Functional Level Research Articles

Knowledge-guided Deep Temporal Clustering for Alzheimer's Disease Subtypes in Completed Clinical Trials.

Alzheimer's disease (AD) is a multifaceted neurodegenerative disorder with varied patient progression. We aim to test the hypothesis that AD patients can be categorized into subgroups based on differences in progression. We leveraged data from three randomized clinical trials (RCTs) to develop a knowledge-guided, deep temporal clustering (KG-DTC) framework for AD subtyping. This model combined autoencoders for contextual information capture, k-means clustering for representation formation, and clinical outcome classification for clinical knowledge integration. The derived representations, encompassing demographics, APOE genotype, cognitive assessments, brain volumes, and biomarkers, were clustered using the Gaussian Mixture Model to identify AD subtypes. Our novel KG-DTC framework was developed using placebo data from 2,087 AD patients across three solanezumab clinical trials (EXPEDITION, EXPEDITION2, and EXPEDITION3), achieving high performance in outcome prediction and clustering. The KG-DTC model demonstrated superior clustering structures, especially when combined with k-means clustering loss. External validation with independent clinical trial data showed consistent clustering results, with a 0.33 silhouette score for three clusters. The model's stability was confirmed through a leave-one-out approach, with an average adjusted Rand Index around 0.945. Three distinct AD subtypes were identified, each exhibiting unique patterns of cognitive function, neurodegeneration, and amyloid beta levels. Notably, Subtype 3 (S3) showed rapid cognitive decline across multiple clinical measures (e.g., 0.64 in S1 vs. -1.06 in S2 vs. 15.09 in S3 of average ADAS total change score, p<.001). This innovative approach offers promising insights for understanding variability in treatment outcomes and personalizing AD treatment strategies.

Does the optimal level of illumination improve both visual functions and visual comfort in schoolchildren with low vision?

Lighting modification is commonly performed by optometrists and occupational therapists to enhance visibility and visual comfort among schoolchildren with low vision. The purpose of this study is to determine the optimal illumination level for visual function and visual comfort of schoolchildren with low vision and the relationship between them. A cross-sectional study was conducted to assess five levels of illumination ranging from 125 lux to 2000 lux to determine the optimal illumination for visual functions and visual comfort in schoolchildren with low vision from a special education school for blind in Malaysia. Purposive sampling was done to recruit forty-two schoolchildren with low vision for this study. Visual functions assessed were visual acuity, measured using the Early Treatment Diabetic Retinopathy Study LogMAR chart at distance and near, contrast sensitivity (CS) measured using the Pelli-Robson chart at distance and the Mars CS chart at near. Reading speed was determined using the Universiti Kebangsaan Malaysia Malay Language Related Word Reading Text test chart. Subjects were asked to rate their visual comfort using a validated questionnaire at the end of each measurement of visual functions and reading speed for the different illumination levels. Visual acuity and contrast sensitivity at distance and near, visual comfort and reading speed improved significantly with increase in illumination levels (p&lt;0.05). However, the interaction between illumination level and level of low vision was not significant (p&gt;0.05). Visual comfort was significantly associated with visual function (p&lt;0.05), while direct association between visual comfort and illumination level was not significant (p&gt;0.05). Optimal illumination for improvement of visual function, reading speed and visual comfort range from 276.67 lux to 701.59 lux. Majority of the schoolchildren with low vision had improved visual function, reading speed and visual comfort with increased illumination. Illumination of at least 600 lux is recommended for maximum visual functioning and visual comfort of schoolchildren with low vision.

Green and solid state reduction of GO monolayers sandwiched between Arachidic acid LB layers

A novel, single step and environment friendly solid state approach for reduction of graphene oxide (GO) monolayers has been demonstrated, in which, arachidic acid/GO/arachidic acid (AA/GO/AA) sandwich structure obtained by Langmuir-Blodgett (LB) technique was heat treated at moderate temperatures to obtain RGO sheets. Heat treatment of AA/GO/AA sandwich structure at 200 °C results in substantial reduction of GO, with concurrent removal of AA molecules. Such developed RGO sheets possess sp2-C content of ∼69 %, O/C ratio of ∼0.17 and significantly reduced I(D)/I(G) ratio of ∼1.1. Ultraviolet photoelectron spectroscopy (UPS) studies on RGO sheets evidenced significant increase in density of states in immediate vicinity of Fermi level and decrease in work function after reduction. Bottom gated field effect transistors fabricated with isolated RGO sheets displayed charge neutrality point at a positive gate voltage, indicating p-type nature, consistent with UPS and electrostatic force microscopy (EFM) measurement results. The RGO sheets obtained by heat treatment of AA/GO/AA sandwich structure exhibited conductivity in the range of 2–7 S/cm and field effect mobility of 0.03–2 cm2/Vs, which are comparable with values reported for RGO sheets obtained by various chemical/thermal reduction procedures. The extent of GO reduction is determined primarily by proximity of AA molecules and found to be unaltered with either escalation of heat treatment temperature or increase of AA content in sandwich structure. The single-step GO reduction approach demonstrated in this work is an effective way for development of RGO monolayers with high structural quality towards graphene-based electronic device applications.

VEGF Polymorphisms (VEGF-936 C/T, VEGF-634 G/C and VEGF-2578 C/A) and Cardiovascular Implications in Long COVID Patients.

The COVID-19 pandemic has raised awareness of the virus's long-term non-pulmonary consequences. This study examined the relationship between genetic polymorphisms of VEGF and cardiac dysfunction and subclinical atherosclerosis in patients recovering from COVID-19. This study included 67 patients previously diagnosed with COVID-19. VEGF-936C/T, VEGF-634G/C, and VEGF-2578C/A statuses were determined. Conventional echocardiography and arterial parameters assessments were performed at inclusion and at six months after the first assessment. For VEGF-936C/T, dominant and over-dominant models showed a significant increase in ejection fraction at six months after COVID (p = 0.044 and 0.048) and was also a predictive independent factor for the augmentation index (β = 3.07; p = 0.024). The dominant model showed a rise in RV-RA gradient (3.702 mmHg) (p = 0.028 95% CI: 0.040-7.363), with the over-dominant model indicating a greater difference (4.254 mmHg) (p = 0.025 95% CI: 0.624-7.884). The findings for VEGF-634G/C were not statistically significant, except for a difference in TAPSE during initial evaluation, using the codominant model. For VEGF-2578C/A, a difference in ventricular filling pressure (E/E'ratio) was best described under the recessive model. Our research suggests that the VEG-936C/T genotype may impact the baseline level and subsequent changes in cardiac function and subclinical atherosclerosis. These findings offer valuable insights into the complex correlation between genetic polymorphisms and cardiovascular disfunction in long COVID patients.

State-Level Education Quality and Trajectories of Cognitive Function by Race and Educational Attainment.

Although educational attainment is consistently associated with better cognitive function among older adults, we know little about how education quality is related to cognitive function. This is a key gap in the literature given that the quality of US education improved considerably during the early to mid-20th century as state and federal investment increased. We posit that growing up in states with higher-quality education systems may protect against poor cognitive function, particularly among Black adults and adults who completed fewer years of school. We used prospective data on cognitive function from the Health and Retirement Study linked to historical data on state investment in public schools, restricting our sample to non-Hispanic White and Black adults born between 1914 and 1959 (19,096 White adults and 4,625 Black adults). Using race-stratified linear mixed models, we considered if state-level education quality was associated with level and decline in cognitive function and if these patterns differed by years of schooling and race. Residing in states with higher-resourced education systems during childhood was associated with better cognitive function, particularly among those who completed less than 12 years of schooling, regardless of race. For White adults, higher-resourced state education systems were associated with higher scores of total cognitive function and episodic memory, but there were diminishing returns as resources increased to very high levels. For Black adults, the relationship between state education resources and cognitive function varied by age with positive associations in midlife and generally null or negative associations at the oldest ages. Federal and state investment in public schools may provide students with opportunities to develop important cognitive resources during schooling that translate into better cognitive function in later life, especially among marginalized populations.

Prenatal surgery in fetal myelomeningocele with severe ventriculomegaly.

Prenatal myelomeningocele (MMC) repair is performed to decrease risk for treatment of hydrocephalus after birth and to preserve motor function. Some centers may not consider patients candidates for surgery if severe ventriculomegaly is present and there is no expected benefit in decreased risk for hydrocephalus treatment. This study sought to compare postnatal outcomes of fetuses with MMC and severe ventriculomegaly (>15mm) who underwent prenatal repair, with fetuses with severe ventriculomegaly who underwent postnatal repair and fetuses with ventriculomegaly (<15mm) who underwent prenatal repair. This was a retrospective study of fetuses with MMC that underwent prenatal or postnatal repair between 2012 and 2021 at a single institution. The cohort was divided based on preoperative fetal ventricular size into two groups, those with severe ventriculomegaly (≥15 mm) and those without severe ventriculomegaly (<15 mm). Fetal ventricular size was measured by MRI prior to surgery using the standardized approach and the mean of the left and right ventricle was used for analysis. Motor function of lower extremities was assessed at the time of referral by ultrasound and if flexion-extension movements of the ankle were seen, it was considered as preserved S1 motor function. Postnatal outcomes including motor function of lower extremities assessed at birth and need for diversion procedure for hydrocephalus treatment during the first year of life were collected and compared between groups. Data was presented as median and range or number and percentages as appropriate. P value >0.05 was considered statistically significant. Multivariate regression analysis was used to adjust for potential confounders. 154 patients were included in this study: 145 patients underwent fetal surgery (101 fetoscopic and 44 open hysterotomy) and 9 patients with severe ventriculomegaly underwent postnatal repair. Among the 145 patients who underwent fetal surgery, 22 presented with severe ventriculomegaly. Prenatally repaired fetuses with severe ventriculomegaly at referral were at a significantly higher need for hydrocephalus treatment by 12 months than those without severe ventriculomegaly (62% vs. 29%, p<0.01). However, motor function assessment at birth was similar between both prenatally repaired groups (OR=0.92, 95% CI [0.33-2.59], p=0.88) adjusted for the anatomical level of the lesion. The prenatally repaired group with severe ventriculomegaly had better preserved motor function levels at birth compared to the postnatal repair group with severe ventriculomegaly (L3 with 11.1% S1 motor function; p=<0.01 and p=<0.01). Prenatally repaired patients with severe ventriculomegaly had an 18.9 times chance of having an intact motor function at birth [95% CI (1.2 - 290.1)] adjusted for ethnicity, presence of clubfeet at referral, and gestational age at delivery compared to postnatal repair. There was not a significant difference in the need for hydrocephalus treatment in the first year of life between prenatal and postnatal repair of patients with severe ventriculomegaly (61.9% vs 87.5%, p=0.18). Although fetuses with MMC and severe ventriculomegaly do not seem to benefit from fetal surgery in terms of postnatal hydrocephalus treatment, they benefit from increased chance of preserved motor function at birth. Results from this study highlight the benefits of having prenatal MMC repair for cases with severe ventriculomegaly at referral to preserve motor function. This article is protected by copyright. All rights reserved.

Unveiling the Nutritional Veil of Sulforaphane: With a Major Focus on Glucose Homeostasis Modulation.

Abnormal glucose homeostasis is associated with metabolic syndromes including cardiovascular diseases, hypertension, type 2 diabetes mellitus, and obesity, highlighting the significance of maintaining a balanced glucose level for optimal biological function. This highlights the importance of maintaining normal glucose levels for proper biological functioning. Sulforaphane (SFN), the primary bioactive compound in broccoli from the Cruciferae or Brassicaceae family, has been shown to enhance glucose homeostasis effectively while exhibiting low cytotoxicity. This paper assesses the impact of SFN on glucose homeostasis in vitro, in vivo, and human trials, as well as the molecular mechanisms that drive its regulatory effects. New strategies have been proposed to enhance the bioavailability and targeted delivery of SFN in order to overcome inherent instability. The manuscript also covers the safety evaluations of SFN that have been documented for its production and utilization. Hence, a deeper understanding of the favorable influence and mechanism of SFN on glucose homeostasis, coupled with the fact that SFN is abundant in the human daily diet, may ultimately offer theoretical evidence to support its potential use in the food and pharmaceutical industries.

Analysis of Students' Algebraic Reasoning Level in Learning Limit Function

Analysis of Students' Algebraic Reasoning Level in Learning Limit Function

Pathways to resilience: The parallel change in children's emotional difficulties and family context during the COVID-19 lockdown in Italy.

The study analyses which pathways to adjustment emerged at the family level during the COVID-19 containment period in Italy, during which children were locked down with their families for 56 days from March 11 to May 6. Using a longitudinal design, with data pre- and postevent, a bivariate latent change score model analyzed the covariance of the change in family well-being (FW) and in emotional difficulties (ED), testing if the longitudinal change in ED is a function of the starting level of FW, and vice-versa. Children's stress reactions to the pandemic and other related experiences were included as additional predictors. A total of 166 middle school students (86 females) with a mean age of 11.14 (SD = .47) completed two online questionnaires, in January 2020 (T0) and in June 2020 (T1). Results showed that children's ED decreased significantly, on average, during the lockdown period, and FW remained constant. ED and FW change scores had a significant and negative covariation (β = - .46; p = .01). When family well-being increased emotional difficulties decreased, and vice versa. FW at T0 predicted no change in FW, nor did T0 scores of ED predict any change in FW. The strong intercorrelated change between children's ED and FW during the lockdown does not seem influenced by preexisting levels of individual and family functioning. Findings supported the view that for some families, the COVID-19 lockdown was also an opportunity to experience deeper emotional connections, contributing to a decrease in ED. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Physical Activity Levels, Correlates, and All-Cause Mortality Risk in People Living With Different Health Conditions.

To better understand physical activity behavior and its health benefits in people living with health conditions, we studied people with and without 20 different self-reported health conditions with regard to (1) their physical activity levels, (2) factors correlated with these physical activity levels, and (3) the association between physical activity and all-cause mortality. We used a subsample (n = 88,659) of the Lifelines cohort study from the Netherlands. For people living with and without 20 different self-reported health conditions, we studied the aforementioned factors in relation to physical activity. Physical activity was assessed with the Short Questionnaire to Assess Health-Enhancing Physical Activity Questionnaire, and mortality data were obtained from the Dutch death register. People with a reported health condition were less likely to meet physical activity guidelines than people without a reported health condition (odds ratios ranging from 0.55 to 0.89). Higher body mass index and sitting time, and lower self-rated health, physical functioning, and education levels were associated with lower odds of meeting physical activity guidelines across most health conditions. Finally, we found a protective association between physical activity and all-cause mortality in both people living with and without different health conditions. People living with different health conditions are generally less physically active compared with people living without a health condition. Both people living with and without self-reported health conditions share a number of key factors associated with physical activity levels. We also observed the expected protective association between physical activity and all-cause mortality.

Ligand Centered Reactivity of a Transition Metal Bound Geometrically Constrained Phosphine.

The electronic properties, coordination chemistry and reactivity of metal complexes of a planar (C2v symmetric) acridane-derived geometrically constrained phosphine, P(NNN), are described. On complexation to metal centers, the phosphine was found to adopt a distorted trigonal pyramidal structure with a high barrier to pyramidal inversion (22.3 kcal/mol at 298 K for Au[P(NNN)]Cl). Spectroscopic data and theoretical calculations carried out at the density functional level of theory indicate that P(NNN) is a moderate σ-donor, with significant π-acceptor properties. Despite the distortion undergone by the phosphorus atom on coordination to metal centers, the P(NNN) ligand retains its ability to react with small molecule substrates with polar E-H bonds (MeOH, NH2Ph, NH3). It does so in a concerted fashion across one of the P-N bonds, and reversibly in the case of amine substrates. This cooperative bond activation chemistry may ultimately prove beneficial in catalysis.

Beyond the Anticodon: tRNA Core Modifications and Their Impact on Structure, Translation and Stress Adaptation.

Transfer RNAs (tRNAs) are heavily decorated with post-transcriptional chemical modifications. Approximately 100 different modifications have been identified in tRNAs, and each tRNA typically contains 5-15 modifications that are incorporated at specific sites along the tRNA sequence. These modifications may be classified into two groups according to their position in the three-dimensional tRNA structure, i.e., modifications in the tRNA core and modifications in the anticodon-loop (ACL) region. Since many modified nucleotides in the tRNA core are involved in the formation of tertiary interactions implicated in tRNA folding, these modifications are key to tRNA stability and resistance to RNA decay pathways. In comparison to the extensively studied ACL modifications, tRNA core modifications have generally received less attention, although they have been shown to play important roles beyond tRNA stability. Here, we review and place in perspective selected data on tRNA core modifications. We present their impact on tRNA structure and stability and report how these changes manifest themselves at the functional level in translation, fitness and stress adaptation.

Architecture and Development Framework for a Web-Based Risk Assessment and Management Platform Developed on WordPress to Address Opioid Overdose.

The number of overdose-related fatalities continues to reach historic levels across Canada, despite ongoing efforts by authorities. To reduce mortality, a clinical trajectory ranging from preventative measures to crisis intervention, skill training to treatment, and risk assessment to risk management needs to be supported. The web-based Risk Assessment and Management Platform (RAMP) was developed to realize this concept and to empower people who use drugs through an integrated tool that allows them to better understand and manage their risk of overdose. This paper outlines the architecture and development of RAMP, which is built on the WordPress platform. WordPress components are mapped onto a 3-tier architecture that consists of presentation, application, and database layers. The architecture facilitates the development of a modular software that includes several features that are independent in functionality but interact with each other in an integrated platform. The relatively low coupling and high coherence of the features may reduce the cost of maintenance and increase flexibility of future developments. RAMP's architecture comprises a user interface, conceptual framework, and backend layers. The RAMP front end effectively uses some of the WordPress' features such as HTML5, CSS, and JavaScript to create a mobile, friendly, and scalable user interface. The RAMP backend uses several standard and custom WordPress plug-ins to support risk assessment and monitoring, with the goal of mitigating the impacts and eliminating risks together. A rule-based decision support system has been hard-coded to suggest relevant modules and goals to complement each user's lifestyle and goals based on their risk assessment. Finally, the backend uses the MySQL database management system and communicates with the RAMP framework layer via the data access layer to facilitate a timely and secure handling of information. Overall, RAMP is a modular system developed to identify and manage the risk of opioid overdose in the population of people who use drugs. Its modular design uses the WordPress architecture to efficiently communicate between layers and provide a base for external plug-ins. There is potential for the current system to adopt and address other related fields such as suicide, anxiety, and trauma. Broader implementation will support this concept and lead to the next level of functionality.

Study of an FBXO7 patient mutation reveals Fbxo7 and PI31 co-regulate proteasomes and mitochondria.

Mutations in FBXO7 have been discovered to be associated with an atypical parkinsonism. We report here a new homozygous missense mutation in a paediatric patient that causes an L250P substitution in the dimerisation domain of Fbxo7. This alteration selectively ablates the Fbxo7-PI31 interaction and causes a significant reduction in Fbxo7 and PI31 levels in patient cells. Consistent with their association with proteasomes, patient fibroblasts have reduced proteasome activity and proteasome subunits. We also show PI31 interacts with the MiD49/51 fission adaptor proteins, and unexpectedly, PI31 acts to facilitate SCFFbxo7-mediated ubiquitination of MiD49. The L250P mutation reduces the SCFFbxo7 ligase-mediated ubiquitination of a subset of its known substrates. Although MiD49/51 expression was reduced in patient cells, there was no effect on the mitochondrial network. However, patient cells show reduced levels of mitochondrial function and mitophagy, higher levels of ROS and are less viable under stress. Our study demonstrates that Fbxo7 and PI31 regulate proteasomes and mitochondria and reveals a new function for PI31 in enhancing the SCFFbxo7 E3 ubiquitin ligase activity.

A novel role for microtubule affinity-regulating kinases in neuropathic pain.

Neuropathic pain affects millions of patients, but there are currently few viable therapeutic options available. Microtubule affinity-regulating kinases (MARKs) regulate the dynamics of microtubules and participate in synaptic remodelling. It is unclear whether these changes are involved in the central sensitization of neuropathic pain. This study examined the role of MARK1 or MARK2 in regulating neurosynaptic plasticity induced by neuropathic pain. A rat spinal nerve ligation (SNL) model was established to induce neuropathic pain. The role of MARKs in nociceptive regulation was assessed by genetically knocking down MARK1 or MARK2 in amygdala and systemic administration of PCC0105003, a novel small molecule MARK inhibitor. Cognitive function, anxiety-like behaviours and motor coordination capability were also examined in SNL rats. Synaptic remodelling-associated signalling changes were detected with electrophysiological recording, Golgi-Cox staining, western blotting and qRT-PCR. MARK1 and MARK2 expression levels in amygdala and spinal dorsal horn were elevated in SNL rats. MARK1 or MARK2 knockdown in amygdala and PCC0105003 treatment partially attenuated pain-like behaviours along with improving cognitive deficit, anxiogenic-like behaviours and motor coordination in SNL rats. Inhibition of MARKs signalling reversed synaptic plasticity at the functional and structural levels by suppressing NR2B/GluR1 and EB3/Drebrin signalling pathways both in amygdala and spinal dorsal horn. These results suggest that MARKs-mediated synaptic remodelling plays a key role in the pathogenesis of neuropathic pain and that pharmacological inhibitors of MARKs such as PCC0105003 could represent a novel therapeutic strategy for the management of neuropathic pain.

Mechanism Research of DHEA Treatment Improving Diminished Ovarian Reserve by Attenuating the AMPK-SIRT1 Signaling and Mitophagy.

This study aims to investigate the effect and mechanism of dehydroepiandrosterone (DHEA) on diminished ovarian reserve (DOR) by modulating the AMPK-SIRT1 signaling and mitophagy in rats. Three-month-old female Sprague-Dawley (SD) rats were randomized and injected intraperitoneally with sesame oil as the control or deoxyvinylcyclohexene (VCD) to induce DOR. The VCD-injected rats were randomized and injected subcutaneously with vehicle as the model group or with DHEA for 21days as the DHEA group. After being identified in proestrus, rat blood sampleswere collected to prepare serum samples, and their ovarian tissues were dissected. Compared with the controls, significantly lower serum estradiol (E2), anti-Müllerian hormone (AMH), and inhibin B (IHNB) and higher follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were detected in the model group (DOR rats). The model group of rats displayed an increase in follicular atresia and a decrease in ovarian volume and the number of growing follicles and corpus luteum, accompanied by increased frequency of oocyte apoptosis and reduced levels of mitochondrial function. Furthermore, significantly higher levels of the AMPK-SIRT1 signaling and mitophagy were observed in the ovaries of rats in the model group. In contrast, treatment with DHEA significantly ameliorated the hormone disorder and morphological changes in the ovaries, reduced the frequency of apoptotic oocytes, and improved mitochondrial function in the ovaries of DOR rats. Mechanistically, DHEA treatment significantly attenuated the AMPK-SIRT1 signaling and mitophagy in the ovaries of DOR rats. DHEA treatment reduced the severity of DOR and enhanced ovarian reserve function by attenuating the AMPK-SIRT1 signaling and mitophagy in the ovaries of rats.

Ercc1 DNA repair deficiency results in vascular aging characterized by VSMC phenotype switching, ECM remodeling, and an increased stress response.

Cardiovascular diseases are the number one cause of death globally. The most important determinant of cardiovascular health is a person's age. Aging results in structural changes and functional decline of the cardiovascular system. DNA damage is an important contributor to the aging process, and mice with a DNA repair defect caused by Ercc1 deficiency display hypertension, vascular stiffening, and loss of vasomotor control. To determine the underlying cause, we compared important hallmarks of vascular aging in aortas of both Ercc1Δ/- and age-matched wildtype mice. Additionally, we investigated vascular aging in 104 week old wildtype mice. Ercc1Δ/- aortas displayed arterial thickening, a loss of cells, and a discontinuous endothelial layer. Aortas of 24 week old Ercc1Δ/- mice showed phenotypical switching of vascular smooth muscle cells (VSMCs), characterized by a decrease in contractile markers and a decrease in synthetic markers at the RNA level. As well as an increase in osteogenic markers, microcalcification, and an increase in markers for damage induced stress response. This suggests that Ercc1Δ/- VSMCs undergo a stress-induced contractile-to-osteogenic phenotype switch. Ercc1Δ/- aortas showed increased MMP activity, elastin fragmentation, and proteoglycan deposition, characteristic of vascular aging and indicative of age-related extracellular matrix remodeling. The 104 week old WT mice showed loss of cells, VSMC dedifferentiation, and senescence. In conclusion, Ercc1Δ/- aortas rapidly display many characteristics of vascular aging, and thus the Ercc1Δ/- mouse is an excellent model to evaluate drugs that prevent vascular aging in a short time span at the functional, histological, and cellular level.

Outcome of Surgery to Improve Swallowing in Patients with Lateral Medullary Syndrome: A Retrospective Cohort Study.

The study investigated surgical interventions to improve dysphagia in patients with lateral medullary syndrome (LMS), along with optimal scheduling of surgery and prognostic factors. In this retrospective, single-center cohort study, dysphagia patients with LMS who underwent surgery between January 2010 and December 2021 were enrolled. The National Outcomes Measurement System (NOMS) was used to classify swallowing function (level 1: only tube feeding, level 5: without tube feeding). Patients were divided into four groups. Groups 1 and 2, LMS onset within 1year, and groups 3 and 4, onset after 1year. Groups 1 and 3 had infarctions confined to the oblongata. Groups 2 and 4 had infarctions extending to the cerebellum. The primary outcome was the time to achieve NOMS ≥ 5. The final NOMS level and pathological findings were considered. Nineteen cases were included. Group 4 comprised one case and was excluded. The mean overall preoperative NOMS was 1.11. The mean time to NOMS ≥ 5 was 9.6months (95% confidence interval: 5.04-14.2), and that to NOMS ≥ 5 was 1.67 (1.07-2.26), 11.4 (4.71-18.1), and 7.6 (5.15-10.1) months for groups 1, 2, and 3, respectively. Group 1 achieved NOMS ≥ 5 earlier than groups 2 and 3 (P = 0.01 and 0.03, respectively). The overall final NOMS value was 4.68. Fourteen patients had atrophy or fibrosis of the cricopharyngeal muscle. In conclusion, surgery was effective for effective for treating dysphagia in LMS patients. However, improvement is prolonged if > 1year has passed since onset or the infarction extended to the cerebellum.

ASSESSMENT OF THE FUNCTIONAL STATE OF THE CARDIOVASCULAR SYSTEM OF STUDENTS

Student youth are constantly in various stressful circumstances associated with social, economic, and psychological changes. These factors, as well as an unbalanced diet, lack of sleep, negatively affect the physical, mental and social health of students, and create prerequisites for reducing the adaptive capacity of the body. Studying the adaptation capabilities of students in conditions of intensive study load will make it possible to analyze their adaptation potential and level of health in order to introduce health-improving, preventive and medical measures if necessary. As a marker for evaluating the work of the human cardiovascular system, we used such indicators as heart rate, adaptation potential, endurance coefficient, Rufier index. We evaluated the functioning of the circulatory system in students of the Faculty of Biology by determining the adaptation potential according to Baevsky, the coefficient of endurance according to the Kvass formula and the Roufier index. Having assessed the level of functioning of the circulatory system in students of the II year according to the indicator of adaptation potential, we found that the majority of students have a satisfactory level of adaptation. In 30% of male students and 35% of female students, a poor and unsatisfactory evaluation of the reaction according to the Rufier index and weakening of the cardiovascular system was found in 40% of male students and 71% of female students, according to the endurance coefficient. This is probably explained by a decrease in the reserve capabilities of the cardiovascular system due to the low physical fitness of the students.

(120) E-Mergir: Preliminary Efficacy of a Digital Psychological Intervention Program for Improving Mental Health, Sexual Health, and Quality of Life of Prostate Cancer Survivors

Abstract Introduction Introduction: Prostate cancer is one of the most common cancers affecting men worldwide. The diagnosis of prostate cancer and associated treatments have a negative impact on people's physical, emotional, and sexual health, compromising their overall well-being and quality of life throughout the course of the disease. Despite the decreased levels of sexual functioning and sexual satisfaction associated with this type of cancer (Quinta-Gomes et al., 2019), patients' access to specialized healthcare and support is still limited. Given their flexibility and convenience, smartphone-based digital interventions can contribute to bridging this gap and constitute an important way to access specialized and personalized supportive care on emotional and sexual health for people with prostate cancer. Objective Objective: The present study aims to evaluate the preliminary efficacy of a digital psychological intervention program using smartphones aimed at improving the mental health, sexual health, and quality of life of prostate cancer survivors. Methods Methods: A randomized controlled pilot study is underway involving 30 prostate cancer survivors randomly assigned to an experimental group (with access to the program) and a waiting list control group (treatment as usual). The program was structured in five modules to be completed by the participants in a maximum period of 6 weeks while receiving support from a psychologist. The study was approved by an institutional Ethical Board. Acceptability, usability, feasibility, and preliminary efficacy (overall improvement in sexual and relational satisfaction, sexual pleasure, sexual distress, psychopathology, and quality of life) were defined as the main outcomes of this study. Participants' assessments will take place in two moments, before and after the implementation of the program. Results Expected results: It is expected that the program and the experimental design adopted will prove to be adequate and have good acceptability by the participants. Improvements in sexual and relational satisfaction, sexual pleasure, sexual distress, psychopathology, and quality of life are also expected for participants using the program compared to those in the waiting-list group. Conclusions Conclusions: As a future empirical-based digital psychological intervention program focused on patients' unmet sexual needs, E-mergir will significantly contribute to addressing the emotional and sexual health and quality of life of people with prostate cancer. Funding: Horizon Europe, NORTE-01-0145-FEDER-000057, CCDRN Disclosure No.