Young Subjects Research Articles

Compensatory reserve index during central hypovolemia and volume loading in healthy young and older hyperthermic adults: A pilot study.

The compensatory reserve index (CRI), derived from machine learning algorithms from peripherally obtained photoplethysmography signals, provides a non-invasive assessment of cardiovascular stability, that may be useful clinically. Briefly, the CRI device provides a value between 0 and 1, with 1 reflecting full compensable capabilities and 0 reflecting little to no compensable capabilities. However, the CRI algorithm was developed in younger to middle aged adults, such that it is unknown if older age modulates CRI responses to cardiovascular challenges. In young and older subjects, we compared CRI responses to normothermic and hyperthermic progressive lower body negative pressure (LBNP), and volume loading with saline infusion. Eleven younger (20-36 years) and 10 older (61-75 years) healthy participants underwent (1) graded normothermic LBNP up to 30 mmHg, (2) graded hyperthermic (1.5°C increase in blood temperature) LBNP up to 30 mmHg, and (3) infusion of 15 mL/kg saline (volume loading) with hyperthermia maintained. CRI was obtained throughout each procedure. CRI at 30 mmHg LBNP was 0.18 and 0.24 units greater in the older group during normothermic and hyperthermic LBNP, respectively. However, CRI was not different between age groups at any other LBNP stage, nor did CRI change with volume loading regardless of age. In response to passive hyperthermia alone, regression analyses showed that heart rate was the strongest predictor of CRI. Blood temperature, rate pressure product, and stroke volume were also predictive of CRI but to a lesser extent. In conclusion, age attenuates the reduction in CRI during progressive normothermic and hyperthermic LBNP, but only at 30 mmHg. Second, the CRI was unchanged during volume loading in all subjects. Future studies should determine whether the age differences in CRI reflect age differences in LBNP tolerance.

Lung ultrasound among Expert operator’S: ScOring and iNter-rater reliability analysis (LESSON study) a secondary COWS study analysis from ITALUS group

BackgroundLung ultrasonography (LUS) is a non-invasive imaging method used to diagnose and monitor conditions such as pulmonary edema, pneumonia, and pneumothorax. It is precious where other imaging techniques like CT scan or chest X-rays are of limited access, especially in low- and middle-income countries with reduced resources. Furthermore, LUS reduces radiation exposure and its related blood cancer adverse events, which is particularly relevant in children and young subjects. The score obtained with LUS allows semi-quantification of regional loss of aeration, and it can provide a valuable and reliable assessment of the severity of most respiratory diseases. However, inter-observer reliability of the score has never been systematically assessed. This study aims to assess experienced LUS operators’ agreement on a sample of video clips showing predefined findings.MethodsTwenty-five anonymized video clips comprehensively depicting the different values of LUS score were shown to renowned LUS experts blinded to patients’ clinical data and the study’s aims using an online form. Clips were acquired from five different ultrasound machines. Fleiss-Cohen weighted kappa was used to evaluate experts’ agreement.ResultsOver a period of 3 months, 20 experienced operators completed the assessment. Most worked in the ICU (10), ED (6), HDU (2), cardiology ward (1), or obstetric/gynecology department (1). The proportional LUS score mean was 15.3 (SD 1.6). Inter-rater agreement varied: 6 clips had full agreement, 3 had 19 out of 20 raters agreeing, and 3 had 18 agreeing, while the remaining 13 had 17 or fewer people agreeing on the assigned score. Scores 0 and score 3 were more reproducible than scores 1 and 2. Fleiss’ Kappa for overall answers was 0.87 (95% CI 0.815–0.931, p < 0.001).ConclusionsThe inter-rater agreement between experienced LUS operators is very high, although not perfect. The strong agreement and the small variance enable us to say that a 20% tolerance around a measured value of a LUS score is a reliable estimate of the patient's true LUS score, resulting in reduced variability in score interpretation and greater confidence in its clinical use.

Clinical and biochemical data for the diagnosis of endogenous hypercortisolism: the "Cushingomic" approach.

The clinical presentation of Cushing's syndrome (CS) overlaps with common conditions. Recommended screening tests are serum cortisol after 1-mg overnight dexamethasone suppression test (DST), urinary free cortisol (UFC), and late-night salivary cortisol (LNSC). We analyzed the diagnostic accuracy of screening tests in 615 patients without CS (263 suspected CS, 319 adrenal and 33 pituitary incidentaloma) and 40 with CS. Principal component analysis, K-means clustering, and neural network were used to compute an integrated analysis among tests, comorbidities, and signs/symptoms of hypercortisolism. The diagnostic accuracy of screening tests for CS was high, DST and UFC were slightly superior to LNSC. The threshold of DST should be adapted to the population considered, especially in adrenal incidentaloma with mild autonomous cortisol secretion: the cutoff to differentiate CS should be increased to 196 nmol/L. Diabetes, hypertension, and obesity were more common in patients without CS: the direction of their vectors was not aligned and their correlation with screening tests was poor. Clustering allowed us to differentiate those patients without CS in cluster one (aged osteoporotic patients with impaired screening tests), cluster two (hypertensive and metabolic phenotype), and cluster three (young subjects with a low likelihood of overt CS). A neural network model that combined screening tests and clinical presentation was able to predict the CS diagnosis in the validation cohort with 99% precision and 86% accuracy. Despite the high diagnostic accuracy of screening tests to detect CS, cortisol-related comorbidities or adrenal incidentaloma should be considered when interpreting a positive test.

Efficacy and safety of oral semaglutide in older patients with type 2 diabetes: a retrospective observational study (the OTARU-SEMA study)

BackgroundOral semaglutide in older subjects with type 2 diabetes was as effective as in younger subjects, according to phase 3 clinical trials. However, its efficacy can be limited in very aged population, due to the presence of impaired cognitive function and the complex instructions for its use. Here, we investigated its efficacy and safety by further age bracket in older subjects in real-world.MethodsWe retrospectively studied subjects > 65 years of age with type 2 diabetes who started oral semaglutide treatment. The primary outcome was the change in glycated hemoglobin (HbA1c) over 6 months. Adverse events and cognitive function were evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) and the Hasegawa Dementia Rating Scale-revised (HDS-R). The achievement rate of glycemic targets was evaluated based on the age, health status of subjects and their use of anti-diabetic agents which can cause hypoglycemia, with additional analysis between two subgroups; early (65–74) versus late (≥ 75) older. Furthermore, we evaluated the relationships between their improvements in HbA1c and the baseline characteristics of the subjects, including their cognitive function and insulin secretory capacity.ResultsWe studied the efficacy of the drug in 24 subjects. Their HbA1c and body weight significantly decreased (− 13.1 ± 7.5 mmol/mol and − 3.0 ± 2.4 kg, respectively; P < 0.01). Although cognitive function was lower in the late older group (r = −0.57, P < 0.01), changes in HbA1c showed no difference between the two subgroups (P = 0.66) and it correlated with the insulin secretory capacity rather than cognitive function (r = −0.49, P < 0.05). Glycemic targets were more likely to be achieved (P < 0.01), but HbA1c excessively decreased in late older subjects who were also using insulin or an insulin secretagogue. The frequency of adverse events was similar to that in the clinical trial, whereas discontinuation of medication were more frequent among the late older subjects (Early; n = 2, Late; n = 4).ConclusionsOral semaglutide improves the glycemic control of older subjects, but it might be a risk for potential hypoglycemia and discontinuation because of adverse events in subjects of ≥ 75 years. Attention should be paid to insulin secretory capacity and concomitant medications rather than concern about adherence.

Sex Differences in the Effect of Brain-derived Neurotrophic Factor (BDNF) Val66Met Polymorphism on Baseline EEG Connectivity

Dependent on Val66Met polymorphism in BDNF gene secretion of neurotrophin affects morphological and functional changes in the developing and mature nervous system, in particular, may contribute to associated with white matter degradation changes in connectivity observed with aging. It was also shown that the associated with Val66Met polymorphism differences in connectivity between cortical structures are moderated by the sex of the subjects. However, there are no studies examining the effect of polymorphism on connectivity, taking into account age and gender differences. In this regard, the present study examined the associations of the Val66Met polymorphism of the BDNF gene with the characteristics of delayed phase synchronization based on EEG data in 223 younger (from 18 to 35 years old) and 134 older (over 55 years old) men and women. The analysis included connections between 84 cortical areas, identified on the basis of 42 Brodmann areas located in the left and right hemispheres. A statistically significant effect, including the factor of polymorphism, was the SEX × GENOTYPE interaction when considering associations at the frequency of the α1-rhythm: in Val/Met men, the strength of thirty-three connections was higher compared to Val/Val. Strengthening of connections was observed mainly between the parahippocampal regions of different hemispheres. At the frequency of the gamma rhythm, associated with the genotype differences in connectivity depended on gender and age. In young subjects, the scores of connectivity in Val/Val women were lower in comparison with men, however, no differences between Val/Val and Met carriers were found in any age group. The combined effect of sex and BDNF genotype on the baseline EEG parameters of brain connectivity may be a background for further study of the role of these factors in the formation of basic characteristics of brain activity.

Effects of Light on Visual Function, Alertness, and Cognitive Performance: A Computerized Test Assessment

Background: Three computerized tests were designed to evaluate visual function, alertness, and visuocognitive integration under three different lighting conditions (white, red, and blue lighting). Methods: Three computerized tests were designed and programmed using the experimental design software PsychoPy version 2023.2.2. Test 1 evaluated visual acuity (VA), Test 2 assessed contrast sensitivity, and Test 3 measured alertness. This study was conducted on 53 young subjects who performed three computerized tests after adapting to each of the three different lighting conditions. A baseline aberrometric measurement was taken before and after the tests for each lighting condition. Measurements of accuracy and reaction time were taken for each test, along with total, high-, and low-order aberration values for each situation. Results: Statistically significant differences (p ≤ 0.05) were found among the different lighting conditions across the three tests, with white lighting yielding better performance in Test 1 and Test 3. Additionally, the aberrometric analysis revealed significant differences (p ≤ 0.05), with the baseline measurement being more myopic. Conclusions: White lighting produced the best VA results and faster reaction times, whereas red lighting had poorer VA effects. These findings suggest that different lighting conditions induce changes in vision and alertness, although further research is needed to understand the underlying causes.

The role of different acoustic environmental stimuli on manual dexterity.

Music has been reported to facilitate motor performance. However, there is no data on the effects of different acoustic environmental stimuli on manual dexterity. The present observational study aimed at investigating the effects of background music and noise on a manual dexterity task in young, middle-aged and elderly subjects. Sixty healthy, right-handed subjects aged between 18 and 80 years were enrolled. Twenty young (mean age: 22±2 years), 20 middle-aged (mean age: 55±8 years) and 20 elderly (mean age: 72±5 years) subjects performed the Nine Hole Peg Test (NHPT) in four different acoustic environments: silence (noise < 20dBA), classical music at 60dBA, rock music at 70 dBA, and a noise stimulus at 80dBA. Performance was recorded using an optical motion capture system and retro-reflective markers (SMART DX, 400, BTS). Outcome measures included the total test time and peg-grasp, peg-transfer, peg-in-hole, hand-return, and removing phases times. Normalized jerk, mean and peak of velocity during transfer and return phases were also computed. No differences were found for NHPT phases and total times, normalized jerk, peak of velocity and mean velocity between four acoustic conditions (p>0.05). Between-group differences were found for NHPT total time, where young subjects revealed better performance than elderly (p˂0.001) and middle-aged (p˂0.001) groups. Music and noise stimuli in the considered range of intensity had no influence on the execution of a manual dexterity task in young, middle-aged and elderly subjects. These findings may have implications for working, sportive and rehabilitative activities.

Age as an Effect Modifier of the Effects of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) on Heart Rate Variability in Healthy Subjects.

Background: Evidence suggests that vagus nerve stimulation can modulate heart rate variability (HRV). However, there is a lack of mechanistic studies in healthy subjects assessing the effects of bilateral transcutaneous auricular vagus nerve stimulation (taVNS) on HRV. Our study aims to investigate how taVNS can influence the HRV response, including the influence of demographic variables in this response. Methods: Therefore, we conducted a randomized controlled study with 44 subjects, 22 allocated to active and 22 to sham taVNS. Results: Our results showed a significant difference between groups in the high-frequency (HF) metric. Active taVNS increased the HF metric significantly as compared to sham taVNS. Also, we found that age was a significant effect modifier of the relationship between taVNS and HF-HRV, as a larger increase in HF-HRV was seen in the older subjects. Importantly, there was a decrease in HF-HRV in the sham group. Conclusions: These findings suggest that younger subjects can adapt and maintain a constant level of HF-HRV regardless of the type of stimulation, but in the older subjects, only the active taVNS recipients were able to maintain and increase their HF-HRV. These results are important because they indicate that taVNS can enhance physiological regulation processes in response to external events.

Ultra-low-field magnetic resonance angiography at 0.05 T: A preliminary study.

We aim to explore the feasibility of head and neck time-of-flight (TOF) magnetic resonance angiography (MRA) at ultra-low-field (ULF). TOF MRA was conducted on a highly simplified 0.05 T MRI scanner with no radiofrequency (RF) and magnetic shielding. A flow-compensated three-dimensional (3D)gradient echo (GRE) sequence with a tilt-optimized nonsaturated excitation RF pulse, and a flow-compensated multislice two-dimensional (2D) GRE sequence, were implemented for cerebral artery and vein imaging, respectively. For carotid artery and jugular vein imaging, flow-compensated 2D GRE sequences were utilized with venous and arterial blood presaturation, respectively. MRA was performed on young healthy subjects. Vessel-to-background contrast was experimentally observed with strong blood inflow effect and background tissue suppression. The large primary cerebral arteries and veins, carotid arteries, jugular veins, and artery bifurcations could be identified in both raw GRE images and maximum intensity projections. The primary brain and neck arteries were found to be reproducible among multiple examination sessions. These preliminary experimental results demonstrated the possibility of artery TOF MRA on low-cost 0.05 T scanners for the first time, despite the extremely low MR signal. We expect to improve the quality of ULF TOF MRA in the near future through sequence development and optimization, ongoing advances in ULF hardware and image formation, and the use of vascular T1 contrast agents.

Estimating the human bottleneck for contact tracing.

The SARS-CoV-2 pandemic has highlighted the importance of contact tracing for epidemiological mitigation. Contact tracing interviews (CTIs) typically rely on episodic memory, which is prone to decline over time. Here, we provide a quantitative estimate of reporting decline for age- and gender-representative samples from the United Kingdom and Germany, emulating >15,000 CTIs. We find that the number of reported contacts declines as a power function of recall delay and is significantly higher for younger subjects and for those who used memory aids, such as a scheduler. We further find that these factors interact with delay: Older subjects and those who made no use of memory aids have steeper decline functions. These findings can inform epidemiological modeling and policies in the context of infectious diseases.

T-Allele Carriers of Mono Carboxylate Transporter One Gene Polymorphism rs1049434 Demonstrate Altered Substrate Metabolization during Exhaustive Exercise.

Polymorphism rs1049434 characterizes the nonsynonymous exchange of adenosine (A) by thymidine (T) in the gene for monocarboxylate transporter 1 (MCT1). We tested whether T-allele carriers of rs1049434 demonstrate increased accumulation of markers of metabolic strain. Physically active, healthy, young male subjects (n = 22) conducted a power-matched one-legged cycling exercise to exhaustion. Metabolic substrates in capillary blood, selected metabolic compounds, and indices for the slow oxidative phenotype of vastus lateralis muscle were quantified in samples collected before and after exercise. The genotypes of the rs1049434 polymorphism were determined with polymerase chain reactions. One-legged exercise affected the concentration of muscle metabolites entering the tricarboxylic acid cycle, such as acetyl-co-enzyme A (+448%) and acetyl-L-carnitine (+548%), muscle glycogen (-59%), and adenosine monophosphate (-39%), 30 min post-exercise. Exercise-related variability in the muscular concentration of glycogen, long-chain acyl co-enzyme As and a triglyceride, nicotinamide adenine dinucleotide (NADH), and adenosine monophosphate (AMP) interacted with rs1049434. T-allele carriers demonstrated a 39% lesser reduction in glycogen after exercise than non-carriers when NADH increased only in the non-carriers. Muscle lactate concentration was 150% higher, blood triacyl-glyceride concentration was 53% lower, and slow fiber percentage was 20% lower in T-allele carriers. The observations suggest a higher anaerobic glycolytic strain during exhaustive exercise and a lowered lipid handling in T-allele non-carriers.

The relationship between aerobic capacity and left atrial size in healthy young males: An observational study.

Aerobic capacity, defined as peak oxygen uptake (peakVO2), is a marker for aerobic fitness and is associated with left ventricular (LV) systolic and diastolic function. The aim of the study was to explore the relation between left atrial (LA) volume index (LAVI) and aerobic capacity in healthy young male adults. One hundred three healthy young male subjects (mean age: 34.2 ± 5.5years) were consecutively included in the study. All subjects underwent echocardiography to assess LAVI, LV systolic and diastolic functions. Aerobic capacity was assessed by cardiopulmonary exercise testing. All patients had normal left ventricular ejection fraction (LVEF). One hundred one subjects had normal LAVI (≤34 mL/m2) while 2 subjects had mildly increased LAVI (35-41 mL/m2). Mean peakVO2 predicted was 82.2 ± 14.4%. 64subjects (62.1%) had a peakVO2 < 85% of age-predicted and sex-predicted values and they had higher LAVI compared to those who had a peakVO2 higher than 85% of age-predicted and sex-predicted values (22.0 ± 4.8 mL/m2 vs 20.3 ± 4.1 mL/m2, P = .055). Notably, only LAVI showed a significant correlation with peakVO2 and predicted breathing reserve (BR), while anaerobic threshold correlated with both LAVI and LVEF. Age was also a significant factor, negatively impacting peakVO2 (r = -0.265, P = .007) and predicted BR (r = -0.282, P = .004). Multivariate analysis revealed that both LAVI and age were independent predictors of peakVO2 and predicted BR. This study suggests that LAVI can be a valuable indicator of aerobic capacity in apparently healthy young males.

An Arduino-Powered Device for the Study of White Perception beyond the Visual Chromatic Critical Flicker Fusion Frequency.

Arduino microcontrollers are used for a wide range of technological and biomedical applications, such as image classification, computer vision, brain-computer interaction and vision experiments. Here, we present a new cost-effective mini-device based on RGB LED flicker stimulation for the assessment of the chromatic temporal resolution of the visual function based on the concept of critical flicker fusion frequency (CFF). The assembly of the device and its testing in thirty young subjects demonstrate the steady white visual perception of a trichromatic flicker stimulus (mixture of red, green and blue stimuli) beyond the CFF. Macular function as measured by photo-stress recovery time (PRT) was found to be independent of the CFF measurements for red, green and blue lights. However, a statistical correlation was found between the contrast modulation for CFF for red and green stimuli and PRT. Finally, wavefront measurements demonstrate that high-order aberrations improve the temporal resolution of the visual function.

Insights into Digital MedicRehApp Maintenance Model for Pulmonary Telerehabilitation: Observational Study.

Maintenance strategies after center-based pulmonary rehabilitation (CBPR) are currently needed. This study aimed to evaluate the feasibility and effect on the quality of life of a home-based pulmonary rehabilitation (HBPR) program delivered by a digital app. As secondary objectives, the patients' adherence, symptoms, effort tolerance changes, and safety were evaluated. This was a single-arm prospective observational monocentric study on 30 patients referred for chronic respiratory diseases. The prescription and evaluations of the HBPR programs performed at the pulmonary facility and delivery of structured exercise and counselling by the digital health tool were achieved under the supervision of a respiratory therapist. Digital capabilities included aerobic, strength, and respiratory exercises, which were monitored with a fitness tracker. The engagement rate of the HBPR after the CBPR was 1:10. The EuroQoL VAS score increased from 66.2 ± 16.28 to 75.60 ± 16.07 (p < 0.001), mainly in younger subjects. No patient was lost during the HBPR program. The global adherence session rate was 94%. The Medical Research Council dyspnea scale (MRC), COPD Assessment Test (CAT) score, and six-minute walking test (6MWT) improved from admission into the pulmonary unit to the end of the HBPR program. Between the beginning and end of the CBPR, the CAT score decreased from 14.4 ± 6.39 to 8.50 ± 5.39 (p < 0.001), the MRC decreased from 1.87 ± 0.9 to 1.17 ± 0.83 (p < 0.001), and the 6MWT increased from 451 ± 93 to 473 ± 115 m (p < 0.05). The average Technology Acceptance Model score for usability was high (145 ± 12.1) and no adverse events occurred during the HBPR program. This HBPR model seemed to be feasible and well-accepted by patients, leading to improvements in quality of life, symptoms, and functional capacity.

Evaluation of Biomarkers of Bone Metabolism on Salivary Matrix in the Remodeling of Periodontal Tissue during Orthodontic Treatment.

The aim of this study was to evaluate changes in the concentration of N-terminal type I collagen extension pro-peptide (PINP), tartrate-resistant acid phosphatase (TRAcP), and parathyroid hormone-related protein (PTHrP) in saliva during orthodontic treatment in order to evaluate whether changes in bone turnover marker (BTM) concentration can help highlight the effects of orthodontic mechanical loading in the absence of clinical evidence of tooth movement in terms of tooth movement. Saliva samples from 25 apparently healthy young subjects (10 females and 15 males) were collected using Salivette® (Sarstedt) with cotton swabs and the concentrations of PTHrP, TRAcP 5b, and PINP were analyzed at time 0 (T1), 25 days (T2), and at 45 days (T3). Differences in the median value of biomarker levels between baseline T1 and follow-up of the different groups (T2 and T3) were assessed using the non-parametric Mann-Whitney U test. Trough concentrations of P1NP, PTHrP, and TRAcP were 0.80 µg/L, 0.21 ng/mL, and 0.90 U/L above the method LOD. The non-parametric Mann-Whitney U test confirmed a statistically significant difference in T1 versus concentrations of T2 and T3. All subjects evaluated had a statistically significant difference between T1 vs. T3. when compared with the specific critical difference (RCV) for the analyte The results obtained demonstrate that the evaluation of BTM changes in saliva can help the evaluation of orthodontic procedures and the monitoring of biomechanical therapy.

Cardiac vagal activity changes moderated the association of cognitive and cerebral hemodynamic variations in the prefrontal cortex

Phasic cardiac vagal activity (CVA), reflecting ongoing, moment-to-moment psychophysiological adaptations to environmental changes, can serve as a predictor of individual difference in executive function, particularly executive performance. However, the relationship between phasic CVA and executive function demands requires further validation because of previous inconsistent findings. Moreover, it remains unclear what types of phasic changes of CVA may be adaptive in response to heightened executive demands. This study used the standard N-back task to induce different levels of working memory (WM) load and combined functional Near-Infrared Spectroscopy (fNIRS) with a multipurpose polygraph to investigate the variations of CVA and its interactions with cognitive and prefrontal responses as executive demands increased in fifty-two healthy young subjects. Our results showed phasic decreases in CVA as WM load increased (t (51) = -3.758, p < 0.001, Cohen's d = 0.526). Furthermore, phasic changes of CVA elicited by increased executive demands moderated the association of cognitive and cerebral hemodynamic variations in the prefrontal cortex (B = 0.038, SE = 0.014, p < 0.05). Specifically, as executive demands increased, individuals with larger phasic CVA withdrawal showed a positive relationship between cognitive and hemodynamic variations in the prefrontal cortex (β = 0.281, p = 0.031). No such significant relationship was observed in individuals with smaller phasic CVA withdrawal. The current findings demonstrate a decrease in CVA with increasing executive demands and provide empirical support for the notion that a larger phasic CVA withdrawal can be considered adaptive in situations requiring high executive function demands.

Autism spectrum disorder in young patients with congenital central hypoventilation syndrome: role of the autonomic nervous system dysfunction

BackgroundCongenital central hypoventilation syndrome (CCHS) is a rare condition characterized by alveolar hypoventilation and autonomic nervous system (ANS) dysfunction requiring long-term ventilation. CCHS could constitute a risk factor of autism spectrum disorder (ASD) due to birth injury related to respiratory failure, which remains to be determined. ANS dysfunction has also been described in ASD and there are indications for altered contribution of ANS-central nervous system interaction in processing of social information; thus, CCHS could be a risk factor for ASD based on pathophysiological background also. Our study aimed to determine the prevalence of ASD among CCHS patients, identify risk factors, and explore the relationship between the ANS, evaluated by heart rate variability indices, and adaptative functioning.ResultsOur retrospective study, based on the analysis of records of a French national center of patients with CCHS under 20 years of age, determined that the prevalence of ASD (diagnosed by a psychiatrist, following the criteria of DSM-4 or DSM-5) was 6/69 patients, 8.7% (95% confidence interval: 3.3–18.0%). In a case (CCHS with ASD, n = 6) – control (CCHS without ASD, n = 12) study with matching on sex, longer neonatal hospitalization stay and glycemic dysfunction were associated with ASD. Adaptative functioning was assessed using Vineland Adaptative behavioral scales (VABS) and heart rate variability indices (including daytime RMSSD as an index of parasympathetic modulation) were obtained from ECG Holter performed the same day. In 19 young subjects with CCHS who had both ECG Holter and VABS, significant positive correlations were observed between RMSSD and three of four sub-domains of the VABS (communication: R = 0.50, p = 0.028; daily living skills: R = 0.60, p = 0.006; socialization: R = 0.52, p = 0.021).ConclusionOur study suggests a high prevalence of ASD in patients with CCHS. Glycemic dysfunction and longer initial hospitalization stays were associated with ASD development. A defect in parasympathetic modulation was associated with worse adaptative functioning.

Increased Neuromuscular Activity, Force Output, and Resistance Exercise Volume When Using 5-Minute Compared with 2-Minute Rest Intervals Between the Sets.

McMahon, G, Best, N, Coulter, T, and Erskine, RM. Increased neuromuscular activation, force output and resistance exercise volume when using 5-minute compared with 2-minute rest intervals between the sets. J Strength Cond Res 38(9): 1527-1534, 2024-Longer rest intervals between resistance exercise (RE) sets may promote greater muscle hypertrophy and strength gains over time by facilitating the completion of greater training volume and intensity. However, little is known about the acute neuromuscular responses to RE sets incorporating longer vs. shorter rest intervals. Using a within-subject, crossover design, 8 healthy, young subjects completed 2 separate acute bouts of 4 sets of 8 × 3-s maximal isometric contractions using either a 2-minute (REST-2) or 5-minute (REST-5) rest interval between sets. Peak torque (PT) and electromyography (EMG) were measured pre and 5 minutes postexercise. Peak torque and mean torque (MT), EMG, mean, and median frequencies were measured during each set, whereas blood lactate (BLa), heart rate (HR), and rating of perceived exertion (RPE) were measured following each set. Peak torque and MT were lower ( p < 0.05) in sets 3 and 4, and sets 2-4 in REST-2 compared with REST-5, respectively. Electromyography and BL were lower and higher, respectively, in REST-2 vs. REST-5. There was no main effect of condition on HR or RPE. Pre-to-post exercise reductions in PT (-17 ± 9% vs. -4 ± 7%) and EMG (-29 ± 14% vs. -10 ± 7%) were greater ( p < 0.001) in REST-2 vs. REST-5. Total exercise volume was less in REST-2 vs. REST-5 (9,748 ± 2296 N·m -1 vs. 11,212 ± 2513 N·m -1 , p < 0.001). These results suggest that incorporating 5-minute between-set rest intervals into a resistance exercise session facilitates improved neuromuscular function, increased exercise volume, and less metabolic stress compared with 2-minute rest intervals. Thus, 5-minute rest intervals may be more efficacious for promoting muscle hypertrophy and strength gains in a chronic resistance training program.

Exposure to serum from exclusive heated tobacco product smokers induces mTOR activation and fibrotic features in human cardiac stromal cells

Chronic smokers have increased risk of fibrosis-related atrial fibrillation. The use of heated-tobacco products (HTPs) is increasing exponentially, and their health impact is still uncertain. We aim to investigate the effects of circulating molecules in exclusive HTP chronic smokers on the fibrotic behavior of human atrial cardiac stromal cells (CSCs). CSCs were isolated from atrial tissue of elective cardiac surgery patients, and exposed to serum lots from young healthy subjects, stratified in exclusive HTP smokers, tobacco combustion cigarette (TCC) smokers, or nonsmokers (NS). CSCs treated with TCC serum displayed impaired migration and increased expression of pro-inflammatory cytokines. Cells cultured with HTP serum showed increased levels of pro-fibrotic markers, and reduced expression of connexin-43. Both TCC and HTP sera increased collagen release and reduced secretion of angiogenic protective factors from CSCs, compared to NS serum. Paracrine support to tube-formation by endothelial cells and to viability of cardiomyocytes was significantly impaired. Treatment with sera of both smokers groups impaired H2O2/NO release balance by CSCs and reduced early phosphorylation of several pathways compared to NS serum, leading to mTOR activation. Cotreatment with rapamycin was able to reduce mTOR phosphorylation and differentiation into aSMA-positive myofibroblasts in CSCs exposed to TCC and HTP sera. In conclusion, the circulating molecules in the serum of chronic exclusive HTP smokers induce fibrotic behavior in CSCs through activation of the mTOR pathway, and reduce their beneficial paracrine effects on endothelial cells and cardiomyocytes. These results point to a potential risk for cardiac fibrosis in chronic HTP users.

Population study of pupillary unrest in ambient light

IntroductionPupillary unrest in ambient light (PUAL) describes the fluctuation of pupil diameter observed in normal, awake subjects under typical levels of indoor light. PUAL becomes low to absent in young healthy subjects during opioid intoxication. We sought to determine the age-related distribution of PUAL values in a random sample of ambulatory participants. MethodsSubjects ≥18 years of age were recruited. All were identified by age range (18–29, 30–49, 50–69, and ≥70), and surveyed for diabetes, beta-blocker use, and prior 24-hour opioid use. Relationship between mean PUAL, age group, comorbidity and opioid use were examined by Kruskal Wallis test, and PUAL and was modeled using stepwise multilevel linear regression, including diabetes, beta blocker use, prior 24-hour opioid use, autonomic dysfunction, and pupil diameter as fixed effects and subject as random effect. ResultsAmong 150 subjects, 17 reported diabetes, 12 reported beta-blocker use, 14 reported prior 24-hour opioid use, and 120 reported no comorbid conditions. PUAL declined in higher age categories (by 0.0307, P < 0.001), with diabetes (by 0.0481, P = 0.025), and with beta-blocker use (by 0.0616, P = 0.005). Opioid related PUAL decline was observed, but statistical significance varied by model. Among healthy subjects, no PUAL value fell within range indicating high likelihood of opioid toxicity based on previous data from healthy subjects undergoing opioid infusion. ConclusionPUAL declined in higher age groups, diabetes and beta-blocker use, conditions associated with impaired autonomic function, and with opioid use but significance varied depending on the chosen model.