Functional Assessment Research Articles

Longitudinal association between DNA methylation and type 2 diabetes: findings from the KORA F4/FF4 study

BackgroundType 2 diabetes (T2D) has been linked to changes in DNA methylation levels, which can, in turn, alter transcriptional activity. However, most studies for epigenome-wide associations between T2D and DNA methylation comes from cross-sectional design. Few large-scale investigations have explored these associations longitudinally over multiple time-points.MethodsIn this longitudinal study, we examined data from the Cooperative Health Research in the Region of Augsburg (KORA) F4 and FF4 studies, conducted approximately seven years apart. Leucocyte DNA methylation was assessed using the Illumina EPIC and 450K arrays. Linear mixed-effects models were employed to identify significant associations between methylation sites and diabetes status, as well as with fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), homoeostasis model assessment of beta cell function (HOMA-B), and homoeostasis model assessment of insulin resistance (HOMA-IR). Interaction effects between diabetes status and follow-up time were also examined. Additionally, we explored CpG sites associated with persistent prediabetes or T2D, as well as the progression from normal glucose tolerance (NGT) to prediabetes or T2D. Finally, we assessed the associations between the identified CpG sites and their corresponding gene expression levels.ResultsA total of 3,501 observations from 2,556 participants, with methylation measured at least once across two visits, were included in the analyses. We identified 64 sites associated with T2D including 15 novel sites as well as known associations like those with the thioredoxin-interacting protein (TXNIP) and ATP-binding cassette sub-family G member 1 (ABCG1) genes. Of these, eight CpG sites exhibited different rates of annual methylation change between the NGT and T2D groups, and seven CpG sites were linked to the progression from NGT to prediabetes or T2D, including those annotated to mannosidase alpha class 2a member 2 (MAN2A2) and carnitine palmitoyl transferase 1 A (CPT1A). Longitudinal analysis revealed significant associations between methylation and FPG at 128 sites, HbA1c at 41 sites, and HOMA-IR at 57 sites. Additionally, we identified 104 CpG-transcript pairs in whole blood, comprising 40 unique CpG sites and 96 unique gene transcripts.ConclusionsOur study identified novel differentially methylated loci linked to T2D as well as to changes in diabetes status through a longitudinal approach. We report CpG sites with different rates of annual methylation change and demonstrate that DNA methylation associated with T2D is linked to following transcriptional differences. These findings provide new insights into the molecular mechanisms of diabetes development.Graphical abstract

The Association Between Left Ventricular Global Function Index and Major Adverse Cardiovascular Events Linked to Systemic Inflammation in Acute Coronary Syndrome.

We aimed to investigate the association between systemic inflammation and the left ventricular global function index (LVGFI) and evaluate the diagnostic performance of LVGFI for MACEs across the acute coronary syndrome (ACS) spectrum. A total of 1697 patients (794 with ST-segment elevation myocardial infarction [STEMI] and 903 with non-STEMI [NSTEMI]) were evaluated. The LVGFI was calculated using echocardiography. Inflammatory status was assessed with C-reactive protein (CRP) and the systemic immune inflammation index (SII). MACEs were defined as non-fatal re-infarction, repeated revascularization of the target vessel, and all-cause mortality at a 3-year follow-up. While the STEMI group exhibited lower LVGFI values compared with the NSTEMI group (P < .001), it had a higher SII level (P < .001) and CRP level (P = .021). The association between higher LVGFI quartiles and lower levels of systemic inflammation was more pronounced in the STEMI group. The threshold value of LVGFI to predict MACEs was <21.8% (Sensitivity = 79.2%, Specificity = 68.7%) for STEMI, while it was <25.4% (Sensitivity = 77.4%, Specificity = 70.8%) for NSTEMI. Considering both the inflammatory status and ACS spectrum when evaluating LVGFI could provide a more comprehensive assessment of cardiac function and prognosis in ACS patients.

Arteriolar Elasticity Measurement in the Fingertip Based on Photoplethysmographic Volume-Oscillometry: A New Approach to the Assessment of Vasomotor Functions in the Microvasculature.

Dysfunction of vasomotor reactions due to arteriolar smooth muscle causes serious adverse events, such as loss of hemodynamic coherence. This in turn can increase risks of cardiovascular-related diseases. A noninvasive and quantitative evaluation of microvascular disorder is therefore very important for early diagnosis and treatment. This paper describes a new approach to the assessment of vasomotor functions using the arteriolar elasticity measurement technique in the fingertip. A recently developed device, modified to detect a photoplethysmogram with green light (gPPG) in arteriolar regions, allowed the measurement of arteriolar blood pressure (BPca.) and gPPG from a left index fingertip placed on an occlusive cuff of the device. Arteriolar stiffness and distensibility were analyzed as effective elasticity indices, as a function of arteriolar distending pressure derived by volume-oscillometry. Cold pressor tests to induce vasoconstriction were carried out whether appropriate elasticity changes could be obtained. Experiments using 6 healthy subjects were successfully made to obtain arteriolar elastic properties before and while immersing a right hand in cold water. The index-values of stiffness and distensibility showed, respectively, a considerable increase and decrease, clearly demonstrating the appropriate elasticity changes with vasoconstrictive reactions. Although a further study using many subjects is needed, the results so far suggest that this method could easily provide important features to acquire quantitatively arteriolar elasticity together with BPca. and to assess vasomotor functions in the microvasculature. This convenient method appears useful for clinical practices and health management and promising also for screening cardiovascular-related diseases. (242/250 words).

Biomarkers of RV Dysfunction in HFrEF Identified by Direct Tissue Proteomics: Extracellular Proteins Fibromodulin and Fibulin-5.

Right ventricular dysfunction (RVD) is common in patients with heart failure with reduced ejection fraction, and it is associated with poor prognosis. However, no biomarker reflecting RVD is available for routine clinical use. Proteomic analysis of myocardium from the left ventricle and right ventricle (RV) of patients with heart failure with reduced ejection fraction with (n=10) and without RVD (n=10) who underwent heart transplantation was performed. Concentrations of 2 ECM (extracellular matrix) proteins with the highest myocardial upregulation in RVD, FMOD (fibromodulin) and FBLN5 (fibulin-5), were assayed in the blood and tested in a separate cohort of patients with heart failure with reduced ejection fraction (n=232) to test for the association of the 2 proteins with RV function and long-term outcomes. Multivariable linear regression revealed that plasma concentrations of both FMOD and FBLN5 were significantly associated with RV function regardless of the RV function assessment method. No association of FMOD or FBLN5 with left ventricular dysfunction, cardiac index, body mass index, diabetes status, or kidney function was found. Plasma levels of FMOD and FBLN5 were significantly associated with patient outcomes (P=0.005; P=0.004). Area under the curve analysis showed that the addition of FBLN5 or FMOD to RV function assessment had a significantly higher area under the curve after 4 years of follow-up (0.653 and 0.631, respectively) compared with RV function alone (0.570; P<0.05 for both). Similarly, the combination of MAGGIC (Meta-Analysis Global Group in Chronic Heart Failure) score, FBLN5, and FMOD had a significantly larger area under the curve (0.669) than the combination of MAGGIC score+RVD grade (0.572; P=0.02). The Kaplan-Meier analysis demonstrated that patients with the elevation of both FMOD and FBLN5 (ie, FMOD >64 ng/mL and FMOD >27 ng/mL) had a worse prognosis than those with the elevation of either FBLN5 or FMOD (P=0.03) demonstrating the additive prognostic value of both proteins. Our study proposes that circulating levels of FMOD and FBLN5 may serve as new biomarkers of RVD in patients with heart failure with reduced ejection fraction.

Feasibility and acceptability of a mindfulness app-based intervention among patients with metastatic renal cell carcinoma: a multinational study.

Patients with metastatic renal cell carcinoma (mRCC) experience emotional distress and limited supportive care access. This study assesses a mindfulness app's feasibility, acceptability, and preliminary efficacy in improving emotional symptoms, trait mindfulness, and overall quality of life for patients with mRCC on immunotherapy. This multinational study recruited patients with mRCC undergoing immunotherapy from Brazil and the United States. Participants were required to engage in mindfulness app-based activities for 20-30min daily, at least 4 days per week, over a 4-week period. Assessments were conducted at weeks 0, 2, 4, and 12 to evaluate emotional symptoms (PROMIS-Anxiety and Depression, Fear of Cancer Recurrence-7), fatigue (Brief Fatigue Inventory), trait mindfulness (Mindfulness Attention Awareness Scale), and quality of life (Functional Assessment of Chronic Illness Therapy-General). Self-reported data were used to assess adherence. Linear mixed-effects models were used to evaluate changes over time for the measured outcomes. Among 50 patients with mRCC, the feasibility of this intervention was demonstrated; 96% of patients were assessed at week 4, with high adherence rates reported by 75% of patients. Participants expressed positive feedback on the smartphone-based approach. Significant improvements were observed in emotional symptoms, fatigue, and quality of life scores from baseline to post-intervention (P = .001 for each), suggesting the positive impact of this intervention. Our findings provide encouraging evidence for the feasibility and acceptability of a mindfulness app-based intervention among patients with mRCC. This intervention may offer a viable and accessible means of providing psychosocial support to patients with mRCC.

Comparison of patient-reported symptoms with multi-item patient-reported outcome measures of fatigue, anxiety, and depression in the clinical care of women undergoing chemotherapy for early breast cancer.

As patient-reported symptoms are increasingly incorporated into routine clinical practice and captured in electronic medical records these data can be used to conduct health-related quality of life research studies. This study compares symptom reports from the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) and its precursor patient reported symptom monitoring (PRSM) (hereafter PRSM/PRO-CTCAE) with multi-item patient-reported outcome (PRO) scales for fatigue (Functional Assessment of Chronic Illness Therapy/FACIT-Fatigue) and depression and anxiety (Mental Health Index/MHI). This is a secondary analysis of data collected from women with early breast cancer (Stage I-III) scheduled for chemotherapy who completed PRSM/PRO-CTCAE, FACIT-Fatigue, and MHI scales pre- and post-chemotherapy. Spearman correlation coefficients estimated the magnitude and direction of correlations between measures (convergent validity). For each symptom, patients were then categorized based on who improved, stayed the same, or worsened on the composite PRSM/PRO-CTCAE score, and changes in scores on the PRO scales were compared. In a sample of 374 women, mean age was 57years (SD 12.6) with 76% White. PRSM/PRO-CTCAE fatigue measures were strongly correlated with FACIT-Fatigue total scale and had mixed moderate to strong correlation for individual items within the FACIT-Fatigue scale. PRSM/PRO-CTCAE Sad and Anxiety measures were strongly correlated with MHI-Depression and MHI-Anxiety total scales, respectively, and had mixed moderate to strong correlation with individual items within the MHI subscales. PRSM/PRO-CTCAE pre-post changes in symptom scores mirrored pre-post changes in FACIT-Fatigue and MHI subscales.

Daily Supplementation with Protein-Enriched Lacto-Vegetarian Soups and Muscle Health in Community-Dwelling Older Adults: A Randomized Controlled Trial.

Dietary protein adequacy is crucial for muscle health in aging individuals, posing a particular challenge for vegetarian seniors. This randomized controlled trial (RCT) investigates the impacts of protein-enriched lacto-vegetarian soup supplementation on body composition, physical performance and muscle strength functional assessment as well as cardiometabolic and inflammatory biomarkers in older adults. We enrolled 100 participants ≥65 years at risk for malnutrition (MNA-SF ≤ 11) and at risk for sarcopenia (SARC-F ≥4 or SARC-CalF ≥11) in this RCT. Participants were randomized assigned to receive a daily protein-enriched lacto-vegetarian soup (24-30 g protein) or usual diet. Primary outcomes of interest including (1) body composition (anthropometric measurements and body composition measured by bioimpedance analysis (BIA)), (2) physical performance (Short Physical Performance Battery, SPPB) and muscle strength (hand grip strength), and (3) functional assessments (including sarcopenia risk scales and nutritional status) as well as secondary outcomes of interests including cardiometabolic and inflammatory biomarkers were assessed at baseline and the 12th week of follow-up. Data of 97 participants (intervention: n = 48, control: n = 49) were analyzed. Despite no significant changes in body composition were observed in the intervention group, compared to the usual diet, those who received protein-enriched lacto-vegetarian soup supplementation had an improved physical performance including an increase in SPPB score (β = 0.83 [95% CI 0.15-1.51], p = 0.02), a decrease in time to complete the 5 times chair rise test (β = -2.25 [-4.04 to -0.44], p = 0.01). Some functional assessments, including improved sarcopenia risk scale (e.g., SARC-F score [β = -0.68, p = 0.04]) and nutritional status (e.g., MNA-SF score [β = 0.44, p = 0.03]) were also observed. Daily supplementation with protein-enriched lacto-vegetarian soups enhanced physical performance and functional assessments (such as sarcopenia risk scale and nutritional status) among older adults at risk of malnutrition and sarcopenia. Further study is needed to explore the long-term benefits of protein-enriched lacto-vegetarian soup supplementation for healthy aging.

Hardy-Rand-Rittler colour vision testing in cone and cone-rod dystrophies: correlation with structural and functional outcome measures.

To determine how Hardy-Rand-Rittler (HRR) colour vision testing correlates with visual functional and structural assessments in Cone and Cone-Rod Dystrophy. Thirty-four Cone and 69 Cone-Rod Dystrophy patients diagnosed by electroretinography (ERG) at the Save Sight Institute in Sydney were included in a retrospective analysis. Each patient's HRR colour vision test scores were compared with markers of cone and rod system function including visual acuity (VA), ERG responses, changes on Spectral Domain Optical Coherence Tomography (OCT) and Fundus Autofluorescence. The number of plates identified on HRR testing correlated with logMAR best-corrected distance VA; r(101) = -0.49, p < 0.0001. HRR scores correlated with markers of cone and macula function including OCT Ellipsoid Zone Gap Width, Central Macular and Outer Nuclear Layer Thickness, Full Field ERG 30 Hz flicker amplitudes, light adapted 3.0 b-wave amplitudes and Pattern ERG 15- and 30-degree p50 amplitudes. HRR colour vision testing correlates with structural and functional measures in Cone and Cone-Rod Dystrophy. HRR colour vision testing provides a simple clinic-based option to monitor disease changes in Cone and Cone-Rod Dystrophy patients, especially when ERG testing is not available.

Effect of Laser Auriculotherapy on Quality of Life, Fatigue, and Anxiety in Women with Advanced Breast Cancer: Randomized Clinical Trial

Objective: To evaluate the effect of laser auriculotherapy on health-related quality of life, cancer-related fatigue, and anxiety in women with advanced breast cancer undergoing palliative chemotherapy. Method: A randomized, parallel, single-blind, single-center clinical trial was conducted in a Brazilian oncology referral hospital. A total of 123 women were randomly divided into groups: 41 in the experimental group (10 weekly laser auriculotherapy sessions), 40 in the sham group (10 weekly sham sessions), and 42 in the control group. Outcomes were assessed at baseline, 5th week, and 11th week, using the Quality of Life Questionnaire Core-30, Functional Assessment of Cancer Therapy: Fatigue and State-Trait Anxiety Inventory. Statistical analyses included Kruskal–Wallis, Mann–Whitney, and Friedman tests. Results: The experimental group exhibited the highest mean overall quality of life, with a significant increase (p &lt; 0.000001) between the second and third evaluations and a significant improvement in fatigue between the second and third evaluations (p = 0.00001). Conversely, women in the sham and control groups experienced a decline and worsening in both their quality of life and fatigue. Women in all three groups showed reduction an anxiety. Changes in anxiety in these women were not statistically significant. Conclusions: reduction improvement in health-related quality of life and a reduction in cancer-related fatigue in the experimental group. These results show a positive effect of auriculotherapy on cancer-related fatigue, demonstrating potential for application in clinical practice in women with advanced breast cancer and in palliative chemotherapy. Brazilian Registry of Clinical Trials: RBR-6hxffx4.

Heart failure treatment and serum carnitines in HFpEF and HFrEF with or without hypertension - a pilot study.

The ratio of serum acylcarnitines to free carnitines (AC/FC) reflects impaired cardiomyocyte β-oxidization. The effect of heart failure (HF) treatment on AC/FC remained unclear. This pilot study retrospectively examined treatment-induced AC/FC changes in patients with HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF) in 148 consecutive inpatients undergoing echocardiography and carnitine measurement at admission and discharge. Symptomatic ACCF/AHA HF stage C/D patients (HFpEF, n = 40; HErEF, n = 24) received standard medical therapy and comprehensive cardiac rehabilitation. At admission, AC/FC levels in HFpEF and HFrEF were significantly higher than in asymptomatic stage A/B (n = 84), decreasing to comparable levels at discharge. AC/FC reduction was associated with improvement of left ventricular ejection fraction through HF treatment in HFpEF, particularly in HFpEF with hypertension, but not in HFrEF. Large-scale, multicenter prospective studies with precise cardiac function assessments are essential to validate the preliminary findings and to clarify the underlying pathophysiological mechanisms.

Stable Gastric Pentadecapeptide BPC 157 as Therapy After Surgical Detachment of the Quadriceps Muscle from Its Attachments for Muscle-to-Bone Reattachment in Rats

Background: This is a novel rat study using native peptide therapy, focused on reversing quadriceps muscle-to-bone detachment to reattachment and stable gastric pentadecapeptide BPC 157 per-oral therapy for shared muscle healing and function restoration. Methods: Pharmacotherapy recovering various muscle, tendon, ligament, and bone lesions, and severed junctions (i.e., myotendinous junction), per-oral in particular (BPC 157/kg/day 10 µg, 10 ng), provides muscle-to-bone reattachment after quadriceps muscle detachment, both complete (rectus muscle) and partial (vastus muscles). Results: Immediately post-injury, and at 1, 2, 3, 5, 7, 14, 21, 28, 60, and 90 days post-injury, quadriceps muscle-to-bone detachment showed definitive healing failure (impaired walking and permanent knee flexure). Contrarily, macro/microscopic, ultrasonic, magnetic resonance, biomechanical, and functional assessments revealed that BPC 157 therapy recovering effects for all time points were consistent. All parameters of the walking pattern fully improved, and soon after detachment and therapy application, muscle approached the bone, leaving a minimal gap (on ultrasonic assessment), and leg contracture was annihilated. The healing process occurs immediately after detachment from both sides: the muscle and the bone. The reattachment fibers from the ends of the muscle could be traced into the new bone formed at the surface (note, at day 3 post-detachment, increased mesenchymal cells occurred with periosteum reactivation). Consequently, at 3 months, the form was stable, and the balance between the muscle and bone was the following: well-organized bone, newly formed as more cortical bone providing a narrower bone marrow space, and the muscle and mature fibers were oriented parallel to the bone axis and were in close contact with bone. Conclusions: Therefore, to achieve quadriceps muscle-to-bone reattachment, the BPC 157 therapy reversing course acts from the beginning, resolving an otherwise insurmountable deleterious course.

Robotically Assisted vs. Manual Total Hip Arthroplasty in Developmental Hip Dysplasia: A Comparative Analysis of Radiological and Functional Outcomes

Background/Objectives: Developmental dysplasia of the hip (DDH), defined by the malalignment of the femoral head and acetabulum, is a major precursor to coxarthrosis, posing substantial challenges during total hip arthroplasty (THA). Patients with coxarthrosis secondary to DDH often exhibit acetabular bone insufficiency, which makes challenging surgical reconstruction difficult. This study aimed to compare the radiologic and functional outcomes of robotically assisted and conventional manual THA techniques in patients with coxarthrosis secondary to Crowe type III–IV DDH. Methods: This prospective study included 40 patients divided into robotically assisted (n = 20) and conventional manual (n = 20) THA groups. Evaluations encompassed hip pain (Visual Analogue Scale, VAS), function (Harris hip score and University of California, Los Angeles, activity scale), quality of life (Short Form-12), and prosthesis sensation (Forgotten Joint Score-12). Radiologic outcomes included acetabular inclination and anteversion angles. Femoral shortening, operative duration, and follow-up times were also analyzed. Results: Demographic characteristics did not differ between groups (p &gt; 0.05). Robotically assisted THA exhibited a significantly longer operative time (171.40 ± 11.96 vs. 150.30 ± 14.67 min; p = 0.001) but a shorter follow-up (29.3 ± 8.51 vs. 52.95 ± 18.96 months; p = 0.001), without a difference in the amount of femoral shortening (p = 0.947). Despite the extended surgical duration, the two techniques achieved comparable radiologic outcomes, with no significant differences in acetabular inclination or anteversion angles (p &gt; 0.05). Functional assessments, including Harris hip scores (73.85 vs. 73.95; p = 0.978), UCLA activity scores, and VAS, indicated similar efficacy between groups. SF-12 physical and mental quality of life and Forgotten Joint Score-12 prosthesis sensation did not differ between groups (p &gt; 0.05). Conclusions: This study concludes that robotically assisted and conventional manual THA present similar radiologic and functional outcomes in patients with coxarthrosis secondary to Crowe type III–IV DDH, as displayed by comparable acetabular anteversion and inclination alignment, femoral shortening, hip function, pain, quality of life, and prosthesis sensation scores. While robotically assisted THA requires a longer operative time, its precision in implant placement may hold potential advantages for long-term outcomes, demanding further investigation in extended follow-up studies.

Effect of Ficus pumila L. on Improving Insulin Secretory Capacity and Resistance in Elderly Patients Aged 80 Years Old or Older Who Develop Diabetes After COVID-19 Infection

(1) Background: It has been reported that people affected by COVID-19, an infectious disease caused by SARS-CoV-2, suffer from various diseases, after infection. One of the most serious problems is the increased risk of developing diabetes after COVID-19 infection. However, a treatment for post-COVID-19 infection diabetes has not yet been established. In this study, we investigated the effects of Ficus pumila L. extract, which has traditionally been used to reduce blood glucose levels in Okinawa, on patients who developed diabetes after COVID-19 infection. (2) Methods: In total, 128 rehabilitation patients aged 80 years old or older who developed diabetes after COVID-19 infection were included. The HOMA-β (Homeostatic model assessment of β-cell function) and HOMA-IR (Homeostatic model assessment of insulin resistance) were assessed to evaluate the glucose tolerance. (3) Results: The HOMA-β decreased and HOMA-IR increased in patients who developed after diabetes after COVID-19 infection. Subsequently, 59 patients were given Ficus pumila L. extract and their HOMA-β and HOMA-IR improved after ingestion. On the other hand, the control group of patients who did not consume Ficus pumila L. showed no improvement in both HOMA-β and HOMA-IR. (4) Conclusions: Ficus pumila L. extract, ingested by patients who developed diabetes after COVID-19 infection, stimulated insulin secretion capacity and improved insulin resistance.

Multidimensional sleep health and cognitive function across adulthood.

Sleep is essential for proper function of the mind and body. Studies report the effect of sleep problems on cognition but focus on only a single or limited number of sleep indicators or on clinical populations (e.g., sleep apnea), and/or provide only cross-sectional results. This study examined cross-sectional and longitudinal associations between multidimensional assessment of sleep health and cognitive function. 3398 adults (Mage=56years) provided self-reported sleep and objective cognitive data for the Midlife in the United States study. A subsample of 2119 participants also provided sleep and cognitive data at follow-up approximately 9years later. A multidimensional, composite measure of sleep health composed of regularity, satisfaction, alertness, efficiency, and duration based on the Ru-SATED model was utilized (higher score=better sleep health) to evaluate self-reported sleep, and cognitive function was assessed using the Brief Test of Adult Cognition by Telephone. Cross-sectionally, better sleep health was associated with better cognition (B=0.121, SE=0.017, p<.001). This relationship remained significant even after adjusting for sociodemographic and health covariates (B=0.039, SE=0.014, p=.006). Longitudinally, improvement in sleep health from baseline to follow-up was associated with better cognitive performance at follow-up (B=0.031, SE=0.011, p=.004); however, this relationship did not remain significant after adjusting for covariates (B=0.015, p=.139). Findings suggest better sleep health measured across multiple domains is associated with higher cognitive function. Future studies may want to examine potential mechanisms by which better sleep health relates to better cognitive function over time, such as reduction in stress or inflammation.

Long-term memory plasticity in a decade-long connectivity study post anterior temporal lobe resection

Approximately 40% of individuals undergoing anterior temporal lobe resection for temporal lobe epilepsy experience episodic memory decline. There has been a focus on early memory network changes; longer-term plasticity and its impact on memory function are unclear. Our study investigates neural mechanisms of memory recovery and network plasticity over nearly a decade post-surgery. We assess memory network changes, from 3–12 months to 10 years postoperatively, in 25 patients (12 left-sided resections) relative to 10 healthy matched controls, using longitudinal task-based functional MRI and standard neuropsychology assessments. We observe key adaptive changes in memory networks of a predominantly seizure-free cohort. Ongoing neuroplasticity in posterior medial temporal regions and contralesional cingulum or pallidum contribute to long-term verbal and visual memory recovery. Here, we show the potential for sustained cognitive improvement and importance of strategic approaches in epilepsy treatment, advocating for conservative surgeries and long-term use of cognitive rehabilitation for ongoing recovery.

Genetically predicted brain cortical structure mediates the causality between insulin resistance and cognitive impairment

BackgroundInsulin resistance is tightly related to cognition; however, the causal association between them remains a matter of debate. Our investigation aims to establish the causal relationship and direction between insulin resistance and cognition, while also quantifying the mediating role of brain cortical structure in this association.MethodsThe publicly available data sources for insulin resistance (fasting insulin, homeostasis model assessment beta-cell function and homeostasis model assessment insulin resistance, proinsulin), brain cortical structure, and cognitive phenotypes (visual memory, reaction time) were obtained from the MAGIC, ENIGMA, and UK Biobank datasets, respectively. We first conducted a bidirectional two-sample Mendelian randomization (MR) analysis to examine the susceptibility of insulin resistance on cognitive phenotypes. Additionally, we applied a two-step MR to assess the mediating role of cortical surficial area and thickness in the pathway from insulin resistance to cognitive impairment. The primary Inverse-variance weighted, accompanied by robust sensitivity analysis, was implemented to explore and verify our findings. The reverse MR analysis was also performed to evaluate the causal effect of cognition on insulin resistance and brain cortical structure.ResultsThis study identified genetically determined elevated level of proinsulin increased reaction time (beta=0.03, 95% confidence interval [95%CI]=0.01 to 0.05, p=0.005), while decreasing the surface area of rostral middle frontal (beta=-49.28, 95%CI=-86.30 to -12.27, p=0.009). The surface area of the rostral middle frontal mediated 20.97% (95%CI=1.44% to 40.49%) of the total effect of proinsulin on reaction time. No evidence of heterogeneity, pleiotropy, or reverse causality was observed.ConclusionsBriefly, our study noticed that elevated level of insulin resistance adversely affected cognition, with a partial mediation effect through alterations in brain cortical structure.

Geroscience in heart failure: the search for therapeutic targets in the shared pathobiology of human aging and heart failure

Age is a major risk factor for heart failure, but one that has been historically viewed as non-modifiable. Emerging evidence suggests that the biology of aging is malleable, and can potentially be intervened upon to treat age-associated chronic diseases, such as heart failure. While aging biology represents a new frontier for therapeutic target discovery in heart failure, the challenges of translating Geroscience research to the clinic are multifold. In this review, we propose a strategy that prioritizes initial target discovery in human biology. We review the rationale for starting with human omics, which has generated important insights into the shared (patho)biology of human aging and heart failure. We then discuss how this knowledge can be leveraged to identify the mechanisms of aging biology most relevant to heart failure. Lastly, we provide examples of how this human-first Geroscience approach, when paired with rigorous functional assessments in preclinical models, is leading to early-stage clinical development of gerotherapeutic approaches for heart failure.

Advances in Cardiovascular Multimodality Imaging in Patients with Marfan Syndrome

Marfan syndrome (MFS) is a genetic disorder affecting connective tissue, often leading to cardiovascular complications such as aortic aneurysms and mitral valve prolapse. Cardiovascular multimodality imaging plays a crucial role in the diagnosis, monitoring, and management of MFS patients. This review explores the advancements in echocardiography, cardiovascular magnetic resonance (CMR), cardiac computed tomography (CCT), and nuclear medicine techniques in MFS. Echocardiography remains the first-line tool, essential for assessing aortic root, mitral valve abnormalities, and cardiac function. CMR provides detailed anatomical and functional assessments without radiation exposure, making it ideal for long-term follow-up. CT offers high-resolution imaging of the aorta, crucial for surgical planning, despite its ionizing radiation. Emerging nuclear medicine techniques, though less common, show promise in evaluating myocardial involvement and inflammatory conditions. This review underscores the importance of a comprehensive imaging approach to improve outcomes and guide interventions in MFS patients. It also introduces novel aspects of multimodality approaches, emphasizing their impact on early detection and management of cardiovascular complications in MFS.

Relationship Between Intraocular Pressure and the True Rate of Functional and Structural Progression in the United Kingdom Glaucoma Treatment Study.

To investigate the effect of average intraocular pressure (IOP) on the true rate of glaucoma progression (RoP) in the United Kingdom Glaucoma Treatment Study (UKGTS). UKGTS participants were randomized to placebo or Latanoprost drops and monitored for up to two years with visual field tests (VF, 24-2 SITA standard), IOP measurements, and optic nerve imaging. We included eyes with at least three structural or functional assessments (VF with <15% false-positive errors). Structural tests measured rim area (RA) with Heidelberg retina tomography (HRT) and average peripapillary retinal nerve fiber layer (pRNFL) thickness with optical coherence tomography (OCT). One eye of 436 patients (222 on Latanoprost) was analyzed. A Bayesian hierarchical model estimated the true RoP of VF and structural metrics, and their correlations, using sign-reversed multivariable exponential distribution. RA and pRNFL measurements were converted to a dB scale, matching the VF metric (mean deviation [MD]). The effect of average IOP on the true RoPs was estimated. True RoP at the mean average IOP (17 mm Hg) was faster (P < 0.001) for VF-MD (-0.59 [-0.73, -0.48] dB/year) than HRT-RA (-0.05 [-0.07, -0.03] dB/year) and OCT-pRNFL (-0.08 [-0.11, -0.06] dB/year). The proportional acceleration of RoP per mm Hg increase was, however, not significantly different (smallest P = 0.15). Accounting for the structural floor-effect largely eliminated the differences in RoPs (smallest P = 0.25). VF appeared to deteriorate at a faster rate than structural measurements. However, this could be explained by the floor-effect from nonfunctional tissue. IOP induced a similar acceleration in RoP per mm Hg increase.

Assessment of Cognitive Functions in Multimorbid Patients in Lithuanian Primary Care Settings: A Cross-Sectional Study Using MMSE and LT-GPCOG

Background and Objectives: The aging population has led to a rise in cognitive impairments, including dementia, often associated with multimorbidity. Early diagnosis of cognitive decline is crucial, especially in primary care, where time constraints and the limitations of diagnostic tools may hinder accurate detection. This study aims to assess the cognitive functions of multimorbid patients using the Mini-Mental State Examination (MMSE) and the Lithuanian version of the General Practitioner Assessment of Cognition (LT-GPCOG). We hypothesized that the LT-GPCOG would perform similarly to the MMSE in suspecting cognitive impairments. Materials and Methods: This cross-sectional study, conducted from 2021 to 2022, included 796 patients aged 40–85, with arterial hypertension and at least one other chronic disease, recruited from seven Lithuanian primary health care centers. Cognitive function was assessed using the MMSE and LT-GPCOG, and statistical analyses were performed using SPSS to determine the association between cognitive impairment and various demographic and clinical variables. Results: Out of 796 participants, 793 completed the study. Cognitive impairment was suspected in 5.1% of participants based on MMSE and 4.2% based on the LT-GPCOG. Statistically significant associations were found between cognitive impairment and chronic obstructive pulmonary disease (COPD) (p = 0.008 and p = 0.003) in both tests and chronic kidney disease (CKD) (p = 0.005) while testing with the MMSE. Lower education and unemployment were also correlated with cognitive impairment (p = 0.008 and p &lt; 0.001). Conclusions: The findings suggest that regular cognitive assessments should be integrated into the management of multimorbid patients, particularly those with COPD and CKD. The LT-GPCOG proved to be an efficient alternative to the MMSE in primary care settings, demonstrating comparable diagnostic accuracy. Further studies are also needed to assess the sensitivity and specificity of the LT-GPCOG test.