Impact of chickpea hummus on postprandial blood glucose, insulin and gut hormones in healthy humans combined with mechanistic studies of food structure, rheology and digestion kinetics.

Slowing the rate of carbohydrate digestion leads to low postprandial glucose and insulin responses, which are associated with reduced risk of type 2 diabetes. There is increasing evidence that food structure plays a crucial role in influencing the bioaccessibility and digestion kinetics of macronutrients. The aims of this study were to compare the effects of two hummus meals, with different degrees of cell wall integrity, on postprandial metabolic responses in relation to the microstructural and rheological characteristics of the meals. A randomised crossover trial in 15 healthy participants was designed to compare the acute effect of 27 g of starch, provided as hummus made from either intact chickpea cells (ICC) or ruptured chickpea cells (RCC), on postprandial metabolic responses. In vitro starch digestibility, microstructural and rheological experiments were also conducted to evaluate differences between the two chickpea hummus meals. Blood insulin and GIP concentrations were significantly lower (P < 0.02, P < 0.03) after the consumption of the ICC meal than the meal containing RCC. In vitro starch digestion for 90 min was slower in ICC than in RCC. Microscopic examination of hummus samples digested in vitro for 90 min revealed more intact chickpea cells in ICC compared to the RCC sample. Rheological experiments showed that fracture for ICC hummus samples occurred at smaller strains compared to RCC samples. However, the storage modulus for ICC was higher than RCC, which may be explained by the presence of intact cells in ICC. Food structure can affect the rate and extent of starch bioaccessibility and digestion and may explain the difference in the time course of metabolic responses between meals. The rheological properties were measured on the two types of meals before ingestion, showing significant differences that may point to different breakdown mechanisms during subsequent digestion. This trial was registered at clinicaltrial.gov as NCT03424187.

Relationship between rheological properties, sensory perception, and overall acceptability of thickened liquids for dysphagia in young and old healthy individuals.

This study investigated the relationship between rheological properties, sensory perception, and overall acceptability in healthy young and old groups for dysphagia thickened liquids. Unflavored (UTL) and flavored (FTLP) thickened liquids were prepared using tap water or pomegranate juice at 10 different viscosity levels. The rheological properties were then evaluated via syringe flow test and line spread test (LST). When the apparent viscosity levels of UTL and FTLP were similar, the syringe test and LST results were also similar, indicating consistent flow behavior. Sensory perception evaluations showed that the young group better distinguished viscosity differences between stages compared to the old group. Regarding overall acceptability, the old group preferred samples with higher apparent viscosity than the young group. Principal component analysis and k-means cluster analysis were used to explore correlations between variables and classify thickened liquids into four groups. This can serve the foundation for standardized texture grades of dysphagia thickened liquids, considering rheological characteristics and sensory profiles.

Sustained bias of spatial attention in a 3 T MRI scanner.

When lying inside a MRI scanner and even in the absence of any motion, the static magnetic field of MRI scanners induces a magneto-hydrodynamic stimulation of subjects' vestibular organ (MVS). MVS thereby not only causes a horizontal vestibular nystagmus but also induces a horizontal bias in spatial attention. In this study, we aimed to determine the time course of MVS-induced biases in both VOR and spatial attention inside a 3 T MRI-scanner as well as their respective aftereffects after participants left the scanner. Eye movements and overt spatial attention in a visual search task were assessed in healthy volunteers before, during, and after a one-hour MVS period. All participants exhibited a VOR inside the scanner, which declined over time but never vanished completely. Importantly, there was also an MVS-induced horizontal bias in spatial attention and exploration, which persisted throughout the entire hour within the scanner. Upon exiting the scanner, we observed aftereffects in the opposite direction manifested in both the VOR and in spatial attention, which were statistically no longer detectable after 7 min. Sustained MVS effects on spatial attention have important implications for the design and interpretation of fMRI-studies and for the development of therapeutic interventions counteracting spatial neglect.

Heatmap Evaluation of Facial Hydration Using a Novel Python Program.

BACKGROUND: Evaluating cleansers and moisturizers provides important information to guide clinicians in the recommendation of these products. This project was performed to visualize skin hydration via heatmap after the use of a gentle skin cleanser (GSC) and moisturizing lotion (ML). METHODS: Half-face, intra-individual open-label study in healthy volunteers. Cleanser was administered in a single application that was then wiped off the face. Moisturizing lotion was applied at least once-daily for one week. Hydration measurements were made at 30 pre-defined points on half of the face, at baseline, and 30 minutes post-application; an additional assessment at week 1 was made for the moisturizing lotion. Heatmaps were generated using Python programming software to interpolate hydration values to colors that were then superimposed onto the volunteer's facial image.  Results: Five subjects completed the cleanser assessments, and 5 subjects completed the 30-minute evaluation for the lotion, with 4 completing the week 1 assessment. There was a visible shift in skin hydration post-GSC application from values approximately in the 12-42 AU (arbitrary unit) range to 30-60 AU at 30 minutes. Similarly, there was a shift in hydration from baseline to 30 minutes that continued to increase through week 1 of ML use. CONCLUSIONS: This innovative heatmap data generation showed a clear, visual change in hydration over time. There was a visible shift in hydration values from baseline to 30 minutes after application of cleanser; hydration also improved after use of moisturizing lotion at 30 minutes and increased after week 1 application.  J Drugs Dermatol. 2024;23(6):463-465.     doi:10.36849/JDD.8221.

Phase 1, randomized, rater and participant blinded placebo-controlled study of the safety, reactogenicity, tolerability and immunogenicity of H1N1 influenza vaccine delivered by VX-103 (a MIMIX microneedle patch [MAP] system) in healthy adults.

BACKGROUND: The MIMIX platform is a novel microneedle array patch (MAP) characterized by slowly dissolving microneedle tips that deploy into the dermis following patch application. We describe safety, reactogenicity, tolerability and immunogenicity for MIMIX MAP vaccination against influenza. METHODOLOGY: The trial was a Phase 1, exploratory, first-in-human, parallel randomized, rater, participant, study analyst-blinded, placebo-controlled study in Canada. Forty-five healthy participants (18 to 39 years of age, inclusive) were randomized in a 1:1:1 ratio to receive either 15 µg or 7.5 µg of an H1N1 influenza vaccine, or placebo delivered via MIMIX MAP to the volar forearm. A statistician used a computer program to create a randomization scheme with a block size of 3. Post-treatment follow-up was approximately 180 days. Primary safety outcomes included the incidence of study product related serious adverse events and unsolicited events within 180 days, solicited application site and systemic reactogenicity through 7 days after administration and solicited application site erythema and/or pigmentation 14, 28, 56 and 180 days after administration. Immunogenicity outcomes included antibody titers and percentage of seroconversion (SCR) and seroprotection (SPR) rates determined by the hemagglutination inhibition (HAI) assay. Exploratory outcomes included virus microneutralization (MN) titers, durability and breadth of the immune response. The trial was registered with ClinicalTrials.gov, number NCT06125717. FINDINGS: Between July 7, 2022 and March 13, 2023 45 participants were randomized to a treatment group. One participant was lost to follow up in the 15 µg group and 1 participant withdrew from the 7.5 µg dose group. Safety analyses included n = 15 per group, immunogenicity analyses included n = 14 for the 15 µg and 7.5 µg treatment groups and n = 15 for the placebo group. No SAEs were reported in any of the treatment groups. All treatment groups reported solicited local events within 7 days after vaccination, with mild (Grade 1) erythema being the most frequent symptom reported. Other local symptoms reported included mostly mild (Grade 1) induration/swelling, itching, pigmentation, skin flaking, and tenderness. Within 7 days after vaccination, 2 participants (4.4%) reported moderate (Grade 2) erythema, 1 participant (2.2%) reported moderate (Grade 2) induration/swelling, and 1 participant (2.2%) reported moderate (Grade 2) itching. There was an overall reduction in erythema and pigmentation reported on Days 15, 29, 57, and 180 among all treatment groups. Systemic symptoms reported within 7 days after vaccination, included mild (Grade 1) fatigue reported among all treatment groups, and mild (Grade 1) headache reported by 1 participant in the 7.5 µg treatment group. No study drug related severe symptoms were reported in the study. Group mean fold rises in HAI titers ranged between 8.7 and 12-fold, SCRs were >76% and SPRs were >92% for both VX-103 dose groups thereby fulfilling serological criteria established by the EMA and FDA for seasonal influenza vaccines. Longitudinal assessments demonstrate persistence of the immune response through at least Day 180. CONCLUSIONS: The MIMIX MAP platform is safe, well tolerated and elicits robust antibody responses.

Simulating Healthy Participant Pharmacokinetics for Renal and Hepatic Impairment Studies: Retrospective Assessment of the Approach.

The recruitment of a parallel, healthy participants (HPs) arm in renal and hepatic impairment (RI and HI) studies is a common strategy to assess differences in pharmacokinetics. Limitations in this approach include the underpowered estimate of exposure differences and the use of the drug in a population for which there is no benefit. Recently, a method was published by Purohit et. al. (2023) that leveraged prior population pharmacokinetic (PopPK) modeling-based simulation to infer the distribution of exposure ratios between the RI/HI arms and HPs. The approach was successful, but it was a single example with a robust model having several iterations of development and fitting to extensive HP data. To test in more studies and models at different stages of development, our catalogue of RI/HI studies was searched, and those with suitable properties and from programs with available models were analyzed with the simulation approach. There were 9 studies included in the analysis. Most studies were associated with models that would have been available at the time (ATT) of the study, and all had a current, final model. For 3 studies, the HP PK was not predicted well by the ATT (2) or final (1) models. In comparison to conventional analysis of variance (ANOVA), the simulation approach provided similar point estimates and confidence intervals of exposure ratios. This PopPK based approach can be considered as a method of choice in situations where the simulation of HP data would not be an extrapolation, and when no other complicating factors are present.

The relationship between heart rate variability and glucose clearance in healthy men and women.

Heart rate variability (HRV) is a non-invasive indicator of the activity of the autonomic nervous system, which regulates many physiological functions including metabolism. The purpose of this study was to quantify the relationship between resting markers of HRV and oral glucose tolerance test (OGTT) response. Eighteen healthy individuals (10 males, 8 females, (23.8±2.9 years) underwent a 10-minute resting HRV recording. The final five minutes were evaluated via Kubios HRV Standard for: root mean square of successive differences (RMSSD), standard deviation of normal-to-normal sinus beats (SDNN), high frequency (HF), and low frequency (LF). A standard 2-hour OGTT was then administered. Glucose was measured via finger stick before, 30-minutes post, 1-hour post, and 2-hours post OGTT. Pearson correlations demonstrated that RMSSD, SDNN, HF and LF were strongly correlated to fasting blood glucose (FBG) for the group (p<0.05) but not for glucose area under the curve (AUC). When analyzed by sex, only males demonstrated significant correlations between AUC and RMSSD, SDNN, and LF (p<0.05). An independent samples t-test revealed no sex differences for FBG, AUC, RMSSD, SDNN, HF and LF. These findings provide new and interesting insights into the relationship of autonomic activity and glucose uptake, highlighting sex-based relationships.

Bioequivalence of a new coated 15 mg primaquine formulation for malaria elimination.

BACKGROUND: With only one 15 mg primaquine tablet registered by a stringent regulatory authority and marketed, more quality-assured primaquine is needed to meet the demands of malaria elimination. METHODS: A classic, two sequence, crossover study, with a 10-day wash out period, of 15 mg of IPCA-produced test primaquine tablets and 15 mg of Sanofi reference primaquine tablets was conducted. Healthy volunteers, aged 18-45 years, without glucose-6-phosphate dehydrogenase deficiency, a baseline haemoglobin ≥ 11 g/dL, creatinine clearance ≥ 70 mL/min/1.73 ms, and body mass index of 18.5-30 kg/m2 were randomized to either test or reference primaquine, administered on an empty stomach with 240 mL of water. Plasma primaquine and carboxyprimaquine concentrations were measured at baseline, then 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2.0, 2.333, 2.667, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0, 10.0, 12.0, 16.0, 24.0, 36.0, 48.0 and 72.0 h by liquid chromatography coupled to tandem mass spectrometry. Primaquine pharmacokinetic profiles were evaluated by non-compartmental analysis and bioequivalence concluded if the 90% confidence intervals (CI) of geometric mean (GM) ratios of test vs. reference formulation for the peak concentrations (Cmax) and area under the drug concentration-time (AUC0-t) were within 80.00 to 125.00%. RESULTS: 47 of 50 volunteers, median age 33 years, completed both dosing rounds and were included in the bioequivalence analysis. For primaquine, GM Cmax values for test and reference formulations were 62.12 vs. 59.63 ng/mL, resulting in a GM ratio (90% CI) of 104.17% (96.92-111.96%); the corresponding GM AUC0-t values were 596.56 vs. 564.09 ngxh/mL, for a GM ratio of 105.76% (99.76-112.08%). Intra-subject coefficient of variation was 20.99% for Cmax and 16.83% for AUC0-t. Median clearances and volumes of distribution were similar between the test and reference products: 24.6 vs. 25.2 L/h, 189.4 vs. 191.0 L, whilst the median half-lives were the same, 5.2 h. CONCLUSION: IPCA primaquine was bioequivalent to the Sanofi primaquine. This opens the door to prequalification, registration in malaria endemic countries, and programmatic use for malaria elimination. Trial registration The trial registration reference is ISRCTN 54640699.

Multimodal sensorimotor assessment of hand and forearm asymmetries: a reliability and correlational study.

Background: Effective rehabilitation of upper limb musculoskeletal disorders requires multimodal assessment to guide clinicians' decision-making. Furthermore, a comprehensive assessment must include reliable tests. Nevertheless, the interrelationship among various upper limb tests remains unclear. This study aimed to evaluate the reliability of easily applicable upper extremity assessments, including absolute values and asymmetries of muscle mechanical properties, pressure pain threshold, active range of motion, maximal isometric strength, and manual dexterity. A secondary aim was to explore correlations between different assessment procedures to determine their interrelationship. Methods: Thirty healthy subjects participated in two experimental sessions with 1 week between sessions. Measurements involved using a digital myotonometer, algometer, inclinometer, dynamometer, and the Nine-Hole Peg test. Intraclass correlation coefficients, standard error of the mean, and minimum detectable change were calculated as reliability indicators. Pearson's correlation was used to assess the interrelationship between tests. Results: For the absolute values of the dominant and nondominant sides, reliability was 'good' to 'excellent' for muscle mechanical properties, pressure pain thresholds, active range of motion, maximal isometric strength, and manual dexterity. Similarly, the reliability for asymmetries ranged from 'moderate' to 'excellent' across the same parameters. Faster performance in the second session was consistently found for the Nine-Hole Peg test. No systematic inter-session errors were identified for the values of the asymmetries. No significant correlations were found between tests, indicating test independence. Conclusion: These findings indicate that the sensorimotor battery of tests is reliable, while monitoring asymmetry changes may offer a more conservative approach to effectively tracking recovery of upper extremity injuries.

Evaluation of Drug-Drug Interaction Between Henagliflozin and Hydrochlorothiazide in Healthy Chinese Volunteers.

Purpose: Henagliflozin is an original, selective sodium-glucose cotransporter 2 (SGLT2) inhibitor. Hydrochlorothiazide (HCTZ) is a common anti-hypertensive drug. This study aimed to evaluate the potential interaction between henagliflozin and HCTZ. Methods: This was a single-arm, open-label, multi-dose, three-period study that was conducted in healthy Chinese volunteers. Twelve subjects were treated in three periods, period 1: 25 mg HCTZ for four days, period 2: 10 mg henagliflozin for four days and period 3: 25 mg HCTZ + 10 mg henagliflozin for four days. Blood samples and urine samples were collected before and up to 24 hours after drug administrations on day 4, day 10 and day 14. The plasma concentrations of henagliflozin and HCTZ were analyzed using LC-MS/MS. The urine samples were collected for pharmacodynamic glucose and electrolyte analyses. Tolerability was also evaluated. Results: The 90% CI of the ratio of geometric means (combination: monotherapy) for AUCτ,ss of henagliflozin and HCTZ was within the bioequivalence interval of 0.80-1.25. For henagliflozin, co-administration increased Css, max by 24.32% and the 90% CI of the GMR was (108.34%, 142.65%), and the 24-hour urine volume and glucose excretion decreased by 0.43% and 19.6%, respectively. For HCTZ, co-administration decreased Css, max by 19.41% and the 90% CI of the GMR was (71.60%, 90.72%), and the 24-hour urine volume and urinary calcium, potassium, phosphorus, chloride, and sodium excretion decreased by 11.7%, 20.8%, 11.8%, 11.9%, 22.0% and 15.5%, respectively. All subjects (12/12) reported adverse events (AEs), but the majority of theses AEs were mild and no serious AEs were reported. Conclusion: Although Css,max was affected by the combination of henagliflozin and HCTZ, there was no clinically meaningful safety interaction between them. Given these results, coadministration of HCTZ should not require any adaptation of henagliflozin dosing. Trial Registration: ClinicalTrials.gov NCT06083116.

Influencing Factors on Pupillary Light Responses as a Biomarker for Local Retinal Function in a Large Normative Cohort.

Purpose: Investigating influencing factors on the pupillary light response (PLR) as a biomarker for local retinal function by providing epidemiological data of a large normative collective and to establish a normative database for the evaluation of chromatic pupil campimetry (CPC). Methods: Demographic and ophthalmologic characteristics were captured and PLR parameters of 150 healthy participants (94 women) aged 18 to 79 years (median = 46 years) were measured with L-cone- and rod-favoring CPC protocols. Linear-mixed effects models were performed to determine factors influencing the PLR and optical coherence tomography (OCT) data were correlated with the pupillary function volume. Results: Relative maximal constriction amplitude (relMCA) and latency under L-cone- and rod-favoring stimulation were statistically significantly affected by the stimulus eccentricity (P < 0.0001, respectively). Iris color and gender did not affect relMCA or latency significantly; visual hemifield, season, and daytime showed only minor influence under few stimulus conditions. Age had a statistically significant effect on latency under rod-specific stimulation with a latency prolongation ≥60 years. Under photopic and scotopic conditions, baseline pupil diameter declined significantly with increasing age (P < 0.0001, respectively). Pupillary function volume and OCT data were not correlated relevantly. Conclusions: Stimulus eccentricity had the most relevant impact on relMCA and latency of the PLR during L-cone- and rod-favoring stimulation. Latency is prolonged ≥60 years under scotopic conditions. Considering the large study collective, a representative normative database for relMCA and latency as valid readout parameters for L-cone- and rod-favoring stimulation could be established. This further validates the usability of the PLR in CPC as a biomarker for local retinal function.

Description of mitochondrial oxygen tension and its variability in healthy volunteers.

OBJECTIVES: Describing mitochondrial oxygenation (mitoPO2) and its within- and between-subject variability over time after 5-aminolevulinic acid (ALA) plaster application in healthy volunteers. DESIGN: Prospective cohort study. SETTING: Measurements were performed in Leiden University Medical Center, the Netherlands. PARTICIPANTS: Healthy volunteers enrolled from July to September 2020. INTERVENTIONS: Two ALA plasters were placed parasternal left and right, with a 3-hour time interval, to examine the influence of the calendar time on the value of mitoPO2. We measured mitoPO2 at 4, 5, 7, 10, 28, and 31 hours after ALA plaster 1 application, and at 4, 5, 7, 25, and 28 hours after ALA plaster 2 application. PRIMARY AND SECONDARY OUTCOME MEASURES: At each time point, five mitoPO2 measurements were performed. Within-subject variability was defined as the standard deviation (SD) of the mean of five measurements per timepoint of a study participant. The between-subject variability was the SD of the mean mitoPO2 value of the study population per timepoint. RESULTS: In 16 completed inclusions, median mitoPO2 values and within-subject variability were relatively similar over time at all time points for both plasters. An increase in overall between-subject variability was seen after 25 hours ALA plaster time (19.6 mm Hg vs 23.9 mm Hg after respectively 10 and 25 hours ALA plaster time). CONCLUSIONS: The mitoPO2 values and within-subject variability remained relatively stable over time in healthy volunteers. An increase in between-subject variability was seen after 25 hours ALA plaster time warranting replacement of the ALA plaster one day after its application. TRIAL REGISTRATION: ClinicalTrials.gov with trial number NCT04626661.

Red wine alleviates atherosclerosis-related inflammatory markers in healthy subjects rather than in high cardiovascular risk subjects: A systematic review and meta-analysis.

BACKGROUND: Moderate red wine (RW) consumption is associated with a low risk of cardiovascular disease (CVD). However, few studies have evaluated the effects of RW and white wine (WW) on inflammatory markers related to atherosclerosis in healthy individuals and high-risk subjects for CVD. This study aimed to assess the effect of RW on inflammatory markers in healthy individuals and high-risk subjects for CVD compared with moderate alcohol consumption. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 (PRISMA) was followed in this study. The PubMed, Embase, Cochrane, Web of Science, SinoMed, EbscoHost, and ScienceDirect databases were searched. The risk of bias and quality of the included trials were assessed using the Cochrane Handbook. The main results are summarized in Stata 12. RESULTS: Twelve studies were included in the meta-analysis. The results demonstrated that RW significantly decreased circulating intercellular cell adhesion molecule-1, vascular cell adhesion molecule-1 (VCAM-1), tumor necrosis factor-alpha (TNF-α), lymphocyte function-associated antigen-1, and Sialyl-Lewis X expression on the surface of monocytes in healthy subjects, but not in patients with CVD. Additionally, RW significantly decreased Sialyl-Lewis X but increased clusters of differentiation 40 (CD40) expressed on the surface of T lymphocytes and significantly decreased C-C chemokine receptor type 2 (CCR2) and very late activation antigen 4 (VLA-4) expressed on the surface of monocytes. Interestingly, subgroup analysis also found that RW significantly decreased circulating interleukin-6 (IL-6) in Spain but not in other countries, and significantly increased αMß2 (Mac-1) in the group that had an intervention duration of less than 3 weeks. CONCLUSIONS: Moderate consumption of RW is more effective than WW in alleviating atherosclerosis-related inflammatory markers in healthy people rather than high-risk subjects for CVD, but this needs to be further confirmed by studies with larger sample sizes.

Comparison of gender identification using exfoliated cells obtained from toothbrush and miswak: A longitudinal study.

Gender identification plays a pivotal role in forensic medicine. Among the various methods used for gender identification, deoxyribose nucleic acid (DNA) based methods are considered accurate. Exfoliated oral mucosal cells that are harvested from oral hygiene aids can be potentially used for gender identification using real-time polymerase chain rection (PCR). The aim of the present longitudinal study is to assess and compare the efficacy of toothbrush and miswak as potential tools to harvest exfoliated cells for gender identification. Forty healthy volunteers were recruited and asked to clean their teeth using new toothbrush and fresh miswak each day for 4 days. Toothbrush and miswak used by the participants were subjected to DNA analysis immediately, 1st, 2nd and 6th month. The absorbance of DNA samples were quantified and gender identification was done by amplification of sex determining gene-Sex determining region Y gene (SRY) and ALT1 genes using real-time PCR. The number of correct and positive identification for samples at various time points were tabulated and subjected to statistical analysis. Post hoc power analysis showed that the study had a power of 93%. Correct and positive gender identification was observed for the samples (100%) obtained using miswak, for tooth brush it reduced to 95%, 80%, and 35% at the end of 1st, 2nd, and 6th month. The differences seen at the end of 2nd month and 6th month were statistically significant. Miswak is a better tool to harvest exfoliated cells for gender identification when compared to a toothbrush. Hence, miswak can serve as a potential tool in forensic medicine for DNA extraction and subsequently victim identification.

Determinants of hand pulse wave velocity and hand pulse transit time in healthy adults.

Arterial pulse wave velocity (PWV) is recognized as a convenient method to assess peripheral vascular stiffness. This study explored the clinical characteristics of hand PWV (hPWV) and hand pulse transit time (hPTT) in healthy adults (sixty males = 42.4 ± 13.9 yrs; sixty-four females = 42.8 ± 13.9 yrs) voluntarily participated in this study. The arterial pulse waveform and the anatomical distance from the radial styloid process to the tip of the middle finger of both hands were recorded in the sitting position. The hPWV was calculated as the traversed distance divided by hPTT between those two points. Male subjects showed significantly greater hPWV, systolic blood pressure, and pulse pressure than age-matched female subjects, while the hPTT was not significantly different between genders. Multiple linear regression analysis showed that gender is a common determinant of hPWV and hPTT, and that age and heart rate (HR) were negatively correlated with hPWV and hPTT, respectively. We conclude that male subjects have greater hPWV than female subjects. Ageing is associated with decreased hPWV, while increased HR is associated with a smaller hPTT. The hPWV and hPTT might be used as non-invasive indices to characterise the ageing and arterial stiffness of peripheral blood vessels.

The effects of music combined to paired associative stimulation on motor-evoked potentials and alertness in spinal cord injury patients and healthy subjects.

Paired associative stimulation (PAS) consisting of high-intensity transcranial magnetic stimulation (TMS) and high-frequency peripheral nerve stimulation (known as high-PAS) induces plastic changes and improves motor performance in patients with incomplete spinal cord injury (SCI). Listening to music during PAS may potentially improve mood and arousal and facilitate PAS-induced neuroplasticity via auditory-motor coupling, but the effects have not been explored. This pilot study aimed to determine if the effect of high-PAS on motor-evoked potentials (MEPs) and subjective alertness can be augmented with music. Ten healthy subjects and nine SCI patients received three high-PAS sessions in randomized order (PAS only, PAS with music synchronized to TMS, PAS with self-selected music). MEPs were measured before (PRE), after (POST), 30 min (POST30), and 60 min (POST60) after stimulation. Alertness was evaluated with a questionnaire. In healthy subjects, MEPs increased at POST in all sessions and remained higher at POST60 in PAS with synchronized music compared with the other sessions. There was no difference in alertness. In SCI patients, MEPs increased at POST and POST30 in PAS only but not in other sessions, whereas alertness was higher in PAS with self-selected music. More research is needed to determine the potential clinical effects of using music during high-PAS.

Comparison of the forearm rotation restriction capacities of four upper-extremity immobilization methods: there is no difference between single and double sugar tong splinting.

BACKGROUND: The aim of this study was to compare the effects of four different immobilization methods [single sugar tong splint (SSTS), double sugar tong splint (DSTS), short arm cast (SAC), and long arm cast (LAC)] commonly used for restricting forearm rotation in the upper extremity. METHODS: Forty healthy volunteers were included in the study. Dominant extremities were used for measurements. Basal pronation and supination of the forearm were measured with a custom-made goniometer, and the total rotation arc was calculated without any immobilization. Next, the measurements were repeated with the SAC, LAC, SSTS and DSTS. Each measurement was compared to the baseline value, and the percentage of rotation restriction was calculated. RESULTS: The most superior restriction rates were observed for the LAC (p = 0.00). No statistically significant difference was detected between the SSTS and DSTS in terms of the restriction of supination, pronation or the rotation arc (p values, 1.00, 0.18, and 0.50, respectively). Statistically significant differences were not detected between the SAC and the SSTS in any of the three parameters (p values, 0.25; 1.00; 1.00, respectively). When the SAC and DSTS were compared, while there was no significant difference between the two methods in pronation (p = 0.50), a statistically significant difference was detected in supination (p = 0.01) and in the total rotation arc (p = 0.03). CONCLUSION: The LAC provides superior results in restricting forearm rotation. The SAC and SSTS had similar effects on forearm rotation. The DSTS, which contains, in addition to the SSTS, a sugar tong portion above the elbow, does not provide additional rotational stability.

Effect of systemic vascular resistance on the agreement between stroke volume by non-invasive pulse wave analysis and Doppler ultrasound in healthy volunteers.

BACKGROUND: Stroke volume can be estimated beat-to-beat and non-invasively by pulse wave analysis (PWA). However, its reliability has been questioned during marked alterations in systemic vascular resistance (SVR). We studied the effect of SVR on the agreement between stroke volume by PWA and Doppler ultrasound during reductions in stroke volume in healthy volunteers. METHODS: In a previous study we simultaneously measured stroke volume by PWA (SVPWA) and suprasternal Doppler ultrasound (SVUS). We exposed 16 healthy volunteers to lower body negative pressure (LBNP) to reduce stroke volume in combination with isometric hand grip to elevate SVR. LBNP was increased by 20 mmHg every 6 minutes from 0 to 80 mmHg, or until hemodynamic decompensation. The agreement between SVPWA and SVUS was examined using Bland-Altman analysis with mixed regression. Within-subject limits of agreement (LOA) was calculated from the residual standard deviation. SVRUS was calculated from SVUS. We allowed for a sloped bias line by introducing the mean of the methods and SVRUS as explanatory variables to examine whether the agreement was dependent on the magnitude of stroke volume and SVRUS. RESULTS: Bias ± limits of agreement (LOA) was 27.0 ± 30.1 mL. The within-subject LOA was ±11.1 mL. The within-subject percentage error was 14.6%. The difference between methods decreased with higher means of the methods (-0.15 mL/mL, confidence interval (CI): -0.19 to -0.11, P<0.001). The difference between methods increased with higher SVRUS (0.60 mL/mmHg × min × L-1, 95% CI: 0.48 to 0.72, P<0.001). CONCLUSION: PWA overestimated stroke volume compared to Doppler ultrasound during reductions in stroke volume and elevated SVR in healthy volunteers. The agreement between SVPWA and SVUS decreased during increases in SVR. This is relevant in settings where a high level of reliability is required.

Exploring the immediate and short-term effect of lumbar spinal manipulation on pressure pain threshold: a randomized controlled trial of healthy participants.

BACKGROUND: Lumbar spinal manipulative therapy (SMT) is a common intervention used to treat low back pain (LBP); however, the exact neurophysiological mechanisms of SMT reducing pain measured through pain pressure threshold (PPT) have not been fully explored beyond an immediate timeframe (e.g., immediately or five-minutes following) referencing a control group. Therefore, the purpose of this study was to investigate the neurophysiological effects of lumbar SMT compared to deactivated ultrasound using PPT immediately following and 30-minutes following SMT. METHODS: A longitudinal, randomized controlled trial design was conducted between September to October 2023. Fifty-five participants were randomized into a control group of deactivated ultrasound (n = 29) or treatment group of right sidelying lumbar SMT (n = 26). PPT, recorded at the right posterior superior iliac spine (PSIS), was documented for each participant in each group prior to intervention, immediately, and 30-minutes after. A repeated measures ANOVA, with a post-hoc Bonferroni adjustment, was used to assess within-group and between-group differences in PPT. The significance level was set at a < 0.05 a priori. RESULTS: Statistically significant differences were found between the deactivated ultrasound and lumbar SMT groups immediately (p = .05) and 30-minutes (p = .02) following intervention. A significant difference in the lumbar SMT group was identified from baseline to immediately following (p < .001) and 30-minutes following (p < .001), but no differences between immediately following and 30-minutes following intervention (p = .10). The deactivated ultrasound group demonstrated a difference between baseline and immediately after intervention with a reduced PPT (p = .003), but no significant difference was found from baseline to 30-minutes (p = .11) or immediately after intervention to 30-minutes (p = 1.0). CONCLUSION: A right sidelying lumbar manipulation increased PPT at the right PSIS immediately after that lasted to 30-minutes when compared to a deactivated ultrasound control group. Future studies should further explore beyond the immediate and short-term neurophysiological effects of lumbar SMT to validate these findings. TRIAL REGISTRATION: This study was retrospectively registered on 4 December 2023 in ClinicalTrials (database registration number NCT06156605).