Sensor-Assisted Analysis of Autonomic and Cerebrovascular Dysregulation following Concussion in an Individual with a History of Ten Concussions: A Case Study.

INTRODUCTION: Concussion is known to cause transient autonomic and cerebrovascular dysregulation that generally recovers; however, few studies have focused on individuals with an extensive concussion history. METHOD: The case was a 26-year-old male with a history of 10 concussions, diagnosed for bipolar type II disorder, mild attention-deficit hyperactivity disorder, and a history of migraines/headaches. The case was medicated with Valproic Acid and Escitalopram. Sensor-based baseline data were collected within six months of his injury and on days 1-5, 10, and 14 post-injury. Symptom reporting, heart rate variability (HRV), neurovascular coupling (NVC), and dynamic cerebral autoregulation (dCA) assessments were completed using numerous biomedical devices (i.e., transcranial Doppler ultrasound, 3-lead electrocardiography, finger photoplethysmography). RESULTS: Total symptom and symptom severity scores were higher for the first-week post-injury, with physical and emotional symptoms being the most impacted. The NVC response showed lowered activation in the first three days post-injury, while autonomic (HRV) and autoregulation (dCA) were impaired across all testing visits occurring in the first 14 days following his concussion. CONCLUSIONS: Despite symptom resolution, the case demonstrated ongoing autonomic and autoregulatory dysfunction. Larger samples examining individuals with an extensive history of concussion are warranted to understand the chronic physiological changes that occur following cumulative concussions through biosensing devices.

A systematic review, meta-analysis, and meta-regression amalgamating the driven approaches used to quantify dynamic cerebral autoregulation.

Numerous driven techniques have been utilized to assess dynamic cerebral autoregulation (dCA) in healthy and clinical populations. The current review aimed to amalgamate this literature and provide recommendations to create greater standardization for future research. The PubMed database was searched with inclusion criteria consisting of original research articles using driven dCA assessments in humans. Risk of bias were completed using Scottish Intercollegiate Guidelines Network and Methodological Index for Non-Randomized Studies. Meta-analyses were conducted for coherence, phase, and gain metrics at 0.05 and 0.10 Hz using deep-breathing, oscillatory lower body negative pressure (OLBNP), sit-to-stand maneuvers, and squat-stand maneuvers. A total of 113 studies were included, with 40 of these incorporating clinical populations. A total of 4126 participants were identified, with younger adults (18-40 years) being the most studied population. The most common techniques were squat-stands (n = 43), deep-breathing (n = 25), OLBNP (n = 20), and sit-to-stands (n = 16). Pooled coherence point estimates were: OLBNP 0.70 (95%CI:0.59-0.82), sit-to-stands 0.87 (95%CI:0.79-0.95), and squat-stands 0.98 (95%CI:0.98-0.99) at 0.05 Hz; and deep-breathing 0.90 (95%CI:0.81-0.99); OLBNP 0.67 (95%CI:0.44-0.90); and squat-stands 0.99 (95%CI:0.99-0.99) at 0.10 Hz. This review summarizes clinical findings, discusses the pros/cons of the 11 unique driven techniques included, and provides recommendations for future investigations into the unique physiological intricacies of dCA.

Transcranial Doppler Ultrasound and Concussion-Supplemental Symptoms with Physiology: A Systematic Review.

Sport-related concussion (SRC) can impair the cerebrovasculature both acutely and chronically. Transcranial Doppler (TCD) ultrasound assessment has the potential to illuminate the mechanisms of impairment and provide an objective evaluation of SRC. The current systematic review investigated studies employing TCD ultrasound assessment of intracranial arteries across three broad categories of cerebrovascular regulation: neurovascular coupling (NVC), cerebrovascular reactivity (CVR), and dynamic cerebral autoregulation (dCA). The current review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (CRD42021275627). The search strategy was applied to PubMed, as this database indexes all biomedical journals. Original articles on TCD for athletes with medically diagnosed SRC were included. Title/abstract and full-text screening were completed by three authors. Two authors completed data extraction and risk of bias using the Methodological Index for Non-Randomized Studies and Scottish Intercollegiate Guideline Network checklists. Of the 141 articles identified, 14 met the eligibility criteria. One article used an NVC challenge, eight assessed CVR, and six investigated dCA. Methodologies varied widely among studies, and results were heterogeneous. There was evidence of cerebrovascular impairment in all three domains roughly 2 days post-SRC, but the magnitude and recovery of these impairments were not clear. There was evidence that clinical symptom resolution occurred before cerebrovascular function, indicating that physiological deficits may persist despite clinical recovery and return to play. Collectively, this emphasizes an opportunity for the use of TCD to illuminate the cerebrovascular deficits caused by SRC. It also highlights that there is need for consistent methodological rigor when employing TCD in a SRC population.

Adolescent Sport-Related Concussion and the Associated Neurophysiological Changes: A Systematic Review.

BACKGROUND: Sport-related concussion (SRC) has been shown to induce cerebral neurophysiological deficits, quantifiable with electroencephalography (EEG). As the adolescent brain is undergoing rapid neurodevelopment, it is fundamental to understand both the short- and long-term ramifications SRC may have on neuronal functioning. The current systematic review sought to amalgamate the literature regarding both acute/subacute (≤28 days) and chronic (>28 days) effects of SRC in adolescents via EEG and the diagnostic accuracy of this tool. METHODS: The review was registered within the Prospero database (CRD42021275256). Search strategies were created and input into the PubMed database, where three authors completed all screening. Risk of bias assessments were completed using the Scottish Intercollegiate Guideline Network and Methodological Index for Non-Randomized Studies. RESULTS: A total of 128 articles were identified; however, only seven satisfied all inclusion criteria. The studies ranged from 2012 to 2021 and included sample sizes of 21 to 81 participants, albeit only ∼14% of the included athletes were females. The studies displayed low-to-high levels of bias due to the small sample sizes and preliminary nature of most investigations. Although heterogeneous methods, tasks, and analytical techniques were used, 86% of the studies found differences compared with control athletes, in both the symptomatic and asymptomatic phases of SRC. One study used raw EEG data as a diagnostic indicator demonstrating promise; however, more research and standardization are a necessity. CONCLUSIONS: Collectively, the findings highlight the utility of EEG in assessing adolescent SRC; however, future studies should consider important covariates including biological sex, maturation status, and development.

The Geras virtual frailty rehabilitation program to build resilience in older adults with frailty during COVID-19: a randomized feasibility trial.

BACKGROUND: The Coronavirus (COVID-19) pandemic has exacerbated the risk for poor physical and mental health outcomes among vulnerable older adults. Multicomponent interventions could potentially prevent or reduce the risk of becoming frail; however, there is limited evidence about utilizing alternative modes of delivery where access to in-person care may be challenging. This randomized feasibility trial aimed to understand how a multicomponent rehabilitation program can be delivered remotely to vulnerable older adults with frailty during the pandemic. METHODS: Participants were randomized to either a multimodal or socialization arm. Over a 12-week intervention period, the multimodal group received virtual care at home, which included twice-weekly exercise in small group physiotherapy-led live-streamed sessions, nutrition counselling and protein supplementation, medication consultation via a videoconference app, and once-weekly phone calls from student volunteers, while the socialization group received only once-weekly phone calls from the volunteers. The RE-AIM (Reach, Effectiveness, Adoption, Implementation and Maintenance) framework was used to evaluate the feasibility of the program. The main clinical outcomes were change in the 5-times sit-to-stand test (5 × STS) and Depression, Anxiety and Stress Scale (DASS-21) scores. The feasibility outcomes were analyzed using descriptive statistics and expressed as frequencies and mean percent with corresponding confidence intervals (CI). Analysis of covariance (ANCOVA) was used for the effectiveness component. RESULTS: The program enrolled 33% (n = 72) of referrals to the study (n = 220), of whom 70 were randomized. Adoption rates from different referral sources were community self-referrals (60%), community organizations (33%), and healthcare providers (25%). At the provider level, implementation rates varied from 75 to 100% for different aspects of program delivery. Participant's adherence levels included virtual exercise sessions 81% (95% CI: 75-88%), home-based exercise 50% (95% CI: 38-62%), protein supplements consumption 68% (95% CI: 55-80%), and medication optimization 38% (95% CI: 21-59%). Most participants (85%) were satisfied with the program. There were no significant changes in clinical outcomes between the two arms. CONCLUSION: The GERAS virtual frailty rehabilitation study for community-dwelling older adults living with frailty was feasible in terms of reach of participants, adoption across referral settings, adherence to implementation, and participant's intention to maintain the program. This program could be feasibly delivered to improve access to socially isolated older adults where barriers to in-person participation exist. However, trials with larger samples and longer follow-up are required to demonstrate effectiveness and sustained behavior change. TRIAL REGISTRATION: ClinicalTrials.gov NCT04500366. Registered August 5, 2020, https://clinicaltrials.gov/ct2/show/NCT04500366.

Protecting the integrity of survey research.

Although polling is not irredeemably broken, changes in technology and society create challenges that, if not addressed well, can threaten the quality of election polls and other important surveys on topics such as the economy. This essay describes some of these challenges and recommends remediations to protect the integrity of all kinds of survey research, including election polls. These 12 recommendations specify ways that survey researchers, and those who use polls and other public-oriented surveys, can increase the accuracy and trustworthiness of their data and analyses. Many of these recommendations align practice with the scientific norms of transparency, clarity, and self-correction. The transparency recommendations focus on improving disclosure of factors that affect the nature and quality of survey data. The clarity recommendations call for more precise use of terms such as "representative sample" and clear description of survey attributes that can affect accuracy. The recommendation about correcting the record urges the creation of a publicly available, professionally curated archive of identified technical problems and their remedies. The paper also calls for development of better benchmarks and for additional research on the effects of panel conditioning. Finally, the authors suggest ways to help people who want to use or learn from survey research understand the strengths and limitations of surveys and distinguish legitimate and problematic uses of these methods.

Effect of the GERAS DANcing for Cognition and Exercise Program on Physical Function in Older Adults.

GERAS DANcing for Cognition and Exercise is a therapeutic dance program for older adults with cognitive or mobility impairments. Using a pre-/posttest study design, we investigated the effect of 12 weeks of dance on the short performance physical battery (SPPB). In 107 participants aged 61-93 (mean 76.1, SD = 7.0; 20% men), over 90% had multifrailty and/or cognitive impairment. The mean attendance rate was 18/24 classes (75%). A substantial minimal clinically important difference (>0.4) occurred for SPPB total (+0.53, SD = 2.04, p = .002) and chair stands (+0.45, SD = 0.92, p < .001). Individuals with baseline SPPB ≤8 points (n = 38)-indicative of sarcopenia and physical frailty-had the most marked improvement (SPPB total: +1.45, SD = 1.97, p < .001; balance: +0.65, SD = 1.27, p = .006; chair stands: +0.68, SD = 0.97, p < .001). GERAS DANcing for Cognition and Exercise may be a promising rehabilitation intervention to improve daily physical function.

Time-course recovery of cerebral blood velocity metrics post aerobic exercise: a systematic review.

Currently, the standard approach for restricting exercise prior to cerebrovascular data collection varies widely between 6 and 24 h. This universally employed practice is a conservative approach to safeguard physiological alterations that could potentially confound one's study design. Therefore, the purpose of this systematic review was to amalgamate the existing literature examining the extent and duration of postexercise alterations in cerebrovascular function, measured via transcranial Doppler ultrasound. Furthermore, an exploratory aim was to scrutinize and discuss common biases/limitations in the previous studies to help guide future investigations. Search strategies were developed and imported into PubMed, SPORTDiscus, and Medline databases. A total of 595 records were screened and 35 articles met the inclusion criteria in this review, which included assessments of basic cerebrovascular metrics (n = 35), dynamic cerebral autoregulation (dCA; n = 9), neurovascular coupling (NVC; n = 2); and/or cerebrovascular reactivity (CVR-CO2; n = 1) following acute bouts of aerobic exercise. Across all studies, it was found that NVC was impacted for 1 h, basic cerebrovascular parameters and CVR-CO2 parameters for 2 h, and dCA metrics for 6 h postexercise. Therefore, future studies can provide participants with these evidence-based time restrictions, regarding the minimum time to abstain from exercise prior to data collection. However, it should be noted that other physiological mechanisms could still be altered (e.g., metabolic, hormonal, and/or autonomic influences), despite cerebrovascular function returning to baseline levels. Thus, future investigations should seek to control as many physiological influences when using cerebrovascular assessments, immediately following these time restraints. The main limitations/biases were lack of female participants, cardiorespiratory fitness, and consideration for vessel diameter.

Community-based group physical activity and/or nutrition interventions to promote mobility in older adults: an umbrella review.

BACKGROUND: Physical activity and a healthy diet are important in helping to maintain mobility with aging. This umbrella review aims to identify group-based physical activity and/or nutrition interventions for community-dwelling older adults that improve mobility-related outcomes. METHODS: Five electronic databases (MEDLINE, Embase, CINAHL, Cochrane CENTRAL, Sociological Abstracts) were searched from inception to December 2021. Eligibility criteria included systematic reviews exploring the effectiveness of physical activity or structured exercise, alone or combined with nutrition interventions on mobility-related outcomes (aerobic capacity, physical function, balance, falls/safety, muscle strength, health-related quality of life/wellbeing). Interventions must have been delivered in a group setting to community-dwelling older adults aged 55+. Two reviewers independently performed eligibility screening, critical appraisal (using AMSTAR 2) and data extraction. The GRADE approach was used to reflect the certainty of evidence based on the size of the effect within each mobility-related outcome category. Older adult/provider research partners informed data synthesis and results presentation. RESULTS: In total, 62 systematic reviews (1 high, 21 moderate, 40 low/critically low quality) were identified; 53 included physical activity only, and nine included both physical activity and nutritional supplements. No reviews included nutrition interventions alone. Combined aerobic/resistance, general physical activity, and mind-body exercise all improved physical function and balance (moderate-high certainty). Aerobic/resistance training improved aerobic capacity (high certainty). Resistance training and general physical activity improved muscle strength (moderate certainty). Aerobic/resistance training and general physical activity are likely to reduce falls among older adults (moderate certainty). There was no evidence of benefit for nutritional supplementation with physical activity. CONCLUSIONS: Group-based physical activity interventions that combine aerobic and resistance, general PA and mind-body exercise can improve measures of mobility in community-dwelling older adults. We found no reviews focused on nutrition only, highlighting a gap in the literature.

Does oscillation size matter? Impact of added resistance on the cerebral pressure-flow Relationship in females and males.

Sinusoidal squat-stand maneuvers (SSM) without resistance have been shown to produce ~30-50 mmHg swings in mean arterial pressure which are largely buffered in the brain via dynamic cerebral autoregulation (dCA). This study aimed to further elucidate how this regulatory mechanism is affected during SSM with added resistance (~20% bodyweight). Twenty-five participants (sex/gender: 13 females/12 males) completed two bouts of 5-min SSM for both bodyweight and resistance conditions (10% bodyweight in each arm) at frequencies of 0.05 Hz (20-s squat/stand cycles) and 0.10 Hz (10-s squat/stand cycles). Middle and posterior cerebral artery (MCA/PCA) cerebral blood velocities were indexed with transcranial Doppler ultrasound. Beat-to-beat blood pressure (BP) was quantified via finger photoplesmography. Transfer function analysis was employed to quantify dCA in both cerebral arteries across the cardiac cycle (diastole, mean, and systole). Two-by-two Analysis of Variance with generalized eta squared effect sizes were utilized to determine differences between resistance vs. bodyweight squats and between sexes/genders. Absolute mean and diastolic BP were elevated during the resistance squats (p < 0.001); however, only the BP point-estimate power spectrum densities were augmented at 0.10 Hz (p < 0.048). No differences were noted for phase and gain metrics between bodyweight and resistance SSM (p > 0.067); however, females displayed attenuated systolic regulation (p < 0.003). Despite augmented systemic BP during resistance SSM, the brain was effective at buffering the additional stress to mitigate overperfusion/pressure. Females displayed less dCA regulation within the systolic aspect of the cardiac cycle, which may be associated with physiological underpinnings related to various clinical conditions/presentations.

Sex differences in autonomic recovery following repeated sinusoidal resistance exercise.

A simple bodyweight squat is sufficient to cause substantial stress on the autonomic nervous system (ANS) via ~30-50 mmHg blood pressure (BP) oscillations. However, it is unknown to the extent of the ANS is impacted during and immediately following bodyweight and resistance squat-stand maneuvers (SSM) while considering chromosomal sex. Thirteen females and twelve males performed four, 5-minute bouts of squat-stand maneuvers (SSM); two at 0.05 Hz (10-second squat/10-second stand) and two at 0.10 Hz (5-s squat/5-s stand). The SSM were performed using bodyweight resistance and additional external resistance (~20% of bodyweight). Five-minutes of quiet-sitting and quiet-standing were completed immediately following both bodyweight and resistance squats. Heart rate variability (HRV) and baroreceptor sensitivity metrics were extracted from beat-to-beat electrocardiography and systemic BP recordings. Repeated measure Analysis of Variance with generalized eta-squared effect sizes assessed differences between SSM task type and chromosomal sex on ANS metrics. Despite added resistance eliciting greater elevations in blood pressure, no differences in ANS function were noted during competition and recovery between SSM tasks (all p > 0.050; negligible/small effect sizes). During recovery, females had an elevated heart rate (p = 0.017; small effect size), greater time-domain HRV measures (p < 0.047; small effect size), greater high-frequency domain HRV measures (p = 0.002; moderate effect size), and reduced low-frequency domain HRV measures (p = 0.002; moderate effect size). A healthy ANS can modulate repetitive cardiovascular stressors via squat-stand maneuvers in a harmonious manner irrespective of added low-level resistance. Females were more parasympathetically driven following low-level resistance exercise/stress, which may be a cardioprotective trait.

Development of GERAS DANcing for Cognition and Exercise (DANCE): a feasibility study.

BACKGROUND: Dance is a mind-body activity of purposeful rhythmic movement to music. There is growing interest in using dance as a form of cognitive and physical rehabilitation. This manuscript describes the development of GERAS DANcing for Cognition and Exercise (DANCE) and evaluates its feasibility in older adults with cognitive and mobility impairments. METHODS: The progressive dance curricula were delivered for 15 weeks (1-h class; twice weekly). Participants were eligible if they were community-dwelling older adults aged 60+ with early cognitive or mobility impairment able to follow three-step commands and move independently. Feasibility outcomes included recruitment/retention, adherence, participant satisfaction, safety, and adverse events. RESULTS: Twenty-five older adults (mean (standard deviation [SD]) age = 77.55 (6.10) years, range 68-90 years) with early cognitive (Montreal Cognitive Assessment score (SD) = 21.77 (4.05)) and mobility (92% were pre-frail/frail as indicated on the Fried Frailty Phenotype) impairments were recruited from a geriatric out-patient clinic or within the community. A total of 20/25 (80%) participants completed the study. Average class attendance was 72%, and self-reported homework adherence "most-days / every day" was 89%. A stepwise progression in the dance curricula was observed with increases in motor complexity and balance demands, and 95% of participants rated the program as a "just-right" challenge. Ninety percent of participants rated GERAS DANCE as excellent, and 100% would recommend the program to a friend or family member. Over 50% of participants connected outside of class time for a self-initiated coffee club. Adverse events of falls and fractures were reported for 2 participants, which occurred at home unrelated to the dance intervention during the study period. Pre-determined thresholds for feasibility were met for all outcomes. DISCUSSION: GERAS DANCE is a feasible and enjoyable program for older adults with early cognitive or mobility impairments. GERAS DANCE curriculum grading (duration; sequence; instructions) and motor complexity increases in agility, balance, and coordination appear appropriately tailored for this population. Future work will explore the feasibility of GERAS DANCE in new settings (i.e., virtually online, community centers, or retirement homes) and the mind-body-social benefits of dance.

Community-based physical activity and/or nutrition interventions to promote mobility in older adults: An umbrella review.

Background: Physical activity and a healthy diet are important in helping to maintain mobility and quality of life with aging. Delivery of physical activity and nutrition interventions in a group setting adds the benefits of social participation. Several published systematic reviews have explored a broad range of PA and/or nutrition interventions for older adults, making it challenging to bring together the best scientific evidence to inform program design and to inform multicomponent intervention development. This umbrella review aims to identify group-based physical activity and nutrition interventions for community-dwelling older adults that improve mobility. Methods: Five electronic databases (MEDLINE, Embase, CINAHL, Cochrane CENTRAL, Sociological Abstracts) were searched from inception to April 28, 2020. Eligibility criteria included systematic reviews exploring the effectiveness of physical activity and/or nutrition interventions, delivered in a group setting for community-dwelling older adults. Two reviewers independently performed eligibility screening, critical appraisal (using AMSTAR 2) and data extraction. The GRADE approach was used to assess the overall certainty of the evidence. Older adult/provider research partners informed data synthesis and results presentation. Results: In total, 54 systematic reviews (1 high, 21 moderate, 32 low/critically low quality) were identified; 46 included physical activity only, and eight included both physical activity and nutritional supplements. No reviews included nutrition interventions alone. Combined aerobic/resistance, general physical activity, and mind-body exercise all improved physical function and balance (moderate-high certainty). Aerobic/resistance training improved aerobic capacity (high certainty). Resistance training and general physical activity improved muscle strength (moderate certainty). Aerobic/resistance training and general physical activity are likely to reduce falls among older adults (moderate certainty). There was no evidence of benefit for nutritional supplementation with physical activity. Conclusions: Multicomponent group-based physical activity interventions can improve measures of mobility in community-dwelling older adults. We found no reviews focused on nutrition only, highlighting a gap in the literature.

The EMBOLDEN Co-design study: Partnering with older adults and communities to develop a community program to enhance mobility.

Context: Physical mobility and social participation are requisite for independence and quality of life as one ages. Barriers to mobility lead to social isolation, poor physical and mental health, all of which are precursors to frailty. To date, most mobility-enhancing interventions in older adults have been designed by researchers without citizen input and delivered in controlled settings; their translation to real-world contexts is often impractical and rarely occurs. Objectives: i) To engage older adults and community service providers to qualitatively explore priorities, needs, enablers and barriers to mobility and community participation faced by older adults, and ii) To co-design an evidence-informed, feasible, acceptable group intervention to support mobility and promote health among older adults facing health inequities. Study Design: Adapted experience-based co-design, conducted in collaboration with a Strategic Guiding Council comprised of older adults and service providers. Setting: Community-based. Population studied: Community-dwelling older adults (55+) and local health and social service providers. Outcome Measures: EMBOLDEN's Strategic Guiding Council and the research team collectively interpreted qualitative study findings, together with results of completed systematic reviews and an environmental scan, to determine priority design features of a community-based mobility-enhancing intervention to enable health and well-being in older adults in Hamilton, ON. Results: Eighteen diverse older adults and 16 service providers completed persona scenario interviews. These lived experience perspectives were analyzed, interpreted, and integrated with research and local evidence in the intervention co-design process. Priority design features for the intervention included duration, intensity, mode of delivery, characteristics of interventionists, and implementation strategies. Findings highlighted key strategies related to participant motivation, recruitment, and engagement, as well as important equity, diversity, and inclusion considerations. Conclusions: Partnering with diverse stakeholders is critical to identifying optimal design features of a community-based intervention to promote mobility. Ultimately, we aim to implement and evaluate a health promoting intervention that is sustainable, scalable, addresses health inequities, and effectively improves the lives of older adults.

Long-term heart transplant recipients: heart rate-related effects on augmented transfer function coherence during repeated squat-stand maneuvers in males.

Previous research has highlighted that squat-stand maneuvers (SSMs) augment coherence values within the cerebral pressure-flow relationship to ∼0.99. However, it is not fully elucidated if mean arterial pressure (MAP) leads to this physiological entrainment independently, or if heart rate (HR) and/or the partial pressure of carbon dioxide (Pco2) also have contributing influences. A 2:1 control-to-case model was used in the present investigation [participant number (n) = 40; n = 16 age-matched (AM); n = 16 donor control (DM); n = 8 heart transplant recipients (HTRs)]. The latter group was used to mechanistically isolate the extent to which HR influences the cerebral pressure-flow relationship. Participants completed 5 min of squat-stand maneuvers at 0.05 Hz (10 s) and 0.10 Hz (5 s). Linear transfer function analysis (TFA) examined the relationship between different physiological inputs (i.e., MAP, HR, and Pco2) and output [cerebral blood velocity (CBV)] during SSM; and cardiac baroreceptor sensitivity (BRS). Compared with DM, cardiac BRS was reduced in AM (P < 0.001), which was further reduced in HTR (P < 0.045). In addition, during the SSM, HR was elevated in HTR compared with both control groups (P < 0.001), but all groups had near-maximal coherence metrics ≥0.98 at 0.05 Hz and ≥0.99 at 0.10 Hz (P ≥ 0.399). In contrast, the mean HR-CBV/Pco2-CBV relationships ranged from 0.38 (HTR) to 0.81 (DM). Despite near abolishment of BRS and blunted HR following heart transplantation, long-term HTR exhibited near-maximal coherence within the MAP-CBV relationship, comparable with AM and DM. Therefore, these results show that the augmented coherence with SSM is driven by blood pressure, whereas elevations in TFA coherence as a result of HR contribution are likely correlational in nature.

Does task complexity impact the neurovascular coupling response similarly between males and females?

BACKGROUND: While previous studies have demonstrated a complex visual scene search elicits a robust neurovascular coupling (NVC) response, it is unknown how the duration of visual stimuli presentation influences NVC metrics. This study examined how stimuli duration, in addition to biological sex and self-reported engagement impact NVC responses. METHODS: Participants (n = 20, female = 10) completed four visual paradigms. Three involved simple visual shapes presented at 0.5-, 2-, and 4-s intervals in randomized orders. The fourth paradigm was a complex visual scene search ("Where's Waldo?"). Participants completed eight cycles of 20-s eyes-closed followed by 40-s eyes-open. Transcranial Doppler ultrasound indexed posterior and middle cerebral artery velocities (PCA and MCA). Participants self-reported their engagement following each task (1 [minimal] to 10 [maximal]). RESULTS: The "Where's Waldo?" task evoked greater PCA percent increase (all p < 0.001) and area under the curve during the first 30-s of the task (all p < 0.001) compared to simple shapes. Females displayed greater absolute baseline and peak PCA and MCA velocities across all tasks (all p < 0.002). Subjective engagement displayed moderate correlation levels with PCA percent increase (Spearman ρ = 0.58) and area under the curve (Spearman ρ = 0.60) metrics in males, whereas these were weak for females (Spearman ρ = 0.43 and ρ = 0.38, respectively). CONCLUSIONS: The complex visual paradigm "Where's Waldo?" greatly augmented the signal-to-noise ratio within the PCA aspects of the NVC response compared to simple shapes. While both sexes had similar NVC responses, task engagement was more related to NVC metrics in males compared to females. Therefore, future NVC investigations should consider task engagement when designing studies.

The Species-Specific Acquisition and Diversification of a K1-like Family of Killer Toxins in Budding Yeasts of the Saccharomycotina.

Killer toxins are extracellular antifungal proteins that are produced by a wide variety of fungi, including Saccharomyces yeasts. Although many Saccharomyces killer toxins have been previously identified, their evolutionary origins remain uncertain given that many of these genes have been mobilized by double-stranded RNA (dsRNA) viruses. A survey of yeasts from the Saccharomyces genus has identified a novel killer toxin with a unique spectrum of activity produced by Saccharomyces paradoxus. The expression of this killer toxin is associated with the presence of a dsRNA totivirus and a satellite dsRNA. Genetic sequencing of the satellite dsRNA confirmed that it encodes a killer toxin with homology to the canonical ionophoric K1 toxin from Saccharomyces cerevisiae and has been named K1-like (K1L). Genomic homologs of K1L were identified in six non-Saccharomyces yeast species of the Saccharomycotina subphylum, predominantly in subtelomeric regions of the genome. When ectopically expressed in S. cerevisiae from cloned cDNAs, both K1L and its homologs can inhibit the growth of competing yeast species, confirming the discovery of a family of biologically active K1-like killer toxins. The sporadic distribution of these genes supports their acquisition by horizontal gene transfer followed by diversification. The phylogenetic relationship between K1L and its genomic homologs suggests a common ancestry and gene flow via dsRNAs and DNAs across taxonomic divisions. This appears to enable the acquisition of a diverse arsenal of killer toxins by different yeast species for potential use in niche competition.

Effects of dance on cognitive function in older adults: a systematic review and meta-analysis.

BACKGROUND: dance is a mind-body activity that stimulates neuroplasticity. We explored the effect of dance on cognitive function in older adults. METHODS: we searched MEDLINE, EMBASE, CENTRAL and PsycInfo databases from inception to August 2020 (PROSPERO:CRD42017057138). Inclusion criteria were (i) randomised controlled trials (ii) older adults (aged ≥ 55 years), (iii) intervention-dance and (iv) outcome-cognitive function. Cognitive domains were classified with the Diagnostic and Statistical Manual of Mental Disorders-5 Neurocognitive Framework. Meta-analyses were performed in RevMan5.3 and certainty of evidence with GradePro. RESULTS: we reviewed 3,997 records and included 11 studies (N = 1,412 participants). Seven studies included only healthy older adults and four included those with mild cognitive impairment (MCI). Dance interventions varied in frequency (1-3×/week), time (35-60 minutes), duration (3-12 months) and type. We found a mean difference (MD) = 1.58 (95% confidence interval [CI) = 0.21-2.95) on the Mini Mental State Examination for global cognitive function (moderate-certainty evidence), and the Wechsler Memory Test for learning and memory had an MD = 3.02 (95% CI = 1.38-4.65; low-certainty evidence). On the Trail Making Test-A for complex attention, MD = 3.07 (95% CI = -0.81 to 6.95; high-certainty evidence) and on the Trail Making Test-B for executive function, MD = -4.12 (95% CI = -21.28 to 13.03; moderate-certainty evidence). Subgroup analyses did not suggest consistently greater effects in older adults with MCI. Evidence is uncertain for language, and no studies evaluated social cognition or perceptual-motor function. CONCLUSIONS: dance probably improves global cognitive function and executive function. However, there is little difference in complex attention, and evidence also suggests little effect on learning and memory. Future research is needed to determine the optimal dose and if dance results in greater cognitive benefits than other types of physical activity and exercise.

Frailty and Life-Space Mobility: Implications for Clinical Practice and Research.

Frailty is an important medical syndrome that can be prevented or treated with specific interventions. However, there is limited research evidence on multifactorial perspectives of frailty management and its impact on daily function including mobility declines and changes in life-space mobility. Using the person-environment-occupation (PEO) model we aim to describe the relationship between frailty and life-space mobility in older adults. This manuscript provides a new framework for clinical practice and research implications of frailty and life-space mobility in older adults including: (1) overview of key concepts, (2) application of the PEO model to describe how frailty (personal) and life-space (environmental) can influence occupational performance, and (3) clinical practice implications to improve frailty-related immobility. This new framework provides a starting point to extend the focus of frailty beyond the individual to encompass the environmental context within which people live and move.

An empirical comparison of methods for analyzing over-dispersed zero-inflated count data from stratified cluster randomized trials.

BACKGROUND: The assessment of methods for analyzing over-dispersed zero inflated count outcome has received very little or no attention in stratified cluster randomized trials. In this study, we performed sensitivity analyses to empirically compare eight methods for analyzing zero inflated over-dispersed count outcome from the Vitamin D and Osteoporosis Study (ViDOS) - originally designed to assess the feasibility of a knowledge translation intervention in long-term care home setting. METHOD: Forty long-term care (LTC) homes were stratified and then randomized into knowledge translation (KT) intervention (19 homes) and control (21 homes) groups. The homes/clusters were stratified by home size (<250/> = 250) and profit status (profit/non-profit). The outcome of this study was number of falls measured at 6-month post-intervention. The following methods were used to assess the effect of KT intervention on number of falls: i) standard Poisson and negative binomial regression; ii) mixed-effects method with Poisson and negative binomial distribution; iii) generalized estimating equation (GEE) with Poisson and negative binomial; iv) zero inflated Poisson and negative binomial - with the latter used as a primary approach. All these methods were compared with or without adjusting for stratification. RESULTS: A total of 5,478 older people from 40 LTC homes were included in this study. The mean (=1) of the number of falls was smaller than the variance (=6). Also 72% and 46% of the number of falls were zero in the control and intervention groups, respectively. The direction of the estimated incidence rate ratios (IRRs) was similar for all methods. The zero inflated negative binomial yielded the lowest IRRs and narrowest 95% confidence intervals when adjusted for stratification compared to GEE and mixed-effect methods. Further, the widths of the 95% confidence intervals were narrower when the methods adjusted for stratification compared to the same method not adjusted for stratification. CONCLUSION: The overall conclusion from the GEE, mixed-effect and zero inflated methods were similar. However, these methods differ in terms of effect estimate and widths of the confidence interval. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01398527. Registered: 19 July 2011.