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Transcranial direct current stimulation (tDCS) has been investigated as a way of improving motor learning. Our purpose was to explore the reversal bilateral tDCS effects on manual dexterity training, during five days, with the retention component measured after 5 days to determine whether somatosensory effects were produced. In this randomized, triple-blind clinical trial, 28 healthy subjects (14 women) were recruited and randomized into tDCS and placebo groups, although only 23 participants (13 women) finished the complete protocol. Participants received the real or placebo treatment during five consecutive days, while performing a motor dexterity training program of 20 min. The motor dexterity and the sensitivity of the hand were assessed pre- and post-day 1, post 5 days of training, and 5 days after training concluded. Training improved motor dexterity, but tDCS only produced a tendency to improve retention. The intervention did not produce changes in the somatosensory variables assessed. Thus, reversal bi-tDCS had no effects during motor learning on healthy subjects, but it could favor the retention of the motor skills acquired. These results do not support the cooperative inter-hemispheric model.

This pilot study aimed at implementing a new food picture database in the context of functional magnetic resonance imaging (fMRI) cognitive food-choice task, with an internal conflict or not, in healthy normal-weight adults. The database contains 170 photographs including starters, main courses, and desserts; it presents a broad-spectrum of energy content and is provided with portion weight and nutritional information. It was tested in 16 participants who evaluated the energy density and gave a liking score for all food pictures via numerical scales. First, volunteers were segregated into two groups according to their eating habits according to a food consumption frequency questionnaire (FCFQ) to assess whether the database might elicit different appreciations according to individual eating habits. Second, participants underwent fMRI cognitive food-choice task (van der Laan et al., 2014), using our picture database, in which they had to choose between high-energy (HE) and low-energy (LE) foods, under a similar liking (SL, foods with similar hedonic appraisals) condition or a different liking (DL, foods with different hedonic appraisals) condition. Participants evaluated correctly the caloric content of dishes (from r = 0.72 to r = 0.79, P < 0.001), confirming a good perception of the caloric discrepancies between food pictures. Two subgroups based on FCFQ followed by a principal component analysis (PCA) and a hierarchical ascendant classification (HAC) were defined, that is, Prudent-type (PTc, N = 9) versus Western-type (WTc, N = 7) consumers, where the WTc group showed higher consumption of HE palatable foods than PTc (P < 0.05). The WTc group showed a higher correlation between liking and caloric evaluation of the food pictures as compared to PTc (r = 0.77 and r = 0.36, respectively, P < 0.001), confirming that food pictures elicited variable responses according to contrasted individual eating habits. The fMRI analyses showed that the DL condition elicited the activation of dorsal anterior cingulate cortex (dACC), involved in internal conflict monitoring, whereas SL condition did not, and that LE food choice involved high-level cognitive processes with higher activation of the hippocampus (HPC) and fusiform gyrus compared to HE food choice. Overall, this pilot study validated the use of the food picture database and fMRI-based procedure assessing decision-making processing during a food choice cognitive task with and without internal conflict. [ABSTRACT FROM AUTHOR]

This study's aim was to evaluate the safety of daily consumption of Kaempferia parviflora extract (KPE) using a randomized double-blind placebo-controlled study with 52 recruited healthy Japanese subjects. Each subject received five KPE tablets (containing 150 mg of KPFORCE™/tablet) or placebo daily for 4 weeks. There were no adverse events related to KPE intake or any abnormalities compared with placebo group in anthropometric, cardiovascular, blood, and urine parameters during the course of the study. Thus, daily KPE ingestion was found to be safe in healthy Japanese men and women. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the PK and safety of siponimod, a substrate of CYP2C9/3A4, in the presence or absence of a CYP3A4 inhibitor, itraconazole. Methods: This was an open-label study in healthy subjects (aged 18–50 years; genotype: CYP2C9 *1*2 [cohort 1; n = 17] or *1*3 [cohort 2; n = 13]). Subjects received siponimod 0.25-mg single dose in treatment period 1 (days 1–14), itraconazole 100 mg twice daily in treatment period 2 (days 15–18), and siponimod 0.25-mg single dose (day 19) with itraconazole until day 31 (cohort 1) or day 35 (cohort 2) in treatment period 3. PK of siponimod alone and with itraconazole and safety were assessed. Results: Overall, 29/30 subjects completed the study. In treatment period 1, geometric mean AUCinf, T1/2, and median Tmax were higher while systemic clearance was lower in cohort 2 than cohort 1. In treatment period 3, siponimod AUC decreased by 10% (geo-mean ratio [90% confidence intervals]: 0.90 [0.84; 0.96]) and 24% (0.76 [0.69; 0.82]) in cohorts 1 and 2, respectively. Siponimod Cmax was similar between treatment periods 1 and 3. In both cohorts, the Cmax and AUC of the metabolites (M17, M3, and M5) decreased in the presence of itraconazole. All adverse events were mild. Conclusions: The minor albeit significant reduction in plasma exposure of siponimod and its metabolites by itraconazole was unexpected. While the reason is unclear, the results suggest that coadministration of the two drugs would not cause a considerable increase of siponimod exposure independent of CYP2C9 genotype. [ABSTRACT FROM AUTHOR]

Problem Statement. In present, the study of the cardiovascular effects of the exposure of the body to various positions during inversion therapy represents a challenging research topic. Purpose. To investigate the peripheral hemodynamic effects of the successive exposure of the body to positions specific to the use of the inversion table during physical therapy sessions. Methods. We realized a prospective observational study on a group of 20 young adults (9 women and 11 men, mean age 28.1 ± 10.10 years). For each subject, we repeatedly determined the blood pressure and pulse rate in three successive positions on an inversion table, in the following order: vertical orthostatic position, supine horizontal position and vertical Trendelenburg position. Results. We revealed a specific pattern of the dynamics of the cardiovascular variables, which as a whole indicates the slight average decrease of pulse rate, systolic blood pressure, diastolic blood pressure, mean blood pressure and a slight increase of ratio between systolic and diastolic blood pressure and of the pressure difference between high and low blood pressure, between the three measurements done. The protocol of changing 3 different postures elicits a statistically significant influence in all parameters, excepted SBP, for certain combinations of comparison of mean scores (p < 0.05). Conclusions. The results of our study demonstrated that the adoption of extreme positions in relation to the gravitational field definitely influences the human body in terms of the investigated cardiovascular parameters. [ABSTRACT FROM AUTHOR]

Introduction: Major depressive disorder (MDD) is associated with a significant burden of disease in China. Awareness and better access to treatments could help alleviate the burden associated with MDD. Because variations have been observed in the pharmacokinetics (PK) of antidepressants across different races and ethnicities, evaluation of the clinical pharmacology of vortioxetine in diverse populations remains important to assess the potential need for dose adjustments.Methods: Data were pooled from two phase I open-label PK studies in healthy Chinese subjects, and one phase III double-blind noninferiority study in Chinese patients with MDD to describe the PK and safety data for vortioxetine. Doses in these studies ranged from 10 mg (single dose) to 10 and 20 mg (multiple daily doses). A population PK analysis of vortioxetine in the Chinese population was conducted using nonlinear mixed-effect modeling.Results: In total, 186 individuals were included in the PK analysis: 79 healthy Chinese subjects and 107 Chinese patients with MDD. No clinically significant differences in the PK of vortioxetine were observed between the Chinese population and the previous data in non-Chinese populations. Because of a generally lower weight in the Chinese population compared with the non-Chinese population, exposures were 19% and 18% higher in the Chinese population than in the non-Chinese population (for maximum observed plasma concentration and area under the plasma concentration-time curve, respectively), which is not considered clinically relevant. A high prevalence of pruritus was observed in one phase I PK study (56% overall); however, this was not reflected in the phase III study in Chinese patients with MDD (0.8%).Conclusions: The PK parameters of vortioxetine in Chinese subjects were comparable to previous data in non-Chinese subjects. Overall, no new safety concerns were raised among the Chinese population. On the basis of this analysis, the tolerability profile of vortioxetine in Chinese healthy subjects and in patients with MDD is expected to be comparable to that in the non-Chinese population.Funding: H. Lundbeck A/S, Valby, Denmark.Trial Registration: NCT01676571. [ABSTRACT FROM AUTHOR]

BACKGROUND: Assessment of local condition specific outcome measures in combination to obtain an idea about the disability status of the whole spine is a conventional method. Oswestry Disability Index (ODI) and Neck Disability Index (NDI) are two outcome measures used together. Test re-test reliability of ODI in healthy subjects has clinical importance and the test re-test reliability of NDI may have clinical significance. OBJECTIVE: The purpose of this study is to investigate the test re-test reliability of the NDI by using long-term test re-test reliability method of ODI on healthy office workers. METHODS: Participants who have no chronic neck pain history were included in the study. Subjects were assessed by the Turkish-NDI (e-forms) on 1st, 2nd, 4th, 8th, 15th, 30th days. 49 (20 female, 29 male) of 106 participants (57 female, 49 male) completed the study. Kolmogorov-Smirnov and Friedman tests were used. RESULTS: The difference between median score of each day (χ= 9.275, p > 0.05) was neither statistically nor clinically significant. CONCLUSIONS: NDI has test re-test reliability in healthy subjects over a 1-month time interval and the test re-test reliability is also valid in cases where both questionnaires are used in combination in this time interval. [ABSTRACT FROM AUTHOR]

Background: Myocardial work (MW) estimation by pressure‐strain loops (PSL) allows the non‐invasive assessment of myocardial performance. Aim of this study is to provide the reference values for global myocardial work index (WI), constructive work (CW), wasted work (WW), and work efficiency (WE) in a group of healthy volunteers accounting for age and gender. Methods and results: 2D standard and speckle‐tracking echocardiography were performed in 115 healthy volunteers (median age 36.3 [18–69] years, males: 67%). PSLs were used to assess MW. Mean ± standard deviation or median and inter‐quartile range, 5° and 95° percentile values for global myocardial WI, CW, WW, and WE in the whole population were 1926 ± 247 mm Hg, (1534–2356); 2224 ± 229 mm Hg, (1894–2647); 90 (61–123) mm Hg%, (38–195); and 96 (94–97)%, (91–98), respectively. Global WI (2031 ± 247 vs 1874 ± 232 mm Hg%, P = .001) and global CW (2289 ± 261 vs 2194 ± 207 mm Hg%, P = .04) were higher in women than in men. Age did not affect MW parameters. The segmental analysis showed that myocardial WI, CW, and WE were lower in the left ventricular basal segments than in the apex. The apex‐to‐base gradient was inverted for WW (all P < .0001). Conclusions: The assessment of MW is feasible in normal subjects. The presented referral ranges of global myocardial WI, CW, WW, and WE were not affected by age. An apex‐to‐base gradient was observed for all MW parameters. Nevertheless, the wide variability of MW parameters prevents for the moment the application of this technique in the routine clinical setting. [ABSTRACT FROM AUTHOR]

Introduction: Inhalation of copper and zinc containing brazing fumes (2.5 mg/m³ for 6 hours) is able to induce asymptomatic systemic inflammation which is supposed to be connected with an increased risk for cardiovascular disease. In this study it was investigated if inflammation can be prevented by reducing the exposure time. Methods: A total of 15 healthy male subjects were exposed to such brazing fumes in a crossover design for 3, 4, and 5 hours in randomized order. Before and 24 hours after exposure, blood samples were taken and c-reactive protein (CRP) as marker for an acute phase reaction was measured. Results: Five-hour exposure induced an increase of CRP, whereas the shorter exposure times did not result in a significant inflammatory reaction. Conclusions: Reducing daily exposure times below 5 hours is able to prevent systemic inflammatory reactions. [ABSTRACT FROM AUTHOR]

Chiglitazar (CHI) is a potent and selective peroxisome proliferator‐activated receptor potentially for the treatment of patients with type 2 diabetes mellitus (T2DM). An open‐label, randomized, 3‐period crossover and self‐controlled study was conducted to investigate drug‐drug interaction potential between CHI and metformin hydrochloride (MET). Eligible subjects received a single oral dose of CHI (48 mg), MET (1000 mg), or a combination in each period, followed by serial blood sampling collected for up to 48 hours postdose, and safety was assessed throughout the trial. The area under the plasma concentration‐time curves from time 0 to 48 hours (AUC0‐48 h) of CHI was similar following administration alone or with MET (AUC0‐48h, 12 540 ng·h/mL [9811‐15 269 ng·h/mL] vs 12 130 ng·h/mL [9304‐14 956 ng·h/mL]; 90% confidence interval [CI] of its geometric mean ratio [GMR], 89.7%–103.8%), whereas the maximum concentration (Cmax) of CHI was reduced during coadministration, as its 90%CI of the GMR was slightly outside the acceptance range for bioequivalence (Cmax, 1620 ng/mL [1418‐1822 ng/mL] vs 1420 ng/mL [1049‐1791 ng/mL], 90%CI GMR, 77.%‐94.1%). However, it was not considered clinically meaningful. The MET exposures remained consistent in the absence or presence of CHI (AUC0‐48 h, 12 570 ng·h/mL [10681‐14 459 ng·h/mL] vs 13 190 [10973‐15 407 ng·h/mL); 90%CI of GMR: 99.1%‐110.5%; Cmax, 1790 ng/mL [1448–2132 ng/mL] vs 1820 ng/mL [1510‐2130 ng/mL]; 90%CI of GMR, 94.2%–110.9%). No moderate to severe adverse events were reported. Our study indicated no clinically significant pharmacokinetic drug‐drug interaction between CHI and MET and demonstrated good tolerance in subjects. These results support future application of CHI in combination with MET for treatment of T2DM. [ABSTRACT FROM AUTHOR]

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Impulsivity as a trait modulates a range of cognitive functions, e.g. planning, decision-making, or response inhibition. Recent behavioural and psychometric findings challenge both the neurobiological models as well as the conceptualisation of psychometric measures of impulsivity. In the present study, we aimed to test the association of brain structure with the Barratt Impulsiveness Scale (BIS-11), a commonly applied self-rating instrument for impulsivity, using both the classical three-factor-model for impulsive behaviour (motor (IM), attentional (IA) and non-planning impulsivity (INP)), as well as the recently proposed alternative model contrasting inability to wait for reward (IWR) as an index of impulsive choice and rapid response style (RRS) as an index of impulsive action. We analysed brain structural data in a community sample of 85 healthy individuals, who completed the BIS-11, using voxel-based morphometry (CAT12: Computational Anatomy Toolbox 12). Regional volumes were correlated with the three traditional BIS-11 subscales, as well as IWR and RRS. BIS-11 total score was positively correlated with right inferior parietal, postcentral, and supramarginal grey matter (p < 0.05, FWE cluster-level corrected). Attentional impulsivity (IA) was also positively correlated with right inferior and superior parietal and supramarginal gyri. Comparison of the other scales did show some divergence, but most correlations did not survive correction for multiple comparisons. Our findings suggest that difference facets of trait impulsivity might be related to different brain areas, and might thus dissociate along distinct but overlapping neural networks. In contrast to lesion or patient studies, these analyses delineate physiological variance, and can thus help to conceptualise network models in the absence of pathology. • Trait impulsivity is associated with brain structural variation in healthy subjects. • Conceptualisation of trait impulsivity impacts on regional associations. • Impulsive choice is related to inferior parietal and superior temporal cortices. • Credit author statement. [ABSTRACT FROM AUTHOR]

Background The high-fat ketogenic diet (KD) has become an increasingly popular diet not only in overweight/obese populations, or those with clinical conditions, but also in healthy non-overweight populations. Objective Because there are concerns about the association between high-fat diets and cognitive decline, this study aimed to determine the effects of a KD compared with an isocaloric high-carbohydrate, low-fat (HCLF) diet on cognitive function, sleep, and mood in healthy, normal-weight individuals. Methods Eleven healthy, normal-weight participants (mean age: 30 ± 9 y) completed this randomized, controlled, crossover study. Participants followed 2 isocaloric diets—an HCLF diet (55% carbohydrate, 20% fat, and 25% protein) and a KD (15% carbohydrate, 60% fat, and 25% protein)—in a randomized order for a minimum of 3 wk, with a 1-wk washout period between diets. Measures of β-hydroxybutyrate confirmed that all participants were in a state of nutritional ketosis during post-KD assessments (baseline: 0.2 ± 0.2 mmol/L; KD: 1.0 ± 0.5 mmol/L; washout: 0.2 ± 0.1 mmol/L; and HCLF: 0.3 ± 0.2 mmol/L). Cognitive function was assessed using a validated, psychological computer-based test battery before and after each diet. Subjective measures of mood and sleep were also monitored throughout the study using validated scales. Results Three weeks of sustained nutritional ketosis, compared with the HCLF diet, had no effect on speed and accuracy responses in tasks designed to measure vigilance (speed: P  = 0.39, Cohen's d  = 0.26; accuracy: P  = 0.99, Cohen's d  = 0.04), visual learning and memory (speed: P  = 0.99, Cohen's d  = 0.04; accuracy: P  = 0.99, Cohen's d  = 0.03), working memory (speed: P  = 0.62, Cohen's d  = 0.26; accuracy: P  = 0.98, Cohen's d  = 0.07), and executive function (speed: P  = 0.60, Cohen's d  = 0.31; accuracy: P  = 0.90, Cohen's d  = 0.19). Likewise, mood, sleep quality, and morning vigilance did not differ (P  > 0.05) between the dietary interventions. Conclusion The results of our randomized, crossover, controlled study suggest that 3 wk of sustained nutritional ketosis had no effect on cognitive performance, mood, or subjective sleep quality in a sample of healthy individuals. This trial was registered in the Pan African Clinical Trial Registry as PACTR201707002406306. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to evaluate the acute effects of different inspiratory loads and different interfaces on the breathing pattern and activity of the respiratory muscles. Methods: Twenty healthy adults were recruited and assigned to two groups (20 and 40% of the Maximal Inspiratory Pressure) by way of randomized crossover allocation. Subjects were evaluated during quiet breathing, breathing against inspiratory load, and recovery. The measurements were repeated using two different interfaces (nasal and oral). Chest wall volumes and respiratory muscle activity were assessed with optoelectronic plethysmography and surface electromyography, respectively. Results: During the application of inspiratory load, significant changes were observed in the respiratory rate (p < 0.04), inspiratory time (p < 0.02), minute ventilation (p < 0.04), tidal volume (p < 0.01), end-inspiratory volume (p < 0.04), end-expiratory volume (p < 0.03), and in the activity of the scalene, sternocleiomastoid, and parasternal portion of the intercostal muscles (RMS values, p < 0.01) when compared to quiet breathing, regardless of the load level or the interface applied. Inspiratory load application yielded significant differences between using nasal and oral interfaces with an increase in the tidal volume (p < 0.01), end-inspiratory volume (p < 0.01), and electrical activity of the scalene and sternocleiomastoid muscles (p < 0.01) seen with using the nasal interface. Conclusion: The addition of an inspiratory load has a significant effect on the breathing pattern and respiratory muscle electrical activity, and the effects are greater when the nasal interface is applied. [ABSTRACT FROM AUTHOR]

Neural processing of speech production has been traditionally attributed to the left hemisphere. However, it remains unclear if there are structural bases for speech functional lateralization and if these may be partially explained by sexual dimorphism of cortical morphology. We used a combination of high-resolution MRI and speech-production functional MRI to examine cortical thickness of brain regions involved in speech control in healthy males and females. We identified greater cortical thickness of the left Heschl's gyrus in females compared to males. Additionally, rightward asymmetry of the supramarginal gyrus and leftward asymmetry of the precentral gyrus were found within both male and female groups. Sexual dimorphism of the Heschl's gyrus may underlie known differences in auditory processing for speech production between males and females, whereas findings of asymmetries within cortical areas involved in speech motor execution and planning may contribute to the hemispheric localization of functional activity and connectivity of these regions within the speech production network. Our findings highlight the importance of consideration of sex as a biological variable in studies on neural correlates of speech control. [ABSTRACT FROM AUTHOR]

Simian virus 40 (SV40) is a small DNA tumor virus of monkey origin. This polyomavirus was administered to human populations mainly through contaminated polio vaccines, which were produced in naturally infected SV40 monkey cells. Previous molecular biology and recent immunological assays have indicated that SV40 is spreading in human populations, independently from earlier SV40-contaminated vaccines. SV40 DNA sequences have been detected at a higher prevalence in specific human cancer specimens, such as the brain and bone tumors, malignant pleural mesotheliomas, and lymphoproliferative disorders, compared to the corresponding normal tissues/specimens. However, other investigations, which reported negative data, did not confirm an association between SV40 and human tumors. To circumvent the controversies, which have arisen because of these molecular biology studies, immunological researches with newly developed indirect ELISA tests were carried out in serum samples from patients affected by the same kind of tumors as mentioned above. These innovative indirect ELISAs employ synthetic peptides as mimotopes/specific SV40 antigens. SV40 mimotopes do not cross-react with the homologous human polyomaviruses, BKPyV, and JCPyV. Immunological data obtained from indirect ELISAs, using SV40 mimotopes, employed to analyze serum samples from oncological patients, have indicated that these sera had a higher prevalence of antibodies against SV40 compared to healthy subjects. The main data on (i) the biology and genetics of SV40; (ii) the epidemiology of SV40 in the general population, (iii) the mechanisms of SV40 transformation; (iv) the putative role of SV40 in the onset/progression of specific human tumors, and (v) its association with other human diseases are reported in this review. [ABSTRACT FROM AUTHOR]

Case-control studies in major depression have established patterns of regional gray matter loss, including the hippocampus, which might show state-related effects dependent on disease stage. However, there is still limited knowledge on compensation effects that might occur in people resilient to depression showing only subclinical symptoms. We used voxel-based morphometry on a multicenter data set of 409 healthy nonclinical subjects to test the hypothesis that local hippocampal volume would be inversely correlated with subclinical depressive symptoms [Symptom Checklist 90-Revised (SCL-90-R) depression scores]. Our region-of-interest results show a significant (p = 0.042, FWE cluster-level corrected) positive correlation of SCL-90-R scores for depression and a left hippocampus cluster. Additionally, we provide an exploratory finding of gyrification, a surface-based morphometric marker, correlating with a right postcentral gyrus cluster [ p = 0.031, family-wise error (FWE) cluster-level corrected]. Our findings provide first preliminary evidence of an inverse relationship for subjects in the absence of clinical depression and might thus point to processes related to compensation. Similar effects have been observed in remission from major depression and thus deserve further study to evaluate hippocampal volume not only as a state-dependent marker of disease but also of resilience. [ABSTRACT FROM AUTHOR]

Background: Achieving a neutral static Hip-Knee-Ankle angle (sHKA) measured on radiographs has been considered a factor of success for total knee arthroplasty (TKA). However, recent studies have shown that sHKA seems to have no effect on TKA survivorship. sHKA is not representative of the dynamic loading occurring during gait, unlike the dynamic HKA (dHKA).Research Question: The primary objective was to see if the sHKA is predictive of the dynamic HKA (dHKA). A secondary objective was to document to what degree the dHKA changes during gait.Methods: We analysed 3D knee kinematics during gait of a cohort of 90 healthy individuals with the KneeKG™ system. dHKA was calculated and compared with sHKA. Knees were considered "Stable" if the dHKA remained in valgus or varus for greater than 95% of the corresponding phase, and "Changer" otherwise. Patient characteristics of the Stable and Changer knees were compared to find associated factors.Results: Absolute variation of dHKA during gait was 10.9 ± 5.3° for the whole cohort. The variation was less for the varus knees (10.3 ± 4.8°), than for the valgus knees (12.8 ± 6.1°, p = 0.008). We found low to moderate correlations (r = 0.266 to 0.553, p < 0.001) between sHKA and dHKA values for varus knees and no significant correlation for valgus knees. Twenty two percent (36/165) of the knees were considered Changers. The proportion of knees that were Changers was 15% of the varus versus 39% of the valgus (p < 0.001).Significance: Lower limb radiographic measures of coronal alignment have limited value for predicting dynamic measures of alignment during gait. [ABSTRACT FROM AUTHOR]

Introduction: Sleep extension has been associated with better alertness and sustained attention capacities before, during and after sleep loss. However, less is known about such beneficial effect on executive functions (EFs). Our aim was to investigate such effects on two EFs (i.e., inhibition and working memory) for subjects submitted to total sleep deprivation and one-night of recovery. Methods: Fourteen healthy men (26–37 years old) participated in an experimental cross-over design with two conditions: extended sleep (EXT, 9.8 ± 0.1 h of Time In Bed, TIB) and habitual sleep (HAB, 8.2 ± 0.1 h TIB). During these two conditions subjects underwent two consecutive phases: Six nights of either EXT or HAB followed by 3 days in-laboratory: baseline (BASE), TSD (38 h) and after recovery (REC). EFs capacities were assessed through Go-NoGo (inhibition) and 2N-Back (working memory) tasks. Both EFs capacities were measured at different time (BASE/TSD/REC: 09:30, 13:00, 16:00; TSD: 21:00, 00:00, 03:00, 06:30). Results: In both conditions (HAB and EXT), TSD was associated with deficits in inhibition (higher errors and mean reaction time from TSD 09:30 until the end; p < 0.05) and working memory (lower corrects responses from TSD 06:30 or 09:30; p < 0.05). We observed no significant differences between HAB and EXT conditions on EFs capacities during BASE, TSD, and REC periods. Conclusion: Six nights of sleep extension is neither efficient to reduce core EFs deficits related to TSD nor to improve such capacities after a recovery night. These results highlight that sleep extension (six nights of 10 h of TIB) is not effective to limit EFs deficits related to TSD suggesting a disconnection inside cognition between executive and sustained attention processes. Clinical Trials: NCT02352272. [ABSTRACT FROM AUTHOR]

Aim: High resolution imaging methods detect a spectrum of inflammatory-like and structural modifications at joint and tendon level in healthy subjects. The knowledge of their extent and degree is important when subclinical disease activity (implying therapy reassessment) must be differentiated from normality. Musculoskeletal ultrasound (MSUS) evaluation may be challenging even for experts when borderline or low grade lesions are present. Our objective was to analyse the frequency of inflammatory-like lesions in hand joint and tendons in healthy young subjects and to evaluate the concordance between MSUSand magnetic resonance imaging (MRI) findings.Material and Methods: Ten healthy young women (age range 24-32 years) clinically asymptomatic (joints and tendons) were selected to have bilateral hand MSUS and MRI evaluation. Based on current definitions, synovitis/tenosynovitis-like lesions, erosions, osteophytes and bone edema were quantified and concordance between the two imaging methods was calculated.Results: Overall, both imaging evaluation methods showed a low frequency of inflammatory-like and structural lesions. No joint presented power Doppler signal or erosions. No abnormalities suggestive for inflammatory or structural pathology were detected at the tendon compartments level. No erosions and no signs of osteitis were detected. The concordance between MSUS and MRI findings was high except for the wrist area.Conclusion: MSUS was demonstrated to be a very accurate imaging method, mostly for hand tendon evaluation. This would allow a better discrimination between normality and pathologic findings, adding supplementary information. [ABSTRACT FROM AUTHOR]

Neural substrates of empathy are mainly investigated through task-related functional MRI. However, the functional neural mechanisms at rest underlying the empathic response have been poorly studied. We aimed to investigate neuroanatomical and functional substrates of cognitive and affective empathy. The self-reported empathy questionnaire Cognitive and Affective Empathy Test (TECA), T1 and T2∗-weighted 3-Tesla MRI were obtained from 22 healthy young females (mean age: 19.6 ± 2.4) and 20 males (mean age: 22.5 ± 4.4). Groups of low and high empathy were established for each scale. FreeSurfer v6.0 was used to estimate cortical thickness and to automatically segment the subcortical structures. FSL v5.0.10 was used to compare resting-state connectivity differences between empathy groups in six defined regions: the orbitofrontal, cingulate, and insular cortices, and the amygdala, hippocampus, and thalamus using a non-parametric permutation approach. The high empathy group in the Perspective Taking subscale (cognitive empathy) had greater thickness in the left orbitofrontal and ventrolateral frontal cortices, bilateral anterior cingulate, superior frontal, and occipital regions. Within the affective empathy scales, subjects with high Empathic Distress had higher thalamic volumes than the low-empathy group. Regarding resting-state connectivity analyses, low-empathy individuals in the Empathic Happiness scale had increased connectivity between the orbitofrontal cortex and the anterior cingulate when compared with the high-empathy group. In conclusion, from a structural point of view, there is a clear dissociation between the brain correlates of affective and cognitive factors of empathy. Neocortical correlates were found for the cognitive empathy dimension, whereas affective empathy is related to lower volumes in subcortical structures. Functionally, affective empathy is linked to connectivity between the orbital and cingulate cortices. [ABSTRACT FROM AUTHOR]

Purpose: Prospective prediction of pharmacokinetic properties for individuals of different ethnic groups could provide useful information for the design of multiregional clinical trials. The accuracy of interethnic scaling of fraction unbound (fu) of a drug could determine in large part the predictive capability of volume of distribution as well as renal clearance. As such, exploring the interethnic extrapolation of fu from healthy Caucasian to Chinese subjects and associated effect on the scaling of volume of distribution is highly warranted.Methods: This study assessed the interethnic scaling of fu from healthy Caucasians to Chinese by using physiologically based principles and verified the approach after examining with experimentally determined fu values of a variety of reference compounds with differing binding characteristics. Moreover, the fundamental assumption of interethnic extrapolation of volume of distribution (Vd), namely the equivalency of unbound Vd (Vd,u) across different ethnic groups, was tested on the basis of observed Vd data derived from comprehensive literature analysis and scaled fu values through qualified extrapolation method.Results: The interethnic extrapolation approach of fu provided a high accuracy with 94.7% scaled Chinese fu values (n = 19) being within a 1.25%-fold error range. Specifically, 100% of scaled Chinese fu values for the albumin-bound compounds and 90% for those bound to alpha 1-acid glycoprotein fell within the 1.25%-fold error range. All the percentage prediction errors of scaled Chinese fu values were ≤ 30%, with a majority of those ≤ 20%. Additionally, correlation between the prediction errors and the observed fu levels was not observed. Regarding interethnic scaling of Vd, the bodyweight-normalized Vd,u instead of Vd was similar across ethnic groups.Conclusion: The current study verified for the first time the ability to scale Chinese fu from Caucasian values after examining with experimentally determined fu values of a variety of reference compounds. Similarities in bodyweight-normalized Vd,u between non-obese Caucasians and Chinese have also been shown for the first time. This investigation could greatly enhance the confidence in the interethnic extrapolation of fu and Vd from healthy non-obese Caucasian to Chinese subjects. [ABSTRACT FROM AUTHOR]

Monitoring of respiratory rate (RR) is very important for patient assessment. In fact, it is considered one of the relevant vital parameters in critical care medicine. Nowadays, standard monitoring relies on obtrusive and invasive techniques, which require adhesive electrodes or sensors to be attached to the patient's body. Unfortunately, these procedures cause stress, pain, and frequently damage the vulnerable skin of preterm infants. This paper presents a “black-box” algorithm for remote monitoring of RR in thermal videos. “Black-box” in this context means that the algorithm does not rely on tracking of specific anatomic landmarks. Instead, it automatically distinguishes regions of interest in the video containing the respiratory signal from those containing only noise. To examine its performance and robustness during physiological (phase A) and pathological scenarios (phase B), a study on 12 healthy volunteers was carried out. After a successful validation on adults, a clinical study on eight newborn infants was conducted. A good agreement between estimated RR and ground truth was achieved. In the study involving adult volunteers, a mean root-mean-square error (RMSE) of ($0.31 \pm 0.09$) breaths/min and ($3.27 \pm 0.72$) breaths/min was obtained for phase A and phase B, respectively. In the study involving infants, the mean RMSE hovered around ($4.15 \pm 1.44$) breaths/min. In brief, this paper demonstrates that infrared thermography might become a clinically relevant alternative for the currently available RR monitoring modalities in neonatal care. [ABSTRACT FROM AUTHOR]

Highlights • First randomized controlled trial of rTMS effects on blink reflex in SCI subjects. • High frequency rTMS modulates brainstem activity in both SCI and healthy subjects. • Dopamine release induced by rTMS may explain modulation of brainstem reflexes. Abstract Background The excitability of brainstem interneuronal circuits is partly under control from descending inputs. Since high frequency repetitive transcranial magnetic stimulation (rTMS) modulates cortical output, we hypothesized that it will also modulate brainstem functions. Such modulation may be different in healthy subjects than in subjects with spinal cord injury (SCI), submitted to an altered integration of body afferent inputs. Methods In this randomized, double-blind, sham-controlled trial, we recruited 22 subjects with SCI assigned to either real (n = 11) or sham (n = 11) rTMS and nine healthy subjects, who served as control group, receiving both real (at 20 Hz, with double cone coil over vertex) and sham rTMS separated by at least one week. We recorded the blink reflex (BR) to supraorbital nerve (SON) electrical stimulation and its modification by another conditioning SON, to study the BR excitability recovery (BRER), or a prepulse electrical stimulus to the right index finger, to study the BR inhibition by prepulse (BRIP). Subjects were examined immediately before and after either sham or real rTMS. Results Real but not sham rTMS significantly reduced the area of the BR R2 response in both SCI and healthy subjects. There were no changes in BRER and BRIP. Conclusion rTMS over the vertex modulates brainstem reflexes with no significant differences between SCI and healthy subjects. [ABSTRACT FROM AUTHOR]

Date palm (Phoenix dactylifera) is one of the oldest trees cultivated by human; Egypt has been ranked as the first country in the production of dates, soft, semi dry and dry date cultivars are cultivated in wide area of Egypt. Therefore, this work was carried out to determine the Glycemic Index (GI) and Glycemic Load (GL) of five Egyptian varieties of date fruit in healthy subjects. Chemical composition analysis was carried out for five types of date fruit (Partamoda, Malakabi, Saadi, Zaghluol and Samani); also, antioxidant power was determined. The study subjects were ten healthy volunteers, each subject was tested on six separate visits with 50 g of glucose and 50 g equivalent of available carbohydrates from the five date varieties. Capillary glucose was measured in the healthy subjects at 0, 30, 60 and 120 min. The GI was determined as ratios of the incremental areas under the response curves for the dates compared to glucose. Collecting data showed that Egyptian varieties of date fruit contain a good nutrients and antioxidant power. Among the five Egyptian varieties of date fruit, the chemical characteristics by moisture content in fruits was the highest in Samani date fruit and lowest in Partamoda dates; also, the five Egyptian varieties of date fruit contain available carbohydrate (7.4% - 69.2%), proteins (1.85 % -7.0%), total dietary fiber, TDF (11.82% - 15.63%) and Energy value (76.2-297.9 Kcal/100g). The antioxidant activity ranged between 52.61 and 79.12% as scavenging activity for free radicals; also, dates rich in phenols. The medium GI was recorded by Malakabi followed by Saadi and Partamoda which had high GL; while, the lowest GI was recorded for soft date fruit (Zaghluol and Samani) which had medium GL. These findings point to the potential benefits of Egyptian date fruit for healthy subjects when used in a stable healthy diet. [ABSTRACT FROM AUTHOR]

Introduction: Assessment of diaphragm compound muscle action potential by noninvasive phrenic nerve stimulation at the neck is well described. However, normal values in a large cohort of healthy subjects are lacking. Our objective was to determine reference values of phrenic nerve conduction in healthy subjects.Methods: We recruited 155 healthy subjects (25-79 years old) and measured mean amplitude (PhrenAmp) and latency (PhrenLat) of motor responses according to Bolton's method.Results: The lower limit for PhrenAmp was 0.28 and 0.25 mV and the upper limit for PhrenLat was 8.41 and 8.56 ms for right and left side, respectively. PhrenLat was correlated with age. PhrenAmp, PhrenLat and area were significantly higher in men. Tolerance to phrenic nerve stimulation was excellent.Conclusions: Our study provides normative values of phrenic nerve motor responses in a large cohort of healthy subjects and identifies age and sex as factors of variation. Muscle Nerve 59:451-456, 2019. [ABSTRACT FROM AUTHOR]

The aim of the present study was to demonstrate the effect of inhalation-flow, inhalation-volume and number of inhalations on aerosol-delivery of inhaled-salbutamol from two different dry powder inhalers (DPIs) in both healthy-subjects and chronic obstructive pulmonary disease (COPD) patients. Relative pulmonary-bioavailability and systemic-bioavailability of inhaled-salbutamol, delivered by Diskus and Aerolizer, was determined in 24-COPD patients and 24-healthy subjects. The healthy-subjects and the COPD-patients participated in the study for 7 days in which they received 4 study doses of 200 μg salbutamol (one slow-inhalation, two slow-inhalations, one fast-inhalation, and two fast-inhalations) in four alternative days with 24 hr washout period after each dose. Two urine-samples were collected from each study subjects. The first was provided 30 min post inhalation (USAL0.5), as an index of relative pulmonary-bioavailability, and the second was pooled to 24 hr post inhalation (USAL24), as an index of systemic-bioavailability. Fast-inhalation resulted in significantly higher USAL0.5 and USAL24 than slow-inhalation (p˂0.05) after one-inhalation in both healthy-subjects and COPD-patients but there was no significant difference between slow and fast-inhalation after two-inhalations. One-inhalation resulted in significantly higher USAL0.5 and USAL24 in healthy-subjects compared to COPD-patient at both slow and fast-inhalation (p˂0.05) except USAL0.5 with Diskus at slow-inhalation there was no significant difference. Also, two-inhalations resulted in significantly higher USAL0.5 and USAL24 compared to one-inhalation at slow-inhalation only (p˂0.05). No significant difference was found between Aerolizer and Diskus except in USAL0.5 of one slow-inhalation in both health-subjects and COPD-patients (p = 0.048 and 0.047, respectively). Device-formula relation is present at low inhalation-flow since Diskus resulted in significantly higher USAL0.5 and USAL24 in healthy-subjects compared to COPD-patient at slow inhalation than Aerolizer. It is essential to inhale-twice and as hard and deep as possible from each dose when using DPI especially with COPD-patients having poor inspiratory efforts such as elderly patients and children. [ABSTRACT FROM AUTHOR]

Background The endocannabinoid system (ECS) is considered a key player in the neurophysiology of food reward. Animal studies suggest that the ECS stimulates the sensory perception of food, thereby increasing its incentive-motivational and/or hedonic properties and driving consumption, possibly via interactions with metabolic hormones. However, it remains unclear to what extent this can be extrapolated to humans. Objective We aimed to investigate the effect of oral Δ9-tetrahydrocannabinol (THC) on subjective and metabolic hormone responses to visual food stimuli and food intake. Methods Seventeen healthy subjects participated in a single-blinded, placebo-controlled, 2 × 2 crossover trial. In each of the 4 visits, subjective "liking" and "wanting" ratings of high- and low-calorie food images were acquired after oral THC or placebo administration. The effect on food intake was quantified in 2 ways: via ad libitum oral intake (half of the visits) and intragastric infusion (other half) of chocolate milkshake. Appetite-related sensations and metabolic hormones were measured at set time points throughout each visit. Results THC increased "liking" (P  = 0.031) and "wanting" ratings (P  = 0.0096) of the high-calorie, but not the low-calorie images, compared with placebo. Participants consumed significantly more milkshake after THC than after placebo during oral intake (P  = 0.0005), but not intragastric infusion, of milkshake. Prospective food consumption ratings during the food image paradigm were higher after THC than after placebo (P  = 0.0039). THC also increased plasma motilin (P  = 0.0021) and decreased octanoylated ghrelin (P  = 0.023) concentrations before milkshake consumption (i.e. in both oral intake and intragastric infusion test sessions), whereas glucagon-like peptide 1 responses to milkshake intake were attenuated by THC during both oral (P  = 0.0002) and intragastric (P  = 0.0055) administration. Conclusions These findings suggest that the ECS drives food intake by interfering with anticipatory, cephalic phase, and metabolic hormone responses. This trial was registered at clinicaltrials.gov as NCT02310347. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to elucidate the contribution of candidate single nucleotide polymorphisms (SNPs) related to pharmacokinetics on the recovery of platelet function after single dose of ticagrelor was orally administered to healthy Chinese subjects. Methods: The pharmacokinetic profiles of ticagrelor and its metabolite AR-C124910XX (M8), and the platelet aggregation (PA), were assessed after 180 mg of single-dose ticagrelor was orally administered to 51 healthy Chinese subjects. Effects of CYP2C19 * 2, CYP2C19 * 3, CYP3A5 * 3, UGT1A1 * 6, UGT1A1 * 28, UGT2B7 * 2, UGT2B7 * 3, SLCO1B1 388A>G, and SLCO1B1 521T>C, on the pharmacokinetics of ticagrelor and M8, and platelet function recovery were investigated. Results: The time to recover 50% of the maximum drug effect (RT50) ranging from 36 to 126 h with 46.9% CV had a remarkable individual difference and was positively associated with the half-life (t1/2) of M8 (r = 0.3901, P = 0.0067). The time of peak concentration (Tmax) of ticagrelor for CYP2C19*3 GG homozygotes was significantly higher than that of GA heterozygotes (P = 0.0027, FDR = 0.0243). Decreased peak concentration (Cmax) of M8 was significantly associated with SLCO1B1 388A>G A allele (P = 0.0152, FDR = 0.1368). CYP2C19 * 2 A was significantly related to decreased Cmax of M8 (P = 0.0455, FDR = 0.2048). While, the influence of these nine SNPs on the recovery of platelet function was not significant. Conclusion: Our study suggests that the elimination of M8 is an important factor in determining the recovery of platelet function. Although CYP2C19 and SLCO1B1 genetic variants were related to the pharmacokinetics of ticagrelor or M8, they did not show a significant effect on the platelet function recovery in this study. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT03092076, identifier: NCT03092076 [ABSTRACT FROM AUTHOR]

Abstract Background Moguisteine is a non-narcotic peripheral antitussive drug that has been effective and well-tolerated in clinical studies. The aim of the present work was to investigate the pharmacokinetics of moguisteine given as single or multiple doses to healthy Chinese subjects. Methods In Stages 1–3 of this study, 12 healthy Chinese subjects (6 males and 6 females) participated in a randomized, open-label, single-dose, 3-period, 3-way crossover study, with a 24-h washout period between each treatment. Eligible subjects were randomized to receive a single dose of 100, 200 or 400 mg moguisteine. Blood was sampled before and up to 10 h after administration. In those receiving 200 mg moguisteine, urine was sampled at intervals of 0–2, 2–4, 4–6, 6–10, and 10–24 h. In Stage 4, subjects received a moguisteine tablet containing 200 mg three times daily for five consecutive days. Blood was sampled for up to 10 h after the last dose. HPLC-tandem mass spectrometry was used to determine concentrations of the moguisteine metabolite M1 in serum, while HPLC-UV was used to determine concentrations of M1 in urine. Safety of the dosing schedules was assessed based on physical examination, recording of adverse events, 12-lead electrocardiography, and laboratory tests. Results All subjects completed all four stages of the study. M1 was detectable at the shortest time points after moguisteine administration; the time to achieve peak concentration was 0.5–1.0 h in single dosing and 1.5 h in multiple dosing. Elimination half-life (t 1/2) was 0.91–1.54 h in single dosing and 1.57 h in multiple dosing. AUC increased roughly proportionally with dose, while C max increased much more gradually with dose. During 5-day dosing of three tablets per day, a steady state concentration was reached on day 3, and the mean accumulation ratio was 0.87. At 24 h after a single dose of 200 mg moguisteine, approximately 34.0% of the resulting M1 was recovered in urine. Pharmacokinetics of moguisteine did not differ significantly between men and women, except among those receiving a single dose of 100 mg (P < 0.05). Mild adverse events (nausea, loose stool, abdominal distention, or dizziness) occurred in six subjects and resolved without treatment, while no serious adverse events were observed. Conclusion Moguisteine was safe and well-tolerated by our healthy subjects, and it exhibited dose linearity but not proportionality when a single dose of 100–400 mg was given. M1 did not accumulate in subjects after multiple doses of moguisteine. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]

Highlights • A 20 cmH 2 O expiratory load (ETL) applied at the mouth induced dyspnea in healthy men. • Concentration in total haemoglobin decreased in intercostal muscles with ETL. • Tissue saturation index in O 2 (TSI) did not vary in the intercostal muscles with ETL. • Changes in TSI and ventilatory flow in response to ETL were negatively correlated. • Dyspnea was correlated with the changes in Vt/Ti but not with those in Vt/Te. Abstract Background During acute bronchial obstruction, despite a higher work of breathing, blood supply and oxygen availability may be reduced in intercostal muscles because of mechanical constraints. This hypothesis was assessed in healthy subjects breathing with and without expiratory load (ETL). Methods Eleven men (24 ± 2 years) breathed at rest for 5 min in unloaded condition and for 20 min through a 20-cmH 2 O ETL. Tissue saturation index (TSI) and changes (Δ) in concentration of total and oxy-haemoglobin ([tHb] and [O 2 Hb]) were measured in the seventh intercostal space by near-infrared spectroscopy. Results [tHb] and [O 2 Hb] decreased with ETL (-5.16 μM and -3.54 μM; p < 0.05). TSI did not vary. Negative correlations were observed between Δ[O 2 Hb] and changes in expiratory flow rate (ΔVt/Te) and between ΔTSI and Δ V ˙ E (r = -0.78 and -0.74; p ≤ 0.01). Conclusion Despite decreases in Hb concentrations, saturation in oxygen was not reduced with ETL in intercostal muscles, suggesting a satisfactory ventilatory and/or hemodynamic arrangement. [ABSTRACT FROM AUTHOR]

Abstract The micronucleus test in peripheral blood lymphocytes is the most widely validated technique to evaluate the DNA damage and chromosomal instability in human populations. The test is largely applied in monitoring environmental and occupational exposure to genotoxic agents. It was also proposed as a biomarker of risk/susceptibility for cancer and other degenerative diseases. The availability of "normal values" in healthy populations is a main requisite for the assay application in human biomonitoring. Age and gender-related ranges of micronucleated binucleated cells (MNBN) baseline values were established in a group of 103 healthy platelet donors (50 males and 53 females) not recently exposed to genotoxic agents and characterized for demographic, lifestyle and dietary factors. Repeatability of the test by the same scorer was evaluated. Reproducibility was estimated through analysis of repeated blood samples. High correlation between the results of the three blood samplings in two separate scoring sessions of MNBN/1000BN (R2 values were 0.83, 0.74 and 0.68; P < 0.0001) and PI values (R2 values were 0.69, 0.62 and 0.65; P < 0.0001) was detected. High consistency among the values obtained in three different samplings in the same individual was observed (Intraclass Correlation Coefficient (ICC) = 0.905, (95% CI = 0.868–0.933, P < 0.0001) The range of "normal" values predicted on the basis of the results of the present study appears to be sufficiently narrow to warrant application of the assay in the comparison of data obtained from groups of exposed or susceptible subjects, supporting its use in preventive programs. The large inter-individual variability predicted by the model used in the present study hampers a clinical application of the assay at individual level. The method applied in the present study represents a generally applicable model to derive "normal values" in any population, as an essential step before starting a biomonitoring study. Graphical abstract Unlabelled Image Highlights • Good repeatability of the micronuclei and proliferative index was observed. • Consistency of MNBN values in individuals was confirmed in repeated blood samples. • Narrow ranges of normal reference group MNBN values were estimated. • Large variability of age- and gender-specific individual MNBN values was observed. • A model to derive MNBN "normal values" in a healthy population was established. [ABSTRACT FROM AUTHOR]

Additional visual feedback (VFB) is a technique allowing improved postural stability in young healthy individuals despite an increased muscular activity, the two trends being assessed through center-of-gravity (CGv) and differences between CGv and center-of-pressure (CP) movements (CP-CGv), respectively. These two opposing effects are likely explained by the respective contribution of automatic and voluntary controls and in turn the neural circuits involved. To specify these specific contributions, a dual-task protocol was set up, consisting in adding to VFB a navigation task performed at the maximum cognitive capacities of the subjects who were evaluated beforehand. Overall, the protocol comprises six conditions: three visual tasks (eyes open without VFB, VFBBW based on body-weight distribution, VFBCP based on CP displacements) associated with or without a cognitive task. Variances of CP-CGv and CGv movements, along the mediolateral (ML) and anteroposterior (AP) axes, and parameters from fractional Brownian motion modeling (transition point coordinates and scaling regimes to assess the level of deterministic or stochastic activity) were used to assess the postural behaviors. The results show that during VFBCP, the dual tasks protocol infers a decreased contribution of deterministic activity in CP-CGv movements, inducing decreased variances, and alters the correction of the CGv over the longest Δt but nonetheless without changing CGv variances. Disturbing the subject's attention during the VFBBW condition induces decreased CP-CGv and CGv movements along the ML and AP axes, respectively. These data demonstrate the high level of attention induced by VFB protocols. If the tonic postural activity, expressed through CP-CGv movements, decreases whatever VFB condition along both the ML and AP axes, the effects on CGv movement appear to be mostly related to the additional information (BW or CP) provided. Overall, if too much voluntary control in upright stance maintenance is detrimental for the magnitudes of the CP-CGv movements, it appears beneficial for those of the CGv movements. By emphasizing the role of automatic and voluntary controls in VFB protocols, these insights document the neural circuits involved in such protocols and specify their conditions of use. [ABSTRACT FROM AUTHOR]

Purpose of the study: the aim of this study was to synthesize PFC fNIRS outcomes on the effects of cognitive tasks compared to resting/baseline tasks in healthy adults from studies utilizing a pre/post design. Material and methods: original research studies were searched from seven databases (MEDLINE, EMBASE, CENTRAL, CINAHL, SCOPUS, PEDro and PubMed). Subsequently, two independent reviewers screened the titles and abstracts followed by full-text reviews to assess the studies' eligibility. Results: eleven studies met the inclusion criteria and had data abstracted and quality assessed. Methodology varied considerably and yet cognitive tasks resulted in the ΔO2Hb increasing in 8 of the 11 and ΔHHb decreasing in 8 of 8 studies that reported this outcome. The cognitive tasks from 10 of the 11 studies were classified as "Working Memory" and "Verbal Fluency Tasks". Conclusions: although, the data comparison was challenging provided the heterogeneity in methodology, the results across studies were similar. [ABSTRACT FROM AUTHOR]

Aims Using non-invasive 3D ultrasound, peak wall stress (PWS) and aortic stiffness can be evaluated, which may provide additional criteria in abdominal aortic aneurysm (AAA) risk assessment. In this study, these measures were determined in both young and age-matched individuals, and AAA patients while its relation to age, maximum diameter, and growth was assessed statistically. Methods and results Time-resolved 3D-US data were acquired for 30 volunteers and 65 AAA patients. The aortic geometry was segmented, and tracked over the cardiac cycle using 3D speckle tracking to characterize the wall motion. Wall stress analysis was performed using finite element analysis. Model parameters were optimized until the model output matched the measured 3D displacements. A significant increase in aortic stiffness was measured between the age-matched volunteers [median 0.58, interquartile range (IQR) 0.48–0.71 kPa⋅m] and the small AAA patients (median 1.84, IQR 1.38–2.46 kPa⋅m; P < 0.001). In addition, an increase in aortic stiffness was evaluated between the small (30–39 mm) and large (≥50 mm) AAAs (median 2.72, IQR 1.99–3.14 kPa⋅m; P  = 0.01). The 99th percentile wall stress showed a positive correlation with diameter (ρ  = 0.73, P < 0.001), and significant differences between age-matched volunteers and AAA patients. Conclusion The AAA pathology causes an early and significant increase in aortic stiffness of the abdominal aorta, even after correcting for the expected effect of ageing and differences in arterial pressure. Moreover, some AAAs revealed relatively high PWS, although the maximum diameter was below the threshold for surgical repair. Using the current method, these measures become available during follow-up, which could improve AAA rupture risk assessment. [ABSTRACT FROM AUTHOR]

Introduction: Toxoplasma gondii is a protozoan parasite which causes a zoonotic disease called toxoplasmosis. The main purpose of this study was to investigate the seropositivity rate of specific antibodies "anti-T. gondii IgG and IgM antibodies using enzyme-linked immunosorbant assay" in hemodialysis patients attending the Teaching Hospital, Baquba City, Diyala Province, Iraq and to determine the potentially preventable risk factors. Methods: Eighty five hemodialysis patients with kidney failure and 85 healthy volunteers were selected for this study. Results: The percentage of seropositivity for IgG antibodies in patients with hemodialysis was 54.1% while it was 38.2% among the healthy control subjects and the difference was significant between the two groups [Odds Ratio (OR)= 1.8586; 95% Confidence Interval (CI)= 1.0097-3.4212; P= 0.0465]. In contrast, IgM antibodies were not detected in any of the patients or the healthy subjects. Many risk factors were identified, including contact with cats (OR, 2.62; P= 0.0398); eating undercooked meat (OR, 2.6, P= 0.0439); drinking unfiltered water (OR, 2.86, P= 0.0433); and eating outside the home (OR, 5.6, P= 0.0024) as risk factors for toxoplasmosis. However, smoking was not found to be as a risk factor for toxoplasmosis (OR, 2.1, P= 0.1204). Conclusion: The results of the present study revealed a high prevalence of toxoplasma infection in hemodialysis patients and therefore, we recommend monitoring these patients for T. gondii infection to minimize the spreading of toxoplasmosis via treating the seropositive patients with the available commercial drugs. [ABSTRACT FROM AUTHOR]

Background: Pulse oximeter is a simple and noninvasive standard device to monitor the saturation of peripheral oxygen (SpO2) and heart rate. The nail polish of different colors may result in inaccurate oximetry reading and interpretation of oxygen saturation. This study aimed at determining the effect of different colors of glittered nail polish on SpO2in healthy students. Materials and Methods: This is a randomized clinical trial on 30 healthy students with SpO2≥95% and without any complications on nail beds and environmental perfusion. SpO2was measured on 10 fingers of the participants after sitting and resting on a seat for 10 min in a room with normal temperature. Then they were asked to apply 10 colors of glittered nail polish randomly to their fingernails as all colors were used. After drying the two-layer nail polish, SpO2was measured again. Results: Of 10 glittered nail-polishes, dark green and purple did not change SpO2reading significantly. All other colors lowered SpO2significantly based on Wilcoxon test (red: p = 0.003; orange: p = 0.002; yellow: p = 0.015; pink: p = 0.017; dark blue: p = 0.001; violet: p = 0.001; brown: p = 0.001; black: p = 0.001). However, those changes were not clinically significant because SpO2differences before and after nail polish were in acceptable range (less than a 2% change). Conclusions: We conclude that different colors of glittered nail polishes do not result in a clinically significant change in pulse oximetry measurements in healthy subjects; therefore, it is not necessary to remove the glittered nail polish routinely in clinical, surgical, and emergency settings. [ABSTRACT FROM AUTHOR]

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Purpose: To assess the potential pharmacokinetic (PK) interactions between siponimod and rifampin, a strong CYP3A4/moderate CYP2C9 inducer, in healthy subjects.Methods: This was a confirmatory, open-label, multiple-dose two-period study in healthy subjects (aged 18-45 years). In Period 1 (Days 1-12), siponimod was up-titrated from 0.25 to 2 mg over 5 days (Days 1-6) followed by 2 mg once daily on days 7-12. In Period 2, siponimod 2 mg qd was co-administered with rifampin 600 mg qd (Days 13-24). Primary assessments included PK of siponimod (Days 12 and 24; maximum steady-state plasma concentration [Cmax,ss], median time to achieve Cmax,ss [Tmax, ss], and area under the curve at steady state [AUCtau,ss]). Key secondary assessments were PK of M3 and M5 metabolites, and safety/tolerability including absolute lymphocyte count (ALC).Results: Of the 16 subjects enrolled (age, mean ± standard deviation [SD] 31 ± 8.3 years; men, n = 15), 15 completed the study. In Period 1, siponimod geometric mean Cmax,ss (28.6 ng/mL) was achieved in 4 h (median Tmax,ss; range, 1.58-8.00) and the geometric mean AUCtau,ss was 546 h × ng/mL. In Period 2, the siponimod geometric mean Cmax,ss and AUCtau,ss decreased to 15.7 ng/mL and 235 h × ng/mL, respectively; median Tmax remained unchanged (4 h). Rifampin co-administration increased M3 Cmax,ss by 53% while M5 Cmax,ss remained unchanged. The AUCtau,ss of M3 and M5 decreased by 10% and 37%, respectively. The majority of adverse events reported were mild, with a higher frequency during Period 2 (86.7%) versus Period 1 (50%). The mean ALC increased slightly under rifampin co-administration but remained below 1.0 × 109/L.Conclusions: The study findings suggest that in the presence of rifampin, a strong CYP3A4/moderate CYP2C9 inducer, siponimod showed significant decrease in Cmax,ss (45%) and AUCtau,ss (57%) in healthy subjects. [ABSTRACT FROM AUTHOR]

BI 655064 is a humanized antagonistic anti‐cluster of differentiation (CD) 40 monoclonal antibody that selectively blocks the CD40‐CD40L interaction. The CD40‐CD40L pathway is a promising treatment target for autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and lupus nephritis. The safety, tolerability, pharmacokinetics, and pharmacodynamics of repeated once‐weekly BI 655064 subcutaneous dosing over 4 weeks were evaluated in a multiple‐dose study in healthy subjects. Subjects (N = 40) were randomized 4:1 to four sequential BI 655064 dose groups (80, 120, 180, 240 mg) or to placebo. Safety and tolerability, plasma exposure, CD40 receptor occupancy, and CD40L‐induced CD54 upregulation were assessed over 64 and 78 days for the 80‐ to 180‐mg and 240‐mg dose groups, respectively. BI 655064 exposure increased in a supraproportional manner, due to target‐mediated drug clearance, for doses between 80 mg and 120 mg, but was near proportional for doses greater than 120 mg. Terminal half‐life ranged between 6 and 8 days. Dose‐dependent accumulation of BI 655064 supports the use of a loading dose in future clinical studies. Following 4 weeks of dosing, >90% CD40 receptor occupancy and inhibition of CD54 upregulation were observed at all dose levels, lasting for 17 days after the last dose. BI 655064 was generally well tolerated. There were no serious adverse events and the frequency and intensity of adverse events were similar for BI 655064 and placebo; no dose relationship or relevant signs of an acute immune reaction were observed. These findings support further investigation of BI 655064 as a potential treatment for autoimmune diseases. [ABSTRACT FROM AUTHOR]

The loop gain (LG) is defined as the ratio of a ventilatory response over the perturbation in ventilation, and it is used to analyze ventilatory control stability. The LG can be derived from minute ventilation (V E), end-tidal PCO2 (PETCO2), and end-tidal PO2 (PETO2) values. Several methods of LG assessment have been developed, which have never been compared. We evaluated the computability, the short-term repeatability, and the agreement of six published (or slightly modified) models for LG determination. These models included three unconstrained autoregressive models, univariate (VE), bivariate (VE, PETCO2), and trivariate (VE, PETCO2, and PETO2), and three analytical transfer function constrained models based on VE, VE and CO2-sensitivity, and VE and central and peripheral CO2 sensitivities, respectively. The models were tested with tidal breathing data in 37 awake healthy subjects (median age 35 yr; 23 women, 14 men). Modeling failed in 11, 0, and 0 subjects for the three unconstrained models, respectively, and 4, 1, and 9 subjects for the three constrained models, respectively. Bland and Altman analyses of the LG values in the medium frequency range of two separate recordings demonstrated good repeatability for four models, excluding univariate and trivariate unconstrained models. The four repeatable models gave LG values that were in agreement (medium frequency LG, median 0.100-0.210), although the constrained model based on VE systematically overestimated LG values. The variances explained by these models were ~20%. In conclusion, model-based analyses of tidal breathing were performed with different approaches that gave comparable results for chemical LG and explained variance. [ABSTRACT FROM AUTHOR]

The primary objective of this single- and multiple-dose pharmacokinetic study was the investigation of rifamycin SV’s pharmacokinetic profile in plasma and urine. All the 18 enrolled healthy men and post-menopausal women received modified release tablets containing 600 mg of the oral non-absorbable antibiotic, rifamycin SV, according to a multiple dose regimen: one tablet three times a day (daily intake: 1800 mg) for 14 consecutive days. Blood sampling and urine collection were performed up to 24 h post-dose after the first dose on Days 1 and 7. On average, on Day 1, Cmax,0–24 was 5.79 ± 4.24 ng/mL and was attained in a median time of 9 h. On Day 7, all the subjects had quantifiable levels of rifamycin SV in plasma at each sampling time. After a peak concentration attained 2 h post-dose (mean ± SD concentration: 10.94 ± 16.41 ng/mL), rifamycin SV decreased in plasma to levels similar to those of Day 1. The amounts of rifamycin SV excreted in urine paralleled the plasma concentration at the corresponding times. On Day 1, the total amount excreted in urine was 0.0013%, and was 0.0029% on Day 7. The study results confirmed those of the previous Phase I study: the systemic absorption of rifamycin SV was also proved negligible after 7 days of the 600 mg t.i.d. dose regimen of the newly formulated tablets, currently under development for the treatment of several small and large intestinal pathologies, including diarrhea-predominant irritable bowel syndrome, hepatic encephalopathy, and others. Registered at ClinicalTrials.gov with the identifier NCT02969252, last updated on 26JAN18.

Resistance exercise improves daily glycemic control. Low-intensity resistance exercise with slow movements and tonic force generation (LST) is a resistance exercise protocol that can increase skeletal muscle mass and strength without considerable physical burden; however, its effect on glycemic variability is unknown. The aim of this study was to investigate the effect of LST on short-term glycemic variability, expressed as the M-value, in healthy individuals. We recruited 20 healthy subjects (mean age: 27.9 ± 3.9 years) with normal glucose tolerance, and subjects were randomly assigned to the control (n = 10) or LST (n = 10) groups. Subjects in the LST group performed the resistance exercise with 40–50% of the one-repetition maximum for 40 min. All subjects wore a subcutaneous continuous glucose monitoring system and a triaxial accelerometer, and their daily glycemic variability and physical activity were measured. One hour after the intervention, in the LST group, the variability of blood glucose levels was significantly decreased compared to the control group (M-values in the LST group: pre 3.5 ± 6.2, post 2.7 ± 2.7, p = 0.575; M-values in the control group: pre 0.4 ± 0.7, post 2.7 ± 2.0, p = 0.017). However, there were no differences in total physical activity and daily glycemic control between groups. The findings of this study suggest that LST improves short-term glycemic variability in healthy subjects.

Background: A number of studies on diseased spine have been published; however, there is a relative paucity of studies investigating spine shape characteristics in healthy populations. Such characteristics are needed for diagnostics of spine disorders and assessment of changes in the spinal shape that may have been caused by influence of the modern life style or intensive sport activity. Objective: The aim of the study was to determine characteristics of the spine shape in a large sample of healthy young adults. Methods: Population cross-sectional study. A non-radiographic surface method (system DTP-3) was used for the assessment of spine shape in the sagittal and frontal planes. A total of 1,020 participants (440 men, 580 women) took part in the study, their mean (± SD) age was 21.8 ± 1.9 years (range 19.1-29.7) for men and 21.9 ± 1.8 years (range 19.3-29.7) for women. All data were checked for normality and are presented as means, standard deviations, ranges, skewness, and kurtosis. Differences between the sexes were assessed with the two-sample t-test. Results: The average sagittal spinal shape was C3 - 12.9° - C7 - 43.0° - T10 - 27.1° - L5 for men and C3 - 12.1° - C6 - 44.5° - T11 - 34.1° - L5 for women. Men showed a significantly smaller thoracic kyphosis and lumbar lordosis curvatures than women. The average curvature due to the lateral deviation in the frontal plane was 6.1° for both sexes, the curvature was larger than 10° in 9.1% of men and 8.8% of women. We found left lateral deviation in 72.5% of men and in 63.6% of women. Conclusions: The study provides characteristics of the spine shape in a large sample of healthy young adults. Such characteristics should be part and parcel of determining the cut-off level for physiological spinal shape. Based on the results of the study, we suggest a lateral deviation of 10° as the maximum for a curvature to be still considered non-pathological.