Elderly Subjects Research Articles

Impact of resistant starch type 3 on fecal microbiota and stool frequency in Thai adults with chronic constipation randomized clinical trial.

Constipation poses a significant health concern affecting individuals of varying ages and geographic locations worldwide. While the impacts of numerous probiotics on constipation are well-characterized, there has been limited assessment of the potential prebiotic effects of resistant starches. We therefore conducted a randomized, double-blind and placebo-controlled, clinical trial of resistant starch type 3 (RS-3) in Thai adults with self-reported chronic constipation. The effects of these mixed natural starch fibers on beneficial gut bacteria, bowel movements and stool consistency were evaluated after 6- and 12-week periods. Regardless of subject age, consumption of RS-3 compared to placebo resulted in significant improvements in gut health by dramatically increasing levels of beneficial bacteria (Bifidobacterium, Prevotella, Akkermansia and Megamonas) in the gut and relieving constipation. RS-3 consumption was associated with a significantly increased frequency of bowel movements, with subjects reporting these as healthy stools. Our findings provide important insights into the therapeutic advantages of RS-3 for constipation, and propose RS-3 as a feasible alternative strategy for management of constipation.

Management of Melanoma in Elderly Patients over 80 Years.

Melanoma is a malignant tumour with a poorer prognosis in stage III and IV patients. Development of effective therapies for the treatment of advanced melanoma has led to an improvement in survival. Furthermore, the French population is ageing, and treatment of melanoma in this population has several specific limitations. This descriptive, retrospective, single-centre study collected data on the diagnostic and therapeutic management of patients with melanoma of Breslow ≥ 1 mm or of unknown primary and metastatic spread, at Limoges University Hospital, between 2018 and 2022, and compared the results obtained between 2 groups: under 80 and over 80 years of age; 344 patients were included. The extension work-up was more frequently complete and the sentinel lymph node technique more frequently performed in patients under 80. Wide excision was more frequently in accordance with guidelines in patients over 80. Adjuvant or first-line metastatic treat-ment was more frequently instituted in patients under 80, but no difference was found as regards the second and third lines, the frequency of adverse events, and the reason for stopping treatment. Our study supports similar management of elderly and young subjects, given the safety profile and efficacy of treatments.

Upadacitinib is associated with clinical response and steroid-free remission for children and adolescents with inflammatory bowel disease.

Upadacitinib, an oral Janus kinase inhibitor (JAKi), is approved for inflammatory bowel disease (IBD) in adults. As on-label use will face significant delay in pediatrics, a real-world understanding of safety and efficacy in children is critical. This is a single-center retrospective cohort of pediatric subjects (ages 9-20 years) with a diagnosis of IBD initiated on upadacitinib. The primary outcome was clinical response following induction (decrease of ≥20 points in the Pediatric Ulcerative Colitis Activity Index [PUCAI] or ≥12.5 points for the Pediatric Crohn's Disease Activity Index [PCDAI]). Secondary outcomes included steroid-free clinical remission (SF-CR) following induction and at Week 24 (PUCAI or PCDAI ≤10), post-induction mucosal response and remission (Mayo for ulcerative colitis [UC]/IBD-unclassified [IBD-U] and simple-endoscopic scoring for CD), and improvement in calprotectin and C-reactive protein (CRP) post-induction. Monitoring for adverse events was recorded. Twenty subjects (40% female with a median age of 16.3 years; 3 CD, 13 UC, 4 IBD-U) were initiated on upadacitinib. Clinical response at Week 8 (UC/IBD-U) and Week 12 (CD), was achieved in 90% (18/20). SF-CR was seen in 75% (16/20) following induction and maintained in 65% (11/17) reaching Week 24 of therapy. In subjects with UC/IBD-U (17), PUCAI was significantly improved at Weeks 8 and 24. Calprotectin post-induction showed a significant downtrend, whereas CRP did not. Endoscopic response was noted in seven of the eight cases, with three achieving endoscopic remission. One patient underwent subtotal colectomy after 2 weeks of upadacitinib induction. Another patient stopped therapy following the creation of a diverting ileostomy secondary to rectal perforation experienced following manual dilation of a rectal stricture. No new safety signals were reported. Therapeutic options for children with IBD remain limited. In cases refractory to approved agents, our experience suggests that upadacitinib is effective with no new safety signals in a small subset of patients with IBD (ages 9-20 years) treated at a children's hospital.

Abstract 4125188: Cardiac Specific Biomarkers of Progression in Duchenne Muscular Dystrophy Detected Using Aptamer-Based Proteomics

Background: Duchenne muscular dystrophy (DMD) is an X-linked, progressive neuromuscular disorder characterized by cardiac and skeletal myopathy. The cardiac and skeletal muscle manifestations have different ages of onset and rates of progression, suggesting variability in the pathophysiology of dystrophin loss within the respective muscle groups. Hypothesis: We hypothesized that proteomics with comprehensive clinical phenotyping would identify novel biomarkers that correlate with cardiac but not skeletal disease progression in boys with DMD. Methods: This single-center cohort study of 56 DMD subjects performed cardiac magnetic resonance (CMR), including left ventricular ejection fraction (LVEF), late gadolinium enhancement (LGE), and myocardial circumferential strain (ECC). Fifty-one subjects underwent quantitative muscle testing, and 33 underwent actigraphy (MSK indices). Aptamer-based technology (SomaScan, SomaLogic, Boulder, CO) evaluated 1128 proteins in plasma sampled at the time of CMR. Correlations between serum protein levels and cardiac or MSK indices were tested using Benjamini-Hochberg corrected p-values (q-values). Results: The mean age of DMD subjects was 15.5 years old +/- 4.30. Twenty-six subjects had left ventricular dysfunction (LVEF <55%), 45 subjects had LGE, and 45 were non-ambulatory. Of 1128 proteins analyzed, 208 demonstrated a significant correlation for cardiac but not MSK indices (Figure 1). Figure 2 lists the 20 proteins with the strongest correlations, which included biomarkers of inflammation, calcium regulation in myocytes, and cell adhesion. Conclusion: We detected 208 novel proteins that correlate with cardiac-specific DMD disease progression. These proteins provide a better understanding of the underlying differences of cardiac disease, compared to MSK disease in DMD and provide clues to potential cardiac therapeutic options.

Indicators of mental adaptation disorders in combatants of the special military operation

Relevance. Participants of armed conflicts are exposed to extreme stress amid life-threatening situations, which can lead to mental adaptation disorders exacerbated by combat stress disorders. Combatants facing these conditions require psychological correction and psychotherapy.The objective is to assess the risk of mental adaptation disorders in combatants using traditional diagnostics and fasts screening methods.Methods. A cohort of 163 combatants who participated in the special military operation underwent clinical and psychological examination. The average age of subjects was 34.3 years, and the average time of service in the special military operation was 8.2 months. The combatants’ psychological status was evaluated using the Mississippi Scale (military version), the Beck Depression Inventory, and the Beck Anxiety Inventory. In addition, a set of screening methods, like PC-PTSD-5, PHQ9, and GAD-7, were used to evaluate the risk of mental maladaptation, depressive symptoms, and anxiety. In the course of examination, the reliability of responses was assessed using 10 adapted questions for sincerity evaluation obtained from a standardized personality assessment method. The present study shows the median value, as well as the upper and lower quartiles (Me [Q1; Q3]). The consistency of the studied indicators was evaluated using Spearman’s rank correlation coefficient.Results and analysis. The average sincerity score was 7 [6; 8] points, showing sufficient reliability of the examination results. The psychological test results re concordant with the overall transformation pattern in the functional and mental profile of stress exposed combatants, depending on the duration of exposure to combat conditions. The average Mississippi Scale scores were 71 [63; 84] points, and 2 [1; 3] points on the PC-PTSD-5, associated with absence of mental adaptation disorders and a low probability of PTSD, respectively. PTSD clinical symptoms were identified in 3.7% of the examined combatants (compared to 14.3% in foreign publications), and mental adaptation disorders were observed in 8.6%. All these methods showed moderate, positive, and statistically significant (r = 0.627; p < 0.001) consistency of obtained indicators. The average Beck Depression Inventory score was 7 [3; 12] points, and the PHQ-9 score was 5 [3; 8] points, suggesting absence or mild depression, respectively. The methods demonstrated strong, positive, and statistically significant (r = 0.799; p < 0.001) consistency among the indicators. The average Beck Anxiety Inventory score was 10 [4; 18] points, and the GAD-7 screening method score was 5 [2; 6] points, corresponding to low or moderate anxiety. For both methods, the consistency among indicators was moderate, positive, and statistically significant (r = 0.567; p < 0.001).Conclusion. The study justified the reliability of results obtained by traditional tests and screening methods, showing trustworthy indications for psychological correction (psychotherapy) in the examined combatants.

Quantitative assessment of neurodevelopmental maturation: a comprehensive systematic literature review of artificial intelligence-based brain age prediction in pediatric populations

IntroductionOver the past few decades, numerous researchers have explored the application of machine learning for assessing children’s neurological development. Developmental changes in the brain could be utilized to gauge the alignment of its maturation status with the child’s chronological age. AI is trained to analyze changes in different modalities and estimate the brain age of subjects. Disparities between the predicted and chronological age can be viewed as a biomarker for a pathological condition. This literature review aims to illuminate research studies that have employed AI to predict children’s brain age.MethodsThe inclusion criteria for this study were predicting brain age via AI in healthy children up to 12 years. The search term was centered around the keywords “pediatric,” “artificial intelligence,” and “brain age” and was utilized in PubMed and IEEEXplore. The selected literature was then examined for information on data acquisition methods, the age range of the study population, pre-processing, methods and AI techniques utilized, the quality of the respective techniques, model explanation, and clinical applications.ResultsFifty one publications from 2012 to 2024 were included in the analysis. The primary modality of data acquisition was MRI, followed by EEG. Structural and functional MRI-based studies commonly used publicly available datasets, while EEG-based studies typically relied on self-recruitment. Many studies utilized pre-processing pipelines provided by toolkit suites, particularly in MRI-based research. The most frequently used model type was kernel-based learning algorithms, followed by convolutional neural networks. Overall, prediction accuracy may improve when multiple acquisition modalities are used, but comparing studies is challenging. In EEG, the prediction error decreases as the number of electrodes increases. Approximately one-third of the studies used explainable artificial intelligence methods to explain the model and chosen parameters. However, there is a significant clinical translation gap as no study has tested their model in a clinical routine setting.DiscussionFurther research should test on external datasets and include low-quality routine images for MRI. T2-weighted MRI was underrepresented. Furthermore, different kernel types should be compared on the same dataset. Implementing modern model architectures, such as convolutional neural networks, should be the next step in EEG-based research studies.

Abstract 4119619: Congruency of Stated Aortic Stenosis Severity and Reported Doppler Exam Values in a Large Health Care System Based on ACC/ASE Guidelines

Background: Peak aortic valve Doppler velocity, mean aortic valve gradient, and Doppler estimated aortic valve area are key measures recommended for assessing aortic stenosis severity. Discordance often occurs among these measures, posing diagnostic challenges. Failure to accurately diagnose severe aortic stenosis is critical. This study focuses on the discordance between reported aortic valve area (AVA) and stenosis severity, comparing guidelines from the ASE and ACC seen in Table 1. Goals: Assess the incidence of discordance between reported AVA and severity of aortic stenosis and compare how the differing guideline recommendations of the ASE versus ACC for defining severe AS by AVA would affect reporting severity in a large clinical practice. Methods: A query of all transthoracic echocardiograms obtained in patients 18 years of age and above was performed in a large multi-hospital healthcare system between Jan 1 and Jun 30 of 2023. This group was then filtered to include only exams in which the reported aortic valve area was 1 cm2 or less, excluding all cases with prosthetic aortic valves. This group was then further filtered to contain only those patients in whom the physician did NOT report severe aortic stenosis. Results: Between Jan and June 2023, 16,675 subjects ages 18-95 (avg 74) underwent transthoracic echocardiograms in our healthcare system, with 190 (1.1%) reported as having an AVA ≤ 1 cm2. Of those exams, 63 (33% of those with AVA ≤ 1) were not reported as having severe aortic stenosis. Of those 63 exams, 35 (56%) had a reported SVI < 35 ml/m2 compatible with a low flow state. However, only 1 of those 35 cases mentioned flow-status in labeling the stenosis severity in the report. Based on the ASE Doppler AVA definition of severe AS (< 1.0 cm2 (≤ 0.94 )) vs ACC (≤ 1 cm2 (≤1.04), the AV Doppler and SVI data contained in the reports should have led to the grading of the aortic valve as being ”Severe” or “Moderate” aortic stenosis as described in Table 2. Conclusion: Discordance in labeling severe aortic stenosis relates to differing AVA criteria. Cases are often termed "moderate to severe" under ACC criteria. The majority (56%) of cases failing to describe severe AS despite meeting AVA criteria were in low flow states, suggesting this phenomenon is not well understood in clinical practice. Various factors contribute to these findings, warranting further investigation.

QOL-28. CANCER-RELATED DISTRESS IN NEURO-ONCOLOGY: PATIENTS INFORM PROGRAM DEVELOPMENT FOR ENHANCING QUALITY OF LIFE

Abstract BACKGROUND Brain tumor diagnosis and treatment result in significant negative sequelae, including cognitive decline, fatigue, and psychosocial symptoms. This study aimed to identify brain tumor patients’ sources of cancer-related distress and examine their interest in various treatment modalities targeting cognitive decline to inform program development for this underserved population. METHODS In pursuit of program development, patients with both primary and secondary brain tumors completed an anonymous survey. They reported demographics, tumor characteristics, subjective cognitive functioning; and, rated sources of cancer-related symptom distress (i.e., cognitive changes, fatigue, physical symptoms, motor functioning, balance, mood, and relationship) and interest in treatments targeting cancer-related cognitive decline (i.e., cognitive rehabilitation, mindfulness-based practices, psychotherapy, and medication). Descriptive statistics, t-tests, chi-square, and linear regressions were conducted. RESULTS Among participants (N=137, Mage=49.6±15.8, 58.1% female, 84.8% White), 50.4% endorsed subjective cognitive functioning below the mean (MFACT-Br-CI=22.6±7.5). Nearly half reported significant distress due to cancer-related fatigue (49.6%) and cognitive change (48.9%). Patients’ mean severity of distress due to cognitive decline was significantly greater relative to all other cancer-related symptoms (ps<.001), except fatigue (p>.05). Age, gender, or time since diagnosis were not significant predictors (ps>.05) of distress due to cognitive decline. Most patients with distress due to cognitive change were interested in cognitive rehabilitation (63.6%) and mindfulness-based practices (61.6%), and only 40.4% were interested in medication. Interest in cognitive rehabilitation was not predicted by symptom distress, subjective cognitive functioning, age, gender, or time since diagnosis (ps>.05). Gender was the only significant predictor of interest in mindful movement (b=.18, p=.041), with greater interest among women (χ2(1)=4.65, p=.031). CONCLUSIONS Fatigue and cognitive decline were the most distressing cancer-related symptoms for neuro-oncology patients. These findings emphasize the need for integrated interventions, including cognitive rehabilitation and mindfulness, as well as multi-targeted and individualized treatments for fatigue and cognitive decline in neuro-oncology.

PATH-57. CLINICAL AND MOLECULAR FEATURES OF METHYLATION CLASS DIFFUSE LEPTOMENINGEAL GLIONEURONAL TUMOR

Abstract Genome-wide DNA methylation profiling can help identify rare CNS tumors, including diffuse leptomeningeal glioneuronal tumor (DLGNT). Due to the infrequency of this entity, DLGNT remains poorly understood. To help resolve uncertainty regarding DLGNT, we examined epidemiologic, histologic, and molecular features of 32 (21 newly profiled, 11 publicly available) tumors matching to DLGNT by the DKFZ classifier (v12, score >=0.85). Of these tumors, 25 matched to DLGNT subtype 1 and seven to subtype 2. Subject median age was 12 years in subtype 1 and 22 years in subtype 2 (14.5 overall, range 2-44), with equal numbers of females and males (n=16 each). Spinal cord was the most frequently involved site (n=21), but intracranial lesions were observed (n=6). Leptomeningeal involvement was noted in only four of 11 tumors with available imaging descriptions. In the subset of cases available for histologic review (n=19), oligodendrocyte-like morphology was present in over half (n=11). Microvascular proliferation was uncommon (n=5). Chromosome 1p loss was observed in 29 (91%), and 1p/19q co-deletion was observed in 18 tumors (56%). Gains of 1q and 7q were each observed in 12 (38%), and whole chromosome 7 gain was observed in eight (25%). Loss of 22q was seen in 12 (38%). In the subset of tumors with fusion testing (n=15), KIAA1549::BRAF fusion was present in 12 (80%), and one showed a QKI::RAF1 fusion. Five tumors harbored BRAF mutations, and one harbored a break-point in BRAF without a known fusion partner. In nine subjects with clinical follow-up, there was one death after 3.1 years, and the remaining subjects were alive with a median follow-up of 6.4 years (maximum 19 years). Progression-free survival (PFS) was available for six subjects with a median PFS of 6 years. Presentation of DLGNT without noted leptomeningeal involvement appears common. Further characterization of subject outcomes will help clarify the clinical behavior of DLGNT.

CNSC-38. INFLUENCE OF AGE, IMMUNOREGULATORY IDO, AND IMMUNOTHERAPY ON THE MICROBIOME IN MICE WITH AN EXPERIMENTAL BRAIN TUMOR

Abstract OBJECTIVE This study aimed to determine how IDO and subject age impact the gut microbiome and microbial metabolites during immunotherapy for glioblastoma (GBM). METHODS Serum and colon contents were collected from young 16-20- or older adult 92-118-week-old wild-type (WT; C57BL/6), IDO knockout (IDOKO), and IDO enzyme null (H350A) mice analyzed for 16S rRNA gut microbiome composition and microbial-derived aromatic amino acid metabolites via LC/MS/MS. Fecal samples from young 7-8 or older adult 81-85 week-old WT mice with intracranial GL261 brain tumors treated with or without brain radiation (RT) and PD-1 mAb were also analyzed. RESULTS Young and old IDOKO and H350A mice demonstrated a unique gut microbiome signature with an elevated abundance of Bifidobacterium and Helicobacter (p<0.05) and a reduced abundance of Ventriosum and Sireaum compared to WT mice (p<0.001). Prevotellaceae, Muribaculum, Alistipes, Enterohabdus, Clostridia, and Akkermansia were different in IDOKO and H350A mice compared to WT - but only in old mice. Serum aryl-lactates including phenyllactate, indolelacatate, and 4-hydroxyphenyllactate were increased in IDOKO mice compared to WT and H350A mice (p<0.001) – again, only in old mice. Older adult WT mice with GL261 showed lower fecal aryl-lactates compared to younger counterparts. Treatment with RT + PD-1 mAb decreased phenyllactate levels in old but not young mice with GL261 (p<0.05). CONCLUSIONS There are IDO enzyme- and non-enzyme-dependent effects on gut microbiota composition and bioactive microbial aromatic amino acid metabolites. These data warrant further investigation into how microbial metabolism affects immunotherapy efficacy and brain tumor survival across the lifespan.

CNSC-47. SENOLYTICS ERADICATE SENESCENT MICROGLIA IN THE BRAIN PARENCHYMA AND IMPROVE SURVIVAL IN OLDER ADULT MICE WITH GLIOBLASTOMA

Abstract BACKGROUND Glioblastoma (GBM) is the most common aggressive primary malignant brain tumor in adults with a poor median survival rate. Despite the aggressive standard of care treatment combining surgical resection, chemo-, and radio-therapy, the median overall survival (OS) is only ~15-18 months. Progressively increasing subject age is inversely associated with GBM patient OS such that older adults tend to have significantly worse survival outcomes compared to younger counterparts. Senescent cells accumulate in the body during progressive aging and contribute to worse outcomes in older adult mice with GBM. Senolytics are pharmacologics that cause senescent cells to undergo cell death. OBJECTIVE To comprehensively profile the treatment effect of senolytics combined with or without immunotherapy in mice with GBM across the lifespan. METHODS Young 7-9- and older adult 97-104-week-old wild-type (WT; C57BL/6) and 110-130-week-old INK-ATTAC mice with or without intracranial SB28 cells were treated with or without brain radiation (RT), PD-1 mAb, and an IDO enzyme inhibitor with the senolytics, dasatinib + quercetin, or the AP compound that induces p16INK4A+ senescent cell death in INK-ATTAC mice (n=5/group). The quantification of beta-galactosidase positive cells by flow cytometry was performed on brain-resident neurons, astrocytes, oligodendrocytes, microglia, as well as dendritic cells, macrophages, neutrophils, T cells in the tumor and non-tumor bulk mass. Overall survival was also evaluated. RESULTS Senolytics or AP compound treatment both decrease beta-galactosidase positive microglia in the older adult brain with GBM (p<0.05). Combining radio- and immuno-therapy with senolytics improves overall survival of older adult mice with intracranial GBM (p<0.05). CONCLUSIONS Our ongoing work aims to understand how senescent microglia affect neuronal health and function in the older adult brain with GBM. KEYWORDS Glioma, senescence, senolytic.

Ageing fast and slow: A longitudinal examination of the gap between subjective age and chronological age and the role of functional health.

While it is known that subjective age is strongly influenced by health, few studies have explored this relation longitudinally. This study aims to examine the longitudinal evolution of the age differential between subjective and chronological age, as well as how functional limitations and birth cohort affect this evolution. This study analyses four waves covering ten years (2004-2014) of the English Longitudinal Study on Ageing, making use of 35,242 observations of 14,219 participants. Using random intercept mixed models in an age vector approach, the difference of the gap between chronological and subjective age is examined over age, conditional on cohort and subsequently by functional limitations group. Participants felt on average about nine years younger than their actual age. Subjective ageing happens about a third slower than objective ageing on average. Later born cohorts feel younger than earlier born cohorts at a given age. The difference between chronological age and subjective age differs about eight years between those with and without functional health limitations, but onset of such functional limitations only decreases the gap with about one to three years. This study found that recent cohorts feel younger than older cohorts. The onset of a health limitation represents only about half of the subjective age effect. . This illustrates there are large selection effects into the group of people to whom health limitations occur, with people already feeling less young before the actual event occurrence.

Significant Within-Individual Variability in VCTE Liver Stiffness Measurements at Two Intercostal Spaces in Subjects with MASLD: Implications for Evaluating Improvement in Liver Fibrosis After Weight-Loss or Liver-Directed Therapy

Introduction: Studies have compared the group-averages of liver stiffness measures (LSMs) from multiple rib spaces by vibration-controlled transient elastography (VCTE) to stage liver fibrosis. No previous study has assessed within-individual liver stiffness variation from two rib spaces in individuals with metabolic-dysfunction associated steatotic liver disease (MASLD). Methods: We evaluated within-individual LSM variation according to body weight classification and its clinical implication. From October 2019 to March 2024, VCTE was performed on MASLD patients or those at high risk, in accordance with FibroScan guidelines. The LSMs were categorized into stages: <5 kPa (stage 0), 5–7.99 kPa (stage 1), 8–9.99 kPa (stage 2), 10–13.99 kPa (stage 3), and 14+ kPa (stage 4). Measurements with 10 values and IQR/median ≤ 0.30 were included, using SPSS V25.0 for analysis. Results: Among 1107 subjects (age 54.4 ± 13.9 years, 56.9% female), 7.7% were normal weight, 20.7% overweight, 28.9% class 1 obesity, 21.3% class 2 obesity, and 21.2% class 3 obesity. Significant within-individual variation was noted: 67% (0–2 kPa) variation, 23.4% (2.1–6 kPa), and 10% (≥6.1 kPa). Class 3 obese individuals had the maximum variation. Comparing the group-average of LSM at each ICS site showed that 95% of individuals were within one fibrosis stage. Conclusions: While LSM group-averages at different rib sites provides reliable fibrosis staging, significant within-individual variability exists especially in class 3 obesity. This should be considered when serial LSM assessments are used to assess medical therapeutic efficacy.

Effect of STIN2VNTR polymorphism of the serotonin transporter gene on background EEG in aged subjects depends on the intellectual environment of professional activity

Previously, we found that associations between the STin2VNTR polymorphism of the serotonin transporter gene and cognitive characteristics during aging depend on the intellectual environment of professional activity. In this regard, the present study was aimed to investigate the age-related characteristics of the electrical activity of the brain depending on this polymorphism and long-term intellectual training. We examined EEG power indicators in subjects of the younger (YG, 18–35 years, N = 261) and older (OG, 55–80 years, N = 142) age groups. According to the intellectual richness of the professional activity environment, the subjects were divided into scientists (SA) and those engaged in non-scientific activities (NSA). All subjects were genotyped for the STin2VNTR polymorphism of the serotonin transporter gene. It was found that the power of delta-beta1 rhythms in older carriers of the 10/10 and 12/12 genotypes was opposite in SA and NSA groups (in the SA group 10/10 12/12, in the NSA 12/12 10/10) while similar effects in young subjects were absent. In the absence of cognitive training, genetic differences were determined by an age-related decrease in the power of delta-alpha3 rhythms in carriers of the 10/10 genotype with no age-related differences in carriers of the 12/12 genotype, suggesting the resistance of the 12/12 genotype to age-related changes. In contrast, under cognitive training conditions, there were no age differences in the 10/10 genotype, and a decrease in power was observed in the 12/12 genotype, suggesting an effect of cognitive training on both homozygous genotypes. The decrease in power observed for the 10/10 NSA and 12/12 SA genotypes appears to have different physiological significance, since it was accompanied by changes in attentional efficiency only in the NSA group. The work shows for the first time that the background EEG features associated with the STin2VNTR polymorphism of the serotonin transporter gene in elderly people are under the modulating influence of long-term cognitive training, determined by the specificity of professional activity.

Determination of the Level of von Willebrand Factor, ADAMTS13, and Ratio of ADAMTS13:von Willebrand Factor in Sickle Cell Disease Patients.

Sickle cell anemia (SCA) is a hypercoagulable state characterized by a significant alteration in hemostatic parameters which may predispose an increased risk of vaso-occlusive crisis (VOC). Sickle cell disease (SCD) is the most common genetic disorder in sub-Saharan Africa. Nigeria bears a high disease burden with an estimated prevalence of 1%-3% of its population being affected by the disease. The study seeks to determine the role of von Willebrand factor (VWF), ADAMTS13, and the ratio of ADAMTS13:VWF antigen in the pathogenesis of VOC. The objective of this study is to evaluate the level of VWF, ADAMTS13, and their ratio in SCD subjects in Calabar and to determine their role in the pathogenesis of VOC. This is a comparative study carried out at the University of Calabar Teaching Hospital (UCTH), Calabar. Sixty SCA patients were evaluated in VOC and steady states as well as five parented healthy controls. VWF: Ag and ADAMTS13:Ag were evaluated using Assaypro enzyme-linked immunosorbent assay kits with Lot nos. 01751728 and 04222167R, respectively. Data were analyzed by IBM SPSS Chicago software version 21. The study was approved by the UCTH Institution Ethical Review Board. The mean ages of the SCA subjects and controls were 23.5 ± 7.2 years and 26.5 ± 5.6 years, respectively (P = 0.706). There were 23 (38.3%) males in the SCA group and 21 (42.0%) females in the controls. There was no significant difference in their sex distribution (P = 0.063). The mean (standard deviation [SD]) of VWF in VOC, steady state, and controls were 2.52 ± 0.34, 1.34 ± 0.23, and 1.41 ± 0.23 IU/mL, respectively. The differences in mean were significantly higher in VOC state (P = 0.003). The mean ± SD of ADAMTS13 in VOC, steady state, and controls were 0.61 ± 0.10, 0.44 ± 0.06, and 0.62 ± 0.10 μg/L, respectively. ADAMTS13 levels did not differ significantly across the groups (P = 0.270). Similarly, there was no significant difference between ADAMTS13:VWF ratios across the groups (P = 0.318). VWF level is elevated in VOC state and thus may be implicated in the pathogenesis of VOC. ADAMTS13 and the ratio of ADAMTS13:VWF are not significantly affected in VOC.

Serum levels of free light chains and syndecan-1 in patients with rheumatoid arthritis and systemic lupus erythematosus.

Systemic autoimmune rheumatic diseases (SARDs) are characterized by chronic inflammation. Reliable biomarkers are crucial for diagnosis, monitoring disease progression and therapeutic responses. This study explores serum Syndecan-1 (SDC-1) as a biomarker for these conditions and its relationship with free light chain (FLC) levels. A retrospective analysis was performed on sera from 60 patients with rheumatoid arthritis (RA) and from 60 with systemic lupus erythematosus (SLE), alongside 50 healthy donors (HD). Κ- and λ- FLCs were determined by turbidimetric assay, while SDC-1 levels by ELISA. Kruskal-Wallis test, Wilcoxon-Mann-Whitney U test, multivariable linear regression and Spearman's correlation were employed to compare biomarker levels across groups and to explore correlations. SDC-1, κ-FLC, and λ-FLC were significantly increased in RA and SLE patients compared with HD (p< 0.001), while no significant differences in the κ/λ ratio were observed among the groups (p= 0.4). A significant difference in subject age was also identified. However, multivariate regression analysis indicated that RA and SLE are significantly associated with the levels of these markers, with minimal confounding by age. A significant correlation was observed separately in all groups between the FLC markers. Conversely, no correlation was detected between SDC-1 and FLCs, nor between these markers and age or disease activity indices. Elevated serum levels of FLCs and SDC-1 in RA and SLE patients compared with HD underscore their potential as biomarkers for SARDs. The findings also suggest sustained plasma cell activation, supporting the multifaceted role of SDC-1 in the pathogenesis of SARDs.

Facial aging, cognitive impairment, and dementia risk

BackgroundFacial aging, cognitive impairment, and dementia are all age-related conditions. However, the temporal relation between facial age and future risk of dementia was not systematically examined.ObjectivesTo investigate the relationship between facial age (both subjective/perceived and objective) and cognitive impairment and/or dementia risk.MethodsThe study included 195,329 participants (age ≥ 60 y) from the UK Biobank (UKB) with self-perceived facial age and 612 participants from the Nutrition and Health of Aging Population in China Project (NHAPC) study (age ≥ 56 y) with objective assessment of facial age. Cox proportional hazards model was used to prospectively examine the hazard ratios (HRs) and their 95% confidence intervals (CIs) of self-perceived facial age and dementia risk in the UKB, adjusting for age, sex, education, APOE ε4 allele, and other potential confounders. Linear and logistic regressions were performed to examine the cross-sectional association between facial age (perceived and objective) and cognitive impairment in the UKB and NHAPC, with potential confounders adjusted.ResultsDuring a median follow-up of 12.3 years, 5659 dementia cases were identified in the UKB. The fully-adjusted HRs comparing high vs. low perceived facial age were 1.61 (95% CI, 1.33 ~ 1.96) for dementia (P-trend ≤ 0.001). Subjective facial age and cognitive impairment was also observed in the UKB. In the NHAPC, facial age, as assessed by three objective wrinkle parameters, was associated with higher odds of cognitive impairment (P-trend < 0.05). Specifically, the fully-adjusted OR for cognitive impairment comparing the highest versus the lowest quartiles of crow’s feet wrinkles number was 2.48 (95% CI, 1.06 ~ 5.78).ConclusionsHigh facial age was associated with cognitive impairment, dementia and its subtypes after adjusting for conventional risk factors for dementia. Facial aging may be an indicator of cognitive decline and dementia risk in older adults, which can aid in the early diagnosis and management of age-related conditions.

Inverse Association between the Body Mass Index and the Incidence of Unruptured Intracranial Aneurysms-Insights from the Hamburg City Health Population Study.

Overweight/obese patients experience a lower incidence of subarachnoid hemorrhage (SAH) compared to non-overweight patients, even though elevated body mass index (BMI) has been associated with various SAH risk factors. Given that intracranial aneurysms are a primary cause of SAH, a potential protective effect of a high BMI on intracranial aneurysms is likely but remains insufficiently investigated. This population-based MRI study aims to conduct detailed analyses on risk factors associated with the incidence of unruptured intracranial aneurysms (UIA). Retrospective analysis of subjects enrolled in the prospective Hamburg City Health study who underwent intracranial magnetic resonance imaging (MRI) was done. MRI scans were screened for UIA using time-of-flight angiography. Subject data including medical history, laboratory examinations, and risk factors for UIA were collected, and a multivariable logistic regression model was used to investigate the relationship between risk factors and UIA incidence. 2688 subjects (mean (IQR) age, 65 (58-71); 1176 female (43.8%) were included. An UIA was detected in 214 subjects with an incidence of 10.6% (6.0%) in females (males). Determinants for UIA were female sex (OR 2.00, 95%CI 1.45-2.77, p < 0.001), hypertension (OR 1.48, 95%CI 1.08-2.04, p = 0.015), smoking (OR 1.41, 95%CI 1.03-1.95, p = 0.036), and BMI (OR 0.95, 95%CI 0.91-0.98, p = 0.004). Among subjects with UIA, 9.4% with a BMI > 25 had multiple aneurysms, compared to 21.6% with BMI ≤ 25 (p = 0.012). This study suggests that a high BMI exhibits a protective effect on UIA incidence and the development of multiple aneurysms. Additionally, the data confirms established risk factors for UIA development, such as female sex, hypertension, and smoking.

Clinical profile of patients with acute traumatic brain injury undergoing cranial surgery in the United States: report from the 18-centre TRACK-TBI cohort study

Contemporary surgical practices for traumatic brain injury (TBI) remain unclear. We describe the clinical profile of an 18-centre US TBI cohort with cranial surgery. The prospective, observational Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study (2014-2018; ClinicalTrials.gov #NCT02119182) enrolled subjects who presented to trauma centre and received head computed tomography within 24-h (h) post-TBI. We performed a secondary data analysis in subjects aged ≥17-years with hospitalisation. Clinical characteristics, surgery type/timing, hospital and six-month outcomes were reported. Of 2032 subjects (age: mean=41.4-years, range=17-89-years; male=71% female=29%), 260 underwent cranial surgery, comprising 65% decompressive craniectomy, 23% craniotomy, 12% other surgery. Subjects with surgery (vs. without surgery) presented with worse neurological injury (median Glasgow Coma Scale=6 vs. 15; midline shift ≥5mm: 48% vs. 2%; cisternal effacement: 61% vs. 4%; p<0.0001). Median time-to-craniectomy/craniotomy was 1.8h (interquartile range=1.1-5.0h), and 67% underwent intracranial pressure monitoring. Seventy-three percent of subjects with decompressive craniectomy and 58% of subjects with craniotomy had ≥3 intracranial lesion types. Decompressive craniectomy (vs. craniotomy) was associated with intracranial injury severity (median Rotterdam Score=4 vs. 3, p<0.0001), intensive care length of stay (median=13 vs. 4-days, p=0.0002), and six-month unfavourable outcome (62% vs. 30%; p=0.0001). Earlier time-to-craniectomy was associated with intracranial injury severity. In a large representative cohort of patients hospitalised with TBI, surgical decision-making and time-to-surgery aligned with intracranial injury severity. Multifocal TBIs predominated in patients with cranial surgery. These findings summarise current TBI surgical practice across US trauma centres and provide the foundation for analyses in targeted subpopulations. National Institute of Neurological Disorders and Stroke; US Department of Defense; Neurosurgery Research and Education Foundation.

Cultural adaptation and validation of the Sinhala version of the spiritual needs assessment for patients (S-SNAP) questionnaire

BackgroundSpiritual support for patients and caregivers of critically ill patients is associated with improved quality of life. This aspect, however, is not incorporated into the current care pathways in Sri Lanka. The Spiritual Needs Assessment for Patients (SNAP) questionnaire, comprised of 3 domains: psychosocial, spiritual and religious, gives a platform for clinicians to assess the spiritual needs of those patients. This study presents the results of validation of the Sinhala version of the SNAP (S-SNAP) questionnaire.MethodsThe SNAP was translated from English to Sinhala using the standard forward and backward translation process. After verifying the content validity, unambiguity and clarity of items in a focused group discussion, and a pilot study, the pre-final version was tested among 267 volunteers with cancer selected from three state-run cancer care institutions. Data were analysed for internal consistency and item-total correlations. Factor analysis was done using Varimax rotation with Kaiser normalization. A Scree plot was also made to determine the number of factors.ResultsThe mean (SD) age of subjects was 63.2 (11.4) years. The total S-SNAP score ranged from 22 to 88 (maximum 88). The overall Cronbach’s alpha was 0.94 while item-total correlations varied from 0.26 to 0.87. Total SNAP score showed inverse correlations with age, Charleson Comorbidity index and Barthel index while a positive correlation was seen with the Karnofsky performance status scale (p < 0.05). Kaiser-Meyer-Olkein value of 0.92 (P = < 0.001) for Bartlett’s test indicated adequate sampling and non-linearity of factors. The scree plot showed a four-factor structure explaining 76% variation. Meaning of life and relationship with a supernatural being and religious rituals are loaded as 2 different factors. Worries, fears and forgiveness are grouped as the third factor while relaxation, coping and sharing feelings are loaded separately.ConclusionsThe S-SNAP is a reliable and valid tool to assess spiritual suffering among patients with cancers conversant in the Sinhala language.