Early Impairment Research Articles

Chest Dynamic MRI as Early Biomarker of Respiratory Impairment in Amyotrophic Lateral Sclerosis Patients: A Pilot Study.

Background: Amyotrophic lateral sclerosis (ALS) is a neuromuscular progressive disorder characterized by limb and bulbar muscle wasting and weakness. A total of 30% of patients present a bulbar onset, while 70% have a spinal outbreak. Respiratory involvement represents one of the worst prognostic factors, and its early identification is fundamental for the early starting of non-invasive ventilation and for the stratification of patients. Due to the lack of biomarkers of early respiratory impairment, we aimed to evaluate the role of chest dynamic MRI in ALS patients. Methods: We enrolled 15 ALS patients and 11 healthy controls. We assessed the revised ALS functional rating scale, spirometry, and chest dynamic MRI. Data were analyzed by using the Mann-Whitney U test and Cox regression analysis. Results: We observed a statistically significant difference in both respiratory parameters and pulmonary measurements at MRI between ALS patients and healthy controls. Moreover, we found a close relationship between pulmonary measurements at MRI and respiratory parameters, which was statistically significant after multivariate analysis. A sub-group analysis including ALS patients without respiratory symptoms and with normal spirometry values revealed the superiority of chest dynamic MRI measurements in detecting signs of early respiratory impairment. Conclusions: Our data suggest the usefulness of chest dynamic MRI, a fast and economically affordable examination, in the evaluation of early respiratory impairment in ALS patients.

GR.3 Distinct longitudinal brain atrophy trajectories in parkinson’s disease clinical subtypes: insight towards precision medicine

Background: Parkinson’s disease (PD) varies widely across individuals in terms of clinical manifestations and course of progression. We aimed to compare patterns of brain atrophy between PD clinical subtypes using longitudinally acquired brain MRIs. Methods: We used T1-weighted MRIs from Parkinson’s Progression Markers Initiative (PPMI) on 134 PD individuals and 60 healthy controls with at least two MRIs. Patients were classified into three clinical subtypes at de novo stage using validated subtyping criteria based on major motor and non-motor classifiers (early cognitive impairment, RBD, dysautonomia): mild-motor predominant (n=74), intermediate (n=44), and diffuse-malignant (n=16). Deformation-based morphometry (DBM) maps were calculated and mixed effect models were used to examine the interaction between PD subtypes and rate of atrophy across brain regions over time, controlling for sex and age at baseline. Results: Individuals with ‘diffuse malignant’ PD showed a significantly higher rate of atrophy across multiple brain regions, including lateral nucleus of the forebrain, precuneus, paracentral lobule, inferior temporal gyrus, fusiform gyrus, and lateral hemisphere of the cerebellum (FDR corrected p<0.05). Conclusions: We demonstrated an accelerated atrophy pattern within several brain regions in ‘diffuse malignant’ PD subtype. These findings suggest the presence of a more diffuse multidomain neurodegenerative process in a subgroup of people with PD, favoring the existence of diverse underlying pathophysiologies.

Assessment and comparison of microalbuminuria in obese and nonobese children

Background Fatty liver, metabolic syndrome, and cardiovascular disease are just a few of the well-known cardiometabolic complications associated with childhood obesity. Microalbuminuria (MA) is a sign of early kidney impairment, as seen in adults, and recent research supports its presence in children with obesity as well as its potential relationship with cardiometabolic variables. Both adults and children share this well-established pathophysiological theory. Indicated a close connection with the main aspect of fatness, such as IR, through the renal hemodynamic effects of insulin. More scientific consideration must be given to the assessment of primary kidney injury in obese children, given the pathological and prognostic implications of this association in everyday practise (counting an elevated danger of developing long term renal disorder over time). Method case-control study is going to be conducted among the patients of AVBRH hospital. A total of thirty participants with fifteen obese and fifteen non obeses controls were included in this study. Result The expected result of the study can determine the correlation between obesity and microalbuminuria, The value of microalbuminuria is high in obese patients as compared to nonobese patients. Conclusion The risk of problems in obese patients can be predicted using microalbuminuria, which can help lower the overall morbidity and mortality associated with renal function. Complications

Health-related quality of life in children with childhood acute myeloid leukemia in China: A five-year prospective study

PurposeThis study aims to identify the key factors influencing health-related quality of life (HRQoL) of pediatric acute myeloid leukemia (AML) patients following their initial diagnosis and examine their impact on the five-year survival prognosis. MethodsA chart review and follow-up were conducted for children with AML who participated in a prospective cohort study between 2017 and 2020. We identified factors influencing HRQoL through Pediatric Quality of Life Inventory™ (PedsQL™ 4.0), PedsQL™ Cancer Module 3.0 (CM 3.0) and PedsQL™ Family Impact Module 2.0 (FIM 2.0), as well as assessed the impact of impaired HRQoL on the overall outcomes of patients. ResultsSixty-four subjects enrolled in the study had complete HRQoL outcome data, and 61 of them completed the 5-year follow-up. In CM 3.0, age was positively associated with parental proxy reports (p = 0.040), whereas divorced families were negatively associated with child self-reports (p = 0.045). A positive medical history correlates with FIM 2.0 (p = 0.025). Residence (p = 0.046), the occupation of caregivers (p = 0.014), disease severity (p = 0.024), and the only child (p = 0.029) exhibited statistically significant associations with the impairment of HRQoL. Impaired HRQoL scores shown by the PedsQL™4.0 parent proxy report (p = 0.013) and FIM 2.0 (p = 0.011) were associated with a reduced 5-year survival rate. ConclusionsThis study demonstrated that early impairment of HRQoL in pediatric acute myeloid leukemia patients has predictive value for long-term prognosis. Once validated, these findings may provide some guidance to clinicians treating children with AML.

#1831 Circulating MiRNA 195-5p may be associated with early renal impairment in patients with prediabetes

Abstract Background and Aims Type 2 diabetes mellitus (DM) is one of the leading causes of chronic kidney disease worldwide. However, there are few data concerning early kidney impairment in prediabetes patients. The aim of the study was to demonstrate early kidney damage in patients with prediabetes by assessing proximal tubule (PT) dysfunction, podocytes injury, and miRNA expression. Method A cohort of 192 individuals were analysed and divided such as follows: 52-normoalbuminuria-, 48-microalbuminuria-, and 50-macroalbuminuria type 2 DM patients, respectively; 12 patients-prediabetes and 30-healthy controls. The miRNA profile was assessed by real-time PCR, while PT dysfunction biomarker, N-acetyl-β-D-glucosaminidase (NAG), and podocyte injury biomarker, podocalyxin, were assessed by ELISA technique. The study was conducted in two distinct stages. In the first part of the study was detected a particular miRNAs profile in serum in patients with prediabetes; subsequently, the expression of the most relevant miRNA in patients with prediabetes was identified. Results i) in prediabetes patients, serum miRNA195-5p was 2.69 fold change as compared to the control group and correlated with NAG (p<0.05) and podocalyxin (p<0.03); ii) in type 2 DM patients, the expression of serum miRNA195-5p was higher and correlated with NAG (p<0.05), podocalyxin (p<0.04), urinary albumin: creatinine ratio (p<0.001) and with eGFR (p<0.001); iii) urinary NAG and urinary podocalyxin were higher in prediabetes patients and type 2 DM patients, even in the normoalbuminuria stage, as compared to controls (p<0.04; p<0.001). Conclusion A panel of molecular biomarkers, such as miRNAs, remain useful tools for the early diagnosis of renal involvement in the course of type 2 DM. MiRNA 195-5p may be associated with PT dysfunction and podocyte damage, and could predict renal dysfunction in both prediabetes and early diabetic kidney disease in type 2 DM patients.

Early cognitive dysfunction development immunological predictors in the ischemic stroke acute period

The purpose of the study is activity identification CXC family cytokines in patients with cognitive impairments in the acute period of ischemic stroke.Material and methods. 78 patients with diagnosis “Ischemic stroke” were examined. Depending on cognitive impairment (Montreal Cognitive Assessment (MoCA)) patients were divided into two groups: the 1st group — 58 patients with cognitive decline (MoCA ≤ 25 points); the 2nd group — 20 patients without cognitive decline. Neuropsychologic testing was performed on the second day of hospitalisation and included episodic memory, executive function, speech, gnosis, praxis and IQCODE parameters examination. Laboratory diagnosis consisted of level assessing of CXC family chemokines (CXCL10, CXCL11, CXCL9, CXCL1, CXCL8) and TNF-α cytokine in patients’ plasma on the second day of hospitalisation. Statistical analysis was employed using the Python programing language and its libraries Pandas and SciPy.Results. Statistical analysis revealed the highest level of IP-10/CXCL10 chemokines (p = 0.002) and Gro-a/CXCL1 (p = 0.044) in patients of the 1st group, statistically significant correlations of MoCA and IQCODE with IP-10/CXCL10 and Gro-a/CXCL1 concentrations, correlations of IP-10/CXCL10 concentrations with semantic information processing functions (r = –0.512), subject gnosis (r = –0.211), memory (r = 0.275), speech (r = –0.400), and Gro-a/ CXCL1 level with semantic information processing (r = –0.418).Conclusion. The study of chemokines of the CXC cluster represents a relevant and promising direction in the diagnosis and assessment of progression of early post-stroke cognitive impairment of mixed genesis due to minimal invasiveness and high specificity. Further studies are needed to verify CXCL chemokines, particularly IP-10/CXCL10 and Gro-a/CXCL1 as potential molecular markers of neurological damage in neurodegenerative and inflammatory diseases of the central nervous system.

Correction to "Sex Differences in Cardiovascular Impact of Early Metabolic Impairment: Interplay between Dysbiosis and Adipose Inflammation".

Correction to "Sex Differences in Cardiovascular Impact of Early Metabolic Impairment: Interplay between Dysbiosis and Adipose Inflammation".

THE COMPLEX WORLD OF NON CRITICAL CORONARY ARTERIES DISEASE

Abstract Background and Aim Acute coronary syndrome (ACS) with non–critical coronary arteries represents a major diagnostic, therapeutic and prognostic challenge for clinicians. The aim was to compare clinical–anamnestic characteristics and assess the prognosis of three cohorts with ACS with non–critical coronary arteries i.e. Myocardial Infarction with Nonobstructive Coronary Arteries (MINOCA), type 2 myocardial infarction (MI) and Takotsubo syndrome (TTS). Methods In this single center observational study, 18223 patients who underwent coronary angiography between 2005 and 2022 were retrospectively analyzed. The final cohort included 676 patients with initial presentation as NSTEMI (301 MINOCA, 237 type 2 MI and 138 TTS). Results The median age was 68±11, with the TTS population being the oldest (72±10, p<0.01), presenting greater hypotension (p<0.01), tachycardia (p<0.01), and fewer cardiovascular risk factors, such as diabetes (p<0.01) and hypertension (p<0.01). The TTS cohort had worse LVEF on admission (p<0.01) and on discharge (p<0.01) (Fig. 1). At Kaplan–Meier analysis, patients with type 2 MI were more prone to the composite endpoint, while the TTS group was less likely (p<0.01) (Fig. 2). In the overall cohort, ACEi/ARB therapy on admission was an independent predictor of the composite endpoint (HR: 1.58;p=0.01), while dual antiplatelet therapy (DAPT) (HR: 0.59;p=0.01) and statin (HR: 0.71;p=0.03) at discharge were protective. After stratification according to diagnosis, ACEi/ARB therapy remained a negative predictor only in the type 2 MI cohort (HR: 2.03;p=0.01) as well as beta–blocker therapy at admission in TTS (HR: 2.97;p=0.03), while statin therapy remained protective in the MINOCA (HR: 0.51;p=0.01) and DAPT therapy in the TTS group (HR: 0.21;p=0.04) at discharge. Although a substantial number of patients with all three diagnoses achieved the endpoint, the multivariable Cox regression analysis indicated that type 2 MI, in addition to older age, male gender, worse LVEF, and anemia, is an independent factor for worse outcomes (Fig. 3). Conclusions Among all cohorts, T2 MI were associated with worse outcome. The use of DAPT in TTS and Statins in the MINOCA group showed a protective role. Since the TTS population was more compromised, BB use in the ADHF phase of TTS could predict a poorer outcome as much as ACEI/ARB use at admission could be a marker of greater early LV impairment of the T2 MI cohort, which was an independent predictor for worst outcome.

Coronary microvascular dysfunction and atrial reservoir function

BackgroundCoronary microvascular dysfunction (CMD) refers to structural and functional abnormalities of the coronary microcirculation, which may be diagnosed using invasive coronary physiology. CMD is responsible for impaired diastolic cardiac function. It has recently been suggested that left atrial strain (LASr) represents a highly sensitive tool for detecting cardiac diastolic function abnormalities. Accordingly, the aim of this study was to investigate the relationship between CMD and LASr.MethodsConsecutively enrolled patients with non-obstructed coronary arteries (NOCA) underwent CMD and LASr evaluation by invasive thermodilution and noninvasive echocardiography, respectively.ResultsForty-two (42) patients were included, out of which 26 presented with CMD. There were no significant differences between CMD-positive and negative patients in terms of clinical and echocardiographic characteristics. LASr was significantly reduced in patients with CMD (24.6% ± 6.1 vs. 30.3 ± 7.8%, p = 0.01). A moderate correlation was observed between coronary flow reserve and LAsr (r = 0.47, p = 0.002). A multivariate logistic regression analysis demonstrated that CMD was independently associated with LASr (OR = 0.88, 95%CI 0.78–0.99.135, p = 0.04). A LASr cut-off of 25.5% enabled an optimal classification of patients with or without CMD.ConclusionPatients with NOCA and CMD had a significantly reduced LASr compared with patients without CMD, suggesting the early impairment of diastolic function in these patients.

Prenatal treatment with preimplantation factor improves early postnatal neurogenesis and cognitive impairments in a mouse model of Down syndrome

Down syndrome (DS) is a genetic disease characterized by a supernumerary chromosome 21. Intellectual deficiency (ID) is one of the most prominent features of DS. Central nervous system defects lead to learning disabilities, motor and language delays, and memory impairments. At present, a prenatal treatment for the ID in DS is lacking. Subcutaneous administration of synthetic preimplantation factor (sPIF, a peptide with a range of biological functions) in a model of severe brain damage has shown neuroprotective and anti-inflammatory properties by directly targeting neurons and microglia. Here, we evaluated the effect of PIF administration during gestation and until weaning on Dp(16)1Yey mice (a mouse model of DS). Possible effects at the juvenile stage were assessed using behavioral tests and molecular and histological analyses of the brain. To test the influence of perinatal sPIF treatment at the adult stage, hippocampus-dependent memory was evaluated on postnatal day 90. Dp(16)1Yey pups showed significant behavioral impairment, with impaired neurogenesis, microglial cell activation and a low microglial cell count, and the deregulated expression of genes linked to neuroinflammation and cell cycle regulation. Treatment with sPIF restored early postnatal hippocampal neurogenesis, with beneficial effects on astrocytes, microglia, inflammation, and cell cycle markers. Moreover, treatment with sPIF restored the level of DYRK1A, a protein that is involved in cognitive impairments in DS. In line with the beneficial effects on neurogenesis, perinatal treatment with sPIF was associated with an improvement in working memory in adult Dp(16)1Yey mice. Perinatal treatment with sPIF might be an option for mitigating cognitive impairments in people with DS.

Choroidal thickness and retinal vascular changes in patients with lichen planus: an inflammatory disease beyond the skin.

Lichen planus (LP) is a common inflammatory condition of unknown etiology that commonly affects the skin and mucous membranes. Optical coherence tomography angiography (OCTA) is a noninvasive technique for identifying early retinal vascular impairment in systemic disease without clinical damage by imaging deep and superficial capillary networks. To assess the impacts of LP on the choroid and assess vascular changes in retinal capillary density using OCTA. This single-center prospective case-control study included 30 therapeutic-naïve LP patients and 30 age and sex-matched healthy individuals. All study subjects underwent a complete ophthalmological examination, including best-corrected visual acuity (BCVA) measurement using a Snellen chart, slit-lamp biomicroscopy, intraocular pressure (IOP) measurement, and fundus examination. They were then examined using spectral domain OCT and choroidal thickness was measured. The vessel density of the superficial and deep capillary networks was measured and assessed using OCTA. Patients had significantly thicker choroidal and retinal thickness than controls, with subfoveal, nasal, and temporal areas showing a significant difference. A significantly higher vascular density in the superficial capillary plexus, particularly in the nasal perifoveal area, was found compared to the control group. Significantly, higher vascular density in the deep capillary plexus in the parafoveal area compared to controls was reported. Significant correlations were found between visual acuity and IOP, and age, duration of disease, and severity of disease. This study is the first to reveal that LP patients exhibit choroidal changes and retinal vascular alterations compared to healthy controls.

Thalamic nuclei segmentation from T1-weighted MRI: Unifying and benchmarking state-of-the-art methods

Abstract The thalamus and its constituent nuclei are critical for a broad range of cognitive, linguistic, and sensorimotor processes, and are implicated in many neurological and neurodegenerative conditions. However, the functional involvement and specificity of thalamic nuclei in human neuroimaging work is underappreciated and not well studied due, in part, to technical challenges of accurately identifying and segmenting nuclei. This challenge is further exacerbated by a lack of common nomenclature for comparing segmentation methods. Here, we use data from healthy young (Human Connectome Project, n = 100) and older healthy adults, plus those with mild cognitive impairment and Alzheimer’s disease (Alzheimer’s Disease Neuroimaging Initiative, n = 540), to benchmark four state-of-the-art thalamic segmentation methods for T1 MRI (FreeSurfer, histogram-based polynomial synthesis [HIPS]-THOMAS, synthesized contrast segmentation [SCS]-convolutional neural network [CNN], and T1-THOMAS) under a single segmentation framework. Segmentations were compared using overlap and dissimilarity metrics to the Morel stereotaxic atlas, a widely accepted thalamic atlas. We also quantified each method’s estimation of thalamic nuclear degeneration across Alzheimer’s disease progression, and how accurately early and late mild cognitive impairment, and Alzheimer’s disease could be distinguished from healthy controls. We show that the HIPS-THOMAS approach produced the most effective segmentations of individual thalamic nuclei relative to the Morel atlas, and was also most accurate in discriminating healthy controls from those with mild cognitive impairment and Alzheimer’s disease using individual nucleus volumes. This latter result was different when using whole thalamus volumes, where the SCS-CNN approach was the most accurate in classifying healthy controls. This work is the first to systematically compare the efficacy of anatomical thalamic segmentation approaches under a unified nomenclature. We also provide recommendations of which segmentation method to use for studying the functional relevance of specific thalamic nuclei, based on their overlap and dissimilarity with the Morel atlas.

Visuospatial processing in early brain-based visual impairment is associated with differential recruitment of dorsal and ventral visual streams.

Visuospatial processing impairments are prevalent in individuals with cerebral visual impairment (CVI) and are typically ascribed to "dorsal stream dysfunction" (DSD). However, the contribution of other cortical regions, including early visual cortex (EVC), frontal cortex, or the ventral visual stream, to such impairments remains unknown. Thus, here, we examined fMRI activity in these regions, while individuals with CVI (and neurotypicals) performed a visual search task within a dynamic naturalistic scene. First, behavioral performance was measured with eye tracking. Participants were instructed to search and follow a walking human target. CVI participants took significantly longer to find the target, and their eye gaze patterns were less accurate and less precise. Second, we used the same task in the MRI scanner. Along the dorsal stream, activation was reduced in CVI participants, consistent with the proposed DSD in CVI. Intriguingly, however, visual areas along the ventral stream showed the complete opposite pattern, with greater activation in CVI participants. In contrast, we found no differences in either EVC or frontal cortex between groups. These results suggest that the impaired visuospatial processing abilities in CVI are associated with differential recruitment of the dorsal and ventral visual streams, likely resulting from impaired selective attention.

Alterations in regulators of the renal-bone axis, inflammation and iron status in older people with early renal impairment and the effect of vitamin D supplementation.

Chronic kidney disease (CKD) leads to alterations in fibroblast growth factor 23 (FGF23) and the renal-bone axis. This may be partly driven by altered inflammation and iron status. Vitamin D supplementation may reduce inflammation. Older adults with early CKD (estimated glomerular filtration rate (eGFR) 30-60ml/min/1.73 m2; CKDG3a/b; n = 35) or normal renal function (eGFR >90ml/min/1.73 m2; CKDG1; n = 35) received 12,000, 24,000 or 48,000IU D3/month for 1year. Markers of the renal-bone axis, inflammation and iron status were investigated pre- and post-supplementation. Predictors of c-terminal and intact FGF23 (cFGF23; iFGF23) were identified by univariate and multivariate regression. Pre-supplementation, comparing CKDG3a/b to CKDG1, plasma cFGF23, iFGF23, PTH, sclerostin and TNFα were significantly higher and Klotho, 1,25-dihydroxyvitamin D and iron were lower. Post-supplementation, only cFGF23, 25(OH)D and IL6 differed between groups. The response to supplementation differed between eGFR groups. Only in the CKDG1 group, phosphate decreased, cFGF23, iFGF23 and procollagen type I N-propeptide increased. In the CKDG3a/b group, TNFα significantly decreased, and iron increased. Plasma 25(OH)D and IL10 increased, and carboxy-terminal collagen crosslinks decreased in both groups. In univariate models cFGF23 and iFGF23 were predicted by eGFR and regulators of calcium and phosphate metabolism at both time points; IL6 predicted cFGF23 (post-supplementation) and iFGF23 (pre-supplementation) in univariate models. Hepcidin predicted post-supplementation cFGF23 in multivariate models with eGFR. Alterations in regulators of the renal-bone axis, inflammation and iron status were found in early CKD. The response to vitamin D3 supplementation differed between eGFR groups. Plasma IL6 predicted both cFGF23 and iFGF23 and hepcidin predicted cFGF23.

Graph Theory Further Revealed Visual Spatial Working Memory Impairment in Patients with Inflammatory Bowel Disease.

Inflammatory Bowel Disease (IBD) patients may experience cognitive impairments in Visuospatial Working Memory (VSWM), significantly impacting their quality of life. However, the mechanisms underlying these impairments remain poorly understood. We studied functional MRI and graph theory analysis to investigate changes in functional connectivity networks during the Mental Rotation Task (MRT) in IBD patients. Twenty IBD patients (13 males, 7 females; mean age = 34.95 ± 13.80 years; mean disease duration = 2.43 ± 2.37 years) participated in the study. Exclusion criteria encompassed recent use of analgesics, 5-Aminosalicylate, corticosteroids, or immunosuppressants within the past three months. Additionally, we recruited 20 age-, gender-, and education-matched healthy controls for comparison. Compared to a control group, IBD patients exhibited significantly longer reaction times and reduced accuracy during the MRT. Our analysis revealed abnormalities in multiple nodal attributes within the functional connectivity network, particularly in regions such as the bilateral orbitofrontal cortex, right supplementary motor area, bilateral parahippocampal gyrus, and bilateral anterior temporal lobe. We observed that the nodal efficiency in the left temporal pole is negatively correlated with Red Blood Cell Distribution Width (RDW) and positively correlated with response time of MRT. Our findings revealed notable abnormalities in multiple node attributes among IBD patients during MRT, providing evidence of cognitive impairments in VSWM in IBD patients. This study found RDW maybe can serve as a clinical indicator for predicting early VSWM impairment in patients with IBD.

Blunted Brachial Blood Flow Velocity Recovery to Acute Mental Stress in Young Women with PTSD Compared to Controls

Introduction: Post-traumatic stress disorder (PTSD) is a debilitating mental illness associated with increased cardiovascular disease (CVD) risk, a major cause of death among women in the United States. Women are twice as likely as men to develop PTSD after trauma exposure, and cardiovascular reactivity to stress is a known risk factor for CVD. Therefore, our aim was to investigate if young women diagnosed with PTSD will present with impaired hemodynamic responses to acute stress compared to controls. We hypothesized that women with PTSD will have high blood pressure (BP), heart rate (HR) and blood flow velocity (BFV) response to a mental stress protocol, and a blunted recovery. Methods: We recruited for this study ten young women with PTSD and nine trauma-exposed women without PTSD (controls) between the ages of 18 to 40 years. We collected data in a single laboratory visit after informed consent and PTSD symptoms severity questionnaire. After demographics and resting hemodynamics, we continuously measured HR using a three-lead EKG, beat-to-beat BP using finger plethysmography and continuous brachial BFV using Doppler ultrasound. A Doppler audio translator was used to transfer the doppler signal in our data analysis software for simultaneous recording of all hemodynamics variables. All variables were recorded during 5 min of supine rest, 5 min of mental stress (via mental arithmetic) and 5 min of recovery. The response and recovery to stress was analyzed using an analysis of covariance with timepoint as within factor and PTSD diagnosis as between-factor. Results: Women with a clinical diagnosis of PTSD had a mean age of 27±10 years and body mass index (BMI) of 30.1±2.9 kg/m2. Controls (trauma-exposed women without PTSD) had a mean age of 26±7 years and body mass index (BMI) of 24± 2.1 kg/m2. Resting seated BP and HR were not different between the groups. The slopes of the overall changes in BFV from baseline to mental stress to recovery were different between young women with PTSD and controls (timepoint*group, P= 0.057) when controlling for PTSD symptoms severity. Specifically, although mental stress elicited similar increases in BFV in women with PTSD (Δ0.80±1.8 cm/sec) and in controls [Δ0.45±1.2 cm/sec, P= 0.44 (timepoint*group)], BFV recovery from stress was impaired in PTSD (Δ0.64±1.3 cm/sec), but not in controls [Δ-2.20±0.84 cm/sec, P= 0.047 (timepoint*group)]. BP and HR reactivity to mental stress and recovery were not different between the groups (P>0.05). Conclusion: The current pilot study revealed that PTSD is associated with blunted recovery from acute mental stress, suggesting early impairment of vascular function in these women at a young age. Young pre-menopausal women are overlooked in prevention strategies and health policies targeting populations at-risk for CVD; with the rising prevalence of trauma exposure in young women, evidence is pointing to a parallel increase in CVD risk. K01HL161027 and UMN CTSI UL1TR002494 No Disclosure. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

IN ARTERIAL HYPERTENSION THE RIGHT VENTRICLE IS NO LONGER THE “FORGOTTEN CAVITY”

Objective: The right ventricle showed late interest in the assessment and stratification of the severity of arterial hypertension. The complex systemic reaction in the context of arterial hypertension, represented in particular by the activation of the renin angiotensin aldosterone system and the increase in sympathetic activity would suggest an early impairment of diastolic and later systolic function also of the right ventricle. Echocardiography is the most accessible way to evaluate the right ventricle in medical practice. Purpose of the study: to evaluate the precocity and the type of right ventricular function impairment in recently diagnosed hypertensive patients. Design and method: The patients were included after following the recommendations for the diagnosis of arterial hypertension according to the guide published by ESH in 2023. Personal biological data and parameters, cardiovascular risk factors, blood pressure values were recorded. Patients with other comorbidities, with secondary hypertension were excluded.Patients on antihypertensive treatment were also excluded. We investigated echocardiographically by analyzing 2D diastolic parameters, Doppler spectral and mitral and tricuspid tissue parameters as well as the global longitudinal strain of both ventricles. We studied right ventricle global longitudinal strain (RVGLS), septal wall longitudinal strain (RVSWLS), right ventricle lateral wall longitudinal strain (RVLWLS). Results: we studied a group of 61 patients who presented with essential hypertension, recently diagnosed, with an average age of 68.1 +- 6.3 years and who were analyzed according to grade, gender, risk factors. The (RVGLS) was analyzed separately and comparatively for the lateral and septal wall and the values were RVGLS =19%+- 3.2%. RVSWLS=-13.1% +-2.9% and RVFWLS=-22.6%+- 3.4%. The filling ratio of the right ventricle E/e’ was 14. Conclusions: the diastolic function of the right ventricle is affected in recently diagnosed hypertensive patients in relation to the degree of hypertension, myocardial mass and the filling ratio of the left ventricle. Slightly increased values of RVLWGLS could be interpreted as a consequence of sympathetic activation

Exploring inertial sensor-based balance biomarkers for early detection of mild cognitive impairment.

Dementia is characterized by a progressive loss of cognitive abilities, and diagnosing its early stages Mild Cognitive Impairment (MCI), is difficult since it is a transitory state that is different from total cognitive collapse. Recent clinical research studies have identified that balance impairments can be a significant indicator for predicting dementia in older adults. Accordingly, the current research focuses on finding innovative postural balance-based digital biomarkers by using wearable inertial sensors and pre-screening of MCI in home settings using machine learning techniques. For this research, sixty subjects (30 cognitively normal and 30 MCI) with waist-mounted inertial sensor performed balance tasks in four different standing postures: eyes-open, eyes-closed, right-leg-lift, and left-leg-lift. The significant balance biomarkers for MCI identification are discovered by our research, demonstrating specific characteristics in each of these four states. A robust feature selection approach is ensured by the multi-step methodology that combines the strengths of Filter techniques, Wrapper methods, and SHAP (Shapley Additive exPlanations) technique. The proposed balance biomarkers have the potential to detect MCI (with 75.8% accuracy), as evidenced by the results of machine learning algorithms for classification. This work adds to the growing body of literature targeted at enhancing understanding and proactive management of cognitive loss in older populations and lays the groundwork for future research efforts aimed at refining digital biomarkers, validating findings, and exploring longitudinal perspectives.

Early Blood-Brain Barrier Impairment as a Pathological Hallmark in a Novel Model of Closed-Head Concussive Brain Injury (CBI) in Mice.

Concussion, caused by a rotational acceleration/deceleration injury mild enough to avoid structural brain damage, is insufficiently captured in recent preclinical models, hampering the relation of pathophysiological findings on the cellular level to functional and behavioral deficits. We here describe a novel model of unrestrained, single vs. repetitive concussive brain injury (CBI) in male C56Bl/6j mice. Longitudinal behavioral assessments were conducted for up to seven days afterward, alongside the evaluation of structural cerebral integrity by in vivo magnetic resonance imaging (MRI, 9.4 T), and validated ex vivo by histology. Blood-brain barrier (BBB) integrity was analyzed by means of fluorescent dextran- as well as immunoglobulin G (IgG) extravasation, and neuroinflammatory processes were characterized both in vivo by positron emission tomography (PET) using [18F]DPA-714 and ex vivo using immunohistochemistry. While a single CBI resulted in a defined, subacute neuropsychiatric phenotype, longitudinal cognitive testing revealed a marked decrease in spatial cognition, most pronounced in mice subjected to CBI at high frequency (every 48 h). Functional deficits were correlated to a parallel disruption of the BBB, (R2 = 0.29, p < 0.01), even detectable by a significant increase in hippocampal uptake of [18F]DPA-714, which was not due to activation of microglia, as confirmed immunohistochemically. Featuring a mild but widespread disruption of the BBB without evidence of macroscopic damage, this model induces a characteristic neuro-psychiatric phenotype that correlates to the degree of BBB disruption. Based on these findings, the BBB may function as both a biomarker of CBI severity and as a potential treatment target to improve recovery from concussion.

Do early musical impairments predict later reading difficulties? A longitudinal study of pre-readers with and without familial risk for dyslexia.

The present longitudinal study investigated the hypothesis that early musical skills (as measured by melodic and rhythmic perception and memory) predict later literacy development via a mediating effect of phonology. We examined 130 French-speaking children, 31 of whom with a familial risk for developmental dyslexia (DD). Their abilities in the three domains were assessed longitudinally with a comprehensive battery of behavioral tests in kindergarten, first grade, and second grade. Using a structural equation modeling approach, we examined potential longitudinal effects from music to literacy via phonology. We then investigated how familial risk for DD may influence these relationships by testing whether atypical music processing is a risk factor for DD. Results showed that children with a familial risk for DD consistently underperformed children without familial risk in music, phonology, and literacy. A small effect of musical ability on literacy via phonology was observed, but may have been induced by differences in stability across domains over time. Furthermore, early musical skills did not add significant predictive power to later literacy difficulties beyond phonological skills and family risk status. These findings are consistent with the idea that certain key auditory skills are shared between music and speech processing, and between DD and congenital amusia. However, they do not support the notion that music perception and memory skills can serve as a reliable early marker of DD, nor as a valuable target for reading remediation. RESEARCH HIGHLIGHTS: Music, phonology, and literacy skills of 130 children, 31 of whom with a familial risk for dyslexia, were examined longitudinally. Children with a familial risk for dyslexia consistently underperformed children without familial risk in musical, phonological, and literacy skills. Structural equation models showed a small effect of musical ability in kindergarten on literacy in second grade, via phonology in first grade. However, early musical skills did not add significant predictive power to later literacy difficulties beyond phonological skills and family risk status.