Safety and immunogenicity of a 4-component GMMA-based Shigella vaccine in healthy European adults: Stage 1 of a randomized, controlled phase I/II clinical trial.

BACKGROUND: We report data from Stage 1 of an ongoing two-staged, phase I/II randomized clinical trial (NCT05073003) with a 4-component Generalized Modules for Membrane Antigens-based vaccine against Shigella sonnei and S. flexneri 1b, 2a and 3a (altSonflex1-2-3, GSK). METHODS: 18-50-year-old Europeans (N=102) were randomized (2:1) to receive two injections of altSonflex1-2-3 or placebo at 3- or 6-month interval. Safety and immunogenicity were assessed at pre-specified timepoints. RESULTS: The most common solicited administration-site event (until 7 days post-each injection) and unsolicited adverse event (until 28 days post-each injection) were pain (altSonflex1-2-3: 97.1%; Placebo: 58.8%) and headache (32.4%; 23.5%), respectively. All serotype-specific functional IgG antibodies peaked 14-28 days post-injection 1 and remained substantially higher than pre-vaccination at 3 or 6 months post-vaccination; the second injection did not boost but restored the initial immune response. The highest seroresponse rates (≥4-fold increase in titers over baseline) were obtained against S. flexneri 2a (ELISA: post-injection 1: 91.0%; post-injection 2 [Day {D}113; D197]: 100%; 97.0%; serum bactericidal activity (SBA): post-injection 1: 94.4%; post-injection 2: 85.7%; 88.9%) followed by S. sonnei (ELISA: post-injection 1: 77.6%; post-injection 2: 84.6%; 78.8%; SBA: post-injection 1: 83.3%; post-injection 2: 71.4%; 88.9%). Immune responses against S. flexneri 1b and S. flexneri 3a, as measured by both ELISA and SBA, were numerically lower compared to those against S. sonnei and S. flexneri 2a. CONCLUSIONS: No safety signals or concerns were identified. altSonflex1-2-3 induced functional serotype-specific immune responses, allowing further clinical development in the target population.

What is the context? Shigella bacteria cause severe and often bloody diarrhea, called shigellosis, that affects mostly young children and can be life-threatening. Shigellosis is particularly common in low- and middle-income countries due to inadequate sanitation and limited access to healthcare. Since the immune response to Shigella is serotype-specific, an ideal vaccine should include multiple Shigella serotypes to ensure broad protection. What is new? We developed a novel vaccine against Shigella that includes Shigella sonnei and three prevalent Shigella flexneri serotypes. In Stage 1 (phase I) of the study, healthy European adults received two vaccine injections given 3 or 6 months apart. We found that: The vaccine was well tolerated, and no safety signals or concerns were identified.Regardless of the interval between injections, specific antibodies were elicited against all four Shigella serotypes, with highest levels against Shigella flexneri 2a and Shigella sonnei.Functional antibody levels peaked after the first injection, remaining higher than the baseline up to 6 months. A second injection did not boost responses but restored functional antibody levels to those after the first injection. What is the impact? The vaccine can now be tested in Stage 2 (phase II) of the study in Africa, a region highly affected by shigellosis.

Fronto-limbic white matter microstructural changes in psychiatrically healthy adults with childhood trauma.

Childhood trauma (CT) may influence brain white matter microstructure; however, few studies have examined the differential impact of distinct CT types on white matter microstructure in psychiatrically healthy adults living in a developing country. In adults without significant medical or psychiatric disorders, we investigated the association(s) between CT, including abuse and neglect, and fractional anisotropy (FA) of limbic tracts previously shown to be associated with CT. Participants underwent diffusion tensor imaging and completed the Childhood Trauma Questionnaire. Multivariate analysis of variance models were used to test the effects of total overall CT, as well as CT subtypes, on FA in six fronto-limbic tracts, adjusting for age, sex, and educational level. The final sample included 69 adults (age 47 ± 17 years; 70% female). Overall, CT had a significant main effect on FA for tracts of interest (p < .001). Greater CT severity was associated with lower FA for the bilateral and left stria terminalis (uncorrected) as well as the bilateral, left, and right anterior limb of the internal capsule (ALIC; corrected). Exposure to total non-violent/deprivational trauma specifically was associated with lower FA of the bilateral, left, and right ALIC, suggesting that distinct types of CT are associated with differential white matter changes in apparently healthy adults. The ALIC predominantly carries fibers connecting the thalamus with prefrontal cortical regions. Microstructural alterations in the ALIC may be associated with functional brain changes, which may be adaptive or increase the risk of accelerated age-related cognitive decline, maladaptive behaviors, and subsyndromal psychiatric symptoms.

Hemispheric asymmetries in cortical grey matter of gyri and sulci in modern human populations from South America.

Structural asymmetries of brain regions associated with lateralised functions have been extensively studied. However, there are fewer morphometric analyses of asymmetries of the gyri and sulci of the entire cortex. The current study assessed cortical asymmetries in a sample of healthy adults (N = 175) from an admixed population from South America. Grey matter volume and surface area of 66 gyri and sulci were quantified on T1 magnetic resonance images. The departure from zero of the differences between left and right hemispheres (L-R), a measure of directional asymmetry (DA), the variance of L-R, and an index of fluctuating asymmetry (FA) were evaluated for each region. Significant departures from perfect symmetry were found for most cortical gyri and sulci. Regions showed leftward asymmetry at the population level in the frontal lobe and superior lateral parts of the parietal lobe. Rightward asymmetry was found in the inferior parietal, occipital, frontopolar, and orbital regions, and the cingulate (anterior, middle, and posterior-ventral). Despite this general pattern, several sulci showed the opposite DA compared to the neighbouring gyri, which remarks the need to consider the neurobiological differences in gyral and sulcal development in the study of structural asymmetries. The results also confirm the absence of DA in most parts of the inferior frontal gyrus and the precentral region. This study contributes with data on populations underrepresented in the databases used in neurosciences. Among its findings, there is agreement with previous results obtained in populations of different ancestry and some discrepancies in the middle frontal and medial parietal regions. A significant DA not reported previously was found for the volume of long and short insular gyri and the central sulcus of the insula, frontomarginal, transverse frontopolar, paracentral, and middle and posterior parts of the cingulate gyrus and sulcus, gyrus rectus, occipital pole, and olfactory sulcus, as well as for the volume and area of the transverse collateral sulcus and suborbital sulcus. Also, several parcels displayed significant variability in the left-right differences, which can be partially attributable to developmental instability, a source of FA. Moreover, a few gyri and sulci displayed ideal FA with non-significant departures from perfect symmetry, such as subcentral and posterior cingulate gyri and sulci, inferior frontal and fusiform gyri, and the calcarine, transverse collateral, precentral, and orbital sulci. Overall, these results show that asymmetries are ubiquitous in the cerebral cortex.

No Effect of High Eating Frequency Compared with Low Eating Frequency on Appetite and Inflammation Biomarkers: Results from a Randomized Crossover Clinical Trial.

BACKGROUND: Eating frequency (EF) focuses on the total number of eating occasions per day and may influence metabolic health. OBJECTIVES: We sought to examine the effect of high compared with low EF on appetite regulation and inflammatory biomarkers among healthy adults. METHODS: Data are from a randomized, crossover trial (the Frequency of Eating and Satiety Hormones study). Participants (n = 50) completed 2 isocaloric 21-d study periods of low EF (3 eating occasions/d) and high EF (6 eating occasions/d) in random order with a 14-d washout period in between. Participants were free-living and consumed their own food, using study-directed, structured meal plans with identical foods and total energy in both study periods. On days 1 and 21 of each EF period, fasting blood was collected during in-person clinic visits to assess plasma concentrations of ghrelin, leptin, adiponectin, and high-sensitivity C-reactive protein (hs-CRP). Linear mixed models with EF, diet sequence, and period as fixed effects and participant as random effect were used to estimate the intervention effect. Interaction effects between EF and body fat percentage were examined. RESULTS: Among the 50 participants who completed the trial, 39 (78%) were women, 30 (60%) were Non-Hispanic White, and 40 (80%) had a body mass index of <25 kg/m2, and the mean age was 32.1 y. The differences between high and low EF in fasting ghrelin (geometric mean difference: 17.76 ng/mL; P = 0.60), leptin (geometric mean difference: 2.09 ng/mL; P = 0.14), adiponectin (geometric mean difference: 381.7 ng/mL; P = 0.32), and hs-CRP (geometric mean difference: -0.018 mg/dL; P = 0.08) were not statistically significant. No significant interaction was observed between EF and body fat percentage on appetite regulation and inflammatory biomarkers. CONCLUSIONS: No differences was observed in fasting ghrelin, leptin, adiponectin, and hs-CRP comparing high and low EF. Future studies are needed to understand the physiology of EF and appetite as they relate to metabolic health. This trial was registered at clinicaltrials.gov as NCT02392897.

Reliability of Measuring Geniohyoid Cross-Sectional Area with B-Mode Ultrasound.

B-mode ultrasound is a safe noninvasive procedure that has been used to characterize aspects of the oropharyngeal swallow. The submental suprahyoid muscles are often investigated with ultrasound because of their contributions to hyolaryngeal elevation. There are several techniques for positioning the ultrasound transducer in the coronal plane, however, there is limited research on how reliability of measurement of the cross-sectional area (CSA) of the geniohyoid differs across transducer placement technique. This study examined three methods of transducer placement in the coronal plane by two examiners to determine the reliability of measurement of CSA of the geniohyoid muscle. Forty healthy adults participated in the study. Each participant's geniohyoid muscles were imaged using B-mode ultrasound under three transducer placement conditions in the coronal plane by two examiners. Geniohyoid CSA was measured from each ultrasound image. A three-way mixed-methods ANOVA was used to determine whether there were significant differences in geniohyoid CSA among transducer position conditions, trials, and examiners. There were significant differences among the transducer placement conditions, indicating that each condition was measuring a different portion of the muscle. There were no significant differences among repeated trials nor between examiners within each method of transducer placement. All three conditions of transducer placement were reliable at measuring geniohyoid CSA across trials and examiners. This study emphasizes the need for consistency of placement, whichever method is selected. It also highlights the need for researchers to provide a precise description of methods for positioning the transducer so that placement is reproducible.

Traumatic bilateral acetabular fracture secondary to high-energy trauma in healthy adults.

BACKGROUND: Bilateral acetabular fracture is a very rare presentation among the trauma patients, as the pattern and the degree of the forces required to fracture both acetabula is very unique. The primary purpose of this study is to report a series of adult patients presenting with post-traumatic bilateral acetabular fracture without any history of pathological or metabolic bone disease. PATIENTS AND METHODS: In this retrospective study, 18 cases of traumatic bilateral acetabular fracture were included. There was predominance of both column (four patients on left and six on right) followed by anterior column (two patients left and four on right) and posterior wall (three patients left and right). They were treated surgically through open reduction and internal fixation. All cases were followed up for at least 13 months. Matta's criteria were used for radiological evaluation on plain radiographs. Functional outcome was evaluated using the Merle d'Aubigne and postel score at final follow-up. RESULTS: No patients were lost during the follow-up period; there was one case of surgical site infection. There were three cases of postoperative osteoarthritis, one case of heterotrophic ossification, one case of persistent sciatic nerve palsy and one case of lateral femoral cutaneous nerve palsy. The radiological evaluation according to Matta's criteria revealed anatomic reduction in 12 patients, imperfect reduction in three patients while other three patients had poor reduction. According to modified Merle d'Aubigne and Postel score, 10 cases were rated as excellent, five cases as good and three cases presented fair (one case) to poor (two cases) results. CONCLUSION: We report an unusual case series of bilateral acetabular fracture successfully managed surgically with good clinical outcome. With the increasing incidence of route traffic accidents, such cases would probably be recurrent in the upcoming years.

Vertical Center-of-Mass Braking and Motor Performance during Gait Initiation in Young Healthy Adults, Elderly Healthy Adults, and Patients with Parkinson's Disease: A Comparison of Force-Plate and Markerless Motion Capture Systems.

BACKGROUND: This study tested the agreement between a markerless motion capture system and force-plate system ("gold standard") to quantify stability control and motor performance during gait initiation. METHODS: Healthy adults (young and elderly) and patients with Parkinson's disease performed gait initiation series at spontaneous and maximal velocity on a system of two force-plates placed in series while being filmed by a markerless motion capture system. Signals from both systems were used to compute the peak of forward center-of-mass velocity (indicator of motor performance) and the braking index (indicator of stability control). RESULTS: Descriptive statistics indicated that both systems detected between-group differences and velocity effects similarly, while a Bland-Altman plot analysis showed that mean biases of both biomechanical indicators were virtually zero in all groups and conditions. Bayes factor 01 indicated strong (braking index) and moderate (motor performance) evidence that both systems provided equivalent values. However, a trial-by-trial analysis of Bland-Altman plots revealed the possibility of differences >10% between the two systems. CONCLUSION: Although non-negligible differences do occur, a markerless motion capture system appears to be as efficient as a force-plate system in detecting Parkinson's disease and velocity condition effects on the braking index and motor performance.

Evaluation of the Margin of Stability during Gait Initiation in Young Healthy Adults, Elderly Healthy Adults and Patients with Parkinson's Disease: A Comparison of Force Plate and Markerless Motion Capture Systems.

Gait initiation (GI) is a functional task classically used in the literature to evaluate the capacity of individuals to maintain postural stability. Postural stability during GI can be evaluated through the "margin of stability" (MoS), a variable that is often computed from force plate recordings. The markerless motion capture system (MLS) is a recent innovative technology based on deep learning that has the potential to compute the MoS. This study tested the agreement between a force plate measurement system (FPS, gold standard) and an MLS to compute the MoS during GI. Healthy adults (young [YH] and elderly [EH]) and Parkinson's disease patients (PD) performed GI series at spontaneous (SVC) and maximum velocity (MVC) on an FPS while being filmed by a MLS. Descriptive statistics revealed a significant effect of the group (YH vs. EH vs. PD) and velocity condition (SVC vs. MVC) on the MoS but failed to reveal any significant effect of the system (MLS vs. PFS) or interaction between factors. Bland-Altman plot analysis further showed that mean MoS biases were zero in all groups and velocity conditions, while the Bayes factor 01 indicated "moderate evidence" that both systems provided equivalent MoS. Trial-by-trial analysis of Bland-Altman plots, however, revealed that differences of >20% between the two systems did occur. Globally taken, these findings suggest that the two systems are similarly effective in detecting an effect of the group and velocity on the MoS. These findings may have important implications in both clinical and laboratory settings due to the ease of use of the MLS compared to the FPS.

Reference values of lymphocyte subsets from healthy Polish adults.

The flow cytometry method could support physicians' decisions in the diagnosis and treatment monitoring of immunodeficient patients. Most clinical recommendations are focused on the search for alterations in T- and B-lymphocyte subsets, less commonly natural killer (NK) cells and granulocytes. While reference values for clinically meaningful lymphocyte subsets have been published ubiquitously among numerous countries, we have not found significant data for a population of adult Polish habitats; thus we determined reference values for T, B, and NK subsets according to sex and age. The female group showed a higher percentage of lymphocytes (CD45++), T helper lymphocytes with a higher absolute count, as well as CD4/CD8 ratio, marginal zone-like B cells, class-switched B cells, and CD21low B cells than the male group. The male group was found to have elevated percentages of naïve B lymphocytes, transitional B cells, and plasmablasts. A weak positive correlation with age was found among double positive T lymphocytes, natural killer T cells (NKT) lymphocytes, and CD21low B cells. A negative correlation with age for double negative T lymphocytes, marginal zone-like B cells, and plasmablasts was noted. The results indicated the importance of creating distinct reference ranges regarding sex and age concerning immunophenotype.

[Comparative analysis of body fat measurement using two bioelectric impedance devices and three household scales (with the function of determining body composition) with dual-energy X-ray absorptiometry].

Body composition assessment is often used in clinical practice to assess and monitor nutritional status. For example, body fat mass is a predictor of metabolic diseases, and for an athlete it is a criterion of performance. "Gold standard" - the method of dual-energy X-ray absorptiometry - in contrast to bioelectrical impedance analysis, is difficult to apply in everyday clinical practice. Therefore, it becomes relevant to compare the consistency of measured body fat mass using densitometry and bioimpedanceometry. The aim of the study was to perform a comparative analysis of body fat mass estimated by bioimpedanceometry (two bioelectric impedance devices and three household scales with a function of determining body composition) and dual-energy X-ray absorptiometry. Material and methods. Sixteen healthy, physically active adults aged 25 [23; 26] years, male (n=7) and female (n=9), participated in the cross-sectional study. Body composition was assessed under standard conditions in the morning, after a 12-hour fast, using densitometry (Stratos Dr X-ray densitometer) and bioimpedanceometry [bioelectric impedance devices: Medass ABC-01, Diamant AIST (with manufacturer's predictive equations); household scales with a function of determining body composition: Tanita BC-718, Picooc Mini, Scarlett SC-216]. Statistical analysis was performed using Statistica 10 package (StatSoft, USA), and included Friedman's chi-criterion, Lin's correlation concordance coefficient, Bland-Altman method, Spearman's correlation coefficient, and Wilcoxon's criterion with Bonferroni correction for multiple studies. Results. None of the bioimpedanceometry devices studied showed a relationship (Bland- Altman coefficient >0.2) or consistency (Lin's correlation concordance coefficient <0.9) when compared to densitometry, although Spearman correlation was moderate for Tanita BC-718 (r=0.603, p<0.05), Diamant AIST (r=0.641, p<0.01) and Scarlett SC-216 (r=0.609, p<0.05), and notable for Medass ABC-01 (r=0.841, p<0.01) and Picooc Mini (r=0.718, p<0.01). Conclusion. This study found that no bioelectrical impedance device has consistency with dual-energy X-ray absorptiometry in assessing body fat mass. Since the accuracy of body fat mass measurement is critical in body composition diagnosis, the assessment results obtained by bioimpedanceometry should be interpreted with caution.

An oral glucose tolerance test does not affect cerebral blood flow: role of NOS.

Animal data indicate that insulin triggers a robust nitric oxide synthase (NOS)-mediated dilation in cerebral arteries similar to the peripheral tissue vasodilation observed in healthy adults. Insulin's role in regulating cerebral blood flow (CBF) in humans remains unclear but may be important for understanding the links between insulin resistance, diminished CBF, and poor brain health outcomes. We tested the hypothesis that an oral glucose challenge (oral glucose tolerance test, OGTT), which increases systemic insulin and glucose, would acutely increase CBF in healthy adults due to NOS-mediated vasodilation, and that changes in CBF would be greater in anterior regions where NOS expression or activity may be greater. In a randomized, single-blind approach, 18 young healthy adults (24 ± 5 yr) underwent magnetic resonance imaging (MRI) with a placebo before and after an OGTT (75 g glucose), and 11 of these adults also completed an NG-monomethyl-l-arginine (l-NMMA) visit. Four-dimensional (4-D) flow MRI quantified macrovascular CBF and arterial spin labeling (ASL) quantified microvascular perfusion. Subjects completed baseline imaging with a placebo (or l-NMMA), then consumed an OGTT followed by MRI scans and blood sampling every 10-15 min for 90 min. Contrary to our hypothesis, total CBF (P = 0.17) and global perfusion (P > 0.05) did not change at any time point up to 60 min after the OGTT, and no regional changes were detected. l-NMMA did not mediate any effect of OGTT on CBF. These data suggest that insulin-glucose challenge does not acutely alter CBF in healthy adults.

Early vascular aging as an index of cardiovascular risk in healthy adults: confirmatory factor analysis from the EVasCu study.

BACKGROUND: The concept of early vascular aging (EVA) represents a potentially beneficial model for future research into the pathophysiological mechanisms underlying the early manifestations of cardiovascular disease. For this reason, the aims of this study were to verify by confirmatory factor analysis the concept of EVA on a single factor based on vascular, clinical and biochemical parameters in a healthy adult population and to develop a statistical model to estimate the EVA index from variables collected in a dataset to classify patients into different cardiovascular risk groups: healthy vascular aging (HVA) and EVA. METHODS: The EVasCu study, a cross-sectional study, was based on data obtained from 390 healthy adults. To examine the construct validity of a single-factor model to measure accelerated vascular aging, different models including vascular, clinical and biochemical parameters were examined. In addition, unsupervised clustering techniques (using both K-means and hierarchical methods) were used to identify groups of patients sharing similar characteristics in terms of the analysed variables to classify patients into different cardiovascular risk groups: HVA and EVA. RESULTS: Our data show that a single-factor model including pulse pressure, glycated hemoglobin A1c, pulse wave velocity and advanced glycation end products shows the best construct validity for the EVA index. The optimal value of the risk groups to separate patients is K = 2 (HVA and EVA). CONCLUSIONS: The EVA index proved to be an adequate model to classify patients into different cardiovascular risk groups, which could be valuable in guiding future preventive and therapeutic interventions.

Mean kurtosis-Curve (MK-Curve) correction improves the test-retest reproducibility of diffusion kurtosis imaging at 3 T.

Diffusion kurtosis imaging (DKI) is applied to gain insights into the microstructural organization of brain tissues. However, the reproducibility of DKI outside brain white matter, particularly in combination with advanced estimation to remedy its noise sensitivity, remains poorly characterized. Therefore, in this study, we investigated the variability and reliability of DKI metrics while correcting implausible values with a fit method called mean kurtosis (MK)-Curve. A total of 10 volunteers (four women; age: 41.4 ± 9.6 years) were included and underwent two MRI examinations of the brain. The images were acquired on a clinical 3-T scanner and included a T1-weighted image and a diffusion sequence with multiple diffusion weightings suitable for DKI. Region of interest analysis of common kurtosis and tensor metrics derived with the MK-Curve DKI fit was performed, including intraclass correlation (ICC) and Bland-Altman (BA) plot statistics. A p value of less than 0.05 was considered statistically significant. The analyses showed good to excellent agreement of both kurtosis tensor- and diffusion tensor-derived MK-Curve-corrected metrics (ICC values: 0.77-0.98 and 0.87-0.98, respectively), with the exception of two DKI-derived metrics (axial kurtosis in the cortex: ICC = 0.68, and radial kurtosis in deep gray matter: ICC = 0.544). Non-MK-Curve-corrected kurtosis tensor-derived metrics ranged from 0.01 to 0.52 and diffusion tensor-derived metrics from 0.06 to 0.66, indicating poor to moderate reliability. No structural bias was observed in the BA plots for any of the diffusion metrics. In conclusion, MK-Curve-corrected DKI metrics of the human brain can be reliably acquired in white and gray matter at 3 T and DKI metrics have good to excellent agreement in a test-retest setting.

Mixed Tree Nuts, Cognition, and Gut Microbiota: A 4-Week, Placebo-Controlled, Randomized Crossover Trial in Healthy Nonelderly Adults.

BACKGROUND: Beneficial effects of nut supplementation on cognitive function have previously been demonstrated in young and older adults. Alterations to gut microbiota have also been shown following tree nut consumption. However, no data exists on the effects of nuts on cognition and intestinal microbial communities assessed within the same study. OBJECTIVES: The study aimed to examine the effects of daily consumption of tree nuts for 4 wk on cognitive function (primary outcome), mood, metabolomics, and gut microbial species (secondary outcomes) in healthy, nonelderly adults. METHODS: This randomized, placebo-controlled, double-blind, counterbalanced crossover study assessed the effects of 4 wk of supplementation with 30 g/d mixed tree nuts versus placebo on cognition and mood in 79 healthy adults aged 18-49 y. Metabolic responses, gut bacterial community structure, and the potential for these to impact cognition were explored using a multi-omic approach. Bacterial community analysis was conducted in Quantitative Insights Into Microbial Ecology 2 (QIIME2). RESULTS: Mixed model analysis indicated that nut consumption led to significant improvements to accuracy (placebo M = 92.2% compared with NUTS M = 94.5%; P = 0.019) and speed of response (placebo M = 788 ms compared with NUTS M = 757 ms; P = 0.004) on a picture recognition task. No significant changes to bacterial community α or ß diversity were observed when comparing nut consumption to the placebo arm. However, an unclassified Lachnospiraceae amplicon sequence variant (ASV) was significantly enriched in participants when supplemented with nuts (P = 0.015). No correlations were observed between the changes to picture recognition and the changes to the unclassified Lachnospiraceae ASV. There were no significant changes to the urinary metabolome. CONCLUSIONS: These findings indicate a positive effect of nut on cognition following only 4 wk of consumption in a healthy nonelderly sample, as well as upregulation of a microbial taxa associated with gut health. The effects appear to be independent of one another, but further exploration is required in those experiencing cognitive decline and/or gut dysbiosis.

Dietary Intake of Monosaccharides from Foods is Associated with Characteristics of the Gut Microbiota and Gastrointestinal Inflammation in Healthy US Adults.

BACKGROUND: Current assessment of dietary carbohydrates does not adequately reflect the nutritional properties and effects on gut microbial structure and function. Deeper characterization of food carbohydrate composition can serve to strengthen the link between diet and gastrointestinal health outcomes. OBJECTIVES: The present study aims to characterize the monosaccharide composition of diets in a healthy US adult cohort and use these features to assess the relationship between monosaccharide intake, diet quality, characteristics of the gut microbiota, and gastrointestinal inflammation. METHODS: This observational, cross-sectional study enrolled males and females across age (18-33 y, 34-49 y, and 50-65 y) and body mass index (normal, 18.5-24.99 kg/m2; overweight, 25-29.99 kg/m2; and obese, 30-44 kg/m2) categories. Recent dietary intake was assessed by the automated self-administered 24-h dietary recall system, and gut microbiota were assessed with shotgun metagenome sequencing. Dietary recalls were mapped to the Davis Food Glycopedia to estimate monosaccharide intake. Participants with >75% of carbohydrate intake mappable to the glycopedia were included (N = 180). RESULTS: Diversity of monosaccharide intake was positively associated with the total Healthy Eating Index score (Pearson's r = 0.520, P = 1.2 × 10-13) and negatively associated with fecal neopterin (Pearson's r = -0.247, P = 3.0 × 10-3). Comparing high with low intake of specific monosaccharides revealed differentially abundant taxa (Wald test, P < 0.05), which was associated with the functional capacity to break down these monomers (Wilcoxon rank-sum test, P < 0.05). CONCLUSIONS: Monosaccharide intake was associated with diet quality, gut microbial diversity, microbial metabolism, and gastrointestinal inflammation in healthy adults. As specific food sources were rich in particular monosaccharides, it may be possible in the future to tailor diets to fine-tune the gut microbiota and gastrointestinal function. This trial is registered at www. CLINICALTRIALS: gov as NCT02367287.

Systematic Review and Meta-Analysis to Estimate a Reference Range for Circulating Ionized Magnesium Concentrations in Adult Populations.

BACKGROUND: There is a lack of consensus on a reference range for ionized magnesium (iMg2+) in blood as a measure of the status of circulating iMg2+ for the screening of populations. OBJECTIVES: We estimated the reference range of iMg2+ levels for healthy adult populations and the ranges for populations with cardiovascular disease (CVD), type 2 diabetes, hypertension, and renal disease. We also estimated 95% ranges for circulating magnesium (Mg) in healthy and those with cardiometabolic diseases. METHODS: We searched Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Embase through 24 July, 2020 to identify articles. We included English, peer-reviewed, randomized controlled trials, prospective and retrospective cohort studies, case-control studies, and cross-sectional studies that measured iMg2+ in blood or circulating Mg at baseline. The protocol was registered on PROSPERO (CRD42020216100). Estimated ranges were calculated by employing a frequentist random-effects model using extracted (or calculated) means and SDs from each included study. We determined the 95% confidence interval of the pooled mean. RESULTS: A total of 95 articles were included with 53 studies having data for healthy participants and 42 studies having data for participants with cardiometabolic diseases. The estimated reference range for iMg2+ for healthy populations was 0.40-0.68 mmol/L, 0.38-0.64 mmol/L for CVD, 0.34-0.66 mmol/L for type 2 diabetes, 0.39-1.04 mmol/L for hypertension, and 0.40-0.76 mmol/L for renal disease. For circulating Mg, the estimated range was 0.72-1.0 mmol/L for healthy adults, 0.56-1.05 mmol/L for CVD, 0.58-1.14 mmol/L for type 2 diabetes, 0.60-1.08 mmol/L for hypertension, and 0.59-1.26 mmol/L for renal disease. CONCLUSIONS: Estimated reference ranges for cardiometabolic disease states for both iMg2+ and circulating Mg were broad and overlapped with the estimated range for healthy populations (0.40-0.68 mmol/L). Further studies should evaluate whether iMg2+ can be used as a biomarker of cardiometabolic disease.

Ultrasound measurement of optic nerve sheath diameter in a healthy adult Colombian population.

BACKGROUND: Measurement of the optic nerve sheath diameter (ONSD) provides a rapid, safe, and easy method for detecting increased intracranial pressure (ICP). However, the normal mean and upper limit values may vary according to sex, age, ethnicity, and ultrasound technique. AIM: We aimed to obtain the mean ONSD in a healthy Colombian adult population and to correlate it with demographic and anthropometric measures. METHODS: In a prospective study using a 10-13 MHz linear ultrasound probe, eye transverse diameter (ETD) and ONSD in the transverse (ONSD-TP) and sagittal planes (ONSD-SP) were measured in healthy adult volunteers in Bogota, Colombia. RESULTS: A total of 100 healthy subjects were included, with a mean age of 26,7 ± 8,3 years and 62 women. The mean ETD, ONSD-TP and ONSD-SP was 23.11 mm (95% confidence interval (CI): 22.90 mm-23.32 mm), 3.96 mm (95% CI: 3.85 mm-4.07 mm) and 4.0 mm (95% CI: 3.90 mm-4.11 mm), respectively. The ONSD in both planes ranged from 2.35 mm to 5.20 mm. There was a significant correlation between ONSD-SP and ONSD-TP (p < 0.0001) but no correlation between the ocular measures and demographic or anthropometric variables (p > 0.05). The intraclass correlation between the eyes was statistically significant. CONCLUSION: Our study shows that ultrasound-measured ONSD in healthy adults in Colombia is similar to that found worldwide. An ONSD of 5.5 mm may be considered the upper limit for healthy adults in Colombia. ONSD can be measured in either plane; there is a good correlation between the two eyes; and ONSD is not modified by demographic or anthropometric characteristics.

Laterality Index Calculations in a Control Study of Functional Near Infrared Spectroscopy.

Hemispheric dominance has been used to understand the influence of central and peripheral neural damage on the motor function of individuals with stroke, cerebral palsy, and limb loss. It has been well established that greater activation occurs in the contralateral hemisphere to the side of the body used to perform the task. However, there is currently a large variability in calculation procedures for brain laterality when using functional near-infrared spectroscopy (fNIRS) as a non-invasive neuroimaging tool. In this study, we used fNIRS to measure brain activity over the left and right sensorimotor cortices while participants (n = 20, healthy and uninjured) performed left and right-hand movement tasks. Then, we analyzed the fNIRS data using two different processing pipelines (block averaging or general linear model [GLM]), two different criteria of processing for negative values (include all beta values or include only positive beta values), and three different laterality index (LI) formulas. The LI values produced using the block averaging analysis indicated an expected contralateral dominance with some instances of bilateral dominance, which agreed with the expected contralateral activation. However, the inclusion criteria nor the LI formulas altered the outcome. The LI values produced using the GLM analysis displayed a robust left hemisphere dominance regardless of the hand performing the task, which disagreed with the expected contralateral activation but did provide instances of correctly identifying brain laterality. In conclusion, both analysis pipelines were able to correctly determine brain laterality, but processes to account for negative beta values were recommended especially when utilizing the GLM analysis to determine brain laterality.

Defining Normal Sequential Swallowing Biomechanics.

Little is known about the physiology of a common fluid ingestion pattern-sequential swallowing. This study investigated sequential swallowing biomechanics in healthy adults. Archival normative videofluoroscopic swallow studies were analyzed for hyolaryngeal complex (HLC) patterning and biomechanical measures from the first 2 swallows of a 90-mL thin liquid sequential swallow task. The effects of age, sex, HLC type, and swallow order were explored. Eighty-eight participants were included in the primary analyses as they performed sequential swallows. HLC Type I (airway opens, epiglottis approaches baseline) and Type II (airway remains closed, epiglottis remains inverted) most commonly occurred (47% each), followed by Type III (mixed, 6%). Age was significantly associated with Type II and longer hypopharyngeal transit, total pharyngeal transit (TPT), swallow reaction time (SRT), and duration to maximum hyoid elevation. Males demonstrated significantly greater maximum hyoid displacement (Hmax) and longer duration of maximum hyoid displacement. Significantly larger maximum hyoid-to-larynx approximation was linked to the first swallow, while the subsequent swallow had significantly longer oropharyngeal transit, TPT, and SRT. Secondary analyses included an additional 91 participants who performed a series of discrete swallows for the same swallow task. Type II had significantly greater Hmax than Type I and series of discrete swallows. Sequential swallowing biomechanics differ from discrete swallows, and normal variance exists among healthy adults. In vulnerable populations, sequential swallowing may challenge swallow coordination and airway protection. Normative data allow comparison to dysphagic populations. Systematic efforts are needed to further standardize a definition for sequential swallowing.

Ultrasonography as Biofeedback to Increase Muscle Activation During the Mendelsohn Maneuver in Healthy Adults.

The Mendelsohn Maneuver (MM) is a therapeutic strategy that targets reduced laryngeal elevation. Both clinicians and clients identify the MM as one of the more difficult interventions to teach and learn. The purpose of this study was to examine the effect of applying real-time ultrasound as visual feedback in teaching the MM to healthy adults. Twenty-four healthy adults were randomized to two-parallel groups. The standard care group (control group) received verbal instruction, verbal reinforcement, and tactile cueing while practicing the maneuver. The experimental group received the same instruction with additional real-time ultrasound as visual biofeedback. Participants completed a single session which consisted of baseline assessment, training, and post-training assessment. Outcomes were submental surface electromyography (sEMG) signal duration, maximum amplitude, and area under the curve. Statistical analysis revealed that training with feedback significantly increased submental sEMG activity during the MM; however, the addition of ultrasound as biofeedback did not significantly increase muscle activation when performing the MM over verbal instruction with verbal/tactile feedback alone. Both groups demonstrated significantly greater muscle activity measured by sEMG when applying the MM. Although the current study did not indicate that adding ultrasound biofeedback was superior to traditional training alone in teaching healthy adults to perform the MM, it does support the clinical use of biofeedback tools for learning swallowing maneuvers. Ultrasound may be a biofeedback option for people with language deficits or differences to learn a swallowing maneuver. Further studies are required to determine the clinical application of ultrasound as biofeedback on people with dysphagia.