System In Healthy Subjects Research Articles

Predictive model for vitamin C levels in hyperinsulinemic individuals based on age, sex, waist circumference, low-density lipoprotein, and immune-associated serum proteins

Vitamin C (ascorbic acid) is an important water-soluble antioxidant associated with decreased oxidative stress in type 2 diabetes (T2D) patients. A previous targeted plasma proteomic study has indicated that ascorbic acid is associated with markers of the immune system in healthy subjects. However, the association between the levels of ascorbic acid and blood biomarkers in subjects at risk of developing T2D is still unknown. Serum ascorbic acid was measured by ultra-performance liquid chromatography and serum proteins were quantified by untargeted liquid-chromatography mass spectrometry in 25 hyperinsulinemia subjects that were randomly assigned a high dairy intake diet or an adequate dairy intake diet for 6 weeks, then crossed-over after a 6-week washout period. Spearman correlation followed by gene ontology analyses were performed to identify biological pathways associated with ascorbic acid. Finally, machine learning analysis was performed to obtain a specific serum protein signature that could predict ascorbic acid levels. After adjustments for waist circumference, LDL, HDL, fasting insulin, fasting blood glucose, age, gender, and dairy intake; serum ascorbic acid correlated positively with different aspects of the immune system. Machine learning analysis indicated that a signature composed of 21 features that included 17 proteins (mainly from the immune system), age, sex, waist circumference, and LDL could predict serum ascorbic acid levels in hyperinsulinemia subjects. In conclusion, the result reveals a correlation as well as modulation between serum ascorbic acid levels and proteins that play vital roles in regulating different aspects of the immune response in individuals at risk of T2D. The development of a predictive signature for ascorbic acid will further help the assessment of ascorbic acid status in clinical settings.

The study of exercise therapy using a virtual reality system on healthy subjects assuming hospital use and intradialytic exercise.

This study aimed to investigate the basic data on the effectiveness and safety of the system in healthy subjects using an immersive virtual reality (VR) exercise system specialized for therapeutic exercise therapy during dialysis or hospital use. A total of 15 healthy adult subjects performed four exercises, namely lifting and rowing exercises using VR and each movement exercise without VR (control). The simulator sickness questionnaire (SSQ) was administered pre- and post-operatively to assess for VR sickness. Blood pressure, heart rate (HR), rating of perceived exhaustion, Profile of Mood States 2nd Edition Japanese version, and muscle activity (iEMG) were measured using electromyography. The correlation between changes in mood states and HR or iEMG results was examined. The SSQ measured post-VR exercise was 11.2 (18.7-7.5) and 11.2 (7.5-29.9) points in the lifting and rowing VR, respectively. The HR in lifting (VR, 82.5 ± 12.7 vs control, 71.6 ± 10.6 bpm, P<0.05) and rowing (VR, 94.2 ± 13.1 vs control, 83.5 ± 12.0, P<0.05) with VR exercise was significantly higher than in control. No significant differences were observed between the other variables. There was a positive correlation between HR and negative mood in the lifting VR condition (r=0.64, P<0.05), but not in the control group. Contrastingly, there was a positive correlation between iEMG and negative mood in rowing control (r=0.56), but not VR. Safety was confirmed, with no VR sickness or discontinuation of the system. Exercise therapy using VR resulted in a higher exercise load. This VR system has the potential for additional effective intradialytic exercises and hospital use.

The Validity and Reliability of a New Intelligent Three-Dimensional Gait Analysis System in Healthy Subjects and Patients with Post-Stroke

Odonate is a new, intelligent three-dimensional gait analysis system based on binocular depth cameras and neural networks, but its accuracy has not been validated. Twenty-six healthy subjects and sixteen patients with post-stroke were recruited to investigate the validity and reliability of Odonate for gait analysis and examine its ability to discriminate abnormal gait patterns. The repeatability tests of different raters and different days showed great consistency. Compared with the results measured by Vicon, gait velocity, cadence, step length, cycle time, and sagittal hip and knee joint angles measured by Odonate showed high consistency, while the consistency of the gait phase division and the sagittal ankle joint angle was slightly lower. In addition, the stages with statistical differences between healthy subjects and patients during a gait cycle measured by the two systems were consistent. In conclusion, Odonate has excellent inter/intra-rater reliability, and has strong validity in measuring some spatiotemporal parameters and the sagittal joint angles, except the gait phase division and the ankle joint angle. Odonate is comparable to Vicon in its ability to identify abnormal gait patterns in patients with post-stroke. Therefore, Odonate has the potential to provide accessible and objective measurements for clinical gait assessment.

Two-dimensional equivalent mechanical modeling and finite element analysis of normal female pelvic floor system

Objective: To construct the geometric model of the pelvic floor by a two-dimensional equivalent mechanics method, and to explore the effect of the shape and position of pelvic floor organs and tissues on the biomechanical properties of the pelvic floor under different abdominal pressure. Methods: A 28-year-old healthy and symmetrical married infertile female volunteer was included. The pelvic floor tissue was scanned in the supine position using a 3.0T magnetic resonance scanner (Philips Company, Holland). Based on the method of magnetic resonance imaging (MRI) two-dimensional parameter measurement and computer aided design, the geometric model and finite element model of the female pelvic floor were established, and the biomechanical characteristics of the pelvic floor support system under different abdominal pressure were analyzed. Results: In this study, four different working conditions of the pelvic floor force were simulated under 60, 99, 168, and 208 cmH2O (1 cmH2O=0.098 kPa) abdominal pressure loads. The trend was as follows: under the abdominal pressure load, the retrograde flexion of the uterus occurred, the cervical, the middle and upper vaginal segment and the levator anus muscle had the characteristic change of mechanical axial direction pointing to the sacrum and coccyx, and the deformation of the levator anus muscle in the horizontal direction was greater than that in the vertical direction. With the increase of the abdominal pressure, the maximum stress values of the pelvic floor whole system of healthy subjects under four different working conditions were 0.194 3, 0.389 6, 0.557 1, and 0.627 5 MPa, respectively, and the maximum displacement values were 10, 14, 21 and 25 mm, respectively. The maximum stress values of the cervical and vaginal middle and upper segment were 0.111 7, 0.161 8, 0.250 6, and 0.304 1 MPa, respectively, and the maximum displacement values were 3, 6, 9, and 11 mm, respectively. The maximum stress of the perineal body was 0.063 4, 0.119 6, 0.235 2, and 0.288 0 MPa, and the maximum displacement was 1, 2, 4, and 5 mm. The maximum stress values of the levator anus muscle were 0.194 3, 0.389 6, 0.557 1, and 0.627 5 MPa, and the maximum displacement values were 2, 4, 7, and 8 mm, respectively. The maximum stress and maximum displacement of pelvic organs increased with the increase of the abdominal pressure under different working conditions. The stress axial relationship of normal female pelvic floor was that the middle and upper segment of uterus and vagina mainly acted on the sacrococcyx and the levator anus muscle, and the lower vaginal segment acts on the perineal body. Conclusions: The two-dimensional equivalent mechanical modeling and finite element analysis of the female pelvic floor system can accurately reflect the biomechanical characteristics of the female pelvic floor, and the resultant stress direction of the pelvic organs points to the sacrum and coccyx. The sacrum and coccyx, levator anus and perineal body play important stress supporting roles in the pelvic floor system.

Applying Combined Action Observation and Motor Imagery to Enhance Classification Performance in a Brain–Computer Interface System for Stroke Patients

Motor imagery (MI) and action observation (AO) are mental practices commonly applied in brain&#x2013;computer interface (BCI) systems for stroke rehabilitation. However, previous studies have reported that combined AO and MI (AOMI) is more effective than MI or AO alone in terms of enhanced event-related desynchronization (ERD), which expresses cortical excitability and improves the classification performance of the BCI system in healthy subjects. Nonetheless, evidence the use of this strategy in stroke patients is still lacking. Hence, this study aimed to investigate the effect of AOMI on classification performance and ERD in chronic stroke patients. Ten chronic stroke participants were recruited for this study. Each participant was asked to perform both MI (control condition) and AOMI (experimental condition) tasks. For the MI task, the participants requested to perform MI while gazing at a static arrow picture. For the AOMI task, the participants were given a video-guided movement while executing MI. An array of 16 Ag/AgCl electrodes were used to record electroencephalographic (EEG) data during the mental tasks to analyze ERD amplitudes. Common spatial patterns (CSPs) combined with support vector machines (SVMs) were employed to evaluate the classification performance (offline analysis) of the baseline and imagery classes under each condition. Our results indicated that the ERD values and classification accuracy in AOMI were significantly greater than those under MI conditions. Moreover, a significant negative correlation between ERD values and classification performance was also found. In other words, enhanced ERD values (more negative values) also increased classification performance.

Sympathetic nerve activity changes following acute exposures to electronic and tobacco cigarette smoking in humans

Abstract Background/Introduction Tobacco cigarette (TC) smoking acutely increases blood pressure and sympathetic nerve activity, whereas there are scarce data on the impact of electronic cigarette (EC). Purpose The aim of the study was to assess the acute effects of TC, EC and sham smoking on blood pressure, heart rate and sympathetic nervous system in healthy subjects. Methods We studied 12 normotensive male habitual smokers (mean age 33 years) free of cardiovascular disease. The study design was randomized and placebo controlled with 3 experimental sessions (sham smoking, tobacco cigarette smoking, and e-cigarette smoking) in random order, each session on a separate day. Subjects smoked 2 tobacco cigarettes containing 1.1 mg nicotine or simulate smoking (sham smoking) with the 2 cigarettes separated by 5 minutes. Additionally, participants smoked e-cigarettes for a period of 5 and 30 minutes. In all occasions, sympathetic drive was assessed by muscle sympathetic nerve activity (MSNA) (baroreflex-dependent) and skin sympathetic nerve activity (SSNA) (baroreflex-independent) based on established methodology (microneurography). Results After the first and second TC smoking, there was significant increase in mean arterial pressure (MAP) (by 6 and 8 mmHg, respectively, overall p&amp;lt;0.001) and heart rate (by 8 and 12 beats/minute, respectively, overall p&amp;lt;0.001) compared to baseline. Similarly, EC smoking at 5 and 30 minutes compared to baseline was accompanied by augmentation of MAP (by 6 and 10 mmHg, respectively, overall p&amp;lt;0.001) and heart rate (by 5 and 9 beats/minute, respectively, overall p&amp;lt;0.001). Sham smoking was accompanied by a reduction in MAP after the first and second cigarette compared to baseline (by 2 and 4 mmHg, respectively, p=0.001), whereas there was no significant difference in heart rate (p=NS). The first and second TC smoking was characterized by lower muscle MSNA (by 6 and 6 bursts/minute, respectively, overall p&amp;lt;0.001) compared to baseline, whereas SSNA was increased (by 9 and 10 bursts/minute respectively, overall p&amp;lt;0.001). Additionally, EC smoking at 5 and 30 minutes caused a decrease in MSNA (by 8 and 8 bursts/minute, respectively, overall p&amp;lt;0.00) and an augmentation in SSNA (by 7 and 9 bursts per minute, respectively, overall p&amp;lt;0.001) compared to baseline. Sham smoking had no significant effect on MSNA and SSNA (p=NS for both). Conclusions Sympathetic, pressor and heart rate unfavorable responses to EC smoking are similar to those elicited by TC in healthy subjects. Our findings provide novel insights into the negative impact of EC on cardiovascular system and support opinions recommending great caution concerning EC use. Funding Acknowledgement Type of funding sources: None.

Repeatability and Reproducibility of Total Retinal Blood Flow Measurements Using Bi-Directional Doppler OCT.

PurposeTo investigate the repeatability and reproducibility of total retinal blood flow measurements using a custom-built dual-beam bidirectional Doppler optical coherence tomography (OCT) system in healthy subjects.MethodsRepeatability and reproducibility were analyzed in 10 and 34 healthy subjects, respectively. For repeatability, measurements were taken twice within 30 minutes, for reproducibility, twice within two to five weeks. Two analysis approaches were compared for calculation of absolute blood velocities: a previously published approach resulting in values for total arterial (QA,abs) and total venous blood flow (QV,abs) and a novel approach taking into account that there is a fixed relation between the phase shift in the two OCT channels (QA,new, QV,new). Repeatability and reproducibility were quantified using intraclass correlation coefficients (ICCs).ResultsFor QA,abs and QV,abs, ICC values between 0.78 and 0.84 were obtained. QA,new and QV,new values revealed better repeatability and reproducibility as compared to the convential appoach. Repeatability ICCs for QA,new and QV,new were between 0.91 and 0.93, and reproducibility ICCs were between 0.87 and 0.91 indicating excellent reproducibility. Good agreement was observed between total retinal blood flow values as measured from retinal arteries and retinal veins.ConclusionsMeasurement of total retinal blood flow using dual-beam Doppler OCT shows excellent reproducibility, which can further be improved by using a novel algorithm for calculating blood velocities in retinal vessels.Translational RelevanceOur data indicate that dual-beam Doppler OCT can be used for longitudinal studies. Hence, quantitative retinal blood flow may be established as a biomarker for progression vascular eye diseases.

Severity of Sleep Bruxism and its Implications for the Stomatognathic System in Healthy Subjects

BACKGROUND: Sleep bruxism (SB) changes the functionality patterns of the stomatognathic system. However, its severity can be an aggravating factor in the function of this complex system.&#x0D; AIM: The purpose of the study was to investigate the stomatognathic system of healthy subjects with different severity of SB, as determined by BiteStrip.&#x0D; METHODS: Thirty-four subjects were divided into two groups: Mild SB (n = 15) and severe SB (n = 19). Electromyograph was used to evaluate the electromyographic activity of the right masseter (RM), left masseter (LM), right temporal (RT), and left temporal (LT) muscles at mandibular rest, right and left laterality, protrusion, and maximum voluntary contraction. Molar bite force was measured by the dynamometer. The data were tabulated and submitted for statistical analysis (p &lt; 0.05).&#x0D; RESULTS: Molar bite force was significantly lower in the severe SB group. There was a significant increase in electromyographic activity in the severe SB group for the mandibular rest tasks (RM, RT, and LT), protrusion (RM, LM, RT, and LT), and right and left laterality in the temporalis muscles. There was a significant decrease in electromyographic activity in the severe SB group in maximum voluntary contraction for the masseter and temporalis muscles.&#x0D; CONCLUSION: Subjects with severe SB demonstrated greater functional impairment of the stomatognathic system, mainly affecting the electromyographic activity and molar bite force.

The Effects of the Suboccipital Release Technique on the Autonomic Nervous System in Healthy Subjects: a Pilot Study

The Effects of the Suboccipital Release Technique on the Autonomic Nervous System in Healthy Subjects: a Pilot Study

P4388Acute detrimental effects of e-cigarette and tobacco cigarette smoking on blood pressure and sympathetic nerve activity in healthy subjects

Abstract Background/Introduction Tobacco cigarette smoking is related with atherosclerosis progression, blood pressure increase and changes in sympathetic nerve activity. However, there are scarce data on the impact of e-cigarettes that have been proposed as less harmful alternatives on the cardiovascular system and sympathetic drive. Purpose This study aimed to assess the acute effects of tobacco cigarettes, e-cigarettes and sham smoking on blood pressure and sympathetic nervous system in healthy subjects. Methods We studied 10 normotensive male habitual smokers (mean age 33 years, body mass index: 24.1 kg/m2, office blood pressure=117/72 mmHg) free of cardiovascular disease. The study design was randomized and placebo controlled with 3 experimental sessions (sham smoking, tobacco cigarette smoking, and e-cigarette smoking) in random order, each session on a separate day. Subjects smoked 2 tobacco cigarettes containing 1.1 mg nicotine or simulate smoking (sham smoking) with the 2 cigarettes separated by 5 minutes, while 45 minutes after finishing the second cigarette, subjects smoked a third cigarette or sham cigarette. Additionally, participants smoked e-cigarettes for a period of 5 and 30 minutes. In all occasions, sympathetic drive was assessed by muscle sympathetic nerve activity (MSNA) (baroreflex-dependent) and skin sympathetic nerve activity (SSNA) (baroreflex-independent) based on established methodology (microneurography). Results After the first, second and third tobacco cigarette smoking there was markedly and significantly increase in mean arterial pressure (by 11.2±1.4%, 12.3±1.3% and 13.1±1.4%, respectively, p&lt;0.05 for all) and heart rate (by 25.1±3.7%, 26.3±2.7% and 25.9±3.7%, respectively, p&lt;0.05 for all). Similarly e-cigarette smoking at 5 and 30 minutes was accompanied by augmentation of mean arterial pressure (by 10.9±1.2% and 12.8±1.4%, respectively, p&lt;0.05 for both) and heart rate (by 22.5±3.3% and 23.9±3.8%, respectively, p&lt;0.05 for both). Regarding the effect on sympathetic nervous system, the first, second and third tobacco cigarette smoking was accompanied by lower MSNA (by 28.1±4.4%, 29.6±5.3% and 30.1±5.2%, respectively, p&lt;0.05 for all), whereas SSNA was increased (by 98.2±19.4%, 100.2±22.7% and 101.5±21.6%, respectively, p&lt;0.05 for all). Additionally, e-cigarette smoking at 5 and 30 minutes caused a decrease in MSNA (by 26.9±3.6%, and 28.3±5.1%, respectively, p&lt;0.05 for both), and an augmentation in SSNA (by 97.9±20.1% and 100.9±20.6%, respectively, p&lt;0.05 for both). Sham smoking was devoid of any effects on blood pressure, MSNA and SSNA. Conclusions E-cigarette smoking acutely increases blood pressure and has a detrimental effect on sympathetic nerve activity regulation similar to tobacco smoking in healthy subjects. Our findings underscore the negative impact of e-cigarettes on cardiovascular and autonomic nervous system and could aid further recommendation in their use.

PER3 variable number tandem repeat (VNTR) polymorphism modulates the circadian variation of the descending pain modulatory system in healthy subjects

We evaluated the circadian pattern of variation of the descending pain modulatory system (DPMS) using a conditioned pain modulation (CPM) paradigm according to the variable-number tandem-repeat (VNTR) of the clock gene PER3 polymorphism. We assessed the relationship between the genotypes PER34/4 and PER35/5 and the temporal pattern of variation across the day using the following measures: the heat pain threshold (HPT), the cold pressure test (CPT), and the serum levels of BDNF and S100-B protein. The ∆-values (from afternoon to morning) of these measures were used for the analysis. The circadian phenotype was according to the mid-point sleep time established by the Munich ChronoType Questionnaire (MCTQ). We included 18 healthy volunteers (15 women) ages 18 to 30. A Generalized Linear Model (GLM) revealed a significant difference in the ∆-CPM-task between Per34/4 and Per35/5 genotypes, with means (SDs) of −0.41 (0.78) vs. 0.67 (0.90) (χ2 = 7.256; df = 1′ P = 0.007), respectively. Both sleep deprivation of at least 2 h/day (B = −0.96, 95% confidence interval (CI) = −1.86 to −0.11)) and the ∆-S100-B protein (−0.03, 95% CI = −0.06 to −0.02) were negatively correlated with the ∆-CPM-task, while the ∆-BDNF was positively correlated with the ∆-CPM-task (0.015, 95% CI = 0.01 to 0.03). We observed a difference in the ∆-CPT between PER34/4 and PER35/5 (0.11 (4.51) vs. 4.00 (2.60), respectively) (χ2 = 22.251; df = 1 P = 0.001). These findings suggest that the polymorphism of PER35/5 is associated with a decrease in the inhibitory function of the DPMS over the course of the day. However, sleep deprivation is an independent factor that also reduces the inhibitory function of the DPMS, regardless of the PER3 VNTR polymorphism.

A new approach for digestive disease diagnosis: Dynamics of gastrointestinal electrical activity

Various methods are used for analyzing the status of the human body. In digestive system, myoelectrical activity is recorded from the abdominal surface. Frequency and power of Gastrointestinal (GI) activity is usually assessed using power spectral analysis. However, spectral analysis of GI electrical activity is a nonspecific test, failing to distinguish diseases. Other dimensions of GI electrical waves may help identify diseases more precisely. Studying complex systems is one of the approaches that can be taken for research on body systems. The dynamic variability of a complex system is estimated by nonlinear methods. Previous studies have identified how functional dynamic variability of organs differ in normal and disease conditions. Variation of electroencephalogram, heart rate, and respiratory rate are known examples of system dynamic fluctuation. If we consider the digestive tract as a complex system, the dynamic variation of the waves in the GI system could be analyzed by nonlinear methods to possibly help clinicians assess various conditions of the GI system in healthy subjects and patients.

A startling acoustic stimulation (SAS)-TMS approach to assess the reticulospinal system in healthy and stroke subjects

Reticulospinal (RS) hyperexcitability is observed in stroke survivors with spastic hemiparesis. Habituated startle acoustic stimuli (SAS) can be used to stimulate the RS pathways non-reflexively. However, the role of RS pathways in motor function and its interactions with the corticospinal system after stroke still remain unclear. Therefore, the purpose of this study was to investigate the effects of conditioning SAS on the corticospinal system in healthy subjects and in stroke subjects with spastic hemiparesis. An established conditioning SAS- transcranial magnetic stimulation (TMS) paradigm was used to test the interactions between the RS pathways and the corticospinal system. TMS was delivered to the right hemisphere of eleven healthy subjects and the contralesional hemisphere of eleven stroke subjects during isometric elbow flexor contraction on the non-impaired (or left) side. Conditioning SAS had similar effects on the corticospinal motor system in both healthy and stroke subjects, including similar SAS-induced motor evoked potential (MEP) reduction at rest, but not during voluntary contraction tasks; similar magnitudes of TMS-induced MEP and force increment and shortening of the silent period during voluntary elbow flexor contraction. This study provides evidence that RS excitability on the contralesional side in stroke subjects with spastic hemiparesis is not abnormal, and suggests that RS projections are likely to be primarily unilateral in humans.

Effect of selected osteopathic lymphatic techniques on immune system in healthy subjects: A randomized control trial

Effect of selected osteopathic lymphatic techniques on immune system in healthy subjects: A randomized control trial

Effects of vertical water immersion on the nervous system: a systematic review

Vertical immersion induces a variety of physiological responses in different body systems, depending on the properties of fluid mechanics, which are the basis that underpins aquatic therapy programs in different pathologies. To perform a systematic review to analyze and describe the effects that vertical immersion produces on the nervous system in healthy subjects. A systematic search of the existing literature was conducted in the databases BRAIN, PubMed, PEDro and Web of Science. Quality was methodologically assessed using the CASPe guideline and the level of evidence was categorized using the Oxford scale. A total of 12 articles were included, with a score range of 7-10 according to CASPe, levels of evidence 1b-2b and grade of recommendation B. All studies showed positive results to the different forms of exposure of vertical immersion in water and the summation of the stimuli used; no adverse effects were reported in any case. The vertical immersion in the water generates positive effects on cerebral blood flows, cortical activation, executive functions and the production of neurotrophins in healthy subjects.

Visualization of the electrical activity of the cauda equina using a magnetospinography system in healthy subjects

ObjectiveTo establish a method to measure cauda equina action fields (CEAFs) and visualize the electrical activities of the cauda equina in a broadly aged group of healthy adults. MethodsUsing a 124-channel magnetospinography (MSG) system with superconducting interference devices, the CEAFs of 43 healthy volunteers (22–64 years of age) were measured after stimulation of the peroneal nerve at the knee. Reconstructed currents were obtained from the CEAFs and superimposed on the X-ray image. Conduction velocities were also calculated from the waveform of the reconstructed currents. ResultsThe reconstructed currents were successfully visualized. They flowed into the L5/S1 foramen about 8.25–8.95 ms after the stimulation and propagated cranially along the spinal canal. In 32 subjects (74%), the conduction velocities of the reconstructed currents in the cauda equina could be calculated from the peak latency at the L2–L5 level. ConclusionsMSG visualized the electrical activity of the cauda equina after peroneal nerve stimulation in healthy adults. In addition, the conduction velocities of the reconstructed currents in the cauda equina could be calculated, despite previously being difficult to measure. SignificanceMSG has the potential to be a novel and noninvasive functional examination for lumbar spinal disease.

Bioequivalence assessment of tulobuterol transdermal delivery system in healthy subjects .

The purpose of this study was to evaluate the bioequivalence in the pharmacokinetics of two 2-mg tulobuterol transdermal delivery systems (TDSs) in healthy subjects. The pharmacokinetic (PK) analysis was performed using data from a randomized, open-label, single-dose, two-way, two-period, crossover study. Eligible subjects received either the Bretol®patch (test drug) or Hokunalin®patch (reference drug) in sequence according to their allocated group. Serial blood samples for PK analyses were collected for up to 48 hours after tulobuterol TDS application. The PK parameters, including the maximum concentration (Cmax) and area under the curve from time zero to the last quantifiable concentration time (AUClast), were estimated by using noncompartmental analysis. The geometric mean ratios (GMRs) of the Cmax and AUClast and their 90% confidence intervals (CIs) were estimated. A total of 27 subjects completed the study as planned. The concentration-time profiles of tulobuterol were similar in both formulations. The GMRs (90% CIs) of Cmax and AUClast were 0.9443 (0.8790 - 1.0144) and 0.9600 (0.8660 - 1.0642), respectively. The PK profiles of both tulobuterol TDSs were comparable. In addition, the 90% CIs of the GMR were within the bioequivalence criteria of 0.800 - 1.250. Therefore, the Bretol®patch can be used as an alternative to the Hokunalin®patch for the treatment of patients with asthma and chronic obstructive pulmonary disease. .

A planar neuro-musculoskeletal arm model in post-stroke patients

Mathematical modeling of the neuro-musculoskeletal system in healthy subjects has been pursued extensively. In post-stroke patients, however, such models are very primitive. Besides improving our general understanding of how stroke affects the limb motions, they can be used to evaluate rehabilitation strategies by computer simulations before clinical evaluations. A planar neuro-musculoskeletal arm model for post-stroke patients is developed. The main idea is to use a set of new coefficients, Muscle Significance Factors (MSF), to incorporate the effects of stroke in the muscle control performance. The model uses the optimal control theory to mimic the performance of the CNS and a two-link skeletal model with six muscles for the biomechanical part. The model was developed and evaluated using experimental data from six post-stroke patients with Brunnstrom levels of 4-6. The results show that MSFs are relatively distinct and independent from the arm motion which is used to determine their values. Its variation is in the range of 0-2.58% and decreases in higher Brunnstrom levels. The mean error of the model in predicting the path of motion varies from 0.9% in level 6 to 5.58% in level 4 subjects which can be considered a promising level of accuracy. Using the proposed model and the MSF to customize the model for each individual stroke patient seems a promising approach. It shows a reasonable level of robustness, i.e., independence from the type of motions and correlated with the severity of stroke, and accuracy in predicting the shape of the motion path.

Autonomic Influence on Heart Rate for Deep Breathing and Valsalva Maneuver in Healthy Subjects

The Autonomic nervous system is responsible for regulation and integration of visceral functions. Disturbance of autonomic nervous system play crucial role in pathogenesis and clinical course of many diseases. In the present study deep breathing test and valsalva maneuver have been described to monitor parasympathetic function genderwise. A cross-sectional study was conducted among 100 subjects, aged 18-25 years, from May to November 2017, in exercise physiology laboratory, Kathmandu University School of Medical Sciences, Chaukot, Kavre. Electrocardiograph recorded by AD instrument was used to calculate the resting heart rate and the heart rate response to deep breathing test and valsalva maneuver. Heart rate response to deep breathing test (31.69±14.79 Vs. 36.08±18.65, P=0.195) and valsalva ratio (1.59±0.39 Vs. 1.69±0.54, P=0.314) tend to be higher in female than male subjects but not significant. The resting heart rate of females was significantly higher than that of males (84.37 ± 11.08 Vs. 78.43 ± 12.06, P<0.05). Heart rate was significantly increased during and decreased after valsalva maneuver in both male and female subjects. This study concludes that both deep breathing test and valsalva maneuver activates parasympathetic system inhealthy subjects. And also dominant parasympathetic activity was found in female comparison to male subjects.

Variability of Tear Osmolarity Measurements With a Point-of-Care System in Healthy Subjects-Systematic Review.

To assess the variability of osmolarity measured by the point-of-care TearLab system in healthy eyes. A systematic review was performed by searching MEDLINE, Scopus, and the Web of Science Databases until November 2016 and checking reference lists of included articles and reviews. The requirements for inclusion were the availability of TearLab results in healthy subjects and a minimum study sample of 20 eyes. Two reviewers assessed articles against the inclusion criteria, extracted relevant data, and examined the methodological quality. We computed the weighted mean osmolarity using the study size as the weighting factor and calculated the rate of subjects with osmolarity values >308 mOsm/L, the Dry Eye Workshop Report 2017 (DEWS) cut-off value for dry eye disease (DED). We repeated the analysis after excluding reports with a possible conflict of interest or missing description of subject selection. Searches retrieved 105 nonduplicate articles, and we included 33 studies investigating 1362 eyes of healthy participants who were asymptomatic and showed no clinical signs of DED. Sixty-three percent were female, and mean age was 37.3 years (range: 21.5-69.0 yr). Weighted mean osmolarity was 298 mOsm/L (95% confidence interval, 282-321 mOsm/L). The result of the subgroup analysis was similar. Overall, 386 of 1362 eyes (28.3%) fulfilled the DEWS's definition of DED (>308 mOsm/L). There is a high variability of osmolarity measurements with the TearLab system. A substantial number of healthy subjects fulfill the DEWS's definition of DED. We propose interpreting the TearLab osmolarity results cautiously and in the context of other established methods.