Xylazine Use Among People Who Inject Drugs, Philadelphia 2022.

OBJECTIVES: Xylazine is commonly mixed with illicit opioids in Philadelphia, and potential associations with wound issues, infectious diseases, and overdoses are of public health concern. We used data from the National HIV Behavioral Surveillance Survey among persons who inject drugs (PWIDs) in Philadelphia to better identify individuals at risk and inform patients and clinicians about xylazine risk factors. METHODS: We compared characteristics of participants who reported using xylazine to those who reported not using xylazine in the past 12 months. Among those who reported xylazine use, we compared characteristics between people who prefer and did not prefer to use xylazine. RESULTS: In this sample of PWIDs, most prefer not to use xylazine, yet use is common. Compared with PWIDs not using xylazine, PWIDs who use xylazine were more likely to have recent homelessness, polysubstance use, overdose history, and hepatitis C virus infection ( P < 0.05 for all comparisons). Compared with concordant xylazine use, discordant xylazine use was associated with lower preference for fentanyl, heroin as the primary injection drug, and lower use of syringe service programs ( P < 0.05 for all comparisons). CONCLUSIONS: Public health entities should prioritize studying the use and health effects of xylazine in their jurisdictions and consider supporting point-of-care and drug-checking surveillance in addition to raising awareness of xylazine in the drug supply.

Hunting for the cause: Evidence for prion-like mechanisms in Huntington's disease.

The hypothesis that pathogenic protein aggregates associated with neurodegenerative diseases spread from cell-to-cell in the brain in a manner akin to infectious prions has gained substantial momentum due to an explosion of research in the past 10-15 years. Here, we review current evidence supporting the existence of prion-like mechanisms in Huntington's disease (HD), an autosomal dominant neurodegenerative disease caused by expansion of a CAG repeat tract in exon 1 of the huntingtin (HTT) gene. We summarize information gained from human studies and in vivo and in vitro models of HD that strongly support prion-like features of the mutant HTT (mHTT) protein, including potential involvement of molecular features of mHTT seeds, synaptic structures and connectivity, endocytic and exocytic mechanisms, tunneling nanotubes, and nonneuronal cells in mHTT propagation in the brain. We discuss mechanisms by which mHTT aggregate spreading and neurotoxicity could be causally linked and the potential benefits of targeting prion-like mechanisms in the search for new disease-modifying therapies for HD and other fatal neurodegenerative diseases.

Adiposity and grip strength: a Mendelian randomisation study in UK Biobank.

BACKGROUND: Muscle weakness, which increases in prevalence with age, is a major public health concern. Grip strength is commonly used to identify weakness and an improved understanding of its determinants is required. We aimed to investigate if total and central adiposity are causally associated with grip strength. METHODS: Up to 470,786 UK Biobank participants, aged 38-73 years, with baseline data on four adiposity indicators (body mass index (BMI), body fat percentage (BF%), waist circumference (WC) and waist-hip-ratio (WHR)) and maximum grip strength were included. We examined sex-specific associations between each adiposity indicator and grip strength. We explored whether associations varied by age, by examining age-stratified associations (< 50 years, 50-59 years, 60-64 years,65 years +). Using Mendelian randomisation (MR), we estimated the strength of the adiposity-grip strength associations using genetic instruments for each adiposity trait as our exposure. RESULTS: In males, observed and MR associations were generally consistent: higher BMI and WC were associated with stronger grip; higher BF% and WHR were associated with weaker grip: 1-SD higher BMI was associated with 0.49 kg (95% CI: 0.45 kg, 0.53 kg) stronger grip; 1-SD higher WHR was associated with 0.45 kg (95% CI:0.41 kg, 0.48 kg) weaker grip (covariate adjusted observational analyses). Associations of BMI and WC with grip strength were weaker at older ages: in males aged < 50 years and 65 years + , 1-SD higher BMI was associated with 0.93 kg (95% CI: 0.84 kg, 1.01 kg) and 0.13 kg (95% CI: 0.05 kg, 0.21 kg) stronger grip, respectively. In females, higher BF% was associated with weaker grip and higher WC was associated with stronger grip; other associations were inconsistent. CONCLUSIONS: Using different methods to triangulate evidence, our findings suggest causal links between adiposity and grip strength. Specifically, higher BF% (in both sexes) and WHR (males only) were associated with weaker grip strength.

Lifetime body mass index and grip strength at age 46 years: the 1970 British Cohort Study.

BACKGROUND: Ongoing rises in obesity prevalence have prompted growing concerns about potential increases in the burden of age-related musculoskeletal conditions including sarcopenia and sarcopenic obesity. This is of particular concern for future generations of older adults who have lived more of their lives in an obesogenic environment than current generations of older adults. We aimed to study longitudinal associations between body mass index (BMI) and grip strength in midlife using data from a large population-based sample, the 1970 British Cohort Study (BCS70). METHODS: BCS70 participants with valid measures of maximum grip strength at age 46 years were included in analyses [3671 males (49%) and 3876 females (51%)]. Using sex-specific linear regression models, we examined associations of (i) BMI at ages 10, 16, 30, and 46 years; (ii) body fat percentage (BF%) and waist-hip ratio at age 46 years; (iii) BMI gains between 10-16, 16-30, and 30-46; and (iv) age at onset of obesity, with grip strength. RESULTS: At age 46 years, mean (standard deviation) grip strength was 48.10 kg (8.98) in males and 29.61 kg (5.81) in females. Higher BMI at all ages was associated with stronger grip, and the scale of associations was greater in males than females from age 16 onwards (Psex interactions  < 0.01). For example, in fully adjusted models, a 1 standard deviation increase in BMI at age 16 was associated with mean differences in grip strength at age 46 years of 1.41 kg (95% confidence interval: 1.07, 1.75) in males and 0.72 kg (0.53, 0.91) in females. Higher BF% at age 46 was also associated with stronger grip in both sexes. Greater gains in BMI between ages 10 and 16 were associated with stronger grip in both sexes, but subsequent gains in BMI were only associated with stronger grip in males. Associations of greater length of exposure to obesity and stronger grip were also more consistent among males than females. For example, in fully adjusted models, mean grip strength at age 46 years of males and females who had been obese since age 10 or 16 years was 4.39 kg (1.85, 6.93) and 1.25 kg (-0.18, 2.69) higher than males and females who had never been obese, respectively. CONCLUSIONS: Higher BMI from childhood onwards is associated with stronger grip at age 46 years. This suggests that, at this age, anabolic effects of fat on muscle are outweighing the catabolic effects thought to lead to the manifestation of sarcopenic obesity later in life, especially among men. Midlife may be an optimal time to intervene to prevent sarcopenic obesity.

Aerobic capacity and skeletal muscle characteristics in glycogen storage disease IIIa: an observational study.

BACKGROUND: Individuals with glycogen storage disease IIIa (GSD IIIa) (OMIM #232400) experience muscle weakness and exercise limitation that worsen through adulthood. However, normative data for markers of physical capacity, such as strength and cardiovascular fitness, are limited. Furthermore, the impact of the disease on muscle size and quality is unstudied in weight bearing skeletal muscle, a key predictor of physical function. We aim to produce normative reference values of aerobic capacity and strength in individuals with GSD IIIa, and to investigate the role of muscle size and quality on exercise impairment. RESULTS: Peak oxygen uptake (V̇O2peak) was lower in the individuals with GSD IIIa than predicted based on demographic data (17.0 (9.0) ml/kg/min, 53 (24)% of predicted, p = 0.001). Knee extension maximum voluntary contraction (MVC) was also substantially lower than age matched predicted values (MVC: 146 (116) Nm, 57% predicted, p = 0.045), though no difference was found in MVC relative to body mass (1.88 (2.74) Nm/kg, 61% of predicted, p = 0.263). There was a strong association between aerobic capacity and maximal leg strength (r = 0.920; p = 0.003). Substantial inter-individual variation was present, with a high physical capacity group that had normal leg strength (MVC), and relatively high V̇O2peak, and a low physical capacity that display impaired strength and substantially lower V̇O2peak. The higher physical capacity sub-group were younger, had larger Vastus Lateralis (VL) muscles, greater muscle quality, undertook more physical activity (PA), and reported higher health-related quality of life. CONCLUSIONS: V̇O2peak and knee extension strength are lower in individuals with GSD IIIa than predicted based on their demographic data. Patients with higher physical capacity have superior muscle size and structure characteristics and higher health-related quality of life, than those with lower physical capacity. This study provides normative values of these important markers of physical capacity.

Rationale and study design of the MINERVA study: Multicentre Investigation of Novel Electrocardiogram Risk markers in Ventricular Arrhythmia prediction-UK multicentre collaboration.

INTRODUCTION: The purpose of this study is to assess the ability of two new ECG markers (Regional Repolarisation Instability Index (R2I2) and Peak Electrical Restitution Slope) to predict sudden cardiac death (SCD) or ventricular arrhythmia (VA) events in patients with ischaemic cardiomyopathy undergoing implantation of an implantable cardioverter defibrillator for primary prevention indication. METHODS AND ANALYSIS: Multicentre Investigation of Novel Electrocardiogram Risk markers in Ventricular Arrhythmia prediction is a prospective, open label, single blinded, multicentre observational study to establish the efficacy of two ECG biomarkers in predicting VA risk. 440 participants with ischaemic cardiomyopathy undergoing routine first time implantable cardioverter-defibrillator (ICD) implantation for primary prevention indication are currently being recruited. An electrophysiological (EP) study is performed using a non-invasive programmed electrical stimulation protocol via the implanted device. All participants will undergo the EP study hence no randomisation is required. Participants will be followed up over a minimum of 18 months and up to 3 years. The first patient was recruited in August 2016 and the study will be completed at the final participant follow-up visit. The primary endpoint is ventricular fibrillation or sustained ventricular tachycardia >200 beats/min as recorded by the ICD. The secondary endpoint is SCD. Analysis of the ECG data obtained during the EP study will be performed by the core lab where blinding of patient health status and endpoints will be maintained. ETHICS AND DISSEMINATION: Ethical approval has been granted by Research Ethics Committees Northern Ireland (reference no. 16/NI/0069). The results will inform the design of a definitive Randomised Controlled Trial (RCT). Dissemination will include peer reviewed journal articles reporting the qualitative and quantitative results, as well as presentations at conferences and lay summaries. TRIAL REGISTRATION NUMBER: NCT03022487.

Ectopy-triggering ganglionated plexuses ablation to prevent atrial fibrillation: GANGLIA-AF study.

BACKGROUND: The ganglionated plexuses (GPs) of the intrinsic cardiac autonomic system may play a role in atrial fibrillation (AF). OBJECTIVE: We hypothesized that ablating the ectopy-triggering GPs (ET-GPs) prevents AF. METHODS: GANGLIA-AF (ClinicalTrials.gov identifier NCT02487654) was a prospective, randomized, controlled, 3-center trial. ET-GPs were mapped using high frequency stimulation, delivered within the atrial refractory period and ablated until nonfunctional. If triggered AF became incessant, atrioventricular dissociating GPs were ablated. We compared GP ablation (GPA) without pulmonary vein isolation (PVI) against PVI in patients with paroxysmal AF. Follow-up was for 12 months including 3-monthly 48-hour Holter monitors. The primary end point was documented ≥30 seconds of atrial arrhythmia after a 3-month blanking period. RESULTS: A total of 102 randomized patients were analyzed on a per-protocol basis after GPA (n = 52; 51%) or PVI (n = 50; 49%). Patients who underwent GPA had 89 ± 26 high frequency stimulation sites tested, identifying a median of 18.5% (interquartile range 16%-21%) of GPs. The radiofrequency ablation time was 22.9 ± 9.8 minutes in GPA and 38 ± 14.4 minutes in PVI (P < .0001). The freedom from ≥30 seconds of atrial arrhythmia at 12-month follow-up was 50% (26 of 52) with GPA vs 64% (32 of 50) with PVI (log-rank, P = .09). ET-GPA without atrioventricular dissociating GPA achieved 58% (22 of 38) freedom from the primary end point. There was a significantly higher reduction in antiarrhythmic drug usage postablation after GPA than after PVI (55.5% vs 36%; P = .05). Patients were referred for redo ablation procedures in 31% (16 of 52) after GPA and 24% (12 of 50) after PVI (P = .53). CONCLUSION: GPA did not prevent atrial arrhythmias more than PVI. However, less radiofrequency ablation was delivered to achieve a higher reduction in antiarrhythmic drug usage with GPA than with PVI.

A prolonged hiatus in postmenopausal HRT, does not nullify the therapy's positive impact on ageing related sarcopenia.

BACKGROUND: Previous work suggest a positive skeletal muscle effect of hormone replacement therapy (HRT) on skeletal muscle characteristics This study aimed to quantify any continued positive effect of HRT even after a sustained hiatus in treatment, controlling for two key muscle modulation hormones: Estradiol (E2) and Tri-iodo-thyronine (T3). METHOD AND FINDINGS: In 61 untrained women (18-78yrs) stratified as pre-menopausal, post-menopausal without (No_HRT) and post-menopausal with (Used_HRT) HRT history, body composition, physical activity, serum E2 and T3 were assessed by dual energy x-ray absorptiometry, Baecke questionnaire and ELISA. Gastrocnemius medialis (GM) and tibialis anterior (TA) electromyographic profiles (mean power frequency (mPowerF)), isometric plantar-flexion (PF) and dorsi-flexion (DF) maximum voluntary contraction (MVC), rate of torque development (RTD), isokinetic MVC and muscle volume, were assessed using surface electromyography, dynamometry and ultrasonography. Muscle quality was quantified as MVC per unit muscle size. E2 and E2:T3 ratio were significantly lower in postmenopausal participants, and were positively correlated with RTD even after controlling for adiposity and/or age. Pre-menopausal females had greater MVC in 8/8 PF and 2/5 DF (23.7-98.1%; P<0.001-0.049) strength measures compared to No_HRT, but only 6/8 PF (17.4-42.3%; P<0.001-0.046) strength measures compared to Used_HRT. Notably, Used_HRT had significant higher MVC in 7 PF MVC (30.0%-37.7%; P = 0.006-0.031) measures than No_HRT, while premenopausal and Used_HRT had similar uncorrected muscle size or quality. In addition, this cross-sectional data suggest an annual reduction in GM muscle volume corrected for intra-muscular fat by 1.3% in No_HRT and only 0.5% in Used_HRT. CONCLUSION: Even years after cessation of the therapy, a history of HRT is positively associated with negating the expected post-menopausal drop in muscle quantity and quality. Whilst mPowerF did not differ between groups, our work highlights positive associations between RTD against E2 and E2:T3. Notwithstanding our study limitation of single time point for blood sampling, our work is the first to illustrate an HRT attenuation of ageing-related decline in RTD. We infer from these data that high E2, even in the absence of high T3, may help maintain muscle contractile speed and quality. Thus our work is the first to points to markedly larger physiological reserves in women with a past history of HRT.

The European TeleCheck-AF project on remote app-based management of atrial fibrillation during the COVID-19 pandemic: centre and patient experiences.

AIMS: TeleCheck-AF is a multicentre international project initiated to maintain care delivery for patients with atrial fibrillation (AF) during COVID-19 through teleconsultations supported by an on-demand photoplethysmography-based heart rate and rhythm monitoring app (FibriCheck®). We describe the characteristics, inclusion rates, and experiences from participating centres according the TeleCheck-AF infrastructure as well as characteristics and experiences from recruited patients. METHODS AND RESULTS: Three surveys exploring centre characteristics (n = 25), centre experiences (n = 23), and patient experiences (n = 826) were completed. Self-reported patient characteristics were obtained from the app. Most centres were academic (64%) and specialized public cardiology/district hospitals (36%). Majority of the centres had AF outpatient clinics (64%) and only 36% had AF ablation clinics. The time required to start patient inclusion and total number of included patients in the project was comparable for centres experienced (56%) or inexperienced in mHealth use. Within 28 weeks, 1930 AF patients were recruited, mainly for remote AF control (31% of patients) and AF ablation follow-up (42%). Average inclusion rate was highest during the lockdown restrictions and reached a steady state at a lower level after easing the restrictions (188 vs. 52 weekly recruited patients). Majority (>80%) of the centres reported no problems during the implementation of the TeleCheck-AF approach. Recruited patients [median age 64 (55-71), 62% male] agreed that the FibriCheck® app was easy to use (94%). CONCLUSION: Despite different health care settings and mobile health experiences, the TeleCheck-AF approach could be set up within an extremely short time and easily used in different European centres during COVID-19.

Identification of deliberate catheter motion at the left atrial posterior wall during pulmonary vein isolation: Validity of respiratory motion adjustment.

BACKGROUND: During automated radiofrequency (RF) annotation-guided pulmonary vein isolation (PVI), respiratory motion adjustment (RMA) is recommended, yet lacks in vivo validation. METHODS: Following contact force (CF) PVI (continuous RF, 30 W) using general anesthesia and automated RF annotation-guidance (VISITAG™: force-over-time 100% minimum 1 g; 2 mm position stability; ACCURESP™ RMA "off") in 25 patients, we retrospectively examined RMA settings "on" versus "off" at the left atrial posterior wall (LAPW). RESULTS: Respiratory motion detection occurred in eight, permitting offline retrospective comparison of RMA settings. Significant differences in LAPW RF auto-annotation occurred according to RMA setting, with curves displaying catheter position, CF and impedance data indicating "best-fit" for catheter motion detection using RMA "off." Comparing RMA "on" versus "off," respectively: total annotated sites, 82 versus 98; median RF duration per-site, 13.3 versus 10.6 s (p < 0.0001); median force time integral 177 versus 130 gs (p = 0.0002); mean inter-tag distance (ITD), 6.0 versus 4.8 mm (p = 0.002). Considering LAPW annotated site 1-to-2 transitions resulting from deliberate catheter movement, 3 concurrent with inadvertent 0 g CF demonstrated < 0.6 s difference in RF duration. However, 13 deliberate catheter movements during constant tissue contact (ITD range: 2.1-7.0 mm) demonstrated (mean) site-1 RF duration difference 3.7 s (range: -1.3 to 11.3 s): considering multiple measures of catheter position instability, the appropriate indication of deliberate catheter motion occurred with RMA "off" in all. CONCLUSIONS: ACCURESP™ respiratory motion adjustment importantly delayed the identification of deliberate and clinically relevant catheter motion during LAPW RF delivery, rendering auto-annotated RF display invalid. Operators seeking greater accuracy during auto-annotated RF delivery should avoid RMA use.

The validity and reliability of the Achilles tendon moment arm assessed with dual-energy X-ray absorptiometry, relative to MRI and ultrasound assessments.

Dual-energy X-ray absorptiometry (DXA) in single energy mode has been shown to permit the visualisation of bone and soft tissue, such as the patellar tendon through two-dimensional sagittal imaging. However, there is no validated DXA-based measurement of the Achilles tendon moment arm (dAT). The aims of this study were: 1) to compare in vivo DXA derived measurements of the dAT at rest against two previously validated methods: tendon excursion (TE) and magnetic resonance imaging (MRI) at three ankle angles (-5°, 0° and +10°). 2) analyse the intra-day reliability of the DXA method at all ankle angles and compare between methods. Twelve healthy adults (mean ± SD: 31.4 ± 9.5 years; 174.0 ± 9.5 cm; 76.2 ± 16.6 kg) participated in this study, involving test-retest DXA scans, ultrasound scans and one MRI scan. The dAT was defined as the distance from the centre of the calcaneal-tibial joint axis to the Achilles tendon (AT) muscle-tendon line of action. DXA derived dAT measures were significantly greater than MRI measurements (19.7-24.9%) and were 45.2% significantly larger than the TE method. The test-retest reliability of the DXA technique at 0° was high [CV = 1.38%; ICC = 0.96] and despite the consistently larger dAT lengths obtained using DXA, MRI and DEXA data were strongly correlated (r = 0.878, p < 0.001). In conclusion, the DXA technique allowed for highly reproducible in vivo dAT measurement at rest, which has implications for the calculation of AT forces in vivo and the ability to predict the measurement from one tool to the other, thereby providing a novel basis to contrast existing and future studies.

The combined effects of obesity and ageing on skeletal muscle function and tendon properties in vivo in men.

PURPOSE: We investigated the combined impact of ageing and obesity on Achilles tendon (AT) properties in vivo in men, utilizing three classification methods of obesity. METHOD: Forty healthy, untrained men were categorised by age (young (18-49 years); older (50-80 years)), body mass index (BMI; normal weight (≥18.5-<25); overweight (≥25-<30); obese (≥30)), body fat% (normal adipose (<28%); high adiposity (≥28%)) and fat mass index (FMI; normal (3-6); excess fat (>6-9); high fat (>9). Assessment of body composition used dual-energy X-ray absorptiometry, gastrocnemius medialis (GM)/AT properties used dynamometry and ultrasonography and endocrine profiling used multiplex luminometry. RESULTS: Older men had lower total range of motion (ROM; -11%; P = 0.020), GM AT force (-29%; P < 0.001), stiffness (-18%; P = 0.041), Young's modulus (-22%; P = 0.011) and AT stress (-28%; P < 0.001). All three methods of classifying obesity revealed obesity to be associated with lower total ROM (P = 0.014-0.039). AT cross sectional area (CSA) was larger with higher BMI (P = 0.030). However, after controlling for age, higher BMI only tended to be associated with greater tendon stiffness (P = 0.074). Interestingly, both AT CSA and stiffness were positively correlated with body mass (r = 0.644 and r = 0.520) and BMI (r = 0.541 and r = 0.493) in the young but not older adults. Finally, negative relationships were observed between AT CSA and pro-inflammatory cytokines TNF-α, IL-6 and IL-1ß. CONCLUSIONS: This is the first study to provide evidence of positive adaptations in tendon stiffness and size in vivo resulting from increased mass and BMI in young but not older men, irrespective of obesity classification.

Minimizing sedentary behavior (without increasing medium-to-vigorous exercise) associated functional improvement in older women is somewhat dependent on a measurable increase in muscle size.

The optimal pattern of sedentarism displacement and mechanisms underlying its health effects are poorly understood. Therefore, the aim of this study was to quantify muscle-tendon adaptation in response to two different sedentarism displacement interventions and relate any adaptations to functional outcomes. Thirty-four older women (73±5yrs) underwent skeletal muscle-tendon size and functional assessments. Participants were randomly allocated to: Sedentary behavior fragmentation (SBF), Light intensity physical activity (LIPA), or Control groups. Measures were taken at weeks 0 and 8. Gait speed significantly increased (p=0.003), in both experimental groups (SBF: 0.06 ± 0.08m/s, 6±10%, LIPA: 0.06 ± 0.07m/s, 6±6%), but not control (-0.02 ± 0.12m/s, -2±9%). Accordingly, the relative change in Vastus Lateralis muscle volume, accounted for 30% (p=0.027), and 45% (p=0.0006) of the explained variance in the relative change in gait speed, for SBF and LIPA respectively. Gastrocnemius Medialis fascicle length changes were positively associated with gait speed changes, following LIPA exclusively (R2= 0.50, p=0.009). This is the first study to show SBF and LIPA are adequate loading in older women, with related muscle adaptation and clinically relevant gait speed improvements. Such adaptations appear similar irrespective of whether sedentarism displacement is prescribed in a single bout (LIPA) or in frequent micro-bouts (SBF).

Displacing Sedentary Behaviour with Light Intensity Physical Activity Spontaneously Alters Habitual Macronutrient Intake and Enhances Dietary Quality in Older Females.

Displacing Sedentary Behaviour (SB) with light intensity physical activity (LIPA) is increasingly viewed as a viable means of health enhancement. It is, however, unclear whether any behavioural compensations accompany such an intervention. Therefore, the aim of this study was to identify any dietary changes that accompany SB displacement. We hypothesised that SB displacement would improve dietary quality. Thirty-five elderly females (73 ± 5 years) were randomly allocated to one of three groups: (1) sedentary behaviour fragmentation (SBF) (n = 14), (2) continuous LIPA (n = 14), or (3) control (n = 7). Habitual diet (four-day food diary) and physical behaviour (accelerometery) were assessed at weeks 0 and 8. Out of 45 nutrients examined, only glucose exhibited a group × time interaction (p = 0.03), mediated by an exclusive reduction following SBF (-31%). SBF was also the sole experimental group to increase nutrients promoting bone health (SBF: 17%, LIPA: -34%. control: 21%), whereas both experimental groups consumed more nutrients promoting anabolism (SBF: 13%, LIPA: 4%, control: -34%) (z-scores). New ambulators (n = 8) also consumed more nutrients promoting bone health (16%)/anabolism (2%) (z-scores), including significantly increased Zinc intake (p = 0.05, 29%). Displacing SB with LIPA improves dietary quality in older females. Furthermore, SB fragmentation appears advantageous for various dietary outcomes.

The Effects of Displacing Sedentary Behavior With Two Distinct Patterns of Light Activity on Health Outcomes in Older Adults (Implications for COVID-19 Quarantine).

Rationale: The COVID-19 pandemic is limiting outdoor and community-based activities, especially for older adults owing to the requirement for self-isolation, potentially increasing prolonged sedentary behavior (SB). Given a poor tolerance for intense exercise, SB displacement with light intensity physical activity (LIPA) is a promising health enhancing alternative. Therefore, the aims of this study were to investigate the effects of two different types of SB displacement on health outcomes in older adults and any differential impact of associated LIPA pattern. Method: 28 older women (age: 73 ± 5 years, height: 1.60 ± 0.07 m, weight: 67 ± 10 kg, and BMI: 26.1 ± 3.6 kg/m2) underwent overnight fasted dual energy x-ray absorptiometry (DEXA) imaging, blood sampling, and functional assessments before being randomly allocated to one of two groups: (1) single continuous bout of 45-50 min LIPA daily (n = 14); or (2) SB fragmentation (SBF; ~48 min LIPA daily, 2 min LIPA for every 30 min of SB; n = 14). Compliance was systematically monitored using tri-axial accelerometery. All measures were taken at weeks 0 and 8. Results: Physical behavior significantly altered (decreased SB/increased LIPA; p < 0.05) and to a similar extent in both groups. We observed a significant reduction in serum triglycerides [p = 0.045, effect size (ɳp 2) = 0.15; SBF: -0.26 ± 0.77 mmol/L, LIPA: -0.26 ± 0.51 mmol/L], improved 30 s sit-to-stand (STS) count (p = 0.002, ɳp 2 = 0.32, 2 ± 3 STS) and speed (p = 0.009, ɳp 2 = 0.35, -10 ± 33%), as well as increased average handgrip strength (p = 0.001, ɳp 2 = 0.45, 6 ± 12%), and gait speed (p = 0.005, ɳp 2 = 0.27, 0.09 ± 0.16 m/s) in both groups. Interestingly, SBF caused a greater increase in peak handgrip strength (8 ± 14%), compared to LIPA (2 ± 10%; p = 0.04, ɳp 2 = 0.38). Conclusion: SB displacement induced significant improvements in fasting triglycerides, gait speed, as-well as STS endurance/speed in older women. Frequent vs. continuous SB displacement also caused greater increases in handgrip strength. While both SB displacement protocols display promise as efficacious home-based interventions for self-isolating older adults, our results would suggest a physical functioning advantage of the SBF protocol for certain outcomes.

Transmural unipolar electrogram change occurs within 7 s at the left atrial posterior wall during pulmonary vein isolation.

BACKGROUND: To assess occurrence of a histologically validated measure of transmural (TM) atrial ablation-pure R unipolar electrogram (UE) morphology change-at first-ablated left atrial posterior wall (LAPW) sites during contact force (CF)-guided pulmonary vein isolation (PVI). METHODS: Objectively annotated VISITAG™ Module and CARTOREPLAY™ (Biosense Webster Inc., Diamond Bar, CA, USA) UE morphology data were retrospectively analyzed in 23 consecutive patients undergoing PVI under general anesthesia. RESULTS: PVI without spontaneous/dormant recovery was achieved in all, employing 16.3 (3.2) min of radiofrequency (RF; 30 W) energy. All first-ablated LAPW sites demonstrated RS UE morphology preablation, with RF-induced pure R UE morphology change in 98%. Time to pure R UE morphology was significantly shorter at left-sided LAPW sites (4.9 [2.1] vs 6.7 [2.5] s; P = .02), with significantly greater impedance drop (median 13.5 vs 9.9 Ω; P = .003). Importantly, neither first-site RF duration (14.9 vs 15.0 s) nor maximum ablation catheter tip distance moved (during RF) was significantly different, yet the mean CF was significantly higher at right-sided sites (16.5 vs 11.2 g; P = .002). Concurrent impedance and objectively annotated bipolar electrogram (BE) data demonstrated ∼6-8 Ω impedance drop and ∼30% BE decrease at the time of first pure R UE morphology change. CONCLUSIONS: Using objective ablation site annotation, UE morphology evidence of TM RF effect was demonstrated far sooner than considered biologically possible according to the "conventional" 20-40 s RF per-site approach, with significantly greater ablative effect evident at left-sided sites. This novel methodology represents a scientifically more rigorous foundation toward future research into the biological effects of RF ablation in vivo.

Body Fat Percentage, Body Mass Index, Fat Mass Index and the Ageing Bone: Their Singular and Combined Roles Linked to Physical Activity and Diet.

This study took a multi-analytical approach including group differences, correlations and unit-weighed directional z-score comparisons to identify the key mediators of bone health. A total of 190 participants (18⁻80 years) were categorized by body fat%, body mass index (BMI) and fat mass index (FMI) to examine the effect of differing obesity criteria on bone characteristics. A subset of 50 healthy-eating middle-to-older aged adults (44⁻80 years) was randomly selected to examine any added impact of lifestyle and inflammatory profiles. Diet was assessed using a 3-day food diary, bone mineral density (BMD) and content (BMC) by dual energy x-ray absorptiometry in the lumbar, thoracic, (upper and lower) appendicular and pelvic areas. Physical activity was assessed using the Baecke questionnaire, and endocrine profiling was assessed using multiplex luminometry. Obesity, classed via BMI, positively affected 20 out of 22 BMC- and BMD-related outcome measures, whereas FMI was associated with 14 outcome measures and adiposity only modulated nine out of 22 BMC- and BMD-related outcome measures. Whilst bivariate correlations only linked vitamin A and relative protein intake with BMD, the Z-score composite summary presented a significantly different overall dietary quality between healthy and osteopenic individuals. In addition, bivariate correlations from the subset revealed daily energy intake, sport-based physical activity and BMI positive mediators of seven out of 10 BMD sites with age and body fat% shown to be negative mediators of bone characteristics. In conclusion, whilst BMI is a good indicator of bone characteristics, high body fat% should also be the focus of osteoporosis risk with ageing. Interestingly, high BMI in conjunction with moderate to vigorous activity supplemented with an optimal diet (quality and quantity) are identified as positive modulators of bone heath.