Longitudinal Study Research Articles

Psychosocial work aspects, work ability, mental health and SARS-CoV-2 infection rates of on-site and remote Brazilian workers during the COVID-19 pandemic – a longitudinal study

Psychosocial work aspects, work ability, mental health and SARS-CoV-2 infection rates of on-site and remote Brazilian workers during the COVID-19 pandemic – a longitudinal study

Lentiviral Gene Therapy for Cerebral Adrenoleukodystrophy

BackgroundCerebral adrenoleukodystrophy is a severe form of X-linked adrenoleukodystrophy characterized by white-matter disease, loss of neurologic function, and early death. Elivaldogene autotemcel (eli-cel) gene therapy, which consists of autologous CD34+ cells transduced with Lenti-D lentiviral vector containing ABCD1 complementary DNA, is being tested in persons with cerebral adrenoleukodystrophy.MethodsIn a phase 2–3 study, we evaluated the efficacy and safety of eli-cel therapy in boys with early-stage cerebral adrenoleukodystrophy and evidence of active inflammation on magnetic resonance imaging (MRI). The primary efficacy end point was survival without any of six major functional disabilities at month 24. The secondary end points included overall survival at month 24 and the change from baseline to month 24 in the total neurologic function score.ResultsA total of 32 patients received eli-cel; 29 patients (91%) completed the 24-month study and are being monitored in the long-term follow-up study. At month 24, none of these 29 patients had major functional disabilities; overall survival was 94%. At the most recent assessment (median follow-up, 6 years), the neurologic function score was stable as compared with the baseline score in 30 of 32 patients (94%); 26 patients (81%) had no major functional disabilities. Four patients had adverse events that were directly related to eli-cel. Myelodysplastic syndrome (MDS) with excess blasts developed in 1 patient at month 92; the patient underwent allogeneic hematopoietic stem-cell transplantation and did not have MDS at the most recent follow-up.ConclusionsAt a median follow-up of 6 years after lentiviral gene therapy, most patients with early cerebral adrenoleukodystrophy and MRI abnormalities had no major functional disabilities. However, insertional oncogenesis is an ongoing risk associated with the integration of viral vectors. (Funded by Bluebird Bio; ALD-102 and LTF-304 ClinicalTrials.gov numbers NCT01896102 and NCT02698579, respectively.)

Real-Time Imaging Assessment of Stress-Induced Vascular Inflammation Using Heartbeat-Synchronized Motion Compensation.

Chronic mental stress accelerates atherosclerosis through complicated neuroimmune pathways, needing for advanced imaging techniques to delineate underlying cellular mechanisms. While histopathology, ex vivo imaging, and snapshots of in vivo images offer promising evidence, they lack the ability to capture real-time visualization of blood cell dynamics within pulsatile arteries in longitudinal studies. An electrically tunable lens was implemented in intravital optical microscopy, synchronizing the focal plane with heartbeats to follow artery movements. ApoE-/- mice underwent 2 weeks of restraint stress before baseline imaging followed by 2 weeks of stress exposure in the longitudinal imaging, while nonstressed mice remained undisturbed. The progression of vascular inflammation was assessed in the carotid arteries through intravital imaging and histological analyses. A 4-fold reduction of motion artifact, assessed by interframe SD, and an effective temporal resolution of 25.2 Hz were achieved in beating murine carotid arteries. Longitudinal intravital imaging showed chronic stress led to a 6.09-fold (P=0.017) increase in myeloid cell infiltration compared with nonstressed mice. After 3 weeks, we observed that chronic stress intensified vascular inflammation, increasing adhered myeloid cells by 2.45-fold (P=0.031), while no significant changes were noted in nonstressed mice. Microcirculation imaging revealed increased circulating, rolling, and adhered cells in stressed mice's venules. Histological analysis of the carotid arteries confirmed the in vivo findings that stress augmented plaque area, myeloid cell and macrophage accumulation, and necrotic core volume while reducing fibrous cap thickness indicating accelerated plaque formation. We visualized the 3-dimensional structure of the carotid artery and 4-dimensional dynamics of the venules in the cremaster muscle. Dynamic focusing motion compensation intravital microscopy enabled subcellular resolution in vivo imaging of blood cell dynamics in beating arteries under chronic restraint stress in real time. This novel technique emphasizes the importance of advanced in vivo imaging for understanding cardiovascular disease.

Application of a validated prognostic plasma protein biomarker test for renal decline in type 2 diabetes to type 1 diabetes: the Fremantle Diabetes Study Phase II

BackgroundThere are scant data relating to prognostic biomarkers for chronic kidney disease (CKD) complicating type 1 diabetes. The aim of this study was to assess the performance of the plasma protein biomarker-based PromarkerD test developed and validated for predicting renal decline in type 2 diabetes in the context of type 1 diabetes.MethodsThe baseline PromarkerD test score was determined in 91 community-based individuals (mean age 46.2 years, 56.5% males) with confirmed type 1 diabetes recruited to the longitudinal observational Fremantle Diabetes Study Phase II. The performance of the PromarkerD test in predicting the risk of incident CKD (estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2 in people without CKD at baseline) or an eGFR decline of ≥ 30% over the next four years was determined. The score can range from 0 to 100%, and is categorized as representing low (< 10%), moderate (10% to < 20%) or high (≥ 20%) risk.ResultsThe area under the receiver operating characteristic curve was 0.93 (95% confidence interval 0.87–0.99) for the composite renal endpoint, indicating strong predictive accuracy. The positive and negative predictive values at moderate (10% to < 20%) and high (≥ 20%) risk PromarkerD cut-offs were 46.7–50.0% and ≥ 92.0%, respectively.ConclusionsThese preliminary data suggest that PromarkerD is at least as good a prognostic test for renal decline in type 1 as type 2 diabetes.

Signaling trust during disruptions: perceived gender differences in trustworthy leadership traits

Purpose This study aims to examine differences in the self-perception and value of four traits associated with trustworthiness: transparency, credibility, accountability and honesty to find out whether these traits are more likely to be adopted by female leaders during episodes of disruption. Design/methodology/approach Regression estimation of perceived trustworthy leadership values using a survey of full-time employed men and women in management working for various organizations. Findings Honesty emerged as the highest rated trait overall, both in the respondents’ self-measure and in their reflected level of desirability. However, women described their honesty as higher than how men relayed their honesty score. Both genders rated their own transparency as their lowest scoring trait and treated it as the least important of the desired traits. Relative to men, not only do women espouse to greater levels of honesty and value it more but they also appear to embrace honesty in their desired behaviors more highly. Research limitations/implications A natural extension of this study is to design a longitudinal study to show causality or whether socialized gender differences, in fact, play a role in measuring the value of trustworthy leadership during disruptions. Practical implications Understanding self-perceptions of leaders’ efficacy and desired expectations helps prepare both current and future leaders to regain followers’ trust, especially during disruptions. Lessons learned to date require investments in building awareness of leaders’ perceptions of trustworthiness and developing relevant skills for dealing with disruptions. Originality/value This research adds further insight to leadership studies by establishing a linkage between characteristics of trustworthy leadership and the ability to lead in challenging times. Cultivating traits of transparency, accountability, credibility and honesty enables leaders to develop the skills needed to be viewed as trustworthy and be prepared for the unexpected.

The development of intrinsic capacity measures for longitudinal research: The Longitudinal Aging Study Amsterdam

BackgroundThe World Health Organization has introduced the construct of intrinsic capacity (IC) as an important component of healthy ageing and overall well-being in older adults The present study aimed to develop domain-specific and composite IC scores and to validate these scores by examining their longitudinal relation with functioning. MethodsWe used prospective data on participants aged 57 to over 90 years, with a 10-year follow-up, from the Longitudinal Aging Study Amsterdam, an ongoing cohort study of older Dutch men and women Using a formative, stepwise approach, we identified indicators across the different domains of IC, i.e. vitality, sensory, cognition, psychology, and locomotion, using a combination of unidimensional factor analyses and Partial Least Squares Structural Equation Modelling (PLS-SEM). Next, domain-specific and composite IC scores were generated, and the construct validity (score across age groups) and criterion validity (relationship with change in functional limitations) were assessed. ResultsThe multiple unidimensional factor analyses and PLS-SEM identified a total of 18 indicators, covering the five domains of IC. The mean composite IC score was 70.9 (SD = 0.9) in men and 69.7 (0.8) in women. The domain-specific and composite IC scores all showed good construct validity, with known-group validation results indicating age-related declines. A higher composite IC score was associated with less functional limitations over time (B = 0.20, 95%CI [0.19, 0.22]). ConclusionThe developed domain-specific IC scores and the composite IC score effectively discriminated age-related declines in IC. Additionally, the composite IC score was longitudinally associated with functional limitations. By creating this comprehensive and reliable tool for tracking IC, we aim to provide valuable insights into the dynamics of ageing and support more effective strategies for promoting health and well-being throughout later life. These scores establish a foundation for future research to track longitudinal changes across various IC domains and relate these changes to key age-related outcomes.

Biomarker role of thyroid irAE and PD-L1 positivity in predicting PD-1 blockade efficacy in patients with non-small cell lung cancer

Thyroid immune-related adverse events (irAEs) are associated with programmed cell death protein 1 (PD-1) blockade efficacy in non-small cell lung cancer (NSCLC). However, their independence from PD-L1 expression and quantitative impact on predicting PD-1 blockade efficacy remain unexplored. This multicenter, retrospective, longitudinal study from Korea included 71 metastatic NSCLC patients who underwent PD-L1 expression and thyroid function testing during PD-1 blockade. Disease progression by the Response Evaluation Criteria for Solid Tumors was the main outcome. Three-stage analyses were performed: (1) multivariate Cox regression models adjusted for PD-L1 expression according to thyroid irAEs; (2) subgroup analyses; (3) regrouping and comparing predictivity of current and alternative staging. Patients with thyroid irAE + exhibited a longer progression-free survival [7/20 vs. 34/51, adjusted HR 0.19 (0.07–0.47); P < 0.001] than those with thyroid irAE-, independent of PD-L1 expression; the results remained across most subgroups without interaction. The three groups showed different adjusted HR for disease progression (Group 1: PD L1 + and thyroid irAE + ; Group 2: PD-L1 + or thyroid irAE + : 5.08 [1.48–17.34]; Group 3: PD-L1− and thyroid irAE− : 30.49 [6.60–140.78]). Alternative staging (Group 1 in stage IVB → stage IVA; Group 3 in stage IVA → stage IVB) improved the prognostic value (PVE: 21.7% vs. 6.44%; C-index: 0.706 vs. 0.617) compared with the 8th Tumor–Node–Metastasis staging. Our study suggests thyroid irAEs and PD-L1 expression are independent biomarkers that improve predicting PD-1 blockade efficacy in NSCLC. Thyroid irAEs would be helpful to identify NSCLC patients who benefit from PD-1 blockade in early course of treatment.

Association of RAAS inhibitors on osteoporosis and fracture risk in the hypertensive population–A prospective population-based cohort study in Lanzhou, China

BackgroundRenin-angiotensin-aldosterone system (RAAS) inhibitors appear to benefit bone tissue in antihypertensive treatment. However, the association between RAAS inhibitors and bone metabolism was inconsistent.Methods and study designBased on the study of Risk Evaluation of Cancers in Chinese Diabetic Individuals(REACTION) conducted in 2011, We followed 6,252 Lanzhou residents aged 40–75 years from 2014 to 2016. Finally, 1,625 hypertension cases with complete data were included in the analysis. The study subjects were divided into four groups according to the type of antihypertensive drugs. We employed logistic or multivariate Cox proportional hazards regression to estimate the association between different antihypertensive drug use and osteoporosis, the risk of fracture, and the change in bone mineral density (BMD) level. The association of osteoporosis or the fracture risk by cumulative duration of use of these medications (< 3 years.) and (> 3 years.) was also estimated.ResultsThe cross-sectional study showed that there was no significant association between baseline antihypertensive drugs (angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB)) use and osteoporosis and fracture. During a mean follow-up of 3.4 years in the longitudinal study, there were 478 new osteoporosis cases and 76 fractures. Compared with patients without antihypertensive drug use, the hazard ratios (HRs) [95% confidence interval (CI)] for the risk of osteoporosis were 1.005(0.651,1.552) and 1.077(0.793,1.462) in ACEI or ARB use (p > 0.05). ACEI or ARB use was also not significantly associated with fracture risk (HR 1.102(0.326,3.726), 0.735(0.251,2.148), p > 0.05). Further analysis showed that the use of ACEI (HR 1.078(0.146,7.950)) or ARB (HR 1.169(0.347,3.939)) was not significantly associated with the improvement of osteoporosis (p > 0.05). In addition, the duration of RAAS inhibitors used showed no apparent correlation with the risk of osteoporosis (≤ 3 years: HR 0.872 (0.516, 1.474), > 3 years: HR 1.151 (0.574, 2.308)), nor with the improvement of osteoporosis and the risk of fracture. Meanwhile, the association mentioned above did not change compared to different RAAS inhibitors.ConclusionsThe use of RAAS inhibitors, including ACEIs and ARBs, was not significantly associated with osteoporosis, risk of fracture, or BMD change.

Teachers’ collective habits as critical for establishing collegial learning

ABSTRACT In the past two decades, scholarly discourse has consistently emphasised the efficacy of collective efforts in professional development and school improvement. Collaborative endeavours among teachers, where they systematically explore their teaching practices and collaboratively address relevant improvement issues, have proven more effective than individual pursuits in educational change. However, research also underscores the inherent challenges of such collective initiatives, particularly in collegial learning. In a longitudinal study, we adopted a pragmatic perspective to delve into the collective habits of teacher teams working towards establishing collegial learning. The identified collective habits, which revolve around collective participation, the improvement process, and scientific activities, play a pivotal role in either facilitating or hindering the establishment of collegial learning to achieve professional development and school improvement. We posit that a critical exploration of collective habits is imperative for teacher teams aiming to nurture novel and impactful practices. Strategies conducive to teachers’ collegial learning encompass fostering pedagogical leadership, cultivating continuity, and embracing scientific rigour in the analysis of classroom data.

Ultra-processed foods intake in relation to metabolic health status, serum brain-derived neurotrophic factor and adropin levels in adults

BackgroundIn recent years, there has been a lot of discussion over the impact of ultra-processed foods (UPFs) intake on overall health of subjects. However, the association between UPFs intake and metabolic unhealthy (MU) status is still in a state of ambiguity. The current study assessed the relationship between UPFs intake and MU status with regard to brain-derived neurotrophic factor (BDNF) and adropin levels.MethodsA sample of Iranian adults (aged 20–65 years) was selected to participate in this cross-sectional study using a multistage cluster random-sampling method. UPFs intake was assessed by a validated food frequency questionnaire and NOVA classification. Concentrations of metabolic parameters, BDNF and adropin were determined through fasting blood samples. MU status was assessed according to the criteria proposed by Wildman.ResultsThe overall prevalence of MU phenotype among study participants (n = 527) was 42.5%. Higher intake of UPFs was associated with elevated odds of MU status in multivariable-adjusted model (ORT3 vs. T1=1.88; 95%CI: 1.02–3.45). Moreover, a positive association was observed between UPFs intake and hypertriglyceridemia after controlling all confounders (ORT3 vs. T1=2.07; 95%CI: 1.15–3.73). However, each tertile increase in UPFs intake was not significantly associated with serum BDNF (\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:\\beta\\:$$\\end{document}=0.15; 95%CI: -0.05, 0.34; P = 0.14) and adropin (\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:\\beta\\:$$\\end{document}=-1.37; 95%CI: -6.16, 3.42; P = 0.58) levels in multivariable-adjusted linear regression models.ConclusionOur findings suggested that higher consumption of UPFs was related to increased likelihood of MU status among a sample of Iranian adults. Further longitudinal studies are needed to verify the directionality and generalizability of the results to all adult populations.

Psychotic symptoms associated increased CpG methylation of metabotropic glutamate receptor 8 gene in Chinese Han males with schizophrenia and methamphetamine induced psychotic disorder: a longitudinal study

Methamphetamine use can produce psychotic symptoms almost indistinguishable from schizophrenia (SCZ). Variation in DNA methylation may be closely implicated in the etiology and longitudinal development of psychiatric disorders. However, the relationship between psychotic symptoms, functional disability, and DNA methylation is still unclear. This study consists of three periods: discovery, validation, and follow-up. In the discovery stage, we employed genome-wide DNA methylation profiling (Illumina 450K) in peripheral blood mononuclear cells to test whether DNA methylation associates with psychotic symptoms and function state in representative SCZ and methamphetamine-induced psychotic disorder (MIP) patients. Then, we found seven differentially methylated regions/genes (DMRs, in UBA6, APOL3, KIF17, MLLT3, GRM8, CSNK1E, SETDB1) overlapping with genetic variants reported in previous studies of psychosis. In the validation stage, we compared the above-mentioned seven genes by MethLight qPCR method in Chinese Han males (N = 109 SCZ patients, N = 99 methamphetamine use disorder with MIP patients, N = 150 methamphetamine use disorder without MIP patients, N = 282 normal controls, age range: 18–50 years). GRM8 showed robustly altered methylation, which has passed rigorous filtration in subsequent validation, suggesting a remarkable contribution to SCZ and MIP. In addition, hypermethylation of GRM8 showed a significant association with the total scores of the Positive Negative Syndrome Scale and WHO disability assessment schedule II in both baseline and follow-up periods. Our findings suggest that increased CpG methylation in the promoter of GRM8 is a potential candidate epigenetic biomarker of psychotic symptoms in transdiagnostic samples of SCZ and MIP.

The associations between dairy product intake, fatigue status, and physical activity among postpartum women in Saudi Arabia: a cross-sectional study

BackgroundFatigue is a major issue that affects women during the postpartum period. A healthy dietary pattern and increased physical activity (PA) are commonly recommended lifestyle modifications to promote health during this time. However, little is known about the interrelationship between dairy product intake, PA level, and postpartum fatigue (PPF) among women. The aim of this study was to evaluate whether PPF is associated with dairy product intake in relation to PA level.MethodsA total of 242 women were included in this cross-sectional study. Data related to dairy product intake and PA were collected using a food frequency questionnaire and the International Physical Activity Questionnaire—Short Form, respectively. PPF was assessed using the Fatigue Severity Scale. Logistic regression models were used to examine associations between the intake of dairy products and PPF among women engaged in low, moderate, and high levels of PA while controlling for potential confounders.ResultsHigher consumption rates of yogurt and total dairy predicted lower odds of PPF in women engaged in moderate levels of PA (aOR = 0.24 [95% CI = 0.07, 0.86] and 0.70 [95% CI = 0.53, 0.93], respectively). In women engaged in high levels of PA, lower odds of experiencing PPF were predicted by higher consumption rates of milk (aOR = 0.24 [95% CI = 0.07, 0.89]), yogurt (aOR = 0.21 [95% CI = 0.05, 0.83]), laban (aOR = 0.16 [95% CI = 0.03, 0.86]), and total dairy (aOR = 0.66 [95% CI = 0.47, 0.92]). However, no association was observed between dairy product intake and PPF in women with low levels of PA.ConclusionsHigher consumption rates of dairy products were associated with lower odds for experiencing PPF, particularly for women engaged in moderate to high levels of PA. These findings support nutritional and PA promotion programs to moderate issues with PPF. However, the cross-sectional design of this study could limit the ability to infer causality between dairy intake, PA, and PPF. Further longitudinal studies are needed to establish causality and explore the mechanisms underlying these associations.

Impact of physical activity on life satisfaction among middle-aged and older adults in China: A longitudinal national study.

This study examined the impact of physical activity on life satisfaction in middle-aged and older adults in China. Utilizing longitudinal data from the China Health and Retirement Longitudinal Study (CHARLS) conducted in 2015 and 2018, a total of 6484 participants aged 45 or older were included in the analysis. Data were collected on sociodemographic, health, and lifestyle variables, physical activity, and life satisfaction. Physical activity was categorized into 3 levels: low (71%), moderate (25%), and high (4%). Ordinal logistic regression and subgroup analysis were used to examine the effect of baseline physical activity on life satisfaction, including the examination of interaction effects. After adjusting for age, gender, education, marriage, residence, smoking, alcohol use, depressive symptoms, and self-rated health at baseline (2015), compared to the moderate-intensity physical exercise group, those in the low-intensity group experienced significantly lower levels of life satisfaction on follow-up (2018). In the subgroup analyses, a significant negative effect of low-intensity physical activity on life satisfaction was found in all groups regardless of age, education, marital status, smoking, alcohol use, sleep duration, weight, presence of chronic diseases, or self-rated health. These results support the promotion of physical exercise to enhance life satisfaction among middle-aged and older adults in China.

Sources of perceived social support and cognitive function among older adults: a longitudinal study in rural China

BackgroundStudies have shown the positive impact of perceived social support on cognitive function among older adults in rural areas. However, existing studies often overlook the impact of different support sources. This study aimed to explore the relationship between the diverse sources of perceived social support and cognitive function.MethodsParticipants were drawn from the Guizhou Rural Older Adults’ Health Study (HSRO) in China. We included 791 participants who participated in a baseline survey in 2019 and a 3-year follow-up survey. Perceived social support was investigated from the six main sources (friend, relative, children, spouse, sibling, and neighbor). Hierarchical linear regression models were used to observe the effects of diverse sources of perceived social support and their combinations on cognitive function.ResultsCognitive function was positively associated with perceived support from children, friends, and neighbors. A positive association was found between cognitive function and increases in each additional source [β = 0.75 (95%CI: 0.51, 0.98), p &amp;lt; 0.001]. Older adults who perceived support from both children and friends showed better cognitive function [β = 2.53 (95%CI: 1.35, 3.72), p &amp;lt; 0.001]. The perception of support from spouse, siblings, and relatives did not show a statistically significant association with cognitive function among older adults in rural areas.ConclusionThis study found that the association between different sources of perceived social support and cognitive function was varied. This study provides scientific evidence that personalized support strategies may benefit in promoting cognitive health in rural older adults.

A Comprehensive and Repeatable Contrast-Enhanced Ultrasound Quantification Approach for Clinical Evaluations of Tumor Blood Flow

Objective The aim of this study is to define a comprehensive and repeatable contrast-enhanced ultrasound (CEUS) imaging protocol and analysis method to quantitatively assess lesional blood flow. Easily repeatable CEUS evaluations are essential for longitudinal treatment monitoring. The quantification method described here aims to provide a structure for future clinical studies. Materials and Methods This retrospective analysis study included liver CEUS studies in 80 patients, 40 of which contained lesions (primarily hepatocellular carcinoma, n = 28). Each patient was given at least 2 injections of a microbubble contrast agent, and 60-second continuous loops were acquired for each injection to enable evaluation of repeatability. For each bolus injection, 1.2 mL of contrast was delivered, whereas continuous, stationary scanning was performed. Automated respiratory gating and motion compensation algorithms dealt with breathing motion. Similar in size regions of interest were drawn around the lesion and liver parenchyma, and time-intensity curves (TICs) with linearized image data were generated. Four bolus transit parameters, rise time (RT), mean transit time (MTT), peak intensity (PI), and area under the curve (AUC), were extracted either directly from the actual TIC data or from a lognormal distribution curve fitted to the TIC. Interinjection repeatability for each parameter was evaluated with coefficient of variation. A 95% confidence interval was calculated for all fitted lognormal distribution curve coefficient of determination (R 2) values, which serves as a data quality metric. One-sample t tests were performed between values obtained from injection pairs and between the fitted lognormal distribution curve and direct extraction from the TIC calculation methods to establish there were no significant differences between injections and measurement precision, respectively. Results Average interinjection coefficient of variation with both the fitted curve and direct calculation of RT and MTT was less than 21%, whereas PI and AUC were less than 40% for lesion and parenchyma regions of interest. The 95% confidence interval for the R 2 value of all fitted lognormal curves was [0.95, 0.96]. The 1-sample t test for interinjection value difference showed no significant differences, indicating there was no relationship between the order of the repeated bolus injections and the resulting parameters. The 1-sample t test between the values from the fitted lognormal distribution curve and the direct extraction from the TIC calculation found no statistically significant differences (α = 0.05) for all perfusion-related parameters except lesion and parenchyma PI and lesion MTT. Conclusions The scanning protocol and analysis method outlined and validated in this study provide easily repeatable quantitative evaluations of lesional blood flow with bolus transit parameters in CEUS data that were not available before. With vital features such as probe stabilization ideally performed with an articulated arm and an automated respiratory gating algorithm, we were able to achieve interinjection repeatability of blood flow parameters that are comparable or surpass levels currently established for clinical 2D CEUS scans. Similar values and interinjection repeatability were achieved between calculations from a fitted curve or directly from the data. This demonstrated not only the strength of the protocol to generate TICs with minimal noise, but also suggests that curve fitting might be avoided for a more standardized approach. Utilizing the imaging protocol and analysis method defined in this study, we aim for this methodology to potentially assist clinicians to assess true perfusion changes for treatment monitoring with CEUS in longitudinal studies.

Advances in VNS efficiency and mechanisms of action on cognitive functions

ObjectiveThis systematic review aims to comprehensively analyze the efficacy and underlying mechanisms of vagus nerve stimulation (VNS) in enhancing cognitive functions and its therapeutic potential for various cognitive impairments. The review focuses on the impact of VNS on emotional processing, executive functions, learning, memory, and its clinical applications in conditions such as epilepsy, depression, Alzheimer’s disease, and other neurological disorders.MethodsA systematic search of electronic databases (PubMed, Scopus, Web of Science) was conducted using the keywords “vagus nerve stimulation,” “cognitive enhancement,” “emotional processing,” “executive function,” “learning and memory,” “epilepsy,” “depression,” “Alzheimer’s disease,” “neurological disorders,” “attention-deficit/hyperactivity disorder,” “sleep disorders,” and “long COVID.” The inclusion criteria encompassed controlled trials, longitudinal studies, and meta-analyses published in English between 2000 and July 2024.ResultsA comprehensive review of 100 articles highlighted the cognitive effects of Vagus Nerve Stimulation (VNS). Studies show that VNS, especially through transcutaneous auricular VNS (taVNS), enhances emotional recognition, particularly for facial expressions, and improves selective attention under high cognitive demands. Additionally, VNS enhances learning and memory, including associative memory and spatial working memory tasks. In clinical applications, VNS exhibits promising benefits for improving cognitive functions in treatment-resistant epilepsy, depression, and Alzheimer’s disease.ConclusionVNS represents a promising therapeutic approach for enhancing cognitive function across diverse patient populations. The reviewed evidence highlights its efficacy in modulating cognitive domains in healthy individuals and improving cognition in neurological conditions. However, the comparative effectiveness of different VNS modalities and the differential effects of online versus offline VNS on cognitive psychology require further investigation. Future research should focus on optimizing VNS protocols and elucidating specific cognitive domains that benefit most from VNS interventions. This ongoing exploration is essential for maximizing the therapeutic potential of VNS in clinical practice.

The prevalence of obesity and underweight in celiac patients at the time of diagnosis: a systematic review and meta-analysis

BackgroundThis study aimed to estimate the prevalence of obesity, overweight, and underweight in celiac disease (CD) at diagnosis before starting the Gluten-free diet (GFD).MethodsA comprehensive search was conducted in PubMed, Embase, Scopus, and Web of Science until July 2024 to find the cross-sectional and longitudinal studies that measured the body mass index (BMI) in CD patients at diagnosis. The risk of bias assessment was conducted using the Newcastle–Ottawa Quality Assessment scale. Meta-regression analyses were applied to understand whether weight status is associated with CD.ResultsA total of 23 studies involving 15,299 CD patients and 815,167 healthy individuals were included in this study. In newly diagnosed CD patients, pooled estimates of the prevalence of obesity, overweight, and underweight before GFD were 11.78%, 18.42%, and 11.04%, respectively. The prevalence of overweight and obesity in newly diagnosed CD patients increased from 22.15% in 2003–2009 to 32.51% in 2016–2021. Meta-regression analyses indicated that the CD patients with higher BMI had a higher mean age (p = 0.001), and female gender had a marginally significant (p = 0.055) association with higher BMI. Only a few CD patients were underweight at the time of diagnosis, and more patients were overweight/obese.Conclusionsour meta-analysis demonstrated that only a few CD patients were underweight at the time of diagnosis, and almost 37% were overweight or obese. Meta-regression showed a significant association between higher BMI and higher mean age and female gender. A delay or failure for diagnosis of CD is more common in overweight/obese patients, resulting in more progression of the disease and counteracting any advantages of diagnosis.

Associations of nutritional status and dietary habits with the development of female infertility. A case–control study

IntroductionFemale infertility is a multifactorial condition influenced by lifestyle and dietary factors. Understanding the relationship between nutritional status, dietary habits, and infertility could provide insights for targeted interventions.MethodsA case-control study was conducted in health centers and hospitals in Alicante, Spain. The study included 60 infertile and 30 fertile women aged 18–40, selected through consecutive sampling. Data on body composition and dietary intake were collected and analyzed.ResultsInfertile women exhibited significantly lower muscle mass (p = 0.005) and larger hip circumference (p = 0.034) compared to fertile women. Additionally, a significant association was found between high red meat consumption and an increased risk of female infertility (p = 0.011).DiscussionThese results suggest that body composition and dietary habits, particularly muscle mass and red meat intake, play a key role in female fertility. Interventions aimed at improving muscle mass, reducing localized body fat, and limiting red meat consumption may enhance fertility outcomes. Further longitudinal research is needed to confirm these findings across diverse populations.

Brain imaging and clinical outcome of embodied VR-BCI training in chronic stroke patients: a longitudinal pilot study

ABSTRACT Introduction Restorative Brain–Computer Interfaces (BCIs) provide an alternative non-muscular channel for stroke patients lacking volitional movement by enhancing sensorimotor rhythm modulation through motor imagery (MI). MI practice can be augmented with embodied feedback via virtual reality (VR). However, the clinical impact of embodied VR-BCI training remains under-explored. Methods This study examines the effects of embodied VR-BCI training on brain activity patterns (measured through EEG and fMRI) and clinical outcomes (assessed by the Fugl–Meyer Assessment, FMA) in four chronic stroke patients. Over a 3-week MI-BCI intervention, patients performed a bimanual rowing task (NeuRow) in VR. EEG data were used to extract Event-related desynchronization (ERD) and lateralization indices, while fMRI data focused on the primary motor (M1) and supplementary motor (SMA) regions of interest. Results Results indicated that all patients significantly induced ERD power, though the affected side exhibited reduced ERD compared to baseline during contralateral MI. Post-intervention, significant ERD differences from both hemispheres were observed, with decreased ERD correlating with no clinical improvement. Patients showing decreased ERD lateralization had no FMA score improvement. Activity within ipsilesional M1 and SMA correlated with FMA scores. Conclusions The findings suggest a relationship between brain activity and clinical outcomes, highlighting that increased ERD lateralization is associated with clinical improvement.

Effect of Adopting a Gluten-Free Diet on Exposure to Arsenic and Other Heavy Metals in Children with Celiac Disease: A Prospective Cohort Study

Objectives: Lifelong adherence to a gluten-free diet (GFD) is the primary treatment for celiac disease (CeD), a gluten-driven enteropathy. Concerns have been raised about increased exposure to arsenic from a GFD because rice, which naturally bioaccumulates arsenic, is commonly used as a substitute for gluten-containing grains such as wheat. We hypothesize that arsenic exposure increases in newly diagnosed children with CeD after they adopt a GFD. Methods: This is a single-center prospective longitudinal cohort study of children (age 2-18 years) with elevated celiac serology who underwent a diagnostic endoscopy prior to initiation of a GFD between January and May 2022. The primary outcome was change in urinary arsenic concentration between endoscopy and after 6 months on a GFD. Results: Of the 67 recruited participants, 50 had a biopsy diagnostic of CeD and were invited to continue the study. Thirty-five participants completed sample collection. Participants were from a middle-class, well-educated population that was predominantly white with presenting symptoms of abdominal pain (51%) and diarrhea (29%). After six months on a GFD, there was a significant increase in the median urinary arsenic concentration (3.3μg/L vs. 13.6μg/L, p=0.000004). In regression models, family history of CeD and Hispanic ethnicity were associated with having a higher urinary arsenic concentration after 6 months on a GFD. Conclusions: Children with newly diagnosed CeD have increased arsenic exposure shortly after transitioning to a GFD. While the arsenic levels were well below acutely toxic concentrations, the clinical impact of chronic exposure to mildly elevated arsenic levels is unknown.