Healthy Young Volunteers Research Articles

Comparison of Four Methods for Measuring Heterophoria and Accommodative Convergence over Accommodation Ratio.

The study aimed to assess the agreement between OptoTab SERIES, alternating Cover Test, Modified Thorington test, and Von Graefe method in measuring heterophoria and accommodative convergence over accommodation (AC/A) ratio. In an initial step, heterophoria was assessed at both distance and near in a cohort of 76 healthy young volunteers using the previously described tests. Subsequently, to determine the AC/A ratio, near-vision measurements were repeated with +1.00 D and -1.00 D lenses. All tests were performed in a randomized order across participants under consistent conditions. Significant differences were found between the Modified Thorington test and all other tests at distance (Wilcoxon test, all p ≤ 0.001) and between Von Graefe and all other tests at near (Wilcoxon test, all p ≤ 0.005). Regarding the AC/A ratio, significant differences were observed between all methods in +1.00 D AC/A ratio, except for the Modified Thorington test vs. the alternating Cover Test (Wilcoxon test, p = 0.024). In the -1.00 D AC/A ratio, differences were observed between OptoTab POCKET and all the other tests (Wilcoxon test, all p ≤ 0.001). The results indicate that all methods are interchangeable except the Modified Thorington test at distance and Von Graefe at near. For the AC/A ratio, only the Modified Thorington test is interchangeable with the alternating Cover Test using +1.00 D lenses and all are interchangeable using -1.00 D lenses except OptoTab POCKET.

Sleep improves accuracy, but not speed, of generalized motor learning in young and older adults and in individuals with Parkinson's disease.

An essential aspect of motor learning is generalizing procedural knowledge to facilitate skill acquisition across diverse conditions. Here, we examined the development of generalized motor learning during initial practice-dependent learning, and how distinct components of learning are consolidated over longer timescales during wakefulness or sleep. In the first experiment, a group of young healthy volunteers engaged in a novel motor sequence task over 36 h in a two-arm experimental design (either morning-evening-morning, or evening-morning-evening) aimed at controlling for circadian confounders. The findings unveiled an immediate, rapid generalization of sequential learning, accompanied by an additional long-timescale performance gain. Sleep modulated accuracy, but not speed, above and beyond equivalent wake intervals. To further elucidate the role of sleep across ages and under neurodegenerative disorders, a second experiment utilized the same task in a group of early-stage, drug-naïve individuals with Parkinson's disease and in healthy individuals of comparable age. Participants with Parkinson's disease exhibited comparable performance to their healthy age-matched group with the exception of reduced performance in recalling motor sequences, revealing a disease-related cognitive shortfall. In line with the results found in young subjects, both groups exhibited improved accuracy, but not speed, following a night of sleep. This result emphasizes the role of sleep in skill acquisition and provides a potential framework for deeper investigation of the intricate relationship between sleep, aging, Parkinson's disease, and motor learning.

Safety, Tolerability, and Pharmacokinetic Profile of the Low‐Impact Ampakine CX1739 in Young Healthy Volunteers

Safety, Tolerability, and Pharmacokinetic Profile of the Low‐Impact Ampakine CX1739 in Young Healthy Volunteers

An Investigational Study on the Role of CYP2D6, CYP3A4 and UGTs Genetic Variation on Fesoterodine Pharmacokinetics in Young Healthy Volunteers.

Introduction: Fesoterodine is one of the most widely used antimuscarinic drugs to treat an overactive bladder. Fesoterodine is extensively hydrolyzed by esterases to 5-hydroxymethyl tolterodine (5-HMT), the major active metabolite. CYP2D6 and CYP3A4 mainly metabolize 5-HMT and are, therefore, the primary pharmacogenetic candidate biomarkers. Materials and Methods: This is a candidate gene study designed to investigate the effects of 120 polymorphisms in 33 genes (including the CYP, COMT, UGT, NAT2, and CES enzymes, ABC and SLC transporters, and 5-HT receptors) on fesoterodine pharmacokinetics and their safety in 39 healthy volunteers from three bioequivalence trials. Results: An association between 5-HMT exposure (dose/weight corrected area under the curve (AUC/DW) and dose/weight corrected maximum plasma concentration (Cmax/DW)), elimination (terminal half-life (T1/2) and the total drug clearance adjusted for bioavailability (Cl/F)), and CYP2D6 activity was observed. Poor/intermediate metabolizers (PMs/IMs) had higher 5-HMT AUC/DW (1.5-fold) and Cmax/DW (1.4-fold) values than the normal metabolizers (NMs); in addition, the normal metabolizers (NMs) had higher 5-HMT AUC/DW (1.7-fold) and Cmax/DW (1.3-fold) values than the ultrarapid metabolizers (UMs). Lower 5-HMT exposure and higher T1/2 were observed for the CYP3A4 IMs compared to the NMs, contrary to our expectations. Conclusions: CYP2D6 might have a more important role than CYP3A4 in fesoterodine pharmacokinetics, and its phenotype might be a better predictor of variation in its pharmacokinetics. An association was observed between different genetic variants of different genes of the UGT family and AUC, Cmax, and CL/F of 5-HMT, which should be confirmed in other studies.

Ocular Accommodative and Pupillary Responses During Fixation on Augmented Reality With a Maxwellian Display.

This study aimed to investigate the changes in ocular refraction and pupillary diameter during fixation on augmented reality (AR) images using a Maxwellian display. Twenty-two healthy young volunteers (average age, 20.7 ± 0.5 years) wore a Maxwellian display device in front of their right eye and fixated on an asterisk displayed on both a liquid-crystal display (real target) and a Maxwellian display (AR target) for 29 seconds (real as a baseline for 3 seconds, AR for 13 seconds, and real for 13 seconds) at distances of 5.0, 0.5, 0.33, and 0.2 meters. A binocular open-view autorefractometer was used to measure the ocular refraction and pupillary diameter of the left eye. Accommodative (5.0 meters, 0.28 ± 0.29 diopter [D]; 0.5 meter, -0.12 ± 0.35 D; 0.33 meter, -0.43 ± 0.57 D; 0.2 meter, -1.20 ± 0.82 D) and pupillary (5.0 meters, 0.07 ± 0.22 mm; 0.5 meter, -0.08 ± 0.17 mm; 0.33 meter, -0.16 ± 0.20 mm; 0.2 meter, -0.25 ± 0.24 mm) responses were negative when the real target distances were farther away. The accommodative response was significantly and positively correlated with the pupillary response during fixation on the AR target (R2 = 0.187, P < 0.001). Fixating on AR images using a Maxwellian display induces accommodative and pupillary responses. Accommodative responses depend on the distance between real objects. Overall, the Maxwellian display does not completely eliminate accommodation in real space.

SARS-COV-2 CORONAVIRUS ANTIGENS MODULATE THE ACTIVITY OF HUMAN T-REGULATORY CELLS

Regulatory T cells (Treg cells) play a crucial role in regulation of immune response. It is believed that excessive activity of Treg cells in the early stages of infectious diseases reduces the pro-inflammatory activity of cells in the innate and adaptive immune response, thereby contributing to the development of chronic inflammation or excessive inflammation. Additionally, it is known that aging leads to changes in the quantity of Treg cells and disrupts their activity. It is established that infection with the SARS-CoV-2 virus leads to fatal and severe cases of the disease, primarily among the elderly population. However, the underlying cause of the development of severe forms in elderly individuals remains incompletely understood. Thus, we hypothesized that the dysregulation of the Treg cell activity in elderly individuals may contribute to the development of severe forms and lethality from SARS-CoV-2, leading to the emergence of hyper inflammation in this population. To investigate the impact of SARS-CoV-2 on the immunosuppressive properties of Treg cells, venous blood samples were obtained from young healthy volunteers and elderly individuals. Dendritic cells were obtained by PBMC adhesion on plastic. Adherent monocytes were cultured in cytokine medium with interleukin 4 (IL-4) and granulocyte-macrophage colony-stimulating factor (GM-SCF), with addition of lipopolysaccharide (LPS) after 48 hours and incubated for an additional 24 hours with S1 or N antigens of SARS-CoV-2 virus. The obtained dendritic cells presenting SARS-CoV-2 antigens were then co-cultured with autologous CD4+-T lymphocytes ex vivo. The expression level of immunosuppressive membrane-associated and soluble molecules expressed by Treg cells was assessed using flow cytometry. Our results indicate that the immunosuppressive activity of Treg cells exhibits contrasting patterns in the two donor groups studied in response to the presentation of SARS-CoV-2 antigens. The proportion of Treg cells, as well as the expression levels of the immunosuppressive molecules, including tumor growth factor beta (TGF-b), CD39, glucocorticoid-induced tumor necrosis factor receptor-related (GITR) protein, and the levels of the intracellular immunosuppressive cytokines, including IL-10 and IL-35, in Treg cells obtained from peripheral blood of elderly donors, significantly increased in response to the presentation of SARS-CoV-2 antigens ex vivo, when compared to the group of young donors. Conversely, in the group of young donors were observed a decrease in the expression of these markers and an increase in the concentration of extracellular pro-inflammatory cytokines IL-2 and IFN-γ ex vivo, which activate the effector immune cells and contribute to virus elimination. In summary, the presented results suggest that Treg cells derived from elderly individuals exhibit elevated immunosuppressive activity in response to SARS-CoV-2 antigens ex vivo. Obtained results may indicate that in elderly individuals on the early stages of SARS-CoV-2 infection Treg cells may also possess enhanced immunosuppressive activity, which may contribute to the overall suppression of anti-viral immune responses, thereby potentially leading to the delayed SARS-CoV-2 virus clearance and development of severe forms of the disease.

Sleepiness may predict hypnotizability, while personality traits do not

ABSTRACT Sleepiness and personality traits have been controversially reported as associated to individual hypnotizability level i.e. receptiveness to hypnotic suggestions and behave accordingly. In this study, we further investigate the relationship between the level of general daytime sleepiness and personality traits with the level of hypnotizability. Seventy-eight healthy young volunteers (34 women) completed the fast assessment of general daytime sleepiness and personality with the Epworth Sleepiness Scale and the 10-item Big Five Inventory respectively, and underwent hypnotic evaluation through the Harvard Group Scale of Hypnotic Susceptibility Form A (HGSHS:A). Main findings revealed a correlation between sleepiness and hypnotizability levels, and no influence of personality traits. Interestingly, women exhibited higher levels of hypnotizability compared to men. Taken together, these results suggest that sleepiness assessment might be considered as a predictive tool to hypnotic suggestions, which would offer practical insight for enhancing hypnosis intervention efficacy.

Forget me not: The effect of doxycycline on human declarative memory

Investigations into neuroprotective drugs are in high demand for the treatment of neurodegenerative diseases, such as multiple sclerosis or Alzheimer's disease, but also psychiatric disorders, such as depression, trauma, and substance use. One potential drug class being investigated are tetracyclines impacting on a variety of neuroprotective mechanisms. At the same time, tetracyclines like doxycycline have been suggested to affect human fear and spatial memory as well as reducing declarative memory retention. Based on the assumed necessity for synaptic consolidation in hippocampus-dependent learning, we hypothesised declarative memory may be similarly impaired by doxycycline as fear and spatial memory. Therefore, in this study we investigate the potential diminishing effects of doxycycline on consolidation of declarative memory in healthy humans. Additionally, to test for effect specificity we assessed motor memory, sustained attention, and processing speed. We administered a neuropsychological test battery in three independent randomized placebo-controlled double-blind trials (RCTs), in which healthy young volunteers (total N = 252) either received a single oral dose doxycycline (200 mg, n = 126) or placebo (n = 126) in a between-subject design. We found no evidence for a detrimental effect of doxycycline on declarative memory; instead, doxycycline improved declarative learning (p-value=0.022, Cohen's d=0.15) and memory consolidation (p=0.040, d=0.26). Contrarily, doxycycline slightly reduced motor learning (p=0.001, d=0.10) but subtly strengthened long-term motor memory (p=0.001, d=0.10). These results suggest that doxycycline can improve declarative learning and memory without having long term negative effects on other cognitive domains in healthy humans. Our results give hope to further investigate doxycycline in neuroprotective treatment applications.

Alignment of behaviour and tDCS stimulation site induces maximum response: evidence from online tDCS and ERP

tDCS modulates the activity of the neuronal networks to induce the desired behavioural changes. Two factors determine its effectiveness- (1) whether the network being stimulated is relevant to the task, and (2) if there is a scope for improvement in behavioral performance. To explore this, both dorsal (sub-lexical) and ventral (lexical) reading networks were stimulated (20 min, 2 mA) in 25 healthy young volunteers. Participants performed two reading tasks with different levels of lexical involvement: word fragment completion tasks (WCT) and word association tasks (WAT), while event-related potentials (ERPs) were recorded simultaneously. The study used a within-subject design over three sessions, comparing various electrode montages targeting the dorsal pathway's left inferior parietal lobule or the ventral reading pathway's left middle temporal lobule, as well as sham stimulation. The impact of tDCS sessions (dorsal, ventral, & sham) and task type (WCT & WAT) on priming effects (primed vs. unprimed) of behavioral performance (accuracy and reaction times), and ERP parameters (N400 amplitudes and latencies) were statistically analyzed.It was found that tDCS modulated the performance of WAT only (a task with a lower priming effect). The failure to modulate WCT (larger priming effect) indicated that tDCS was effective for conditions with room for improvement compared to a task where performance has reached the ceiling. Ventral stimulation enhanced accuracy in the WAT condition and shortened the N400 latency of the priming effect. In contrast, dorsal stimulation delayed the priming effect reaction time in the WAT condition and enhanced the N400 amplitude. To conclude, enhancement in performance due to tDCS occurs when the network (ventral) being stimulated aligns with the cognitive demands of the task and there is a scope for improvement.

Association of macular pigment optical density with plasma macular carotenoids levels and serum lipids in South Indian healthy volunteers and patients with early age-related macular degeneration.

Purpose: The objective of the present study was to investigate the relationship between macular pigment optical density (MPOD) and plasma carotenoids [(L) and (Z)] and serum lipids in South Indian young healthy volunteers and patients with early age-related macular degeneration (AMD). Methods: Two hundred and fourteen (N = 214) study participants (Healthy control group (N) = 178; Early AMD group (N) = 36) were enrolled after getting their written informed consent. The MPOD of the study participants was assessed using MPS II (Electron Technology, UK) after completing their routine ocular examination. Serum lipids were measured by the standard technique. Plasma levels of L, Z, lycopene and beta-carotene were estimated by high performance liquid chromatography with photo diode array detector. Statistical analysis used: Correlations among variables in serum, plasma and the MPOD were established using Spearman's rho correlation coefficient. Results: The overall mean MPOD in healthy control group and early AMD group were found to be 0.47 ± 0.16 (N = 178; 317 eyes) and 0.35 ± 0.22 (N = 36; 38 eyes) at 1° eccentricity respectively and were found to be statistically significant (p < 0.001). A strong positive association was found between plasma L, Z and L + Z and MPOD. Serum HDL showed a strong negative association with MPOD and other lipids showed a very weak association. MPOD was unaffected by body mass index. Conclusions: MPOD is positively associated with plasma L,Z and L + Z, adding further evidence that additional intake of L/Z may be beneficial in delaying the risk of AMD in our population.

Dorsal Anterior Cingulate Cortex Coordinates Contextual Mental Imagery for Single-Beat Manipulation during Rhythmic Sensorimotor Synchronization.

Flexible pulse-by-pulse regulation of sensorimotor synchronization is crucial for voluntarily showing rhythmic behaviors synchronously with external cueing; however, the underpinning neurophysiological mechanisms remain unclear. We hypothesized that the dorsal anterior cingulate cortex (dACC) plays a key role by coordinating both proactive and reactive motor outcomes based on contextual mental imagery. To test our hypothesis, a missing-oddball task in finger-tapping paradigms was conducted in 33 healthy young volunteers. The dynamic properties of the dACC were evaluated by event-related deep-brain activity (ER-DBA), supported by event-related potential (ERP) analysis and behavioral evaluation based on signal detection theory. We found that ER-DBA activation/deactivation reflected a strategic choice of motor control modality in accordance with mental imagery. Reverse ERP traces, as omission responses, confirmed that the imagery was contextual. We found that mental imagery was updated only by environmental changes via perceptual evidence and response-based abductive reasoning. Moreover, stable on-pulse tapping was achievable by maintaining proactive control while creating an imagery of syncopated rhythms from simple beat trains, whereas accuracy was degraded with frequent erroneous tapping for missing pulses. We conclude that the dACC voluntarily regulates rhythmic sensorimotor synchronization by utilizing contextual mental imagery based on experience and by creating novel rhythms.

Creating similar food boluses as that in vivo using a novel in vitro bio-inspired oral mastication simulator (iBOMS-Ⅲ): The cases with cooked rice and roasted peanuts

Food bolus is the major outcome of oral processing of foods. Its structure and properties are crucial for safe swallowing and subsequent gastric digestion. However, collecting the ready-to-swallow bolus for further analysis in either normal or deficient human subjects is difficult, regulatorily or practically. Here, a novel in vitro bio-inspired oral mastication simulator (iBOMS-Ⅲ) was developed to be capable of replicating food boluses comparable to those in vivo. Cooked rice and roasted peanuts were used as the model foods (soft and hard) respectively. Particle size distribution, moisture content and rheology of the food boluses produced in the iBOMS-Ⅲ were assessed. A conventional food blender was also employed as a non-consequential comparation. Eighteen healthy young volunteers of the ages from 20-30 years (10 male and 8 female) were invited to provide the in vivo data. For cooked rice boluses produced by the iBOMS-Ⅲ with 10, 12, 14, and 20 chewing number of cycles, the moisture content exhibited minimal variation (68.3–68.8 wt%), aligning closely with values obtained from the average value of the human subjects (67.5 wt%). Similarly, the boluses from roasted peanut displayed similar moisture contents across masticatory number of cycles (36, 40, and 44 number of cycles), averaging at 35.3 %, mirroring the average in vivo results (33.8 wt%). Furthermore, the shear viscosity of both cooked rice and roasted peanut boluses exhibited minimal variations with iBOMS-Ⅲ chewing number of cycles. The particle size distributions of the boluses produced with 14 and 44 chewing number of cycles matched well with the in vivo data for cooked rice and roasted peanuts, with median particle size (d50) being 1.07 and 0.78 mm, respectively. The physical properties of the food boluses collected from the food blender, with varying grinding times, differed significantly. This study demonstrates the value of the iBOMS-Ⅲ in achieving realistic boluses with two very different food textures.

Hyperpolarized 129Xe MRI and spectroscopy of gas-exchange abnormalities in bilateral lung transplant recipients

BACKGROUNDThere is currently no sensitive, non-invasive method of screening for chronic lung allograft dysfunction (CLAD), the primary barrier to long-term survival after lung transplant. Conventional pulmonary function testing is imprecise absent a sustained decline. Hyperpolarized 129Xe MRI is a sensitive tool for 3D imaging of regional pulmonary ventilation and gas exchange abnormalities and may aid in early detection of CLAD. METHODSAdult patients post bilateral lung transplant were screened for CLAD based on the ISHLT criteria. Those with established allografts (n=10) underwent 129Xe gas exchange MRI and spectroscopy and were compared to results from 16 young healthy volunteers and 16 age-matched healthy volunteers. One lung transplant recipient was excluded from final data analysis due to a concurrent lung infection found incidentally after MRI. Imaging provided quantitative maps of the ventilation defect percent (VDP), membrane high percent, and RBC defect percent. Spectroscopy yielded RBC/membrane ratio, oxygenation-dependent RBC shift, and RBC oscillation amplitude. RESULTSThe analysis included nine lung transplant recipients, seven with CLAD and two without. CLAD patients exhibited VDP values consistent with their FEV1 decline (rho=0.79, p=0.048). Hemoglobin-corrected RBC transfer was reduced in all transplant recipients vs. young healthy controls (median [first quartile–third quartile] of 13% [9%-22%] vs 2% [1.75%-3%], P=0.003) as well as vs. age-matched controls (5.5% [2% - 9.25%], p=0.039). Spectroscopy demonstrated reduced RBC/membrane signal (0.26 [0.17-0.31] vs. 0.62 [0.50-0.66], p< 0.001 and vs. 0.48 [0.42-0.55], p = 0.002), reduced RBC chemical shift (217.4 [217.2-217.7]ppm vs 218.2 [218.0-218.5]ppm, p=0.009 and vs. 218.3 [218.2-218.5]ppm, p=0.003), and increased RBC oscillation amplitude vs. the young healthy controls (14.1% [12.2%-16.4%] vs 11.1% [9.9%-11.9%], p=0.003). CONCLUSIONSPatients with CLAD exhibited significant ventilation defects that correlated with FEV1 decline, that, along with RBC transfer defects and other 129Xe gas exchange and hemodynamic abnormalities, could provide a promising means of early detection of physiological changes in patients with CLAD.

Vago-splenic signal transduction of cardioprotection in humans.

The spleen serves as an important relay organ that releases cardioprotective factor(s) upon vagal activation during remote ischaemic conditioning (RIC) in rats and pigs. The translation of these findings to humans was attempted. Remote ischaemic conditioning or electrical auricular tragus stimulation (ATS) were performed in 10 healthy young volunteers, 10 volunteers with splenectomy, and 20 matched controls. Venous blood samples were taken before and after RIC/ATS or placebo, and a plasma dialysate was infused into isolated perfused rat hearts subjected to global ischaemia/reperfusion. Neither left nor right RIC or ATS altered heart rate and heart rate variability in the study cohorts. With the plasma dialysate prepared before RIC or ATS, respectively, infarct size (% ventricular mass) in the recipient rat heart was 36 ± 6% (left RIC), 34 ± 3% (right RIC) or 31 ± 5% (left ATS), 35 ± 5% (right ATS), and decreased with the plasma dialysate from healthy volunteers after RIC or ATS to 20 ± 4% (left RIC), 23 ± 6% (right RIC) or to 19 ± 4% (left ATS), 26 ± 9% (right ATS); infarct size was still reduced with plasma dialysate 4 days after ATS and 9 days after RIC. In a subgroup of six healthy volunteers, such infarct size reduction was abrogated by intravenous atropine. Infarct size reduction by RIC or ATS was also abrogated in 10 volunteers with splenectomy, but not in their 20 matched controls. In humans, vagal innervation and the spleen as a relay organ are decisive for the cardioprotective signal transduction of RIC and ATS.

Quantitative Assessment of True Vocal Fold Movement by the Lateral-Approach Laryngeal Ultrasonography: A Pilot Study

Background/ObjectivesUltrasonography is a new method for subjective and qualitative assessment of true vocal fold movement, and true vocal fold visualization with the lateral approach could be better than that with the anterior approach. Our aim was to explore the feasibility of the lateral-approach ultrasonography in objective and quantitative assessment of true vocal fold movement. MethodsThe lateral-approach laryngeal ultrasonography was performed during calm breathing and breath-holding in young healthy adult volunteers. The morphology and anatomical position of false vocal fold, true vocal fold and arytenoid cartilage were observed and measured through the ultrasonic self-contained measurement function. All parameters, including the distance from false vocal fold to thyroid cartilage lamina, true vocal fold length, and the distance from true vocal fold to thyroid cartilage lamina, were obtained at the end of the calm inspiratory and breath-holding phases. Data were analyzed using a t test (P <0.05). ResultsForty healthy adult volunteers (age 20-34 years, Body Mass Index 19.5-23.8 kg/m2, 20 males and 20 females) with satisfactory ultrasonic images were included in the study. There were no significant differences in all laryngeal parameters between the left and right sides in either phase (P > 0.05). From the end of the calm inspiratory phase to the breath-holding phase, changes in all laryngeal parameters were significantly different (P < 0.05), regardless of gender. ConclusionsThis study demonstrated that the lateral-approach laryngeal ultrasonography seemed feasible to quantify and objectively assess true vocal fold movement, utilizing differences between laryngeal parameters before and after true vocal fold movement.

3D motion analysis dataset of healthy young adult volunteers walking and running on overground and treadmill

Used on clinical and sportive context, three-dimensional motion analysis is considered as the gold standard in the biomechanics field. The proposed dataset has been established on 30 asymptomatic young participants. Volunteers were asked to walk at slow, comfortable and fast speeds, and to run at comfortable and fast speeds on overground and treadmill using shoes. Three dimensional trajectories of 63 reflective markers, 3D ground reaction forces and moments were simultaneously recorded. A total of 4840 and 18159 gait cycles were measured for overground and treadmill walking, respectively. Additionally, 2931 and 18945 cycles were measured for overground and treadmill running, respectively. The dataset is presented in C3D and CSV files either in raw or pre-processed format. The aim of this dataset is to provide a complete set of data that will help for the gait characterization during clinical gait analysis and in a sportive context. This data could be used for the creation of a baseline database for clinical purposes to research activities exploring the gait and the run.

Gum Arabic Increases Phagocytosis of Escherichia coli by Blood Leukocytes of Young and Old Healthy Volunteers.

Gum arabic, a polysaccharide exudate from Acacia senegal (L.) Willdenow trees, has already been used by African native people in natural medicine. Using whole-blood samples from young (20-35 years) and older (>80 years) healthy volunteers (each group n = 10), the effect of an aqueous solution of GA on phagocytosis of Escherichia coli was examined with a gentamicin protection assay. Whole-blood samples of each volunteer were stimulated with GA and as a control with CpG oligodeoxynucleotides (Toll-like receptor -9 agonists) for 2 h, then co-incubated with E. coli for 30 min and thereafter treated with gentamicin for up to 240 min to kill extracellular bacteria. Then, whole-blood cells were lysed with distilled water, and colony-forming units were counted by quantitative plating. Cytokine enzyme-linked immunosorbent assay for the detection of TNF-α and IL-6 was performed using the blood supernatant. The GA concentration tested (20 mg/mL) did not affect the viability of eukaryotic cells. Phagocytosis of E. coli by whole-blood leukocytes derived from young (p = 0.008) and older (p = 0.004) healthy volunteers was increased by 120.8% (young) and 39.2% (old) after stimulation with GA. In contrast, CpG only stimulated the bacterial phagocytosis by cells derived from young volunteers (p = 0.004). Stimulation of whole blood with GA increased the intracellular killing of E. coli in young (p = 0.045) and older volunteers (p = 0.008) and induced a TNF-α release in whole blood collected from older volunteers but not from younger ones (p = 0.008). These data encourage the isolation of active compounds of GA and the initiation of clinical trials addressing the preventive effect of GA on bacterial infections.

Assessment of Dynamic Cerebral Autoregulation During Long-Term Exposure to High Altitude in Normal Subjects by Ultrasonography.

To evaluate changes in dynamic cerebral autoregulation (CA) during short-term and long-term exposure to high altitude with ultrasonography, and also study the sex differences in the response of CA to altitude. We assessed the differences in dynamic CA and measured with Doppler ultrasound of the bilateral internal carotid artery (ICA), vertebral artery (VA), and middle cerebral artery (MCA) and the values of basic information within 48 hours and at 2 years after arrival at Tibet in 65 healthy Han young Chinese volunteers, meanwhile, we compared the resistance index (RI) and pulsatility index (PI) of the right MCA at inhale oxygen 8 minutes when a newcomer with 2 years after arrival at Tibet. With 2 years of altitude exposure, the SaO2 of all subjects was above 90%, the mean PEF, DAP, and HR values decreased, HGB increased compared within 48 hours in same-gender groups. Comparisons of cerebral hemodynamics between before 2 years and after 2 years within male and female groups, the mean RI and PI values of bilateral MCA after 2 years were significantly higher than before 2 years, at the same time, the mean RI and PI values of bilateral ICA were significant differences (P < .05) between male groups, with regard to female groups, showed that the mean RI and PI values of bilateral VA were significant differences (P < .05). Comparisons of Right MCA hemodynamics between after oxygen uptake 8 minutes and 2 years, the mean RI and PI values were no significant difference within male and female groups (P > .05). Acute mountain sickness could result from an alteration of dynamic autoregulation of cerebral blood flow, but the impaired autoregulation may be corrected with the extension of time, furthermore, the response of CA to altitude in males and females are different.

Effect of Right Nostril Breathing on Cardiorespiratory Parameters and Reaction Time in Young, Healthy Humans: An Interventional Study.

Yogic breathing helps in reduction of stress and strain in the body. Right and left nostril breathings (RNB and LNB, respectively) have different effects on cardiorespiratory parameters. The study was performed to examine the effect of RNB exercise on cardiorespiratory parameters and reaction time in young, healthy human volunteers. In this prospective, interventional study, 110 young healthy volunteers underwent systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse rate (PR), respiratory rate (RR), vital capacity (VC), peak expiratory flow rate (PEFR), and reaction time (RT) examination before and after 2 weeks of performing 45 min of RNB exercise daily. There was notable increment in SBP (113.39 ± 17.72 vs. 117.74 ± 10.83 mmHg, P = 0.002) and DBP (67.64 ± 10.32 vs. 71.27 ± 8.68 mmHg, P = 0.002). PR increased nonsignificantly (86.44 ± 12.65/min vs. 87.32 ± 13.43/min, P = 0.476). Significant decrease in RR (14.40 ± 2.48/min vs. 12.31 ± 2.23/min, P < 0.0001) was observed. VC (3.57 ± 0.57 vs. 3.82 ± 0.55 L/min, P < 0.0001) and PEFR (441.36 ± 50.22 vs. 468.91 ± 53.66 L/min, P < 0.0001) also increased significantly. Substantial reduction in auditory reaction time (ART) (165.58 ± 32.18 vs. 147.42 ± 23.39 ms, P < 0.0001) and visual reaction time (VRT) (191.04 ± 37.94 vs. 165.86 ± 28.74 ms, P < 0.0001) was seen. After engaging in cardiorespiratory exercise, the maximal heart rate (MHR) remained unchanged (P = 0.929). RNB results in increase in blood pressure, heart rate, VC, and PEFR and decrease in ART and VRT. Further studies in patients with cardiorespiratory diseases are necessary to understand its clinical utility.

First-in-human controlled inhalation of thin graphene oxide nanosheets to study acute cardiorespiratory responses

Graphene oxide nanomaterials are being developed for wide-ranging applications but are associated with potential safety concerns for human health. We conducted a double-blind randomized controlled study to determine how the inhalation of graphene oxide nanosheets affects acute pulmonary and cardiovascular function. Small and ultrasmall graphene oxide nanosheets at a concentration of 200 μg m−3 or filtered air were inhaled for 2 h by 14 young healthy volunteers in repeated visits. Overall, graphene oxide nanosheet exposure was well tolerated with no adverse effects. Heart rate, blood pressure, lung function and inflammatory markers were unaffected irrespective of graphene oxide particle size. Highly enriched blood proteomics analysis revealed very few differential plasma proteins and thrombus formation was mildly increased in an ex vivo model of arterial injury. Overall, acute inhalation of highly purified and thin nanometre-sized graphene oxide nanosheets was not associated with overt detrimental effects in healthy humans. These findings demonstrate the feasibility of carefully controlled human exposures at a clinical setting for risk assessment of graphene oxide, and lay the foundations for investigating the effects of other two-dimensional nanomaterials in humans. Clinicaltrials.gov ref: NCT03659864.