Healthy Adults Research Articles

Establishing Wideband Tympanometry Clinical Normative Data for the Iranian Young Adult Population

Background and Objectives: Wideband acoustic immittance (WBT) is a new method for assessing middle ear status by using a wide spectrum stimulus instead of the traditional 226 Hz probe tone. This study focuses on establishing normative data for WBT in the Iranian young adults. We aim to provide clinicians with specific norms for the Iranian population to enhance accuracy in diagnosing middle ear conditions and diseases. Methods: The research involved 20 healthy Iranian young adults who underwent WBT measurements. Results: Results showed differences in the WBT parameters compared to other populations, emphasizing the importance of using ethnicity-specific norms in clinical evaluations. Conclusion: The findings can help in diagnosing various middle ear disorders and monitoring treatment progress.

Relative muscular effort in the older adults during the sit-to-stand task: Monitoring neuromuscular reserve and movement limitations

BackgroundDue to lower maximum strength, older adults purportedly need to exert greater muscular effort to stand up from a chair. This study investigated joint-specific muscular effort during a sit-to-stand by calculating relative-muscular-effort and investigating differences between healthy older and young adults. MethodsFifteen older (age: 69.9 ± 3.5 years) and 15 young (age: 22.2 ± 2.6 years) adults performed five self-paced sit-to-stand trials. Kinematic and kinetic data were collected and used to calculate inverse dynamics net joint moment. Peak isometric knee and hip extensor torques were measured and used as inputs to regression models that predicted angle- and velocity-dependent maximum potential net joint moment. Knee and hip relative-muscular-effort were calculated as the net joint moment during the task and their maximum capacity. FindingsKnee and hip extensor relative-muscular-effort did not differ between age groups during momentum-transfer and extension phases of the sit-to-stand. However, peak knee and hip moments during the sit-to-stand, knee and hip maximum potential moments as well as peak knee and hip torques were significantly lower in older adults compared to young adults. InterpretationAlthough there were age-related decreases in muscle strength and joint kinetics during the sit-to-stand task in older adults, the findings that older adults exhibited similar knee and hip relative-muscular-effort to young adults suggests that neither knee nor hip extensors operated close to their maximum capacity during this task. Therefore, neuromuscular reserve in knee and hip strength may not be a critical limiting factor for healthy older adults during the two phases of sit-to-stand.

7858 Increasing Severity of Growth Hormone Deficiency is Associated with Lower Vertebral Strength

Abstract Disclosure: R. Boutin: None. M. Haines: None. R. Shahid: None. C. Mark: None. C. Gill: None. M. Bredella: None. K.K. Miller: Other; Self; Pfizer, Inc. L.E. Dichtel: Consulting Fee; Self; Lumos Pharma. Grant Recipient; Self; Lumos Pharma, Perspectum Ltd. Research Investigator; Self; Recordati, Novo Nordisk. Stock Owner; Self; Marea Therapeutics. Other; Self; Third Rock Ventures. Objective: Growth hormone (GH) stimulates osteoblast differentiation, while insulin-like growth factor-1 (IGF-1) stimulates osteoblast proliferation and bone formation. Retrospective studies have demonstrated a 2-to-3-fold increased fracture risk in adults with GH deficiency (GHD) due to organic hypothalamic or pituitary disease, particularly at vertebral sites. Adults with overweight/obesity produce relatively less GH than lean individuals, and serum IGF-1 levels are associated positively with BMD in adults with obesity. Yet, no published studies have examined the relationship between degree of GHD across these groups and vertebral strength, an understudied measure of bone quality in part because HR-pQCT cannot image this skeletal site. We hypothesized that there would be an inverse association between degree of GHD and vertebral strength, independent of age and BMI. Methods: Cross-sectional study of 134 estrogen-replete (with regular menses or taking estrogen) women: 16 with GHD secondary to hypopituitarism (HP, severe GHD), 91 with obesity (OB) without a hypothalamic/pituitary disorder (relative GHD), and 37 lean controls (LC) without a hypothalamic/pituitary disorder (normal GH production). Peak-stimulated GH was assessed by GHRH-arginine testing. CT imaging at the L4 vertebra was performed to determine vertebral cross-sectional area and total integrated volumetric bone mineral density (Int.vBMD), from which estimates of vertebral strength were calculated. Results: Mean age [44±9 (mean±SD) (HP) vs. 35±7 (OB) vs. 30±7 (LC) y, p<0.005] and BMI [30±6 (HP) vs. 34±6 (OB) vs. 22±2 (LC) kg/m2, p<0.004] differed between all groups. As expected, peak-stimulated GH was highest in LC (28.3 ± 9.5 ng/mL) followed by OB (12.4 ± 8.9 ng/mL) and HP (2.4 ± 1.7 ng/mL), p<0.0001. IGF-1 Z-scores were higher in LC (0.0 ± 0.6) and OB (0.0 ± 0.7) vs. HP (-1.4 ± 0.7), p<0.0001. Int.vBMD and vertebral strength were higher in LC and OB vs. HP [Int.vBMD (g/cm3) LC 0.21±0.04 and OB 0.21±0.04 vs. HP 0.16±0.03, and vertebral strength (N) LC 4540±850 and 4743±91 vs. HP 3542±651, both p<0.0001], which remained significant when adjusted for age and BMI (p≤0.01). Peak-stimulated GH and IGF-1 Z-scores were positively associated with vertebral strength (GH R=0.33, p=0.003 and IGF-1 Z-score R=0.41, p<0.0001) and Int.vBMD (GH R=0.46, p<0.0001 and IGF-1 Z-score R=0.40, p<0.0001), which remained significant when adjusted for age and BMI. Among the subset of patients without organic pituitary disease (LC and OB only), IGF-1 Z-scores remained positively associated with vertebral strength (R=0.24, p<0.03) and Int.vBMD (R=0.22, p<0.05). Conclusions: These findings suggest that severe GHD is associated with impaired vertebral volumetric bone density and strength. Moreover, the relative GHD of obesity may contribute to lower vertebral bone density and strength in otherwise healthy adults with overweight/obesity. Presentation: 6/3/2024

Transiently worse postural effects after vestibulo-ocular reflex gain-down adaptation in healthy adults.

Suffering an acute asymmetry in vestibular function (i.e., vestibular neuritis) causes increased sway. Non-causal studies report associations between lateral semicircular canal function and balance ability, but direct links remain controversial. We investigate the immediate effect on body sway after unilateral vestibulo-ocular reflex (VOR) gain down adaptation simulating acute peripheral vestibular hypofunction. Eighteen healthy adults, mean age 27.4 (± 12.4), stood wearing an inertial measurement device with their eyes closed on foam before and after incremental VOR gain down adaptation to simulate mild unilateral vestibular neuritis. Active head impulse VOR gain was measured before and after the adaptation to ensure VOR gain adaptation. Percentage change for VOR gain was determined. Sway area was compared before and after VOR adaptation. VOR gain decreased unilaterally exceeding meaningful change values. Sway area was significantly greater immediately after VOR gain down adaptation, but quickly returned to baseline. In a subset of subjects VOR gain was re-assessed and found to remain adapted despite sway normalization. These results indicate that oculomotor adaptation targeting the lateral semicircular canal VOR pathway has an immediate, albeit transient increase in body sway. Rapid return of body sway to baseline levels suggests dynamic sensory reweighting between vestibular and somatosensory inputs to resolve the undesirable increased body sway.

Pharmacokinetics, Pharmacodynamics, and Safety of Intravenous Efgartigimod and Subcutaneous Efgartigimod PH20 in Healthy Chinese Participants.

Efgartigimod, a human immunoglobulin G (IgG)1-derived Fc fragment targeting the neonatal Fc receptor, has been developed into intravenous (IV) and subcutaneous (SC) formulations for treating generalized myasthenia gravis (gMG) and other autoimmune diseases. Data in the Chinese population were not available to date, and while both formulations have been approved in the USA, the EU, Japan and Chinafor the treatment of gMG. We present the pharmacokinetic, pharmacodynamic, and safety of IV and SC PH20 efgartigimod in healthy Chinese participants. In two independent, double-blinded, placebo-controlled, phase I studies of the IV and SC formulations of efgartigimod, healthy Chinese adults were randomized 3:1 to receive active treatment or matching placebo once every 7 days for four doses. Primary endpoints were pharmacokinetic parameters. After the fourth IV infusion, a mean maximum observed concentration (Cmax) of 194 µg/mL was reached at the end of the 1 h infusion; the mean area under concentration-time curve from time zero to 168 h (AUC0-168h) was 5300 µg × h/mL. After the fourth SC injection, a mean Cmax of 42.1 µg/mL was achieved with a median Tmax of 47.74 h; the mean AUC0-168h was 4790 µg × h/mL. Maximal mean reductions from baseline in total IgG levels were reached approximately 24 days after the first dose (60.7%, IV formulation; 66.4%, SC formulation). Treatment-related adverse events (TRAEs) were reported in seven (58.3%) participants receiving SC efgartigimod, mostly injection-site reactions. No TRAEs or AEs of special interest were reported in the IV study. The efgartigimod IV and SC pharmacokinetic, pharmacodynamic, and safety profiles in Chinese participants were similar to the known profiles in non-Chinese participants. Both formulations effectively reduced total IgG levels by a similar percentage. CTR20211952 and CTR20211805.

Attention, working memory, and inhibitory control in aging: Comparing amateur singers, instrumentalists, and active controls.

Despite the ubiquity of musical activities, little is known about the specificity of their association with executive functions. In this cross-sectional study, we examined this relationship as a function of age. Our main hypotheses were that executive functions would decline in older age, that this relationship would be reduced in singers and instrumentalists compared to nonmusician active controls, and that the amount of musical experience would be more strongly associated with executive functions compared to the specific type of activity. A sample of 122 cognitively healthy adults aged 20-88 years was recruited, consisting of 39 amateur singers, 43 amateur instrumentalists, and 40 nonmusician controls. Tests of auditory processing speed, auditory selective attention, auditory and visual inhibitory control, and auditory working memory were administered. The results confirm a negative relationship between age and executive functions. While musicians' advantages were found in selective attention, inhibitory control, and auditory working memory, these advantages were specific rather than global. Furthermore, most of these advantages were independent of age and experience. Finally, there were only limited differences between instrumentalists and singers, suggesting that the relationship between music-making activities and executive functions may be, at least in part, general as opposed to activity-specific.

Assessment of pharmacokinetic and pharmacodynamic interactions between zavegepant and sumatriptan: A phase 1, randomized, placebo-controlled study in healthy adults.

To evaluate the pharmacodynamic (PD) and pharmacokinetic (PK) interactions between zavegepant and sumatriptan in healthy adults. Zavegepant is a high-affinity, selective, small-molecule calcitonin gene-related peptide receptor antagonist administered as a nasal spray approved in the United States for the acute treatment of migraine. Triptans, including sumatriptan, are a different class of drugs for acute migraine treatment and are associated with a risk of increased blood pressure (BP). Hence, it is important to study the drug-drug interactions between zavegepant and sumatriptan due to potential coadministration in clinical settings. This was a Phase 1, single-center, partially blind, randomized, placebo-controlled, single-arm study. Eligible participants were males aged ≥ 18 and ≤ 40 years or females aged ≥ 18 and ≤ 50 years. On Day 1, participants received sumatriptan 2 × 6 mg subcutaneous injections (1 h apart) and were then randomized (6:1 ratio) to receive zavegepant 2 × 10 mg nasal spray (1 in each nostril) or placebo on Days 2 and 3. On Day 4, zavegepant or placebo was coadministered with sumatriptan after the second sumatriptan injection. BP, PK, and safety were evaluated at pre-specified time points. Forty-two participants enrolled in the study received at least one dose of any treatment and were included in the safety analyses. Forty-one participants who completed the study were included in the BP and PK analyses. The mean (standard deviation) time-weighted average (TWA) of mean arterial pressure (MAP [sumatriptan+ zavegepant 87.2 (6.8) vs. sumatriptan 86.9 (6.0)]), diastolic BP (DBP [sumatriptan + zavegepant 72.3 (6.8) vs. sumatriptan 72.1 (6.2)]), and systolic BP (SBP [sumatriptan + zavegepant 116.8 (10.2) vs. sumatriptan 116.2 (8.6)]) did not change following zavegepant and sumatriptan coadministration on Day 4 compared to sumatriptan alone on Day 1. Statistical comparisons of the TWA of MAP, DBP, and SBP between sumatriptan and zavegepant coadministration and sumatriptan alone were similar; the differences observed were 0.04 mmHg for MAP (90% confidence interval [CI]: -0.69, 0.77 mmHg), 0.00 mmHg for DBP (90% CI: -0.76, 0.76 mmHg), and 0.33 mmHg for SBP (90% CI: -0.97, 1.63 mmHg). Sumatriptan PK after sumatriptan and zavegepant coadministration versus sumatriptan alone was similar; the comparison ratios were 102.5% (90% CI: 100.7%, 104.2%) for AUC0-inf and 104.1% (90% CI: 98.0%, 110.6%) for Cmax. A small difference in zavegepant PK exposure after sumatriptan and zavegepant coadministration versus zavegepant alone was not considered clinically relevant: the comparison ratios were 112.4% (90% CI: 103.4%, 122.3%) for AUC0-24 and 96.7% (90% CI: 88.9%, 105.2%) for Cmax. Overall, 90% (38/42) of participants experienced ≥ 1 treatment-emergent adverse event that was mild or moderate in severity. All treatments were generally safe and well tolerated. Coadministration of zavegepant with sumatriptan was safe and without PD or PK interactions in healthy adults.

Emotional competence self-help mobile phone app versus cognitive behavioural self-help app versus self-monitoring app to promote mental wellbeing in healthy young adults (ECoWeB PROMOTE): an international, multicentre, parallel, open-label, randomised controlled trial.

Based on evidence that mental health is more than an absence of mental disorders, there have been calls to find ways to promote flourishing at a population level, especially in young people, which requires effective and scalable interventions. Despite their potential for scalability, few mental wellbeing apps have been rigorously tested in high-powered trials, derived from models of healthy emotional functioning, or tailored to individual profiles. We aimed to test a personalised emotional competence self-help app versus a cognitive behavioural therapy (CBT) self-help app versus a self-monitoring app to promote mental wellbeing in healthy young people. This international, multicentre, parallel, open-label, randomised controlled trial within a cohort multiple randomised trial (including a parallel trial of depression prevention) was done at four university trial sites in four countries (the UK, Germany, Spain, and Belgium). Participants were recruited from schools and universities and via social media from the four respective countries. Eligible participants were aged 16-22 years with well adjusted emotional competence profiles and no current or past diagnosis of major depression. Participants were randomised (1:1:1) to usual practice plus either the emotional competence app, the CBT app or the self-monitoring app, by an independent computerised system, minimised by country, age, and self-reported gender, and followed up for 12 months post-randomisation. The primary outcome was mental wellbeing (indexed by the Warwick-Edinburgh Mental Well Being Scale [WEMWBS]) at 3-month follow-up, analysed in participants who completed the 3-month follow-up assessment. Outcome assessors were masked to group allocation. The study is registered with ClinicalTrials.gov, NCT04148508, and is closed. Between Oct 15, 2020, and Aug 3, 2021, 2532 participants were enrolled, and 847 were randomly assigned to the emotional competence app, 841 to the CBT app, and 844 to the self-monitoring app. Mean age was 19·2 years (SD 1·8). Of 2532 participants self-reporting gender, 1896 (74·9%) were female, 613 (24·2%) were male, 16 (0·6%) were neither, and seven (0·3%) were both. 425 participants in the emotional competence app group, 443 in the CT app group, and 447 in the self-monitoring app group completed the follow-up assessment at 3 months. There was no difference in mental wellbeing between the groups at 3 months (global p=0·47). The emotional competence app did not differ from the CBT app (mean difference in WEMWBS -0·21 [95% CI -1·08 to 0·66]) or the self-monitoring app (0·32 [-0·54 to 1·19]) and the CBT app did not differ from the self-monitoring app (0·53 [-0·33 to 1·39]). 14 of 1315 participants were admitted to or treated in hospital (or both) for mental health-related reasons, which were considered unrelated to the interventions (five participants in the emotional competence app group, eight in the CBT app group, and one in the self-monitoring app group). No deaths occurred. The emotional competence app and the CBT app provided limited benefit in promoting mental wellbeing in healthy young people. This finding might reflect the low intensity of these interventions and the difficulty improving mental wellbeing via universal digital interventions implemented in low-risk populations. European Commission.

Age-related decline of motor unit firing rate in community-dwelling healthy older adults and daily ingestion of fish protein of Alaska pollack: a randomised trial

Neuromuscular properties decline with ageing and low-level physical activities. Alaska pollack protein (APP) is reportedly effective for improving skeletal muscular functions, even if the amount is small and exercise is not conducted. However, it is unclear whether APP intake without an exercise program affects neuromuscular dysfunction in community-dwelling adults conducting normal, everyday activities. This study aimed to investigate changes in motor unit firing properties by adding APP to daily meals in community-dwelling older adults. They were divided into an APP group or a placebo control (CON) group for randomised, double-blind treatment. Participants in APP (n = 15) and CON (n = 17) groups ingested 4.5 g/d APP and whey protein, respectively, added to daily meals for 3 months without a specific exercise intervention. High-density surface electromyography of the vastus lateralis to assess the individual motor unit firing rate during 70% of maximum voluntary ramp-up contraction (MVC), maximum knee extensor strength, muscle thickness, echo intensity, and a physical function test were evaluated at the baseline, as well as 1.5 and 3 months after the intervention. While muscle strength, muscle thickness, and motor function were not changed, the motor unit firing rate at 50%–70% of MVC showed a significant decline at 1.5 and 3 months in the CON group, but this decline was not observed in the APP group. These findings suggest that neuromuscular properties show a detectable decline on performing daily activities without a specific exercise intervention, but such a decline was not observed in the APP intake group.

Mobile Spatiotemporal Gait Segmentation Using an Ear-Worn Motion Sensor and Deep Learning.

Mobile health technologies enable continuous, quantitative assessment of mobility and gait in real-world environments, facilitating early diagnoses of gait disorders, disease progression monitoring, and prediction of adverse events like falls. Traditionally, mobile gait assessment predominantly relied on body-fixed sensors positioned at the feet or lower trunk. Here, we investigate the potential of an algorithm utilizing an ear-worn motion sensor for spatiotemporal segmentation of gait patterns. We collected 3D acceleration profiles from the ear-worn sensor during varied walking speeds in 53 healthy adults. Temporal convolutional networks were trained to detect stepping sequences and predict spatial relations between steps. The resulting algorithm, mEar, accurately detects initial and final ground contacts (F1 score of 99% and 91%, respectively). It enables the determination of temporal and spatial gait cycle characteristics (among others, stride time and stride length) with good to excellent validity at a precision sufficient to monitor clinically relevant changes in walking speed, stride-to-stride variability, and side asymmetry. This study highlights the ear as a viable site for monitoring gait and proposes its potential integration with in-ear vital-sign monitoring. Such integration offers a practical approach to comprehensive health monitoring and telemedical applications, by integrating multiple sensors in a single anatomical location.

The effect of squats on muscle activity in standing, kneeling, and half-kneeling positions: A cross-sectional study.

Kneeling and half-kneeling training are common positions used in physical therapy. however, research on lower extremity muscle activity is lacking compared to the ergonomic aspects and trunk muscle activity. The purpose of this study is to investigate the effects on lower extremity muscle activity during squats in kneeling and half-kneeling positions. The study was designed as a cross-sectional study with a single group of healthy adults. Participants were instructed to perform squats while assuming 3 positions (standing, kneeling, and half-kneeling). Surface electromyography data were recorded 3 times from the rectus femoris (RF), gluteus maximus (GMax), gluteus medius (GMed), and biceps femoris (BF) on the participant's dominant side, and the mean values were analyzed. The participants performed squats for 9 seconds, with 4 seconds of the descent phase, 1 second of the maintenance phase, and 4 seconds of the ascent phase. A metronome was used to ensure precise timing. The study included 30 participants (19 males and 11 females). The muscle activities of the RF, GMed, and BF showed statistically significant differences among the 3 positions, being highest in the half-kneeling position (HKP), followed by the standing position (SP) and kneeling position (KP). The muscle activity of the GMax was significantly higher in the HKP than in the SP and KP (P < .05). The co-contraction ratio was significantly higher with KP than with the SP and HKP (P < .05). In the SP and KP, there were statistically significant differences between the ascent and descent phases of the RF, GMax, GMed, and BF (P < .05). In the HKP, there were statistically significant differences between the ascent and descent phases of the RF, GMax, and GMed (P < .05). The results of this study indicate that squats in the HKP (especially during the ascent phase) require the highest muscle activity, whereas squats in the KP (especially during the descent phase) can be performed with the lowest muscle activity. It can be concluded that these findings could serve as selective indicators for squat exercises and in enhancing postural control, muscle strength, and lower extremity stabilization.

Oxytocin differentially modulates reward system responses to social and non-social incentives.

Oxytocin has been shown to modulate behavior related to processing of monetary incentives and to regulate social and reproductive behavior, yet little is known about how oxytocin differentially influences neural responses to social and non-social incentives. We aimed to evaluate the effects of oxytocin administration on behavioral and neural responses to social and monetary incentives. Twenty-eight healthy adults (age 18-45 years) performed both monetary and social incentive tasks during blood oxygenation level dependent (BOLD) imaging. Intranasal oxytocin or placebo was administered before each scan using a double blind, randomized, cross-over design. Task performance and self-reported motivation and mood states were collected. Time-series analysis was conducted to assess the influence of oxytocin on the hemodynamic response in the ventral tegmental area and substantia nigra (VTA/SN) and nucleus accumbens (NAc). Oxytocin demonstrated a multifaceted effect on VTA/SN and NAc when processing reward incentives, with it increasing BOLD response in VTA/SN and decreasing BOLD response in NAc during social incentive anticipation. A reversal of this was shown with decreased BOLD responses in the VTA/SN and increased BOLD response in the NAc during monetary incentive anticipation. Our findings suggest a more nuanced purpose of oxytocin when evaluating reward incentive decision making. It is possible that while oxytocin does increase salience to rewards, that it is more important for cognitive control when determining short-term versus long-term benefits in rewards. Future studies should more closely examine the relationship between oxytocin and delay discounting.

Enhancing motor skill learning through multiple sessions of online high-definition transcranial direct current stimulation in healthy adults: insights from EEG power spectrum.

The purpose of this study was to evaluate the influence of high-definition transcranial direct current stimulation (HD-tDCS) on finger motor skill acquisition. Thirty-one healthy adult males were randomly assigned to one of three groups: online HD-tDCS (administered during motor skill learning), offline HD-tDCS (delivered before motor skill learning), and a sham group. Participants engaged in a visual isometric pinch task for three consecutive days. Overall motor skill learning and speed-accuracy tradeoff function were used to evaluate the efficacy of tDCS. Electroencephalography was recorded and power spectral density was calculated. Both online and offline HD-tDCS total motor skill acquisition was significantly higher than the sham group (P < 0.001 and P < 0.05, respectively). Motor skill acquisition in the online group was higher than offline (P = 0.132, Cohen's d =1.46). Speed-accuracy tradeoff function in the online group was higher than both offline and sham groups in the post-test. The online group exhibited significantly lower electroencephalography activity in the frontal, fronto-central, and centro-parietal alpha band regions compared to the sham (P < 0.05). The findings suggest that HD-tDCS application can boost finger motor skill acquisition, with online HD-tDCS displaying superior facilitation. Furthermore, online HD-tDCS reduces the power of alpha rhythms during motor skill execution, enhancing information processing and skill learning efficiency.

Safety and Humoral Immunogenicity of Different Dose Levels of Ad26.COV2.S as a 2-Dose Regimen in COVID-19 Vaccine-Naïve Healthy Adults: A Phase 3 Randomized Clinical Trial.

This study aimed to support the end-of-shelf life specification (2.5 × 1010 virus particles [vp]) for the standard Ad26.COV2.S dose (5 × 1010 vp). This randomized, double-blind Phase 3 study evaluated immunogenicity, reactogenicity, and safety of several Ad26.COV2.S dose levels (range 1.25 to 9 × 1010 vp) in 1593 adults between June 2021 and July 2023. Spike-binding antibody responses 28 days post-dose 1 were non-inferior for the 9 × 1010 vp, but not the 2.5 × 1010 vp group when compared with the standard dose. Non-inferiority was demonstrated in terms of spike-binding antibody responses 14 days post-dose 2 for each dose level, including the lowest dose level of 1.25 × 1010 vp, compared to 28 days after one dose and 14 days after two doses of the standard dose. Spike-binding antibody levels correlated well with virus neutralizing titers. There was no impact of pre-existing Ad26.COV2.S neutralizing titers on immunogenicity at any dose level. All dose levels were well tolerated. This study highlights the challenges associated with conducting clinical studies in a rapidly evolving environment and underscores the importance of platform data that can guide initial vaccine specifications such as shelf life during accelerated vaccine development. The present study supports the end-of-shelf life specifications for the approved Ad26.COV2.S dose, and could provide useful information in future vaccine developments using adenovirus vector vaccines.

Impaired brain ability of older adults to transit and persist to latent states with well-organized structures at wakeful rest.

The intrinsic brain functional network organization continuously changes with aging. By integrating spatial and temporal information, the process of how brain networks temporally reconfigure and remain well-organized spatial structure largely reflects the brain function, thereby holds the potential to capture its age-related declines. In this study, we examined the spatiotemporal brain dynamics from resting-state functional Magnetic Resonance Imaging (fMRI) data of healthy young and older adults using a Hidden Markov Model (HMM). Six brain states were generated by HMM, with the young group showing higher fractional occupancy and mean dwell time in states 1, 3, and 4 (SY1, SY2 and SY3), and the older group in states 2, 5, and 6 (SO1, SO2 and SO3). Importantly, comparisons of transition probabilities revealed that the older group showed a reduced brain ability to transition into states dominated by the younger group, as well as a diminished capacity to persist in them. Moreover, graph analysis revealed that these young-specific states exhibited higher modularity and k-coreness. Collectively, these findings suggested that the older group showed impaired brain ability of both transition into and sustain well spatially organized states. This emphasized that the temporal changes in brain state organization, rather than its static mode, could be a key biomarker for detecting age-related functional decline. These insights may pave the way for targeted interventions aimed at mitigating cognitive decline in the aging population.

The Effects of Social Interaction Intervention on Cognitive Functions Among Older Adults Without Dementia: A Systematic Review and Meta-Analysis

Abstract Background and Objectives Previous systemic reviews, predominantly including observational studies, have shown that participation in social activities is a protective factor against cognitive decline. However, this association is subject to potential reverse causality, creating a knowledge gap in our understanding of the effect of social interaction interventions on cognitive function. Therefore, this study aims to conduct a systematic review and meta-analysis of randomized controlled trials to examine the effects of social interaction interventions on cognitive decline among older adults without dementia. Research Design and Methods This systematic review, registered in PROSPERO (CRD42022367828), systematically searched 6 databases from inception to May 6, 2022, to identify relevant articles on the effects of activities with social interaction components on cognitive function in community-dwelling older adults without dementia aged above 60. Two independent reviewers conducted study selection, data extraction, and bias assessment, with RevMan5.3 used for meta-analysis. Subgroup analysis was conducted to assess variation in intervention effects among subgroups. Results We included 11 studies for qualitative analysis and 8 studies for the meta-analysis. The results showed that social interaction intervention had a significant effect on executive function (standardized mean difference [SMD] = 1.60; 95% CI, 0.50 to 2.70; p = .004), but not attention and memory. The subgroup analysis showed a greater cognitive benefit for healthy older adults, but not those with mild cognitive impairment. Moreover, in-person social interaction positively affected global cognition, whereas online interaction did not. Discussion and Implications Social interaction interventions have a limited impact on cognitive function in older adults without dementia but showed potential effects on executive function. This finding offers insights for implementing social intervention in the community.

The sulci of the lateral superior parietal lobule: anatomical overview and nomenclatural consideration.

Discrepancies in the terminology describing sulcal structures within the lateral superior parietal lobule prompted our comprehensive investigation to clarify their morphology and nomenclature. We reviewed literature from the 19th century to the present, focusing on the intraparietal sulcus, interparietal sulcus, superior parietal sulcus, transverse parietal sulcus, paroccipital sulcus, and transverse occipital sulcus. Additionally, we analyzed neuroimaging data from 40 healthy young adults and two cadavers. Our investigation revealed that the original term intraparietal sulcus, introduced by Sir Turner, described a complex structure comprising the inferior segment of the postcentral sulcus, a horizontally extending component into the occipital lobe, and the transverse occipital sulcus. We also found that the superior parietal sulcus is often synonymous with transverse parietal sulcus, the sulcus of Brissaud is an eponym that shall describe the paroccipital sulcus's dorsal parietal ramus, and the transverse occipital sulcus is the combination of the occipital rami of the paroccipital sulcus. Additionally, we identified an unnamed transverse segment of the intraparietal sulcus, the intraparietal sulcus-transverse. Based on these observations, we consider that the sulci of the lateral superior parietal lobule primarily include the intraparietal sulcus, with longitudinal and transverse segments, the transverse parietal sulcus of Brissaud, and the paroccipital sulcus of Wilder.

Cognitive synaptopathy: synaptic and dendritic spine dysfunction in age-related cognitive disorders.

Cognitive impairment is a leading component of several neurodegenerative and neurodevelopmental diseases, profoundly impacting on the individual, the family, and society at large. Cognitive pathologies are driven by a multiplicity of factors, from genetic mutations and genetic risk factors, neurotransmitter-associated dysfunction, abnormal connectomics at the level of local neuronal circuits and broader brain networks, to environmental influences able to modulate some of the endogenous factors. Otherwise healthy older adults can be expected to experience some degree of mild cognitive impairment, some of which fall into the category of subjective cognitive deficits in clinical practice, while many neurodevelopmental and neurodegenerative diseases course with more profound alterations of cognition, particularly within the spectrum of the dementias. Our knowledge of the underlying neuropathological mechanisms at the root of this ample palette of clinical entities is far from complete. This review looks at current knowledge on synaptic modifications in the context of cognitive function along healthy ageing and cognitive dysfunction in disease, providing insight into differential diagnostic elements in the wide range of synapse alterations, from those associated with the mild cognitive changes of physiological senescence to the more profound abnormalities occurring at advanced clinical stages of dementia. I propose the term "cognitive synaptopathy" to encompass the wide spectrum of synaptic pathologies associated with higher brain function disorders.

Adaptation patterns and their associations with mismatch negativity: An electroencephalogram (EEG) study with controlled expectations.

Adaptation refers to the decreased neural response that occurs after repeated exposure to a stimulus. While many electroencephalogram (EEG) studies have investigated adaptation by using either single or multiple repetitions, the adaptation patterns under controlled expectations manifested in the two main auditory components, N1 and P2, are still largely unknown. Additionally, although multiple repetitions are commonly used in mismatch negativity (MMN) experiments, it is unclear how adaptation at different time windows contributes to this phenomenon. In this study, we conducted an EEG experiment with 37 healthy adults using a random stimulus arrangement and extended tone sequences to control expectations. We tracked the amplitudes of the N1 and P2 components across the first 10 tones to examine adaptation patterns. Our findings revealed an L-shaped adaptation pattern characterised by a significant decrease in N1 amplitude after the first repetition (N1 initial adaptation), followed by a continuous, linear increase in P2 amplitude after the first repetition (P2 subsequent adaptation), possibly indicating model adjustment. Regression analysis demonstrated that the peak amplitudes of both the N1 initial adaptation and the P2 subsequent adaptation significantly accounted for variance in MMN amplitude. These results suggest distinct adaptation patterns for multiple repetitions across different components and indicate that the MMN reflects a combination of two processes: the initial adaptation in the N1 and a continuous model adjustment effect in the P2. Understanding these processes separately could have implications for models of cognitive processing and clinical disorders.

Establishing the TSH reference intervals for healthy adults aged over 70 years: the Australian ASPREE cohort study.

As thyroid disorders are common amongst the elderly, this study aims to evaluate the reference interval (RI) for thyroid stimulating hormone (TSH) in healthy adults aged 70 years and over. A proposed RI was determined from the Australian participants of the ASPirin in Reducing Events in the Elderly (ASPREE) randomised trial. Participants had nohistory of cardiovascular disease, thyroid cancer, dementia, or life-threatening illnesses. Participants prescribed with any thyroid-related medication at baseline were excluded. TSH levels were measured using a commercial chemiluminescence microparticle immunoassay. The RI was determined using the middle 95th percentile of the logarithmic transformed data of baseline TSH. Cox proportional hazard regression models were used to validate the RI by assessing disease incidence over time. A total of 10,995 participants had baseline TSH measures. Median (IQR) age was 73.9 (71.8-77.3) years. We propose a RI of 0.34-3.75 mU/L. TSH levels did not differ by age or sex. At baseline, there was no association between symptoms associated with thyroid disease and levels of TSH. Over the follow-up period of up to 11 years, no association was seen between baseline TSH levels and relevant disease outcomes for participants within the RI. From a group of initially healthy, community-dwelling adults aged >=70 years, we propose a RI of TSH to best represent euthyroidism. This concentration was not associated with an increased risk of thyroid related symptoms or outcomes, confirming its appropriateness for clinical use.