combined with other procedures, was 69% (95% CI: 64–79). The majority of studies reported low level of evidence but suggested that TORS BOT reduction may be a safe procedure associated with improvement of AHI, ESS, and lowest O2 saturation.

International audience; Objective: Drug-induced-sedation endoscopy (DISE) has proved superior to awake clinical examination for diagnosis of upper-airway obstruction sites and surgical planning. Our question is: does multilevel obstruction on DISE systematically entail failure for surgery limited to the upper pharynx? Material & methods: We conducted a retrospective single-center study in patients with obstructive sleep apnea syndrome (OSAS) treated by single-level surgery of the upper pharynx (tonsillectomy with or without pharyngoplasty). Preoperative assessment included polysomnography (PSG) and DISE. Surgical efficacy was assessed on postoperative PSG. Treatment response was defined by postoperative apnea-hypopnea index (AHI) < 20 events/h with 50% reduction, and cure by AHI < 10 (patients with preoperative AHI ≤ 10 being excluded). Efficacy was compared between groups without (group A) and with basilingual or laryngeal collapsus on DISE (group B). Results: We analyzed 63 patients, with mean preoperative AHI 33.8 ± 17.9 events/h. The two groups (A, n = 36; B, n = 27) were clinically comparable. Postoperative PSG took place at a mean 8.5 ± 11.5 months. The success rate was 66.7% in group A (mean reduction in AHI, 57.3 ± 36.2%) and 59.3% in group B (mean reduction, 53.9 ± 39.2%). Cure rates were respectively 48.5% and 48.1%. There was no statistically significant difference between the two groups (P > 0.1). Conclusions: Oropharyngeal surgery can alleviate associated obstructive sites found on DISE in the lower pharynx, and step-by-step treatment shows efficacy equal to that of single-step multilevel surgery.

A severe and debilitating consequence of a spinal cord injury (SCI) is central neuropathic pain (CNP). Our aim was to investigate the processes leading to CNP emergence and chronification by analyzing causal relationship over time between spinothalamic function, pain excitability, and pain inhibition after SCI.This longitudinal follow-up study included 53 patients with acute SCI and 20 healthy controls. Spinothalamic, pain excitability, and intra-segmental and extra-segmental pain inhibition indices were repeatedly evaluated at 1.5, 3, and 6 months post-SCI. Between- and within-group analyses were conducted among those patients who eventually developed CNP and those who did not. Healthy controls were evaluated twice for repeatability analysis.Patients who developed CNP, compared with those who did not, exhibited increased thermal thresholds (p

Greater gait variability predicts dementia. However, little is known about the neural correlates of gait variability. The aims of this study were to determine (1) grey matter volume covariance patterns associated with gait variability and (2) whether these patterns were associated with specific cognitive domains. Participants (n = 351; mean age 71.9 ± 7.1) were randomly selected from the Southern Tasmanian electoral roll. Step time, step length, step width and double support time were measured using an electronic walkway. Gait variability was calculated as the standard deviation of all steps for each gait measure. Voxel-based morphometry and multivariate covariance-based analyses were used to identify grey matter patterns associated with each gait variability measure. The individual expressions of grey matter patterns were correlated with processing speed, memory, executive and visuospatial functions. The grey matter covariance pattern of double support time variability included frontal, medial temporal, anterior cingulate, insula, cerebellar and striatal regions. Greater expression of this pattern was correlated with poorer performance in all cognitive functions (p 0.001). The covariance pattern of step length variability included frontal, temporal, insula, occipital and cerebellar regions and was correlated with all cognitive functions (p 0.05), except memory (p = 0.76). The covariance pattern of step width variability was limited to the cerebellum and correlated only with memory (p = 0.047). No significant pattern was identified for step time variability. In conclusion, different grey matter covariance patterns were associated with individual gait variability measures. These patterns were also correlated with specific cognitive functions, suggesting common neural networks may underlie both gait and cognition.

We studied gray matter volume covariance networks associated with normal pace walking (NPW) speed and dual-task costs (DTCs) during walking-while-talking (WWT)-a mobility stress test that involves walking while reciting alternate letters of the alphabet. Using a multivariate covariance-based analytic approach, we identified gray matter networks associated with NPW speed (mean 102.1 cm/s ±22.5 cm/s) and DTC (percent difference in gait speed between NPW and WWT, mean 25.9% ± 18.8%) in 139 older adults without dementia (M = 75.3 ± 6.1 years). The gray matter network associated with NPW was primarily composed of supplementary motor area, precuneus cortex, and the middle frontal gyrus. Greater expression of this NPW network was associated with better processing speed (trail-making test A [r = -0.30, p = 0.005]) and executive function (trail-making test B - A [r = -0.43, p < 0.0001]). The gray matter network associated with DTC was primarily composed of medial prefrontal, cingulate, and thalamic regions. Greater expression of this DTC network was associated with better episodic memory performance on the free and cued selective reminding test (r = 0.30, p = 0.007). These results suggest that NPW speed and DTC are supported by different networks, and are associated with different cognitive domains.

Extensive social networks are associated with better physical, mental, and cognitive health in aging, but the underlying brain substrates remain largely unexplored. Voxel-based morphometry and multivariate statistics were used to identify gray matter volume covariance networks associated with social networks in 86 older adults without dementia (M Age = 75.20 years, 53% women). Gray matter networks associated with the number of high-contact social roles and the total number of network members were identified after adjusting for age, sex, education, global health, and total intracranial volume – and shared nodes included medial, lateral and orbital prefrontal, hippocampal, precuneus, insular, and cingulate regions. Greater expression of these gray matter networks was associated with better memory scores on the Free and Cued Selective Reminding Test. A more distributed network was associated with high-contact social roles than total number of networks members – also extending into amygdala and entorhinal cortex. Thus, high-contact social roles and total number of network members in older adults are associated with gray matter networks composed of regions previously linked to memory and affected by both healthy aging and Alzheimer disease – and high-contact social roles are more strongly associated with brain structures than the total number of network members.

Background The first edition of the European position paper (EPP) on drug-induced sleep endoscopy (DISE) was published in 2014 with the aim to standardise the procedure, to provide an in-depth insight into the main aspects of this technique and to have a basis for future research. Since 2014, new studies have been published concerning new sedative agents or new insights into the pattern/levels of the obstruction depending on the depth of sedation. Therefore, an enlarged group of European experts in the field of sleep breathing disorders (SBD), including the most of the first DISE EPP main authors, has decided to publish an update of the European position paper on DISE, in order to include new evidence and to find a common language useful for reporting the findings of this endoscopic evaluation in adult population affected by SBD. Methods The authors have evaluated all the available evidence reported in the literature and have compared experience among various departments in leading European centres in order to provide an update regarding the standardisation of the DISE procedure and an in-depth insight into the main aspects of this technique. Results After the first European Position Consensus Meeting on DISE and its update, consensus was confirmed for indications, required preliminary examinations, where to perform DISE, technical equipment required, staffing, local anaesthesia, nasal decongestion, other medications, patient positioning, basics and special diagnostic manoeuvres, drugs and observation windows. So far, no consensus could be reached on a scoring and classification system. However, regarding this aim, the idea of an essential classification, such as VOTE with the possibility of its graded implementation of information and descriptions, seems to be the best way to reach a universal consensus on DISE classification at this stage. A common DISE language is mandatory, and attempts to come to a generally accepted system should be pursued.

The maximization principle—that people aspire to the highest possible level of something good if all practical constraints are removed—is a common yet untested assumption about human nature. We predict that in holistic cultures—where contradiction, change, and context are emphasized—ideal states of being for the self will be more moderate than in other cultures. In two studies ( Ns = 2,392 and 6,239), we asked this question: If participants could choose their ideal level of happiness, pleasure, freedom, health, self-esteem, longevity, and intelligence, what level would they choose? Consistent with predictions, results showed that maximization was less pronounced in holistic cultures; members of holistic cultures aspired to less happiness, pleasure, freedom, health, self-esteem, longevity, and IQ than did members of other cultures. In contrast, no differences emerged on ideals for society. The studies show that the maximization principle is not a universal aspect of human nature and that there are predictable cultural differences in people’s notions of perfection.

Background Structural and functional brain imaging methods have identified age-related changes in brain structures involved in gait control. This cross-sectional study aims to investigate gray matter networks associated with gait control in aging using structural covariance analysis. Methods Walking speed were measured in 326 nondemented older community-dwellers (age 71.3 ± 4.5; 41.7% female) under three different walking conditions: normal walking and two challenging tasks: motor (ie, fast speed) and an attention-demanding dual task (ie, backward counting). Results Three main individual gray matter regions were positively correlated with walking speed (ie, slower walking speed was associated with lower brain volumes): right thalamus, right caudate nucleus, and left middle frontal gyrus for normal walking, rapid walking, and dual-task walking condition, respectively. The structural covariance analysis revealed that prefrontal regions were part of the networks associated with every walking condition; the right caudate was associated specifically with the hippocampus, amygdala and insula for the rapid walking condition, and the left middle frontal gyrus with a network involving the cuneus for the dual-task condition. Conclusion Our results suggest that brain networks associated with gait control vary according to walking speed and depend on each walking condition. Gait control in aging involved a distributed network including regions for emotional control that are recruited in challenging walking conditions.

Norm enforcement may be important for resolving conflicts and promoting cooperation. However, little is known about how preferred responses to norm violations vary across cultures and across domains. In a preregistered study of 57 countries (using convenience samples of 22,863 students and non-students), we measured perceptions of the appropriateness of various responses to a violation of a cooperative norm and to atypical social behaviors. Our findings highlight both cultural universals and cultural variation. We find a universal negative relation between appropriateness ratings of norm violations and appropriateness ratings of responses in the form of confrontation, social ostracism and gossip. Moreover, we find the country variation in the appropriateness of sanctions to be consistent across different norm violations but not across different sanctions. Specifically, in those countries where use of physical confrontation and social ostracism is rated as less appropriate, gossip is rated as more appropriate.

WOS: 000442930300311, PubMed ID: 29955865, Olfaction plays an important role in human social communication, including multiple domains in which people often rely on their sense of smell in the social context. The importance of the sense of smell and its role can however vary inter-individually and culturally. Despite the growing body of literature on differences in olfactory performance or hedonic preferences across the globe, the aspects of a given culture as well as culturally universal individual differences affecting odor awareness in human social life remain unknown. Here, we conducted a large-scale analysis of data collected from 10 794 participants from 52 study sites from 44 countries all over the world. The aim of our research was to explore the potential individual and country-level correlates of odor awareness in the social context. The results show that the individual characteristics were more strongly related than country-level factors to self-reported odor awareness in different social contexts. A model including individual-level predictors (gender, age, material situation, education, and preferred social distance) provided a relatively good fit to the data, but adding country-level predictors (Human Development Index, population density, and average temperature) did not improve model parameters. Although there were some cross-cultural differences in social odor awareness, the main differentiating role was played by the individual differences. This suggests that people living in different cultures and different climate conditions may still share some similar patterns of odor awareness if they share other individual-level characteristics., Polish Ministry of Science and Higher Education Iuventus Plus grant [IP2014 043773]; Deanship of Scientific Research at King Saud University [RG-1439-012]; Estonian Ministry of Education of Science [IUT2-13]; NIR [01201370995], This work was supported by the Polish Ministry of Science and Higher Education Iuventus Plus grant # IP2014 043773 to AS. Data collection in Saudi Arabia was funded by Deanship of Scientific Research at King Saud University through research group No (RG-1439-012). The data collection in Estonia was supported by institutional research funding (IUT2-13) from the Estonian Ministry of Education of Science and the data collection in Russia was conducted with in the scope of the NIR project, No. 01201370995, "Cross-cultural and interdisciplinary researches. Biosocial and cross-cultural analysis of models of tolerance and basic values of culture in modern society" (MB and DD).

Over a third of community-residing elderly have clinical gait abnormalities, and gait impairment is associated with morbidity, mortality and dementia. Motor imagery – envisioning motor actions without actual execution – has been used to improve gait in Parkinson's disease and poststroke, but the efficacy of motor imagery in healthy elderly is unknown. This single-blind pilot randomized-controlled trial aims to establish feasibility and explore the efficacy of a 3-month, telephone-based motor imagery intervention – that involves imagined walking, imagined talking and imagined walking while talking for improving gait in 48 healthy elderly. The primary outcomes will be gait speed during actual walking and walking while talking. Secondary outcomes will include cognitive performance during actual talking and walking while talking, and functional neuroplasticity during imagined walking and walking while talking. This clinical trial has been registered on clinicaltrials.gov (identifier NCT02762604).

Surgical results in obstructive sleep apnea syndrome (OSAS) vary greatly, whatever the surgical technique or site. Most authors agree that rigorous patient selection is logical and mandatory. Drug-induced sleep endoscopy (DISE) was introduced in 1991 and has been rediscovered and used extensively since the 2000s. It attempts to mimic natural sleep in order to observe the upper airway on flexible endoscopy in a situation in which obstruction may occur. A review of the DISE literature was performed, and is reported in two parts. The present second part reports DISE results concerning obstruction sites, impact on treatment efficacy and the consequent indications for this exploration.

Background To compare the efficacy of phacoemulsification (PKE) combined with nonpenetrating deep sclerectomy (NPDS) with mitomycin C (MMC) versus XEN® gel stent with MMC. Methods In this nonrandomized, retrospective, comparative, single-center pilot study, 105 consecutive eyes of 75 patients with uncontrolled primary open-angle glaucoma (POAG) and cataract who underwent PKE combined with either XEN implantation (n = 47) or NPDS (n = 58) between May 2013 and November 2018 were included. The primary outcome was complete success at 9 months, which was defined as intraocular pressure (IOP) ≤18, 15 or 12 mmHg without treatment; qualified success was IOP ≤18, 15 or 12 mmHg with antiglaucoma medications. Secondary outcome measures included the number of antiglaucoma medications, visual acuity (VA), and postoperative adverse events. Results Using the 18 mmHg threshold, complete or qualified success was achieved in 69.6 and 89.1% in the PKE + XEN group, and 63.8 and 89.7% in the PKE + NPDS group (p = .54 and p = .93), respectively, at 9 months. The mean IOP decreased from 20.8 ± 6.8 mmHg to 16.2 ± 2.8 mmHg in the PKE + XEN group (p p p p p Conclusions The XEN stent combined with PKE seemed to be as effective and safe as PKE + NPDS at 9 months in this pilot study.

Central neuropathic pain (CNP) after spinal cord injury (SCI) is debilitating and immensely impacts the individual. Central neuropathic pain is relatively resistant to treatment administered after it develops, perhaps owing to irreversible pathological processes. Although preemptive treatment may overcome this shortcoming, its administration necessitates screening patients with clinically relevant biomarkers that could predict CNP early post-SCI. The aim was to search for such biomarkers by measuring pronociceptive and for the first time, antinociceptive indices early post-SCI. Participants were 47 patients with acute SCI and 20 healthy controls. Pain adaptation, conditioned pain modulation (CPM), pain temporal summation, wind-up pain, and allodynia were measured above, at, and below the injury level, at 1.5 months after SCI. Healthy control were tested at corresponding regions. Spinal cord injury patients were monitored for CNP emergence and characteristics at 3 to 4, 6 to 7, and 24 months post-SCI. Central neuropathic pain prevalence was 57.4%. Central neuropathic pain severity, quality, and aggravating factors but not location somewhat changed over 24 months. Spinal cord injury patients who eventually developed CNP exhibited early, reduced at-level pain adaptation and CPM magnitudes than those who did not. The best predictor for CNP emergence at 3 to 4 and 7 to 8 months was at-level pain adaptation with odds ratios of 3.17 and 2.83, respectively (∼77% probability) and a cutoff value with 90% sensitivity. Allodynia and at-level CPM predicted CNP severity at 3 to 4 and 24 months, respectively. Reduced pain inhibition capacity precedes, and may lead to CNP. At-level pain adaptation is an early CNP biomarker with which individuals at risk can be identified to initiate preemptive treatment.

Background Gait variability is a marker of cognitive decline. However, there is limited understanding of the cortical regions associated with gait variability. We examined associations between regional cortical thickness and gait variability in a population-based sample of older people without dementia. Method Participants (n = 350, mean age 71.9 ± 7.1) were randomly selected from the electoral roll. Variability in step time, step length, step width, and double support time (DST) were calculated as the standard deviation of each measure, obtained from the GAITRite walkway. Magnetic resonance imaging (MRI) scans were processed through FreeSurfer to obtain cortical thickness of 68 regions. Bayesian regression was used to determine regional associations of mean cortical thickness and thickness ratio (regional thickness/overall mean thickness) with gait variability. Results Smaller global cortical thickness was only associated with greater step width and step time variability. Smaller mean thickness in widespread regions important for sensory, cognitive, and motor functions were associated with greater step width and step time variability. In contrast, smaller thickness in a few frontal and temporal regions were associated with DST variability and the right cuneus was associated with step length variability. Smaller thickness ratio in frontal and temporal regions important for motor planning, execution, and sensory function and greater thickness ratio in the anterior cingulate was associated with greater variability in all measures. Conclusions Examining individual cortical regions is important in understanding the relationship between gray matter and gait variability. Cortical thickness ratio highlights that smaller regional thickness relative to global thickness may be important for the consistency of gait.

Dual-task gait performance is impaired in older adults with mild cognitive impairment, but the brain substrates associated with dual-task gait performance are not well-established. The relationship between gray matter and gait speed under single-task and dual-task conditions (walking while counting backward) was examined in 560 seniors with mild cognitive impairment (non-amnestic mild cognitive impairment: n = 270; mean age = 72.4 yrs., 63.6 % women; amnestic mild cognitive impairment: n = 290; mean age = 73.4 yrs., 45.4 % women). Multivariate covariance-based analyses of magnetic resonance imaging data, adjusted for potential confounders including single-task gait speed, were performed to identify gray matter patterns associated with dual-task gait speed. There were no differences in gait speed or cognitive performance during dual-task gait between individuals with non-amnestic mild cognitive impairment and amnestic mild cognitive impairment. Overall, increased dual-task gait speed was associated with a gray matter pattern of increased volume in medial frontal gyrus, superior frontal gyrus, anterior cingulate, cingulate, precuneus, fusiform gyrus, middle occipital gyrus, inferior temporal gyrus and middle temporal gyrus. The relationship between dual-task gait speed and brain substrates also differed by mild cognitive impairment subtype. Our study revealed a pattern of gray matter regions associated with dual-task performance. Although dual-task gait performance was similar in amnestic and non-amnestic mild cognitive impairment, the gray matter patterns associated with dual-task gait performance differed by mild cognitive impairment subtype. These findings suggest that the brain substrates supporting dual-task gait performance in amnestic and non-amnestic subtypes are different, and consequently may respond differently to interventions, or require different interventions.

Poor social networks and decreased levels of social support are associated with worse mood, health, and cognition in younger and older adults. Yet, we know very little about the brain substrates associated with social networks and social support, particularly in older adults. This study examined functional brain substrates associated with social networks using the Social Network Index (SNI) and resting-state functional magnetic resonance imaging (fMRI). Resting-state fMRI data from 28 non-demented older adults were analyzed with independent components analyses. As expected, four established resting-state networks-previously linked to motor, vision, speech, and other language functions-correlated with the quality (SNI-1: total number of high-contact roles of a respondent) and quantity (SNI-2: total number of individuals in a respondent's social network) of social networks: a sensorimotor, a visual, a vestibular/insular, and a left frontoparietal network. Moreover, SNI-1 was associated with greater functional connectivity in the lateral prefrontal regions of the left frontoparietal network, while SNI-2 was associated with greater functional connectivity in the medial prefrontal regions of this network. Thus, lateral prefrontal regions may be particularly linked to the quality of social networks while medial prefrontal regions may be particularly linked to the quantity of social networks.

International audience; BACKGROUND: The purpose of this study was to evaluate the changes in choroidal thickness and lamina cribrosa position after nonpenetrating deep sclerectomy (NPDS) and trabeculectomy.METHODS: Twenty-three eyes with glaucoma that required filtering surgery were included (12 NDPS and 11 trabeculectomies) in this prospective observational study. OCT-enhanced depth imaging (OCT-EDI) was used to measure choroidal thickness, prelaminar tissue thickness and lamina cribrosa position before and 7 days and 1 month after surgery. All results are shown as median (interquartile range values).RESULTS: Intraocular pressure (IOP) was significantly lower 1 week after surgery than at baseline (7 (6/10) mmHg vs. 21 (18/26) mmHg; p

Objectives/Hypothesis The retrolingual space is one of the potential sites of obstruction identified in patients with obstructive sleep apnea syndrome (OSAS). Hypertrophied lingual tonsils (LT) can obstruct the airway at this level. The goal of this study was to measure the tolerance and efficacy of lingual tonsillectomy in patients with OSAS. Study design A retrospective chart review was conducted recruiting all patients with OSAS confirmed on sleep recording, who either had failed or refused medical treatment and who underwent lingual tonsillectomy. Materials and methods Diagnosis of LT hypertrophy was made by full ENT clinical examination using a flexible endoscopy, completed by MRI and followed by drug-induced sleep endoscopy. The surgical intervention was carried out endoscopically by diode laser or coblation. The primary endpoint to measure efficacy was drop in apnea-hypopnea index (AHI) on sleep recording at 6 months. Secondary endpoints comprised reduced snoring and Epworth Sleepiness Scale (ESS) and postoperative symptom tolerance. Results Eleven patients aged 44.3 ± 12.6 years were included. AHI dropped from 29.5 ± 21.7/h to 11.6 ± 9.6/h: i.e., by 60% (P = 0.005). Five patients had AHI Conclusions LT ablation seemed effective in OSAS with retrolingual obstruction in failure of medical treatment. Level of evidence 4.

Clinical studies have suggested association of some hepatitis C virus (HCV) subtypes or isolates with progression toward hepatocellular carcinoma (HCC). HCV core protein has been reported to interfere with host Wnt/β-catenin pathway, a cell fate-determining pathway, which plays a major role in HCC. Here, we investigated the impact of HCV core genetic variability in the dysregulation of Wnt/β-catenin pathway. We used both transient expression of core proteins from clinical isolates of HCV subtypes 1a (Cambodia), 4a (Romania) and 4f (Cameroon) and infection systems based on a set of engineered intergenotypic recombinant viruses encoding core from these various clinical strains. We found that TCF transcription factor-dependent reporter activity was upregulated by core in a strain-specific manner. We documented core sequence-specific transcriptional upregulation of several β-catenin downstream target genes associated with cell proliferation and malignant transformation, fibrogenesis or fat accumulation. The extent of β-catenin nuclear translocation varied in accordance with β-catenin downstream gene upregulation in infected cells. Pairwise comparisons of subgenotypic core recombinants and mutated core variants unveiled the critical role of core residues 64 and 71 in these dysregulations. In conclusion, this work identified natural core polymorphisms involved in HCV strain-specific activation of Wnt/β-catenin pathway in relevant infection systems.

Velopharyngoplasty and palatine tonsillectomy are at the very heart of the surgical treatment of obstructive sleep apnea syndrome (OSAS) care. In cases of major tonsil hypertrophy, we evaluated the relevance of associating soft palate surgery with palatine tonsillectomy, independent of the soft palate length. We conducted a retrospective single-center study in OSAS patients with grade III or IV tonsils treated with tonsillectomy. Preoperative assessment included an upper airway examination performed while the patient was awake, a polysomnography and a drug-induced sedation endoscopy (DISE). Surgical efficacy was assessed on postoperative polysomnography. Success was considered when the postoperative apnea-hypopnea index (AHI) was less than 20 events/h with a 50% reduction. We compared palatine tonsillectomy efficacy alone (group A) and associated with soft palate surgery (group B). We analyzed 33 patients who had undergone surgery between December 2006 and May 2018. Their preoperative mean BMI and mean AHI were 27.3 ± 7.5 kg/m2 and 38.6 ± 21.4 events/h, respectively. The two groups (A, n = 18 and B, n = 15) were clinically comparable. The success rate was 72.2% in group A and 60% in group B. There was no statistically significant difference between the two groups (p > 0.1). According to this study, in our institution, in cases of major tonsillar hypertrophy, simultaneous soft palate surgery had no significant impact on the success rate, regardless of soft palate length. Associating soft palate surgery with palatine tonsillectomy does not seem mandatory to increase the success rate. III. Retrospective comparative study

PURPOSE To report on the frequency, efficacy, and safety of laser goniopuncture (LGP) in lowering intraocular pressure (IOP) following mitomycin-C-augmented nonpenetrating deep sclerectomy (NPDS) in a large cohort of eyes. MATERIALS AND METHODS This is a monocenter database retrospective study. We reviewed records of 350 eyes that underwent NPDS between 2009 and 2015, at the National Ophthalmology Center of XV-XX (Paris, France). We recorded the incidence of LGP, the time between NPDS and LGP, IOP efficacy, and the occurrence of complications. The success of the LGP was defined by an IOP

BACKGROUND/OBJECTIVES: To assess the risk of immediate sudden visual loss (“wipe-out” phenomenon) following non-penetrating deep sclerectomy (NPDS) for end-stages glaucoma within the first 6-months postoperative period. SUBJECTS/METHODS: Monocenter database study. We reviewed the results for 73 eyes with severe or end-stage glaucoma that underwent NPDS. End-stage glaucoma (stage 5) was defined by the inability of patients to perform the Humphrey visual field test or by a visual acuity

We report cases of delayed, sustained elevated intraocular pressure (IOP) associated with repeated intravitreal anti-VEGF injections (IVI), which ultimately resulted in the need for filtering surgery. Two of the three cases demonstrated severe IOP elevation despite maximal medical treatment following unilateral IVI and required urgent filtering surgery. Optic nerve involvement was severe in all three cases. These intravitreal injections were performed for exudative age-related macular degeneration (AMD), and the patients did not show any sign of glaucoma or ocular hypertension prior to the initiation of treatment. Elevated IOP secondary to intravitreal steroids is a well-known side effect, as is immediate transient IOP elevation associated with anti-VEGF injection. Late, sustained IOP elevation after repeated injections of anti-VEGF, described approximately ten years ago, is often underestimated. Its incidence is estimated between 2.1% and 13% according to studies and increases with the number of IVI (cumulative effect). The pathophysiologic process is becoming increasingly understood, and several risk factors for this chronic IOP elevation have been identified. Most often, it is a moderate IOP elevation for which topical monotherapy is sufficient, or sometimes two, three or four medications or even selective laser trabeculoplasty (SLT). However, filtering surgery may rarely be required. Our findings illustrate a little-described phenomenon: a sudden, severe, late IOP elevation in response to anti-VEGF by an "overflow" effect, requiring urgent filtering surgery.

Over the recent years, several homologues with varying degrees of genetic relatedness to hepatitis C virus (HCV) have been identified in a wide range of mammalian species. HCV infectious life cycle relies on a first critical proteolytic event of its single polyprotein, which is carried out by nonstructural protein 2 (NS2) and allows replicase assembly and genome replication. In this study, we characterized and evaluated the conservation of the proteolytic mode of action and regulatory mechanisms of NS2 across HCV and animal hepaciviruses. We first demonstrated that NS2 from equine, bat, rodent, New and Old World primate hepaciviruses also are cysteine proteases. Using tagged viral protein precursors and catalytic triad mutants, NS2 of equine NPHV and simian GBV-B, which are the most closely and distantly related viruses to HCV, respectively, were shown to function, like HCV NS2 as dimeric proteases with two composite active sites. Consistent with the reported essential role for NS3 N-terminal domain (NS3N) as HCV NS2 protease cofactor via NS3N key hydrophobic surface patch, we showed by gain/loss of function mutagenesis studies that some heterologous hepacivirus NS3N may act as cofactors for HCV NS2 provided that HCV-like hydrophobic residues are conserved. Unprecedently, however, we also observed efficient intrinsic proteolytic activity of NS2 protease in the absence of NS3 moiety in the context of C-terminal tag fusions via flexible linkers both in transiently transfected cells for all hepaciviruses studied and in the context of HCV dicistronic full-length genomes. These findings suggest that NS3N acts as a regulatory rather than essential cofactor for hepacivirus NS2 protease. Overall, unique features of NS2 including enzymatic function as dimers with two composite active sites and additional NS3-independent proteolytic activity are conserved across hepaciviruses regardless of their genetic distances, highlighting their functional significance in hepacivirus life cycle., Author summary Despite remarkable progress in the development of therapeutic options, more than 70 million individuals are chronically infected by hepatitis C virus (HCV) worldwide and major challenges in basic and translational research remain. Phylogenetically-related HCV homologues have recently been identified in the wild in several mammalian species, whose host restriction and potential for zoonosis remain largely unknown. We comparatively characterized the functions and properties of nonstructural proteins 2 (NS2) from several animal hepaciviruses and HCV. We demonstrated that NS2 from animal hepaciviruses, like HCV NS2, are cysteine proteases, which function as dimers with two composite active sites to ensure a key proteolytic event of the single viral polyprotein at the NS2/NS3 junction. In addition to the activation of HCV NS2 protease by NS3 N-terminal domain, our data revealed a novel NS3-independent substrate specificity and efficient intrinsic proteolytic activity of NS2. The conservation of its properties and peculiar mode of action among distantly related hepaciviruses supports an important regulatory role for NS2 protein in the life cycle of these viruses. It also strengthens the value of animal, notably rodent hepaciviruses for the development of surrogate, immunocompetent models of HCV infection to address HCV-associated pathogenesis and vaccine strategies.

Background and purposeThe differences in gait abnormalities from the earliest to the later stages of dementia and in the different subtypes of dementia have not been fully examined. This study aims to compare spatiotemporal gait parameters in cognitively healthy individuals, patients with amnestic mild cognitive impairment (MCI) and non-amnestic MCI, and patients with mild and moderate stages of Alzheimer's disease (AD) and non-Alzheimer's disease (non-AD). MethodsBased on a cross-sectional design, 1719 participants (77.4 7.3 years, 53.9% female) were recruited from cohorts from seven countries participating in the Gait, Cognition and Decline (GOOD) initiative. Mean values and coefficients of variation of spatiotemporal gait parameters were measured during normal pace walking with the GAITRite system at all sites. ResultsPerformance of spatiotemporal gait parameters declined in parallel with the stage of cognitive decline from MCI status to moderate dementia. Gait parameters of patients with non-amnestic MCI were more disturbed compared to patients with amnestic MCI, and MCI subgroups performed better than demented patients. Patients with non-AD dementia had worse gait performance than those with AD dementia. This degradation of gait parameters was similar between mean values and coefficients of variation of spatiotemporal gait parameters in the earliest stages of cognitive decline, but different in the most advanced stages, especially in the non-AD subtypes. ConclusionsSpatiotemporal gait parameters were more disturbed in the advanced stages of dementia, and more affected in the non-AD dementias than in AD. These findings suggest that quantitative gait parameters could be used as a surrogate marker for improving the diagnosis of dementia. Click to view the accompanying paper in this issue.

Objective: Distal hereditary motor neuropathies (dHMN) form a clinically and genetically heterogeneous group of disorders, characterized by muscle weakness and atrophy predominating at the distal part of the limbs, due to the progressive degeneration of motor neurons in the spinal cord. We report here a novel rare variant of dHMN with autosomal recessive inheritance in a large Jewish family originating from Morocco. The disease is characterized by a predominance of paralysis at the lower limbs and an early adulthood onset. We performed a genetic study in this family to identify and characterized the causing mutation. Methods: Homozygosity mapping strategy and sequencing of the candidate genes were performed. Expression studies were made on patient fibroblasts. Functional experiments were performed on a cellular model of motor neuron disease. Results: We mapped the disease to the 2q34–q36.1 chromosomal region and identified a homozygous splice mutation in the gene HSJ1 (DNAJB2) decreasing the expression of the 2 main isoforms HSJ1a and HSJ1b. Overexpression of both HSJ1a and HSJ1b reduced inclusion formation induced by the mutated SOD1-A4V in a neuronal cellular model. Interpretation: HSJ1 is a neuronal enriched member of the HSP40/DNAJ co-chaperone family. Previous studies have shown that HSP40 proteins play a crucial role in protein aggregation and neurodegeneration in several neuronal types, in animal models and human diseases. Interestingly, this mutation causing a loss-of-function of HSJ1 is linked to a pure lower motor neuron disease, strongly suggesting that HSJ1 also plays an important and specific role in motor neurons. ANN NEUROL 2012

To report the impact of non-penetrating deep sclerectomy (NPDS) in severe and end-stage glaucoma treatment on the central 10° visual field progression (mean deviation, four central points, foveal threshold) and assess the risk of sudden visual loss.Monocenter database study. We reviewed records of 34 eyes with severe or end-stage glaucoma that underwent NPDS between 2009 and 2015, at the National Ophthalmology Center of XV-XX (Paris, France). Severe and end-stage glaucoma were defined according to the Bascom Palmer Modified Glaucoma Staging System classification. All eyes had a constricted visual field 10° (severe injury by the Humphrey visual field automated (HVFA) 10-2). Visual fields were recorded every 6 months after the procedure. Data from the last visit was used for the statistical analysis.The mean follow-up duration was 29 months (range 6 to 54) and 33 (97%) eyes were followed for more than 1 year. There were no cases of postoperative sudden visual loss. The intraocular pressure (IOP) decreased from 21.9 ± 8.1 to 15.0 ± 5.4 mmHg (P .001). Twenty-eight (82%) eyes had an IOP 21 mmHg and 19 (56%) an IOP 16 mmHg. The MD 10-2 remained stable (- 19.8 ± 7.4 to - 19.4 ± 8.1 dB, non-significant improvement of + 0.4 dB, P = .1). The MD 10-2 slope showed an insignificant improvement of + 0.25 ± 1.8 dB per year (dB/y) (P = 0.1), but this slope was significantly better when the IOP was reduced to 16 mmHg than when the IOP was ≥ 16 mmHg at the last visit (+ 0.84 1.2 versus - 0.48 ± 2.2 dB/y, P = .05). The mean number of the four central test points with sensitivity ≤ 5 dB and the change in mean sensitivity of the four central field points remained stable. There were no significant changes in the VFI (from 25.4% ± 13 to 25.8% ± 20) and in foveal threshold.NPDS appears to provide stability of the central 10° visual field (with a trend towards improvement but non-significant) with no occurrence of "wipe-out" phenomenon and few other complications. Consideration of NPDS in end-stage and severe glaucoma is advisable given its low risk of complications and its considerable IOP decrease with a relative stability of the central visual field.