Healthy Volunteers Age Research Articles

Correlation of obesity indices with metabolic syndrome among Igbos in Enugu and their optimal cut-off points

Background: Metabolic syndrome also known as insulin resistance syndrome or Syndrome X, represents an association of risk factors for cardiovascular disease and type 2 diabetes mellitus. Its central diagnostic criteria include obesity, impaired fasting glucose, low HDL-cholesterol; elevated triglycerides levels and high blood pressure. Insulin resistance is believed to be the main cause of Metabolic Syndrome and is connected to the level of visceral or intra-abdominal adipose tissue, which could be assessed either by calculating body mass index or by measuring waist circumference. Objectives: This study aimed at determining the correlation of indices of obesity with metabolic syndrome among Igbos in Enugu and their optimal cut-off points. Method: This was a cross-sectional community-based descriptive survey carried out in Enugu Metropolis involving 469 apparently healthy adult volunteers age range 18-75 screened for metabolic syndrome using the Joint Interim Statement definition. Stratified random sampling technique was used in the selection of participants. The data obtained were coded and analyzed into percentages, mean and standard deviation using the Statistical Package for Social Sciences (SPSS), version 23. t-test was used to compare continuous variables for associations, while Youden index and Receiver Operating Characteristic analysis were used to determine optimal cut-off point of the obesity indices that best balances sensitivity and specificity of the obesity indices. Pearson correlation coefficient was used to examine correlation between obesity indices and cardiovascular risks. Statistical significance is set at p< 0.05 and 95% confidence interval. Result: The study revealed that all indices of obesity showed positive correlation with metabolic syndrome. BMI showed the least strength of correlation while WC is the best discriminator for predicting Metabolic Syndrome however, the optimal cut-off point of the obesity indices differ from the standard cut-off points. Conclusion: All the obesity indices used in the study showed positive correlation with metabolic syndrome however, WC is to be preferred in screening for metabolic syndrome. The optimal cut-off point obtained can be applied specifically for Igbos in Enugu

Hippocampal microscopic fractional anisotropy is reduced in temporal lobe epilepsy

Abstract Surgical resection is the method of choice for treating drug-resistant focal temporal lobe epilepsy (TLE). Postsurgical outcomes are better when magnetic resonance imaging (MRI) findings can localize the seizure focus for resection. However, many patients are MR-negative, meaning the focus cannot be differentiated from normal tissue in relaxation-weighted MRI. Diffusion MRI shows promise as a preoperative marker of neuronal abnormalities due to its sensitivity to cellular changes such as axon damage, indexed by fractional anisotropy. Microscopic fractional anisotropy is a recently introduced diffusion MRI metric that is sensitive to axon integrity regardless of axon orientation in both grey and white matter. In contrast, regular fractional anisotropy is only sensitive to axon integrity in coherently oriented bundles of fibers. This work investigated whether microscopic fractional anisotropy is sensitive to hippocampal abnormalities in drug-resistant TLE. Diffusion MRI was performed on a 3T scanner in 19 patients (age = 31±10 years) with drug-resistant TLE (of which 10 were MR-negative) and 18 healthy volunteers (age = 38±15). A deep-learning method was employed to segment the hippocampus into smaller subregions corresponding to the subiculum, cornu ammonis (CA) 1, CA2/3, and CA4 plus dentate gyrus (DG). Mean measurements of subregion volume, diffusivity, fractional anisotropy, and microscopic fractional anisotropy were compared between cohorts. In a subset of the TLE cohort suspected to have unilateral pathology (n=15, age = 32±10 years), the percentage differences between measurements ipsilateral and contralateral to the epileptogenic zone were evaluated to assess asymmetry. Microscopic fractional anisotropy was reduced in the hippocampus of drug-resistant TLE patients relative to healthy volunteers. In subregion-specific analysis, microscopic fractional anisotropy was significantly reduced in only the CA4/DG region in patients compared to healthy volunteers, after corrections for multiple comparisons. In the 15 patients with suspected unilateral pathology, microscopic fractional anisotropy was reliably and statistically lower in the ipsilateral CA4/DG region compared to the contralateral side. Significant differences were not observed between TLE patients and healthy volunteers, or between hemispheres for patients with suspected unilateral pathology, for the fractional anisotropy or volume metrics. Diffusion MRI may complement standard imaging procedures by detecting abnormalities in MRI-negative patients. Due to its ability to detect abnormality regardless of axon orientation, microscopic fractional anisotropy may improve seizure focus localization in surgical candidates.

Reliability of a new stabilization device for measurement of muscle strength using a hand-held dynamometer.

The hand-held dynamometer (HHD) is a reliable and portable tool for quantitatively assessing muscle strength. However, a number of variables, including the strength of the tester, the adequacy of stabilization, and the selected testing position, can affect the reliability of the device. The objective of the present study was to examine the reproducibility and inter-rater reliability of strength assessments using HHD with and without a stabilization device. Strength assessments were conducted with and without the stabilization device by two independent raters. Healthy volunteers with no history of musculoskeletal disorders were included in the study. The strength of the shoulder flexion, scapula elevation, knee extension, and hip abduction muscle groups was evaluated using HHD. The reliability of the measurements was evaluated using intra-class correlation (ICC), standard error of measurement, and minimal detectable change. Fifty-two healthy volunteers (age 21.51 ± 2.02 years) participated in the study. The reproducibility was found to be excellent (ICC = 0.89-0.99). While reliability between the assessors was good to excellent (ICC = 0.85-0.93), reliability between assessors and device was found moderate to good (ICC = 0.48-0.78). The strength values obtained for all directions of movement with the stabilization device were found to be significantly higher than those obtained without fixation of the HHD. It can be concluded that the data obtained from the assessors and HHD with stabilization device are not comparable. Moreover, the utilization of a stabilization device may serve to enhance the reliability of the measurements by eliminating the rater effect.

Analysis of Frequencies and Subsets of Peripheral Helper T Cells in Patients with Immune Thrombocytopenia

To investigate the frequencies and subset distribution of peripheral helper (Tph) T cells in patients with immune thrombocytopenia (ITP), and explore the pathogenesis of ITP. A total of 25 newly diagnosed ITP patients treated in The Second Affiliated Hospital of Dalian Medical University from January to December 2022 were selected, and 25 healthy volunteers (age- and sex-matched) were recruited as the control group. Flow cytometry was used to detect the subsets of CD4+ T cells and Tph cells. The frequency of effector memory (CCR7- CD45RO+CD4+) T cells in ITP patients was significantly higher than that in healthy controls(P < 0.05). The frequency of Tph cells in ITP patients was also significantly higher than that in healthy controls (P < 0.001), and most of the Tph cells in ITP patients were effector memory T cells. Furthermore, the expressions of T-cell costimulatory molecules in Tph cells, including ICOS and CD84, were similar to those in follicular helper T(Tfh) cells. CXCR3 - CCR6 -Tph (Tph2) subgroup was dominant in Tph cells, but the frequency of CXCR3+CCR6- Tph (Tph1) cells in ITP patients was much higher than that in healthy controls (P < 0.05). Tph cells, especially Tph1 cells, were abnormally expanded in ITP patients, which may be a potential etiology of ITP.

Validation of the abbreviated version of the Token Test in Latin American Spanish stroke patients.

The abbreviated version of the Token Test (aTT) is widely used to assess language comprehension deficits in stroke patients (SPs). However, aTT has not been validated for Latin American Spanish speakers, so clinicians tend to use cut-off scores for aTT validated in developed countries. To provide normative data for the Spanish aTT (Sp-aTT) in healthy Chilean Spanish-speaking and SP, determining the influence of sociodemographic variables such as gender, age and education on Sp-aTT performance. A total of 210 healthy volunteers (age range = 18-88 years) and 197 SPs (age range = 23-94 years), all native speakers of Chilean Spanish, were recruited. The association of age, gender and years of education on the Sp-aTT performance was analysed. Specificity and sensibility analyses of the Sp-aTT to diagnose language comprehension deficits were completed. Only age (p < 0.001) and years of education (p < 0.001) impacted the total score of Sp-aTT. Gender did not show an association with Sp-aTT performance (p = 0.181). For SPs, the Sp-aTT score showed a significant positive correlation (rho = 0.4, p < 0.001) with the aphasia severity rating scale (ASRS) score. For Sp-aTT, the area under the curve was 0.97, and the optimal cut-off score for the Sp-aTT was 30 (0.73 of sensitivity, 0.92 of specificity and a Youden index of 0.644). Age and years of education are two key factors to be controlled for when determining the optimal cut-off points for the Sp-aTT. Our results also highlight the need for language-specific norms in stroke and aphasia research. What is already known on the subject The aTT has been validated and adapted in several countries. Its properties in screening and detecting comprehensive deficits in SPs highlight its potential as a screening tool in clinical practice. Moreover, considering that stroke is the third largest cause of death worldwide, research and clinical practice have focused on how to improve early detection of deficits in these people, especially those related to cognition, language and functionality in SPs. Therefore, counting with validated and adapted tools is essential for clinicians because it could contribute to accurate intervention and classification of language disorders. What this paper adds to the existing knowledge The main contribution of this study is to provide normative data for the aTT in Latin American Spanish speakers. No previous studies have focused on validating this test and analysing the influence of three critical variables (age, gender and years of education) on its performance in SPs from Latin America. In addition, we propose a classification of the severity of comprehension deficits in SPs. Finally, we found comprehension deficits in patients with right and left hemisphere stroke, which would imply that these deficits would not be exclusive to left hemisphere stroke. What are the potential or actual clinical implications of this work? Contribute with validation of language comprehension tools, such as the aTT, could improve early diagnosis of patients with language disorders. This validation provides a test based on the sociodemographic characteristics of Latin American Speakers, which has yet to be established. Due to this, normative data considering the sociodemographic characteristics of the target population is crucial for accurately classifying comprehension deficits after brain damage.

Microvascular effects of a mixed meal tolerance test: a model validation study

AbstractPurposeEndothelial dysfunction is a pathophysiological change preceding many cardiovascular events. Measuring improvements of endothelial function is challenging when function is already optimal, which may be remediated using a physiological challenge. This study aimed to determine whether imaging assessments can detect microvascular effects of a mixed meal tolerance test (MMTT).MethodsTwenty healthy volunteers (age ≥45 and ≤70 years) underwent two MMTTs at the beginning (Day 1) and end (Day 84) of a twelve‐week period. Imaging methods included laser speckle contrast imaging (LSCI) combined with post‐occlusive reactive hyperaemia (PORH) and local thermal hyperaemia (LTH) challenges, passive leg movement ultrasonography (PLM), and sidestream dark field microscopy (SDFM). Measurements were conducted pre‐MMTT and at 5 timepoints post‐MMTT for PLM and SDFM and 3 timepoints post‐MMTT for PORH and LTH.ResultsNo consistent effects of the MMTT were detected on LSCI LTH, PLM and SDFM endpoints. LSCI PORH maximum perfusion was significantly suppressed 46, 136, and 300 min post‐MMTT administration on Day 1, while residual perfusion decreased significantly 46 and 136 min post‐MMTT on Day 1. However, when repeated on Day 84, PORH endpoints were not significantly affected by the MMTT.ConclusionSDFM, PLM and LSCI LTH endpoints displayed high intra‐subject variability and did not detect consistent effects of MMTT. LSCI PORH endpoints displayed the lowest intra‐subject variability of all assessed endpoints and were affected by the MMTT on Day 1, but not on Day 84. Further standardization of methods or more robust challenges to affect vascular endpoints may be needed.

Rapid imaging of intravenous gadolinium-based contrast agent (GBCA) entering ventricular cerebrospinal fluid (CSF) through the choroid plexus in healthy human subjects

BackgroundPathways for intravenously administered gadolinium-based-contrast-agents (GBCAs) entering cerebrospinal-fluid (CSF) circulation in the human brain are not well-understood. The blood-CSF-barrier (BCSFB) in choroid-plexus (CP) has long been hypothesized to be a main entry-point for intravenous-GBCAs into CSF. Most existing studies on this topic were performed in animals and human patients with various diseases. Results in healthy human subjects are limited. Besides, most studies were performed using MRI methods with limited temporal resolution and significant partial-volume effects from blood and CSF.MethodsThis study employs the recently developed dynamic-susceptibility-contrast-in-the-CSF (cDSC) MRI approach to measure GBCA-distribution in the CSF immediately and 4 h after intravenous-GBCA administration in healthy subjects. With a temporal resolution of 10 s, cDSC MRI can track GBCA-induced CSF signal changes during the bolus phase, which has not been investigated previously. It employs a long echo-time (TE = 1347 ms) to suppress tissue and blood signals so that pure CSF signal is detected with minimal partial-volume effects. GBCA concentration in the CSF can be estimated from cDSC MRI. In this study, cDSC and FLAIR MRI were performed immediately and 4 h after intravenous GBCA administration in 25 healthy volunteers (age 48.9 ± 19.5 years; 14 females). Paired t-tests were used to compare pre-GBCA and post-GBCA signal changes, and their correlations with age were evaluated using Pearson-correlation-coefficients.ResultsAt ~ 20 s post-GBCA, GBCA-induced cDSC signal changes were detected in the CSF around CP (ΔS/S = − 2.40 ± 0.30%; P < .001) but not in the rest of lateral ventricle (LV). At 4 h, significant GBCA-induced cDSC signal changes were observed in the entire LV (ΔS/S = − 7.58 ± 3.90%; P = .002). FLAIR MRI showed a similar trend. GBCA-induced CSF signal changes did not correlate with age.ConclusionsThese results provided direct imaging evidence that GBCAs can pass the BCSFB in the CP and enter ventricular CSF immediately after intravenous administration in healthy human brains. Besides, our results in healthy subjects established a basis for clinical studies in brain diseases exploiting GBCA-enhanced MRI to detect BCSFB dysfunction.

Reliability of In Vivo Creatine-Weighted Chemical Exchange Saturation Transfer (CrCEST) MRI in Calf Skeletal Muscle of Healthy Volunteers at 3 T.

Skeletal muscle mitochondrial oxidative phosphorylation (mtOXPHOS) is important for ATP generation and its dysfunction leads to exercise intolerance. Phosphorus magnetic resonance spectroscopy (31P-MRS) is a useful, noninvasive technique for mtOXPHOS assessment but has limitations. Creatine-weighted chemical exchange saturation transfer (CrCEST) MRI is a potential alternative to assess muscle bioenergetics. To evaluate the interscan repeatability, intra- and interobserver reproducibility of CrCEST during mild plantar flexion exercise. Retrospective. Twenty healthy volunteers (age 37.6 ± 12.4 years, 11 females). 3 T/CEST imaging using gradient echo readout. τCrCEST (postexercise Cr recovery time) was assessed in two scans for each participant, following mild plantar flexion exercises targeting the medial gastrocnemius (MG), lateral gastrocnemius (LG), and soleus (Sol) muscles. Three observers measured τCrCEST for interobserver reproducibility. Three readings by one observer were used to measure intraobserver reproducibility. Two scans were used for within-participant interscan repeatability. Paired t tests, intraclass correlation coefficient (ICC), and Pearson correlation were conducted. Bland-Altman plots were used to analyze the interobserver variability. A P-value of 0.05 was considered statistically significant. There was excellent intra- (ICC ) and interobserver (ICC ) reproducibility, with moderate interscan repeatability for τCrCEST in LG and MG (ICC ) and poor-to-moderate interscan repeatability in Sol (ICC ). Excellent interobserver reproducibility was confirmed by Bland-Altman plots (fixed bias P-value ). CrCEST MRI shows promise in assessing muscle bioenergetics by evaluating τCrCEST during mild plantar flexion exercise with reasonable reliability, particularly in LG and MG. 4 TECHNICAL EFFICACY: Stage 1.

Feasibility of 3D MRI fingerprinting for rapid knee cartilage T1, T2, and T1ρ mapping at 0.55T: Comparison with 3T.

Low-field strength scanners present an opportunity for more inclusive imaging exams and bring several challenges including lower signal-to-noise ratio (SNR) and longer scan times. Magnetic resonance fingerprinting (MRF) is a rapid quantitative multiparametric method that can enable multiple quantitative maps simultaneously. To demonstrate the feasibility of an MRF sequence for knee cartilage evaluation in a 0.55T system we performed repeatability and accuracy experiments with agar-gel phantoms. Additionally, five healthy volunteers (age 32 ±4years old, 2 females) were scanned at 3T and 0.55T. The MRI acquisition protocols include a stack-of-stars T1ρ-enabled MRF sequence, a VIBE sequence with variable flip angles (VFA) for T1 mapping, and fat-suppressed turbo flash (TFL) sequences for T2 and T1ρ mappings. Double-Echo steady-state (DESS) sequence was also used for cartilage segmentation. Acquisitions were performed at two different field strengths, 0.55T and 3T, with the same sequences but protocols were slightly different to accommodate differences in signal-to-noise ratio and relaxation times. Cartilage segmentation was done using five compartments. T1, T2, and T1ρ values were measured in the knee cartilage using both MRF and conventional relaxometry sequences. The MRF sequence demonstrated excellent repeatability in a test-retest experiment with model agar-gel phantoms, as demonstrated with correlation and Bland-Altman plots. Underestimation of T1 values was observed on both field strengths, with the average global difference between reference values and the MRF being 151 ms at 0.55T and 337 ms at 3T. At 0.55T, MRF measurements presented significant biases but strong correlations with the reference measurements. Although a larger error was present in T1 measurements, MRF measurements trended similarly to the conventional measurements for human subjects and model agar-gel phantoms.

Usability and Tolerability of Virtual Reality-Based Cognitive Stimulation in Healthy Elderly Volunteers-A Feasibility Clinical Trial.

Background: The aim of the current pilot study was to evaluate the usability, acceptability, and tolerability of virtual reality (VR)-based cognitive stimulation exercises (CSEs) in healthy young versus old populations before health care integration. A secondary aim was to assess the accuracy of VR games as a proxy for cognitive stimulation, specifically for attention. VR-based CSEs promise to improve attention and brain function through varied learning systems. Methods: This is a Phase 1 feasibility clinical trial at a single center. It involves 30 healthy volunteers randomly selected using the American Society of Anesthesiologists (ASA) physical status classification system. Participants fall into ASA 1 (age >18-35 years, n = 15) or ASA 2 (age >60 years, n = 15) categories. All participants tested the ReCognitionVR-based CSEs. Feasibility criterion: Participants in each group were monitored for completion of 20 minutes of VR-based CSEs. Acceptability criterion: Proportion of participants with system usability scale (SUS) >35 or SUS score of 87.5. Safety (tolerability) monitoring: Sessions were monitored for neurological, cardiovascular, or pulmonary adverse events (AEs). Safety criterion: No more than 10% of sessions stopped due to neurological, cardiovascular, or pulmonary AEs. Results: The primary outcome (feasibility) of ReCognitionVR-based CSEs was 100%. For the secondary outcome (acceptability), there was no group difference in SUS scores (ASA 1 = 88.17 ± 12.83 vs. ASA 2 = 88.39 ± 10.22, P = 0.81). For the tertiary outcome (safety), mild transient uneasiness was reported by two (13.4%) ASA 1 participants (resolved in 2 minutes), and one (6.67%) ASA 1 participant experienced a temporary >20% increase in blood pressure from baseline. No ASA 2 participants had AEs. Conclusion: The feasibility, acceptability, and safety of ReCognitionVR-based CSEs in healthy elderly volunteers are acceptable, indicating that the evaluation of the ReCognitionVR-based CSEs in hospitalized patients is reasonable.

Age related changes in skin sensitivity assessed with smartphone vibration testing

The capacity to perceive tactile input at the fingertips, referred to as tactile sensitivity, is known to diminish with age due to regressive changes to mechanoreceptor density and morphology. Sensitivity is measured as perceptual responses to stimuli of varying intensity. Contrary to traditional sensitivity monitoring instruments, smartphones are uniquely suited for remote assessment and have shown to deliver highly calibrated stimuli along a broad spectrum of intensity, which may improve test reliability. The aim of this study was to evaluate a vibration-emitting smartphone application, the Vibratus App, as a mode of estimating tactile sensory thresholds in the aging adult. The peripheral nerve function of 40 neurologically healthy volunteers (ages 18–71) was measured using monofilaments, a 128-Hz tuning fork, the Vibratus App, and nerve conduction studies (NCS). Between group differences were analyzed to determine each measurement’s sensitivity to age. Spearman correlation coefficients depicted the associative strength between hand-held measurements and sensory nerve action potential (SNAP) amplitude. Inter-rater reliability of traditional instruments and the software-operated smartphone were assessed by intraclass correlation coefficient (ICC2,k). Measurements taken with Vibratus App were significantly different between age groups (p < 0.001). The inter-rater reliability of monofilament, smartphone vibration, and tuning fork testing was moderate to good (ICC2,k = 0.65, 0.69, and 0.79, respectively). The findings of this study support further investigation of smartphones as sensitivity monitoring devices for at home monitoring of skin sensitivity.

Effect of L-theanine on selective attention in a traffic-related reaction task in sleep-deprived young adults: a double-blind placebo-controlled, crossover study

ABSTRACT Background L-theanine is a non-protein-forming amino acid found in tea. Limited evidence suggests that it improves selective attention. Sleep deprivation impairs attention and psychomotor reactions, affecting automobile driving. We aimed to determine whether L-theanine improves neurobehavioral measures of visual attention in acutely sleep-deprived healthy adults in a traffic-scene-based attention task. Methods In a double-blind, placebo-controlled, counterbalanced, two-way crossover study, we compared the effects of a 200-mg dose of L-theanine with a placebo (150 ml of distilled water) on a computerised, traffic-scene-based visual recognition reaction task in 24 healthy volunteers (age 20–25 years; 13 males) sleep-deprived overnight. The participants made speeded button-presses to imminent accident scenes (i.e. hits), while ignoring safe scenes. They were tested pre-dose and 45 min post-dose, each treatment administered one week apart. Results Hit rates were more than 90% in all sessions, and were similar in two treatments, pre- vs post-dose. L-theanine significantly reduced false alarms (i.e. responses to safe scenes) (p = 0.014) and increased A′ (i.e. target-distractor discriminability) (p = 0.009), whereas placebo did not (p > 0.05). L-theanine reduced hit reaction time by 38.65 ms (p = 0.007), and placebo by 19.08 ms (p = 0.016), however reaction time changes from baseline were not significantly different between treatments (p > 0.05). Conclusions L-theanine in high doses appears to improve selective visual attention by concurrently improving information processing speed and target-distractor discriminability in acutely sleep-deprived individuals. This is consistent with previous functional neuroimaging findings, where L-theanine suppressed distractor-processing and default-mode-network activity in visual selective attention tasks.

MRI Assessment of Diastolic Dysfunction in People Living With the Human Immunodeficiency Virus: Correlation With Markers of Disease Activity.

Despite the advent of combination antiretroviral therapy, people living with human immunodeficiency virus (PLWH) are at an increased risk for cardiac disease. To explore the presence and extent of diastolic atrial and left ventricular dysfunction in PLWH using cardiac MRI in correlation with clinical markers of disease activity. Prospective. A total of 163 participants comprising 101 HIV-infected individuals (age: 52 years [42-62 years]; 92% male) and 62 age- and sex-matched healthy volunteers (age: 51 years [30-72 years]; 85% male). 3.0 T, cardiac MRI including balanced steady-state free precession (SSFP) for the short-axis, two-, three-, and four-chamber views were performed. Assessment of cardiac function and strain analysis were accomplished by CVI42 software. Blood samples for CD4+ T cells and cardiac risk factors were also collected before MRI. Independent t tests, Mann-Whitney U test, Pearson's correlation analysis, and multivariate linear analyses (significance level: P < 0.05). PLWH had a significantly larger left atrial volume maximum index (LAVImax: 32.6 ± 8.7 vs. 28.7 ± 8.1 mL/m2), minimum (LAVImin: 14.8 ± 5.5 vs. 11.5 ± 5.4 mL/m2,), and prior to atrial contraction (LAVIpre-a: 23.4 ± 6.7 vs. 19.7 ± 7.2 mL/m2) as compared to healthy volunteers. The LA reservoir (LAtEF: 55.0 ± 10.2 vs. 61.4 ± 10.4; Sls: 29.0 ± 8.1 vs. 33.8 ± 11.8), conduit (LApEF: 28.4 ± 8.2 vs. 32.3 ± 11.3, P = 0.01; Sle: 16.3 ± 6.5 vs. 18.9 ± 8.2), and booster pump function (LAaEF: 37.4 ± 12.4 vs. 42.7 ± 13.1, P = 0.01, Sla: 12.7 ± 5.1 vs. 14.9 ± 5.7) were all significant impaired in PLWH. Global circumferential left ventricular diastolic strain rate (LVGCS-d) was significantly lower in the HIV patients. Multivariate analysis results showed that Nadir CD4+ T cells had a significant adverse association with LVGCS-d (β = 0.51). LA structure abnormalities and LV diastolic dysfunction were manifested in PLWH, with Nadir CD4+ T cell counts potentially serving as a risk factor for early cardiac diastolic dysfunction. 2 TECHNICAL EFFICACY: Stage 3.

Assessment of the Relationship between Antero-Posterior Dental Malocclusions, Body Posture Abnormalities and Selected Static Foot Parameters in Adults.

Objectives: This study aimed to find if a relationship exists between antero-posterior malocclusions and the level of musculoskeletal disorders in adults, including body posture and static foot analysis. Methods: In all, 420 participants were recruited through convenience sampling (Kraków University students and patients of a local dentist's practice). Following general medical interviews, dental examinations and consideration of inclusion and exclusion criteria, 90 healthy volunteers (ages 19-35) were enrolled and assigned to three groups (n = 30) based on occlusion type (Angle's molar Class I, II or III). The research procedure involved occlusion and temporomandibular disorder assessment conducted by a dental specialist. Comprehensive morphological measurements of body asymmetry were performed using the Videography 2D package and FreeSTEP software, which calculated the parameters determined from anterior, posterior and lateral projection photos. Foot loading distribution was analyzed using the FreeMED baropodometric platform. Results: Significant differences were demonstrated in the positioning of the head, cervical and lumbar spine in the sagittal plane among individuals with the analyzed occlusal classes (p < 0.05). Individuals with Angle's Class II exhibited significantly greater forward head positions and greater depths of cervical and lumbar lordosis compared with individuals with Class III or Class I. Those with overbites had higher forefoot loading. The Class III individuals exhibited greater L-R displacement, indicating a larger angle of displacement of the centers of the right and left feet relative to the lower edge of the measurement platform, suggesting pelvic rotation. Conclusions: An inclination for concurrent occurrences of malocclusions and posture deviations in the sagittal plane was observed. An interdisciplinary approach involving dentistry and physiotherapy specialists which utilizes tools for comprehensive posture assessment is crucial for diagnosing and treating such conditions.

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

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

A standardized combination of Terminalia chebula and Withania somnifera extracts enhances immune function in adults: a pilot randomized, double-blind, placebo-controlled clinical study.

The use of botanical medicine has been demonstrated as a potential strategy to manage or treat a variety of health issues. Terminalia chebula (Retz) fruit and Withania somnifera (L.) Dunal roots are important medicinal herbs described in Ayurveda and traditional therapy for diverse health benefits. This pilot study aimed to evaluate the immune function-enhancing potential of a unique blend of T. chebula fruit and W. somnifera root extracts, LN20189, in healthy men and women. Forty healthy volunteers (age: 35-60 years) were randomized into two groups receiving either LN20189 (500 mg per day) or a matched placebo over 28 consecutive days. The total T-cell population was the primary efficacy measure in this study. The secondary efficacy measures included counts of CD4, CD8, natural killer (NK) cells, serum levels of interleukin-2 (IL-2), interferon-gamma (IFN-γ), total immunoglobulin-G (IgG), and Immune Function Questionnaire (IFQ) scores. Safety parameter assessments were also conducted. Post-trial, in LN20189-supplemented subjects, T cells, CD4, NK cells count, and the CD4:CD8 ratio were increased by 9.32, 10.10, 19.91, and 17.43%, respectively, as compared to baseline. LN20189 supplementation increased serum IFN-γ and IgG levels by 14.57 and 27.09% from baseline and by 13.98 and 21.99%, compared to placebo, respectively. Also, the IFQ scores in the LN20189 group were 84.68% (vs. baseline) and 69.44% (vs. placebo) lower at the end of the trial. LN20189 improved the study volunteers' cellular and humoral immune functions. In summary, LN20189 supplementation was found tolerable and improved the key cellular and humoral factors of the immune system and helped improve immune function of the trial volunteers.

#2048 Exploring somatic mutation mechanisms in pre-cystic renal cells of autosomal dominant polycystic kidney disease patients

Abstract Background and Aims Genetic changes accumulate in our cells during a lifetime, at a rate that varies according to cell type and mutagen exposure [1]. Somatic mutations are the driving force of cancer and contribute to “second hit” disorders, such as Autosomal Dominant Polycystic Kidney Disease (ADPKD). ADPKD is caused by inherited mutations that disrupt one allele of PKD1 or PKD2 genes. Somatic loss of the second allele triggers tubule cell clonal expansion and the formation of renal cysts. Given the high number of cysts that form during a lifetime, somatic mutation rates may be abnormally high in the kidney of ADPKD patients. The identification of factors enhancing somatic mutation rates can lead to preventive strategies to limit cyst formation. Metabolic alterations, i.e. increased glutamine utilization and reduced urea cycle, have been shown to induce somatic mutations in cancer [2]. Loss of urea cycle increases pyrimidine synthesis, which unbalances the nucleotide pools and results in a distinct signature of single base substitutions (SBSs) [1]. Similar metabolic changes have been observed in ADPKD [3, 4]. Thus, we sought to test metabolism-driven somatic mutagenesis in pre-cystic kidneys and its contribution to second hit mutations in ADPKD. Method We clonally expanded normal kidney cells from human urine samples and performed a gene expression study by qPCR. We studied 31 clones from 4 ADPKD patients (age range: 25-45) with truncating mutations in PKD1 and normal kidney function, despite a clear cystic phenotype. ADPKD cells were compared to 55 clones from 5 healthy volunteers (age range: 24-53), and 32 clones from 6 patients with another cystic kidney disease, Von Hippel Lindau disease (VHL; age range: 29-56). A subset of clones (n = 19 controls, n = 12 ADPKD) was subjected to whole genome sequencing and somatic mutation analysis. Results Urines of ADPKD patients contained higher numbers of cells that expanded in vitro, compared to both control (p = 0.0008) and VHL individuals (p = 0.01). Gene expression analyses showed that irrespective of genetic background, all cultured clones originated from the kidney tubule epithelium (high PAX2 and PAX8), and some originated from damaged tubules (VCAM1, KIM1). We tested the hypothesized metabolic rewiring by analyzing expression levels of enzymes involved in glutamine utilization, urea cycle, and pyrimidine biosynthesis. Except for ASNS (Asparagine Synthetase), which was higher in ADPKD vs control clones (p = 0.0098), no gene-expression differences were observed. However, clones from ADPKD patients showed signs of the metabolic rewiring responsible for increased pyrimidine production, i.e. a positive correlation (r = 0.691; p &amp;lt; 0.0001) between urea cycle enzymes downregulation and upregulation of the pyrimidine synthesis enzyme CAD. Since excessive pyrimidines lead to mutation [2], we analyzed the number of somatic SBSs per genome, after filtering for germline variants. We did not find increased mutation rates in ADPKD compared to controls, but an analogous, linear increase of mutations with age and similar levels of the pyrimidine-rich mutational signature. Conclusion Urine-derived kidney tubule epithelial cells with heterozygous truncating mutations in PKD1 exhibit certain characteristics of metabolic reprogramming typical of kidneys from ADPKD patients with advanced pathology. Nevertheless, in the limited number of pre-cystic cells that we have analyzed, this metabolic reprogramming did not translate into an excess of somatic mutations.

Deep cardiac phenotyping by cardiovascular magnetic resonance reveals subclinical focal and diffuse myocardial injury in patients with psoriasis (PSOR-COR study).

Psoriasis vulgaris (PV) is a chronic inflammatory disorder frequently associated with cardiovascular disease (CVD). This study aims to provide a prospective tissue characterization in patients with PV without major CVD using cardiovascular magnetic resonance (CMR). Patients with PV underwent laboratory assessment, a 12-lead and 24-h ECG, and a CMR exam at a 1.5-T scanner. Scan protocol included assessment of left (LV) and right (RV) ventricular function and strain analysis, native and post-contrast T1 mapping, T2 mapping and late gadolinium enhancement (LGE). In total, 60 PV patients (median(IQR) age in years: 50.0 (36.0-60.8); 34 men (56.7%)) were recruited and compared to 40 healthy volunteers (age in years: 49.5 (37.3-57.8); 21 men (53.0%)). No differences were found regarding LV and RV function (p = 0.78 and p = 0.75). Global radial and circumferential strains were lower in patients (p < 0.001 and p < 0.001, respectively). PV had higher global T1 times (1001 (982-1026) ms vs. 991 (968-1005) ms; p = 0.01) and lower global T2 times (48 (47-49) ms vs. 50 (48-51) ms; p < 0.001); however, all values were within local reference ranges. Focal non-ischemic fibrosis was observed in 17 (28.3%) PV patients. Deep cardiac phenotyping by CMR revealed subclinical myocardial injury in patients with PV without major CVD, despite preserved LV and RV function. Diffuse and focal fibrosis might be the first detectable signs of adverse tissue remodeling leading to reduced circumferential and radial myocardial deformation. In the background of local and systemic immunomodulatory therapy, no signs of myocardial inflammation were detected. The exact impact of immunomodulatory therapies on the myocardium needs to be addressed in future studies. ISRCTN71534700.

Changes in Retinal Hemodynamics in the Optic Nerve Head of Healthy Participants Measured Using Laser Speckle Flowgraphy after a Cold Pressor Test.

Autoregulation of retinal vessels is stronger than that of choroidal vessels. This study aimed to use laser speckle flowgraphy to determine the time course of changes in retinal hemodynamics of healthy eyes after a cold pressor test. This prospective study included 44 right eyes of 44 healthy volunteers (age, 21.7 ± 5.0 years). The mean blur rate, which is a quantitative index of the relative blood flow velocity in the retina, was measured using laser speckle flowgraphy. The vessel average of mean blur rate at the optic nerve head, intraocular pressure, systolic blood pressure, diastolic blood pressure, mean blood pressure, heart rate, and ocular perfusion pressure were evaluated at baseline, immediately after the cold pressor test, and 10, 20, and 30 minutes after the test. Immediately after the test (0 minutes), systolic blood pressure, diastolic blood pressure, mean blood pressure, and ocular perfusion pressure were significantly increased compared with those at baseline; however, no changes were observed at 10, 20, and 30 minutes after the test. In contrast, intraocular pressure, heart rate, and the vascular mean blur rate values at the optic nerve head did not change throughout the course of the study. Sympathetic hyperactivity induced by the cold pressor test increased systemic circulatory dynamics, but not retinal circulatory hemodynamics, suggesting the involvement of vascular autoregulation.

Gene expression patterns of Sirtuin family members (SIRT1 TO SIRT7): Insights into pathogenesis and prognostic of Myelodysplastic neoplasm

To assess and validate the gene expression profile of SIRTs (SIRT1, SIRT2, SIRT3, SIRT4, SIRT5, SIRT6, and SIRT7) in relation to the pathogenesis and prognostic progression of Myelodysplastic neoplasm (MDS). Eighty bone marrow samples of patients with de novo MDS were diagnosed according to WHO 2022 and IPSS-R criteria. Ten bone marrow samples were obtained from elderly healthy volunteers and used as control samples. Gene expression levels of all SIRTs were assessed using RT-qPCR assays. Downregulation of SIRT2 (p = 0.009), SIRT3 (p = 0.048), SIRT4 (p = 0.049), SIRT5 (p = 0.046), SIRT6 (p = 0.043), and SIRT7 (p = 0.047) was identified in MDS patients compared to control individuals. Also, we identified that while SIRT2-7 genes are typically down-regulated in MDS patients compared to normal controls, there are relative expression variations among MDS patient subgroups. Specifically, SIRT4 (p = 0.029) showed increased expression in patients aged 60 or above, and both SIRT2 (p = 0.016) and SIRT3 (p = 0.036) were upregulated in patients with hemoglobin levels below 8 g/dL. SIRT2 (p = 0.045) and SIRT3 (p = 0.033) were highly expressed in patients with chromosomal abnormalities. Different SIRTs exhibited altered expression patterns concerning specific MDS clinical and prognostic characteristics. The downregulation in SIRTs genes (e.g., SIRT2 to SIRT7) expression in Brazilian MDS patients highlights their role in the disease's development. The upregulation of SIRT2 and SIRT3 in severe anemia patients suggests a potential link to manage iron overload-related complications in transfusion-dependent patients. Moreover, the association of SIRT2/SIRT3 with genomic instability and their role in MDS progression signify promising areas for future research and therapeutic targets. These findings underscore the importance of SIRT family in understanding and addressing MDS, offering novel clinical, prognostic, and therapeutic insights for patients with this condition.