Functional Impairment Research Articles

Role of NLRP3 Inflammasome in Chronic Pain and Alzheimer's Disease-A Review.

The coexistence of Alzheimer's disease (AD) and chronic pain (CP) in the elderly population has been extensively documented, and a growing body of evidence supports the potential interconnections between these two conditions. This comprehensive review explores the mechanisms by which CP may contribute to the development and progression of AD, with a particular focus on neuroinflammatory pathways and the role of microglia, as well as the activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome. The review proposes that prolonged pain processing in critical brain regions can dysregulate the activity of the NLRP3 inflammasome within microglia, leading to the overproduction of pro-inflammatory cytokines and excessive oxidative stress in these regions. This aberrant microglial response also results in localized neuroinflammation in brain areas crucial for cognitive function. Additionally, CP as a persistent physiological and psychological stressor may be associated with hypothalamic-pituitary-adrenal (HPA) axis dysfunction, systemic inflammation, disruption of the blood-brain barrier (BBB), and neuroinflammation. These pathophysiological changes can cause morphological and functional impairments in brain regions responsible for cognition, memory, and neurotransmitter production, potentially contributing to the development and progression of CP-associated AD. Resultant neuroinflammation can further promote amyloid-beta (Aβ) plaque deposition, a hallmark of AD pathology. Potential therapeutic interventions targeting these neuroinflammatory pathways, particularly through the regulation of microglial NLRP3 activation, hold promise for improving outcomes in individuals with comorbid CP and AD. However, further research is required to fully elucidate the complex interplay between these conditions and develop effective treatment strategies.

Food choice motives mediate the relationship between delay discounting and binge eating: A structural equation modelling approach.

Binge eating (BE) is associated with psychological distress, functional impairment, and elevated risk of eating disorder diagnoses, and BE prevalence is increasing. Motivational and self-regulatory processes such as delay discounting may be important influences on BE; however, evidence is inconclusive, and lacks explanation of mechanisms. This study investigated how food choice motives mediate the pathway from delay discounting (DD) to BE symptomatology. Adult participants (N=391, 80% female, mean age 38.93) completed the Monetary Choice Questionnaire (DD), Food Choice Questionnaire (food choice motives), and Binge Eating Scale online. We used structural equation modelling (SEM) to analyse hypothesised partially-mediated pathways from DD to BE via Health, Mood, and Sensory Appeal food choice motives, incorporating participant age, sex, BMI, and Weight Control motives. The best fitting SEM indicated steeper DD was associated with greater BE, but this effect was fully mediated by lesser endorsement of Health motives. Greater endorsement of Mood and Weight Control motives, along with female sex and higher BMI, also accompanied greater BE symptomatology. Counter to hypotheses, Mood and Sensory Appeal did not mediate the relationship between DD and BE. The novel finding that Health motives mediated the effect of DD on BE suggests steeper discounting may hinder the longer-term perspective needed to value the health attributes of food, and thus promote food intake for immediate reinforcement. The significant effects of Weight Control and Mood motives independent of DD suggest support for overvaluation of weight and shape and negative reinforcement mechanisms in the etiology of BE. Our study highlights the influence of food choice motives and DD in BE, and supports the integration of individualised motivational and neurocognitive interventions in eating disorder treatment.

Gender differences in clinical presentations and sensory profiles in patients with fibromyalgia: implications of peripheral and central mechanisms.

Fibromyalgia has a high female predominance and research work has been focussing mainly on women. We aimed to answer (1) gender differences in pain scores and quality of life, (2) any gender-specific subgroups defined by quantitative sensory testing (QST), and (3) correlations of QST parameters with pain intensity and questionnaire scores. We evaluated clinical presentations and QST profiles from 38 male and 38 age-matched female patients. Women reported significantly higher scores in average daily pain, daily sleep interference score, average weekly pain, weekly sleep interference score, and revised fibromyalgia impact questionnaire (rFIQ). Based on LOGA classification, L0G2, mechanical allodynia or hyperalgesia without abnormal sensory loss, was the most common QST subtype which accounted for 28.9% of men and 26.3% of women. Approximately 34.2% of men and 26.3% of women displayed loss of function of small fibres with an increased cold or warm detection threshold. Cold detection threshold was negatively correlated with pain intensity and functional impairment, suggesting a peripheral mechanism. Central sensitization, defined as allodynia and hyperalgesia to thermal or mechanical stimuli, was found in two-thirds of male and female patients. Mechanical pain sensitivity was positively correlated with the severity of pain and associated symptoms in women, but not men. There was a marked gender difference in reported pain and quality of life. We have confirmed that central sensitization is a major mechanism for women. Our data suggested an important role of small fibre pathology in both men and women.

Design and Validation of a Preclinical Model for Oral Commissure and Lower Eyelid Thermal Injury

IntroductionOral commissure stenosis and lower eyelid ectropion from burns are functionally impairing and challenging to treat. Evaluation of various treatment modalities is limited by a lack of preclinical models. Described is a method for inducing controlled, titratable oral commissure and lower eyelid burns in swine for future treatment research. MethodsBurn wounds 3cm in diameter were applied to the lower eyelid and oral commissure of seven anesthetized Yorkshire swine for 10, 15, 20, or 30seconds at 100°C with a custom designed thermocouple-controlled burn device and observed for 3, 30, or 90 days. Tissue underwent laser speckle imaging (LSI) to assess vascular perfusion and histologic analysis after harvest. Statistical comparisons were calculated using Wilcoxon rank-sum tests. ResultsSubdermal extension was noted in oral commissure and lower eyelid burns with contact time of 20seconds or greater. Wound area progressively contracted from post-operative day (POD) 0 to 90 in both sites, but was not statistically significant based on contact time or burn site (p>0.20). Burns of 20-30seconds demonstrated increased neutrophil influx for oral commissure injuries (p<0.01) and leukocyte and macrophage influx for lower eyelid injuries (p=0.02). Degree of vascular congestion increased with 20-30second burns in both the oral commissure (p=0.015) and lower eyelid (p=0.04). Normalized LSI readings showed increased speckle size in both oral commissure (4.0-fold increase, p<0.01) and lower eyelid (3.2-fold increase, p<0.01) burns on POD 90 compared to pre-injury. No change in oral or ocular function was noted in any of the groups (p = 0.96). ConclusionOral commissure and lower eyelid burns create scars which may be modified by burn duration. This model may evaluate a therapeutic’s ability to limit functional impairment from burns.

Mechanisms and pharmacotherapy of cancer cachexia-associated anorexia.

Cachexia is a multifactorial metabolic syndrome characterized by weight and skeletal muscle loss caused by underlying illnesses such as cancer, heart failure, and renal failure. Inflammation, insulin resistance, increased muscle protein degradation, decreased food intake, and anorexia are the primary pathophysiological drivers of cachexia. Cachexia causes physical deterioration and functional impairment, loss of quality of life, lower response to active treatment, and ultimately morbidity and mortality, while the difficulties in tackling cachexia in its advanced phases and the heterogeneity of the syndrome among patients require an individualized and multidisciplinary approach from an early stage. Specifically, strategies combining nutritional and exercise interventions as well as pharmacotherapy that directly affect the pathogenesis of cachexia, such as anti-inflammatory, metabolism-improving, and appetite-stimulating agents, have been proposed, but none of which have demonstrated sufficient evidence to date. Nevertheless, several agents have recently emerged, including anamorelin, a ghrelin receptor agonist, growth differentiation factor 15 neutralization therapy, and melanocortin receptor antagonist, as candidates for ameliorating anorexia associated with cancer cachexia. Therefore, in this review, we outline cancer cachexia-associated anorexia and its pharmacotherapy, including corticosteroids, progesterone analogs, cannabinoids, anti-psychotics, and thalidomide which have been previously explored for their efficacy, in addition to the aforementioned novel agents, along with their mechanisms.

Current evidence of arterial spin labeling in amyotrophic lateral sclerosis: A systematic review.

This study aimed to evaluate the utility of arterial spin labeling (ASL) in assessing cerebral blood flow (CBF) changes in amyotrophic lateral sclerosis (ALS), and its potential as a biomarker for early diagnosis. A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies that employed ASL to compare CBF between ALS patients and healthy controls were included. Seven studies were included. A consistent finding across these studies was hypoperfusion in both the motor and non-motor regions, particularly in the frontotemporal cortex. Hypoperfusion in motor regions was correlated with functional impairment and was observed prior to structural changes, suggesting its potential as an early biomarker. There is limited evidence to suggest that monitoring changes in CBF patterns in the brain. Besides, limited findings showed initial hyperperfusion in regions not yet involved in the pathological process, and progressing hypoperfusion in regions with increasing pathological burden. This review highlights the potential of ASL as a valuable tool for understanding the neurovascular dysfunction in ALS. Further research is required to validate its clinical utility for diagnosing ALS and monitoring disease progression.

Describing quality of life trajectories in young Hispanic women with breast cancer: 5-year results from a large prospective cohort.

Cancer treatments have a detrimental impact on the quality of life (QoL) of young women with breast cancer (YWBC). Research exploring QoL trajectories has been mostly centered on postmenopausal women. Here we report longitudinal changes across all QoL domains and associated factors in YWBC. In this prospective longitudinal cohort study, women aged ≤40 with stage I-III BC completed the European Organization for the Research and Treatment of Cancer Core QoL questionnaire at diagnosis and during 4 follow-up visits over 5 years, alongside demographic and clinical data collection. Group-based multivariate trajectory modeling was used to identify patient groups based on their functional and symptom scores, finding 3 groups (best, good, and poor). Factors associated with each trajectory pattern were identified with multinomial logistic models. A total of 477 women (median age: 36; IQR: 32-38) were clustered into the best (n=259, 54%), good (n=79, 17%), or poor trajectory groups (n=139, 29%). Throughout the disease, patients with a poor QoL experienced clinically significant impairment in emotional functioning, nausea and vomiting, and pain. They also had significant cognitive impairment, dyspnea, and diarrhea. Patients with a good QoL had clinically meaningful diarrhea for the first 7 months, while those with the best QoL had clinically important nausea and vomiting during the first 2 months since diagnosis. Noteworthy, all groups experienced significant financial difficulties throughout their follow-up. Regular alcohol consumption at diagnosis (aOR [adjusted odds ratio] 1.64; 95% CI [confidence interval] 1.02-2.65) and HER2-positive BC (aOR 2.53; 95% CI 1.35-4.73) were independent factors associated with classification to the poor and good groups, respectively. This study underscores the variability in QoL among YWBC and the importance of ongoing monitoring. Strategies to improve access to economic resources, manage treatment-related adverse effects, and support patients in discontinuing modifiable risk factors are needed.

Emotional intelligence as a predictor of functional outcomes in psychotic disorders.

Psychotic disorders are associated with significant impairment in psychosocial functioning, yet mechanisms associated with this impairment remain poorly understood. Emotional intelligence, a component of social cognition, is associated with psychosocial functioning in this population. However, prior work has used relatively small samples, reported inconsistent relations between functioning domains and emotional intelligence, and inconsistently considered negative symptoms. To address these limitations, we examined the predictive ability of emotional intelligence on functional outcomes using a five-year longitudinal design. We used a large sample of individuals with and without psychotic disorder diagnoses (N=324), a performance-based measure of emotional intelligence, and three measures of functioning (i.e., social performance, assessor-rated social and occupational functioning, self-rated functioning in independent living). Results revealed individuals diagnosed with a psychotic disorder have lower emotional intelligence than those without a history of psychosis. Emotional intelligence was associated with social performance and social and occupational functioning in both those with and without a history of psychosis. In those diagnosed with a psychotic disorder, emotional intelligence and negative symptoms better predict social performance (βEmotional=0.36, R2delta=0.09) and social and occupational functioning (βEmotional=0.21, R2=0.03), but not self-rated functioning in independent living (βEmotional=-0.08, R2delta=0.00), as compared to negative symptoms alone. Overall, findings support the use of emotional intelligence as a longitudinal predictor of social and occupational outcomes above and beyond negative symptoms alone. This work highlights potential, specific intervention targets for individuals with psychotic disorders.

The relationship between cognitive and affective control and symptoms of depression and anxiety across the lifespan: A 3-wave longitudinal study

IntroductionThe association between cognitive functioning and mental health symptoms across the lifespan remains poorly understood. Understanding the directional associations between mental health and cognition is important as most gold-standard psychological therapies, such as cognitive-behaviour therapy, are cognitively demanding. Here, we examined the directionality of the association between cognitive and affective control with symptoms of depression and anxiety across the lifespan. Methods1002 participants (87.2 % female, age range: 11–89 years) completed self-report measures of depressive and anxiety symptoms and an affective backward digit span task thrice at 3-month intervals. Cross-lagged panel models (CLPMs) were used to model the longitudinal relationships between affective and cognitive control with depressive and anxiety symptoms. Multiple-group CLPMs were applied to test the model invariance between adolescents and adults. ResultsThe results supported a unidirectional relationship, where symptoms of depression and anxiety predicted impaired affective control across time points, over and above cognitive control. There was no evidence for affective or cognitive control capacity predicting emotional disorder symptomatology. In addition, multiple-group analysis revealed that depressive symptoms also predicted impaired cognitive control among adolescents only. There were no age-related differences in the associations between cognitive and affective control with anxiety symptoms. ConclusionsOur findings support depression and anxiety as antecedents, but not consequences, of impaired affective control, suggesting that timely management of emotional disorders, in particular for adolescents, is essential to prevent deterioration in cognitive functioning. The results further signal that practitioners should consider impaired affective control capacity in therapeutic contexts.

Long-term follow-up of corrective jaw surgery including distraction osteogenesis in 32 patients with juvenile idiopathic arthritis

Dentofacial deformity following juvenile idiopathic arthritis (JIA) with temporomandibular joint (TMJ) involvement is associated with functional, aesthetic, and psychosocial impairment. Corrective surgical treatment includes combinations of orthognathic surgeries (OS). The aims of this study were to assess orofacial symptoms, functional and aesthetic status, and stability after OS including mandibular distraction osteogenesis (MDO). A prospective study was conducted of 32 patients with JIA of the TMJ and dentofacial deformities who underwent MDO as the only surgery or in combination with bilateral sagittal split osteotomy, Le Fort I, and/or genioplastybetween 2003 and 2018. Data from clinical examinations and cephalograms performed pre- and postoperative and at long-term (mean 4 years) were analysed. Patients experienced unchanged orofacial symptoms (all P > 0.05), short-term TMJ functional impairment (all P < 0.001), and long-term morphological improvements in SNB angle (P < 0.001), anterior facial height (P < 0.001), mandibular length (P = 0.049), overjet (P < 0.001 and P = 0.005), and posterior facial symmetry (P = 0.046). MDO as the only surgery or with secondary adjunctive OS improved dentofacial morphology in terms of mandibular advancement, anterior facial height, posterior facial symmetry, and incisal relationships without long-term deterioration in TMJ function or orofacial symptoms.

Assessing Communication Impairments in a Rare Neurodevelopmental Disorder: The SCN2A Clinical Trials Readiness Study.

SCN2A-related disorders (SCN2A-RDs) entail severe impairments in multiple domains that could serve as nonseizure outcomes in clinical trials. This study evaluated the fitness for purpose of several clinical instruments with both standardized and alternative scoring and with some measures used out of their intended age range for assessing communication in SCN2A-affected participants. Parents of SCN2A-affected children were recruited through FamilieSCN2A Foundation outreach for a combined cross-sectional and longitudinal study. They completed assessments of their children at study entry and 6 and 12 months later. Assessments included the Vineland Adaptive Behavior Scale (VABS-3), Adaptive Behavior Assessment System (ABAS), Communication Matrix, and Communication and Symbolic Behavior Scale (CSBS). Analyses examined floor and ceiling effects, inter-rater and test-retest reliability, discrimination among different levels of functional impairment, and sensitivity to clinical aspects of SCN2A-RDs. Of 65 participants (28 females, median age 6.4 years, IQR 4.1-10.5), 56 (86%) had epilepsy. Eleven (17%) used speech as their primary communication mode; 84% were considered ineffective communicators. The mean Vineland composite standardized score (SS) was 34 (IQR 26-46). Cross-sectionally, standardized scores decreased with increasing age. There were substantial floor effects for receptive (75%) and expressive (83%) communication. SSs discriminated poorly between verbal vs nonverbal and communicative vs noncommunicative participants and were not sensitive to features reflecting epilepsy severity (e.g., epileptic spasms and number of current medications). By contrast, Vineland growth scale value (GSV) and ABAS, Matrix, and CSBS raw scores had minimal floor effects; most increased with age. These alternative scores distinguished clearly between participants with different levels of communication and were sensitive to aspects of epilepsy severity. Longitudinally, SSs decreased, but other scores remained relatively stable over a year. SCN2A-RD is characterized by severe-to-profound impairment with a SS <4 SDs of the norm-referenced mean. Owing to severe floor effects and their insensitivity to markers of communication function, age-standardized scores (e.g., Vineland SS) are not fit for purpose in clinical trials or other settings for evaluating nonseizure outcomes such as communication. GSVs and alternative scoring and assessments have much better measurement profiles in all these regards and should be considered in future precision medicine trials for SCN2A-RDs and other similar rare diseases.

Quality of life following complete clinical response to chemoradiotherapy for rectal cancer: Patient-reported outcomes.

120 Background: Complete clinical response (cCR) after neoadjuvant therapy (chemoradiotherapy/total neoadjuvant treatment) for rectal cancer may permit an organ-preserving approach with “watch and wait” (W&amp;W) surveillance. This confers comparable survival, while avoiding the sequelae of pelvic surgery. Data on quality of life (QOL) for this cohort are lacking. Methods: Patient-reported outcomes were collated for patients on W&amp;W following cCR in a single hospital network. Validated questionnaires evaluating surgical, radiation and chemotherapy-related QOL were completed, including Low Anterior Resection Syndrome (LARS) score, Functional Assessment of Chemotherapy: Colorectal (FACT-C), EORTC QLQ-CIPN20, EQ-5D-5L and a linear analogue and ordinal scale ranking self-perception of health. Results: From 2016-2023, 76 patients were enrolled on W&amp;W. Median follow-up is 37 months (IQR20-63). 12 patients (15.8%) had local regrowth, of whom 11 (92%) had salvage surgery. Five patients (6.5%) developed metastases at median 8 months (IQR3-12) from W&amp;W entry. Of 57 patients (75%) with sustained cCR on surveillance, 44 (77%) responded to structured questionnaires. Two with stomas were excluded from LARS. 74% of respondents had no LARS, 9% minor LARS and 17% major LARS. 43% reported faecal urgency and 33% faecal incontinence. 41% experienced functional impairment due to chronic chemotherapy-related side effects (Table). Median EORTC CIPN20 score was 23 (IQR20-28; possible range 19-76, high score = poor QOL). Median sensory score was 11 (IQR9-15.5, PR 9-36), median motor score 8 (IQR8-11, PR 8-32) and median autonomic score 4 (IQR3-6) for males (PR 3-12) and 2 (IQR2-2.5) for females (PR 2-8). 54% of men reported erectile dysfunction, of whom 62% experienced severe dysfunction (33% of all males). Median FACT-C score was 123.5 (IQR108-131; PR 0-136, high score = better QOL). Median overall health score was 80% (IQR70-95). 36% of patients reported difficulty with mobility, 27% with usual activities and 11% with self-care. 30% declared ongoing physical pain/discomfort, while 23% live with anxiety/depression related to their diagnosis. Overall, 86% of reported problems were mild/moderate and 14% severe/very severe. Conclusions: This study highlights self-reported QOL in patients on W&amp;W pathway following neoadjuvant treatment of rectal cancer. It provides important insight to side-effects of treatment escalation in hope of organ preservation, and presents vital information for the counselling of future patients. Patients (n=41) Upper limb paraesthesia 12 (29%) Lower limb paraesthesia 17 (41%) Difficulty with: - Walking/standing (foot drop or impaired sensation) 10 (24%) - Stairs/sit-to-stand (leg weakness) 11 (27%) - Hot/cold differentiation 4 (10%) - Holding pen/manipulating small objects/opening jar/bottle 12 (29%) Hearing impairment 13 (32%) Blurred vision 4 (10%)

From innovation to clinic: Emerging strategies harnessing electrically conductive polymers to enhance electrically stimulated peripheral nerve repair.

Peripheral nerve repair (PNR) is a major healthcare challenge due to the limited regenerative capacity of the nervous system, often leading to severe functional impairments. While nerve autografts are the gold standard, their implications are constrained by issues such as donor site morbidity and limited availability, necessitating innovative alternatives like nerve guidance conduits (NGCs). However, the inherently slow nerve growth rate (∼1mm/day) and prolonged neuroinflammation, delay recovery even with the use of passive (no-conductive) NGCs, resulting in muscle atrophy and loss of locomotor function. Electrical stimulation (ES) has the ability to enhance nerve regeneration rate by modulating the innate bioelectrical microenvironment of nerve tissue while simultaneously fostering a reparative environment through immunoregulation. In this context, electrically conductive polymer (ECP)-based biomaterials offer unique advantages for nerve repair combining their flexibility, akin to traditional plastics, and mixed ionic-electronic conductivity, similar to ionically conductive nerve tissue, as well as their biocompatibility and ease of fabrication. This review focuses on the progress, challenges, and emerging techniques for integrating ECP based NGCs with ES for functional nerve regeneration. It critically evaluates the various approaches using ECP based scaffolds, identifying gaps that have hindered clinical translation. Key challenges discussed include designing effective 3D NGCs with high electroactivity, optimizing ES modules, and better understanding of immunoregulation during nerve repair. The review also explores innovative strategies in material development and wireless, self-powered ES methods. Furthermore, it emphasizes the need for non-invasive ES delivery methods combined with hybrid ECP based neural scaffolds, highlighting future directions for advancing preclinical and clinical translation. Together, ECP based NGCs combined with ES represent a promising avenue for advancing PNR and improving patient outcomes.

Enhanced Advance care planning and life Review Longitudinal Intervention (EARLI): Protocol for a cluster randomized controlled cross-over trial of life story work and facilitated advance care planning among older Australian adults in community settings.

Advance care planning (ACP) is potentially helpful for older adults, however, the rate of uptake in community aged care settings is low. Previous pilot studies suggest that holistic, person-centered ACP approaches may be effective for older adults who experience functional impairment but do not necessarily have life-limiting conditions with clear prognoses. This paper describes the protocol of a randomized trial to test the effectiveness of combined life story work and facilitated ACP in promoting ACP engagement among older adults receiving community aged care services. The Enhanced Advance care planning and life Review Longitudinal Intervention (EARLI) trial is an open-label, cross-over, cluster randomized controlled trial with 12 participating aged care organizations in New South Wales and Western Australia. Participants are aged 65 years or older, receiving home care services and capable of providing informed consent at initial recruitment. Recruitment occurs across a two-year period, with study sites randomized to receive the four-session intervention in the first or second year (or a single session 'active control' condition). Primary outcomes are participant-reported ACP engagement and ACP documentation in the aged care client record 12 weeks post-recruitment. Secondary outcomes include measures of decisional conflict, anxiety and depression, meaning-based coping and relationship quality. Analysis will take an intention-to-treat approach. This trial tests a novel method of reaching older adults using a holistic, person-centered approach to promoting ACP engagement. Enhancing ACP engagement may reduce decisional conflict, minimize hospital admissions and improve outcomes for people and their families. ANZCTR Trial Registration ID: ACTRN12622001399785.

Nrf2 activator tertiary butylhydroquinone enhances neural stem cell differentiation and implantation in Alzheimer’s disease by boosting mitochondrial function

AimsTo investigate the effects of Nrf2 agonist tertiary butylhydroquinone (TBHQ)-stimulated neural stem cells (NSCs) transplantation (NSC(TBHQ)) on neuronal damage and cognitive deficits in an AD model and its underlying principles. MethodsBHQ-treated NSCs were examined with or without Aβ1-42 to investigate the effects of TBHQ on the proliferation and differentiation functions. The mitophagy inhibitor Cyclosporine A (CSA) was used to explore the regulation of mitophagy by TBHQ. The no-, ethanol-, and TBHQ-treated NSCs were transplanted into the bilateral hippocampal region of model mice to explore the effects of NSC(TBHQ) on neuronal, cognitive, and mitochondrial functional impairments in mice. ResultsTBHQ reversed the Aβ1-42-caused inhibition on NSC proliferation and differentiation, as well as on levels of mitochondrial membrane potential, adenosine triphosphate (ATP), and mitochondrial fusion-associated proteins. TBHQ alleviated the Aβ1-42-induced increase in apoptosis, mitochondrial damage, mitochondria-derived reactive oxygen species (mtROS), and mitochondrial fission-related proteins. TBHQ activated the Parkin, Beclin, LC3II/I, and COXIV expression, while inhibiting the p62 expression. CSA reversed the effects of TBHQ on NSC proliferation and differentiation. After NSC(TBHQ) transplantation, it not only further extended the dwell time in the target quadrant and shorten the time and distance for finding the hidden platform, but also further decreased the Aβ and p-Tau/Tau levels, while increasing the expression of NeuN. The effects of NSC(TBHQ) transplantation on mitochondrial function were consistent with the in vitro experiments. ConclusionsThe study shows that NSC(TBHQ) intensifies the beneficial impact of NSCs transplantation on cognitive impairment and neuronal damage in AD models, likely due to TBHQ’s role in promoting NSCs growth and differentiation via mitophagy, thus laying a theoretical foundation for improving NSCs transplantation for AD.

Effects of Probiotics and Magnesium Co-supplementation on Stress Levels and Quality of Life in Obese Patients with Depressed Mood: A Randomized, Double-blinded Placebo-controlled Clinical Trial

Background and Objectives: Obesity is strongly associated with mood disorders. There is evidence that obesity and mood disorders may be related pathologically. Depression and manic episodes are more common among overweight or obese individuals. Human subjects have reported the restorative effects of probiotic supplementation on neuroendocrine functions. Gut microbiota, neuroendocrine status, and obesity are related. Magnesium enriches the gut microbiota. Based on the association between gut microbiota, magnesium levels, obesity, and neuropsychiatric disorders, we examined the possibility of co-supplementation of probiotics and magnesium in humans. Methods: For 74 individuals, demographic data, quality of life scores (SF -12), depression, anxiety, and stress scores (DASS-21) were collected, along with body mass index (BMI), waist circumfer-ence, and serum cortisol levels. An SPSS analysis was performed. Results: Both the intervention and control groups experienced significant reductions in depression, anxiety, and stress. A significant improvement in mental health, role-emotional function, and vital-ity was observed in the probiotic and magnesium supplement group. Conclusion: Magnesium supplements and probiotics increased vitality (VT) and mental health (MH) and reduced functional impairment from emotional stress (RE). They experienced fewer functional limitations because of physical conditions.

A fluorescent protein C-terminal fusion knock-in is functional with TRPA1 but not TRPC5.

Transgenic mice with fluorescent protein (FP) reporters take full advantage of new in vivo imaging technologies. Therefore, we generated a TRPC5- and a TRPA1-reporter mouse based on FP C-terminal fusion, providing us with better alternatives for studying the physiology, interaction and coeffectors of these two TRP channels at the cellular and tissue level. We generated transgenic constructs of the murine TRPC5- and TRPA1-gene with a 3*GGGGS linker and C-terminal fusion to mCherry and mTagBFP, respectively. We microinjected zygotes to generate reporter mice. Reporter mice were examined for visible fluorescence in trigeminal ganglia with two-photon microscopy, immunohistochemistry and calcium imaging. Both TRPC5-mCherry and TRPA1-mTagBFP knock-in mouse models were successful at the DNA and RNA level. However, at the protein level, TRPC5 resulted in no mCherry fluorescence. In contrast, sensory neurons derived from the TRPA1-reporter mice exhibited visible mTag-BFP fluorescence, although TRPA1 had apparently lost its ion channel function. Creating transgenic mice with a TRP channel tagged at the C-terminus with a FP requires detailed investigation of the structural and functional consequences in a given cellular context and fine-tuning the design of specific constructs for a given TRP channel subtype. Different degrees of functional impairment of TRPA1 and TRPC5 constructs suggest a specific importance of the distal C-terminus for the regulation of these two channels in trigeminal neurons.

ECGEFNet: A two-branch deep learning model for calculating left ventricular ejection fraction using electrocardiogram.

Left ventricular systolic dysfunction (LVSD) and its severity are correlated with the prognosis of cardiovascular diseases. Early detection and monitoring of LVSD are of utmost importance. Left ventricular ejection fraction (LVEF) is an essential indicator for evaluating left ventricular function in clinical practice, the current echocardiography-based evaluation method is not avaliable in primary care and difficult to achieve real-time monitoring capabilities for cardiac dysfunction. We propose a two-branch deep learning model (ECGEFNet) for calculating LVEF using electrocardiogram (ECG), which holds the potential to serve as a primary medical screening tool and facilitate long-term dynamic monitoring of cardiac functional impairments. It integrates original numerical signal and waveform plots derived from the signals in an innovative manner, enabling joint calculation of LVEF by incorporating diverse information encompassing temporal, spatial and phase aspects. To address the inadequate information interaction between the two branches and the lack of efficiency in feature fusion, we propose the fusion attention mechanism (FAT) and the two-branch feature fusion module (BFF) to guide the learning, alignment and fusion of features from both branches. We assemble a large internal dataset and perform experimental validation on it. The accuracy of cardiac dysfunction screening is 92.3%, the mean absolute error (MAE) in LVEF calculation is 4.57%. The proposed model performs well and outperforms existing basic models, and is of great significance for real-time monitoring of the degree of cardiac dysfunction.

Geriatric Syndromes in Older Adults With and Without Diabetes: A Systematic Review and Meta-Analysis.

Diabetes prevalence is increasing among older adults globally. The current study aimed to compare geriatric syndrome prevalence in older adults with and without diabetes. Primary research (2011 to 2024) in English, French, or Spanish was included. We used multiple databases following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Pooled log odds ratios (ORs) and prevalence rates were calculated using random-effects models. Sensitivity analysis explored heterogeneity, and publication bias was assessed. Older adults with diabetes exhibited higher prevalence rates of cognitive impairment (9.13% vs. 4.22%, log OR: 0.1884), depression (8.96% vs. 5.44%, log OR: 0.3543), falls (11.5% vs. 4.47%, log OR: 0.4237), functional impairment (14.2% vs. 10.6%, log OR: 1.02), urinary incontinence (9.72% vs. 4.35%, log OR: 1.3668), frailty (22.8% vs. 12.1%, log OR: 1.3443), and polypharmacy (22.9% vs. 5.78%, log OR: 2.5420). Diabetes was also associated with a higher comorbidity burden. Multidisciplinary strategies addressing diabetes and associated conditions are crucial for older adults with diabetes. Future research should delve into underlying mechanisms and optimize care strategies. [Research in Gerontological Nursing, xx(x), xx-xx.].

Functional impairment in COPD can be predicted using genomic-derived data

ObjectiveReduced functional capacity and muscle weakness are two major contributors to functional impairment in chronic obstructive pulmonary disease (COPD). The underlying causes of functional impairment are poorly understood and, therefore,...