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The concept behind 4D morphing biopolymers represents a further improvement in reconstructive plastic surgery, as it can now create scaffolds that are stimulus-responsive, allowing them to exhibit flexibility in shape and functionality once implanted. Such materials have the potential to address the shortcomings of conventional autologous reconstruction through enhanced integration, vascularization, and minimally invasive implantation. Nevertheless, significant issues of translation, regulation, and ethics remain, underscoring the need for in vivo research, surgeon-engineer partnerships, and fair clinical practice.
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X-ray imaging has attracted significant attention for information encryption and anti-counterfeiting. However, ensuring information security under multi-level encryption scenarios remains challenges. Herein, we have developed a reversible X-ray memory imaging technique for CsCdCl3:Pb perovskite, which integrates blue emission, persistent luminescence, and photochromic behavior into four stimulus response modes, enabling the multi-level information encryption. Notably, CsCdCl3:Pb exhibits photochromic deepening, accompanied by a two-fold enhancement in radioluminescence (RL) intensity with increasing X-ray irradiation time. This enhancement originates from the formation of a new deep trap (0.79 eV) that facilitates energy transfer from the color centers to the Pb2+ emission centers. Importantly, X-ray memory imaging is attributed to the differences in RL enhancement between extending X-ray irradiation time and turning on the X-ray tube after removing capsule, which is demonstrated by cycling tests and stability characterizations under different dose rates. As a result, the RL enhancement and X-ray memory imaging share common advantages: reversibility, fast response (5 s), rapid erasure capability (450 nm, 10-20 s), fatigue resistance (more than 100 cycles), and long-term stability (more than half a year). This work presents an effective strategy for designing multi-mode stimulus response perovskite materials and opens a new avenue for advanced multi-level information security.
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BACKGROUND: Determining the cognitive processes involved in maintaining tobacco use is an important step toward explaining the nature of addiction. Studies have found that young smokers are more impulsive than nonsmokers. Working memory (WM) is needed to prevent and control impulsivity in unwanted situations. OBJECTIVES: This study examined the relationship between WM capacity and impulsivity and how WM load influences impulsive decision making with smokers, nonsmokers, and abstinent participants (ntotal = 36) with an experimental dual-task. Participants completed the N-back (WM) and delay discounting (DD-impulsivity) tasks simultaneously, whilst their eye movements were recorded. RESULTS: The results showed accuracy in the n-back task reduced as n increased, there was no evidence of delay discounting in any of the groups. There was no correlation of WMC and trait impulsivity. Participants' first fixation durations, indicating attention and information processing, increased with increasing WM load. All participants had shorter first fixation durations on proximal rewards than on distal rewards and revisited proximal rewards more. CONCLUSION: Participants may change their attentional strategies under WM load, and different attentional processes measured by eye movements may be an indicator of impulsivity.
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In this study, we investigated the impact of aspartame and sucrose on short-term cognitive performance. We employed a quasi-randomized-controlled, double-anonymous design, and had 130 participants undergo two study visits in a randomized order. The shorter visit included a dual-energy x-ray absorptiometry (DXA) scan, a fasting blood glucose (BG) test, and cognitive assessments from the NIH-toolbox. During the longer visit, participants underwent fasting BG testing before consuming a 500 ml beverage of either a 0.05% aspartame solution, an 11% sucrose solution, or water (with these beverage groups randomized). BG tests and cognitive assessments were completed twice more, at 20-min post-beverage consumption (20m PC) and at 60-min post-beverage consumption (60m PC). BG responses were as predicted, with participants in the water and AS groups responding similarly and remaining at fasting levels, and the sucrose group showing a spike in BG at 20m PC and returning to baseline by 60m PC (p < .0001). We found no group differences in cognitive performance at any time point (p = .6172). Cognitive test performance improved from the first test to subsequent tests regardless of beverage group (p < .0001). Although we found no group differences in short-term cognitive performance as a function of sweetener condition, more research is needed to determine the short and long-term cognitive effects of artificial sweeteners.
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The development of effective cancer vaccines remains challenged by tumor heterogeneity and insufficient T-cell activation. Whole-cell vaccines, which deliver a broad spectrum of tumor-associated antigens, represent a promising approach, especially when their immunogenicity is enhanced via strategies such as immunogenic cell death (ICD). Here, we developed a novel whole-cell vaccine, termed MDLSD, by combining mitoxantrone (MTX)-induced ICD with the TLR9 agonist SD-101. In murine Lewis lung carcinoma (LLC) models, MDLSD demonstrated superior prophylactic and therapeutic efficacy. Mechanistically, MTX-induced dying tumor cells (MDL) promoted dendritic cell (DC) phagocytosis, while the addition of SD-101 was essential for driving complete DC maturation through potent upregulation of CD80. Consequently, only the combined MDLSD vaccine robustly primed antigen-specific T cells in vivo, eliciting elevated IFN-γ secretion. Prophylactic vaccination with MDLSD conferred 100 % protection against initial tumor challenge and durable immunity upon rechallenge. In a therapeutic setting, MDLSD treatment achieved a 55 % complete regression rate, significantly suppressing established tumor growth and prolonging survival. This potent antitumor immunity was driven by MDLSD-enhanced Th1/Tc1 polarization, evidenced by increased T-bet, IFN-γ, and TNF-α, along with boosted cytolytic function via Granzyme B in both systemic and tumor-infiltrating T cells. Furthermore, mice cured by MDLSD developed long-term immunological memory, characterized by a recall response dominated by IFN-γ+ CD8+ and TNF-α+ T cells, enabling rejection of secondary tumor challenges. Collectively, our findings illustrate that the MDLSD vaccine synergizes the antigenic breadth of ICD with potent TLR9 stimulation to elicit robust DC activation, polyfunctional T-cell responses, and durable immunological memory, offering a compelling strategy for cancer immunotherapy.
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Disruption of the blood-brain barrier (BBB) increases vascular permeability and promotes neuroinflammation, contributing to Alzheimer's disease (AD) progression. However, the molecular drivers of BBB dysfunction and neuroinflammation in AD remain poorly defined. Here, we identify angiopoietin-2 (ANGPT2) as a central mediator of BBB breakdown and AD progression. Transcriptomic analyses of human AD brains revealed elevated ANGPT2 expression in endothelial cells correlating with disease severity. In 5xFAD mice, endothelial-specific Angpt2 deletion reduced ß-amyloid deposition, while Angpt2 overexpression via an adeno-associated viral vector exacerbated the plaque burden. Mechanistically, ANGPT2 suppression of TIE2 signaling increased vascular leakage and fibrin deposition, triggering microglial activation and neuroinflammatory responses that accelerated disease progression. Single-nucleus transcriptomic analyses further revealed Angpt2-driven microglial dysfunction and neuronal impairment consistent with memory deficits observed in behavioral assays. These findings establish ANGPT2 as a critical driver of BBB dysfunction and neuroinflammation in AD and highlight its therapeutic potential.
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Tumor growth and angiogenesis drive complex spatiotemporal variation in micro-environmental oxygen levels. Previous experimental studies have observed that cancer cells exposed to chronic hypoxia retained a phenotype characterized by enhanced migration and reduced proliferation, even after being shifted to normoxic conditions, a phenomenon which we refer to as hypoxic memory. However, because dynamic hypoxia and related hypoxic memory effects are challenging to measure experimentally, our understanding of their implications in tumor invasion is quite limited. Here, we propose a novel phenotype-structured partial differential equation modeling framework to elucidate the effects of hypoxic memory on tumor invasion along one spatial dimension in a cyclically varying hypoxic environment. We incorporated hypoxic memory by including time-dependent changes in hypoxic-to-normoxic phenotype transition rate upon continued exposure to hypoxic conditions. Our model simulations demonstrate that hypoxic memory significantly enhances tumor invasion without necessarily reducing tumor volume. This enhanced invasion was sensitive to the induction rate of hypoxic memory, but not the dilution rate. Further, shorter periods of cyclic hypoxia contributed to a more heterogeneous profile of hypoxic memory in the population, with the tumor front dominated by hypoxic cells that exhibited stronger memory. Overall, our model highlighted the complex interplay between hypoxic memory and cyclic hypoxia in shaping heterogeneous tumor invasion patterns.
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Modelos Biológicos , Neoplasias , Invasividad Neoplásica/patología , Humanos , Conceptos Matemáticos , Fenotipo , Neoplasias/patología , Neoplasias/irrigación sanguínea , Neoplasias/metabolismo , Simulación por Computador , Microambiente Tumoral/fisiología , Movimiento Celular , Hipoxia de la Célula/fisiología , Proliferación Celular , Animales , Hipoxia Tumoral/fisiología , Neovascularización Patológica/patologíaRESUMEN
PURPOSE: Understanding how to optimally measure symptoms and wellbeing of people with advanced cancer is crucial for supporting patient-centered care. We aimed to (1) compare repeated in-the-moment assessments (experience sampling methods/ESM) and retrospective assessments (traditional patient-reported outcome measures/PROMS) of symptoms and well-being among people with advanced breast or lung cancer; and (2) explore factors associated with discrepancies between these methods. METHODS: In an observational study among people with advanced breast or lung cancer, participants completed up to 60 in-the-moment ESM assessments over 7 days, followed by a 7-day recall (i.e., retrospective) questionnaire covering the same period. We compared in-the-moment and retrospective scores of 16 symptom and wellbeing items visually and through correlations. We examined factors associated with discrepancies using linear regression. RESULTS: We analyzed 1676 in-the-moment assessments from 36 participants. Visually, higher in-the-moment scores were associated with higher retrospective scores across the sample. But, participants with identical retrospective scores often had different means (especially when they had higher recalled scores) and fluctuation patterns of in-the-moment scores. Item correlations between in-the-moment and retrospective scores ranged between .24 and .70. The largest discrepancies occurred for pain (Mdiff = -13.2) and tiredness (Mdiff = -12.4). Several parameters of in-the-moment scores and participants' active treatment status were associated with discrepancies. CONCLUSION: Individuals' retrospective symptom and wellbeing scores positively correlated with their in-the-moment scores over 1 week. Pain and tiredness showed the largest discrepancies. In-the-moment scores revealed considerable variability between individuals and fluctuations over time, which may be relevant to assess depending on the clinical or research objective.
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Neoplasias de la Mama , Neoplasias Pulmonares , Medición de Resultados Informados por el Paciente , Humanos , Femenino , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Neoplasias de la Mama/patología , Neoplasias de la Mama/psicología , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/psicología , Encuestas y Cuestionarios , Adulto , Anciano de 80 o más Años , Calidad de VidaRESUMEN
Biocompatible poly(lactic acid) (PLA) was plasticized with poly(ethylene glycol) (PEG) added at concentrations of 10, 15, and 20 wt.% relative to PLA, and then processed into gyroid triply periodic minimal surface (TPMS) scaffolds using fused filament fabrication (FFF) 3D printing. The influence of PEG concentration and gyroid structure (50% infill density) on thermal transitions, crystallinity, and low-temperature shape-memory performance was systematically investigated. The shape-memory effect (SME) of the PLA-based scaffolds was tailored through compositional control and structural design. Shape recovery under thermal activation at 40 °C and 50 °C was examined to reveal the correlation between composition and structure in governing low-temperature shape-memory behavior. The optimal composition (PLA/10 PEG, 50% gyroid infill) achieved shape recovery with a recovery ratio (Rr) of 97 ± 1% at 40 °C within 6 ± 1 min, demonstrating optimal shape-memory activation close to physiological temperature. Structural and morphological changes were characterized using ATR-FTIR, Raman spectroscopy, DSC, XRD, and SEM, providing comprehensive insight into the plasticization of the PLA matrix and its impact on structure-property relationships relevant to bone tissue engineering.
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Tissue-resident memory CD4+ T cells (CD4+ TRMs) are pivotal in immune responses during inflammation and infection, yet their phenotype and function within the tumor microenvironment (TME) remain elusive. Here, we delineated CD4+ TRMs in non-small cell lung cancer (NSCLC) using CD103 and CD69 as defining markers and demonstrated that their transcriptional and phenotypic profiles closely resembled those observed in murine models. Tumor-infiltrating CD4+ TRMs exert helper antitumor effects by secreting the chemokine XCL1 to recruit conventional type 1 dendritic cells (cDC1s), facilitating antigen presentation and priming cytotoxic T lymphocyte responses. Mechanistically, we identified the costimulatory molecule JAML as essential for CD4+ TRM-mediated cDC1 mobilization. Compared with their counterparts in normal lung tissue, tumor-infiltrating CD4+ TRMs exhibited elevated expression of immune checkpoint molecules, indicating a dysfunctional state, accompanied by significantly reduced XCL1 expression. PD-1 signaling within the NSCLC TME suppressed JAML expression-an effect reversible by PD-1 blockade-while the administration of a JAML agonist further enhanced the antitumor efficacy of PD-1 inhibitors in tumor-bearing mice. Clinically, the presence of XCL1-secreting CD4+ TRMs positively correlated with favorable clinical outcomes and enhanced responses to anti-PD-1 immunotherapy in NSCLC patients. Our findings reveal a critical role for JAML in facilitating CD4+ TRM-mediated cDC1 mobilization within the NSCLC TME and highlight the translational potential of targeting CD4+ TRMs to enhance the efficacy of immune checkpoint blockade therapies.
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Tissue-resident memory T cells (TRM), which function against tumors, infections, and non-self antigens in organ transplantation, exhibit both effector and memory functionality. However, the homeostasis and differentiation of TRM is not clear. Using a murine kidney transplant model for long-term observation, our single-cell and spatial transcriptomics showed that CD49a+PD1hi CD8+ TRM exhibited an effector phenotype with enhanced cytotoxicity at a later stage. This subset might mature from a CXCR6hi precursor-like state with proliferation capacity in tertiary lymphoid structures (TLSs) in allografts. Mechanically, BHLHE40 is required for CD49a+PD1hi CD8+ TRM differentiation and effector function, thereby driving rejection in allo-transplantation. In TLSs, TGF-ß orchestrated BHLHE40 expression in TRM and effector TRM differentiation. Our findings identified an effector subset of TRM as CD49a+PD1hi CD8+ TRM, and highlighted a BHLHE40-orchestrated, resident immune component, rather than circulating cells, as a major contributor to allograft rejection.
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Promoter-proximal pausing of RNA polymerase II (Pol II) primes genes for rapid activation, yet how Pol II dynamics are temporally organized in adult stem cells to enable fast and flexible responses to environmental cues remain unknown. To address this, we developed sciCUT&Tag2in1 for joint profiling of Pol II and histone modifications in single cells. By profiling over 200,000 CD34+ hematopoietic stem cells (HSCs) and progenitors, we identify a Pol II regulatory cascade that directs the response to granulocyte colony-stimulating factor (G-CSF)-induced inflammatory stress. HSCs are activated by elevated Pol II occupancy and reduced Polycomb repression of immune response genes. Lineage commitment proceeds through sequential modes of Pol II activation, beginning with rapid pause-and-release genes, followed by slower initiate-and-release of Polycomb-repressed targets. sciCUT&Tag2in1 defines the temporal logic of how adult stem cells use paused Pol II to enable flexible lineage decisions, providing a powerful tool for studying the intersection of development, inflammation, and disease.
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PURPOSE: To evaluate the safety, feasibility, and clinical efficacy of stereotactic body radiation therapy (SBRT) combined with pembrolizumab in patients with recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) who progressed on prior PD-1 inhibitor therapy. METHODS AND MATERIALS: This prospective, non-randomized phase II trial enrolled patients with PD-1 inhibitor-refractory R/M HNSCC. In Cohort A, a single lesion was treated with SBRT while other sites were left unirradiated. In Cohort B, all known oligometastatic lesions were treated with SBRT. Pembrolizumab was administered every 3 weeks in both cohorts. The primary endpoint was 3-month progression-free survival (PFS). Correlative immune analyses were performed on peripheral blood mononuclear cells using mass cytometry and TCRß sequencing. RESULTS: Eighteen patients were treated (6 in Cohort A, 12 in Cohort B). Median PFS was 1.8 months in Cohort A and 5.7 months in Cohort B. The 3-month PFS rate was 17% (1/6) in Cohort A and 67% (8/12) in Cohort B, with an overall response rate of 25% (3/12) in Cohort B and no objective responses in Cohort A. Median OS was 7.6 months (95% CI: [0.7-32.9])in Cohort A and 10.1 months (95% CI: [5.8-49.7]) in Cohort B. In Cohort B there were 2 (2/12, 17%) Grade 4 toxicities observed in the setting of re-irradiation. Correlative studies showed that patients with PFS >3 months had higher baseline frequencies of CD8+ central memory T cells and elevated CXCR5 expression on memory B cells. CONCLUSIONS: In anti PD-1-refractory R/M HNSCC, SBRT with pembrolizumab was safe and feasible, suggesting activity when all progressing lesions were treated. Immune profiling describes pre-existing memory T and B cell phenotypes that appear to correlate with treatment benefit. These findings support further study and clinical use of comprehensive SBRT plus PD-1 blockade in this hard-to-treat population.
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Costimulatory blockade has emerged as a promising alternative to conventional immunosuppression with the potential to reduce chronic allograft injury and minimize drug-related toxicities including nephrotoxicity, cardiometabolic complications, and malignancies. Belatacept, the most extensively studied agent, has been associated with improved allograft function and reduced donor-specific antibody formation while associated with increased risk of acute, early graft rejection and increased risk for infections due to cytomegalovirus (CMV), Epstein-Barr virus (EBV), and Pneumocystis jirovecii. These effects may reflect the impact of costimulatory blockade on naïve T-cell activation while relatively sparing memory responses. Susceptibility to infections is, therefore, influenced by prior infectious exposures and the maintenance of immune memory in the face of diverse adjunctive immunosuppressive programs. Next-generation approaches, including Fc-silent anti-CD154 antibodies and CD28-directed therapies, are in early clinical trials with infectious complications incompletely defined. Recently, immunosuppression for clinical xenotransplantation has included costimulatory blockade as a component of generally complex immunosuppressive regimens; intensive microbiological surveillance will provide insights into any associated xenozoonotic infections. Successful integration of costimulatory blockade in allotransplantation and clinical xenotransplantation require further prospective trials coupled with robust microbiological surveillance.
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Although transient receptor potential melastatin 3 (TRPM3) channels are primarily known for their role in spinal nociception, emerging evidence suggests their involvement in psychiatric conditions and central reward processing. Menopause, characterized by estrogen decline, induces neuroimmune activation and increases pro-inflammatory factors such as ciliary neurotrophic factor (CNTF). While a direct regulatory effect of CNTF on TRPM3 is not well established, both are involved in inflammation-related signaling, suggesting potential crosstalk. TRPM3 responds to neuroinflammatory and neurotrophic signals and may contribute to postmenopausal cognitive decline. However, this link remains unexplored. Naringenin, a natural flavonoid with estrogen-like properties, has been reported to inhibit TRPM3 channels and may help to alleviate postmenopausal memory impairment. This study aimed to investigate the role of elevated CNTF levels in increasing TRPM3 expression in the dentate gyrus (DG), contributing to cognitive deficits, and to assess the potential of naringenin in reversing these effects. Bilateral ovariectomy (OVX) was performed on female Sprague-Dawley rats, followed by treatment with naringenin (2.5, 5 and 10 mg/kg, intraperitoneal) for 14 days. Cognitive functions were assessed using the novel object recognition and passive avoidance tests. CNTF levels in the plasma and the DG, along with TRPM3 expression in the DG, were measured using ELISA and immunohistochemistry, respectively. Dendritic arborization in DG neurons was analyzed using Golgi-Cox staining. OVX rats showed impaired cognition, elevated CNTF and TRPM3 expression, and reduced dendritic complexity. Naringenin treatment reversed these changes, suggesting its potential to improve postmenopausal cognitive decline by modulating CNTF levels and TRPM3 activity in the DG.
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Factor Neurotrófico Ciliar , Cognición , Giro Dentado , Flavanonas , Menopausia , Canales Catiónicos TRPM , Animales , Flavanonas/farmacología , Femenino , Ratas , Canales Catiónicos TRPM/biosíntesis , Canales Catiónicos TRPM/metabolismo , Ratas Sprague-Dawley , Cognición/efectos de los fármacos , Cognición/fisiología , Ovariectomía , Giro Dentado/efectos de los fármacos , Giro Dentado/metabolismo , Factor Neurotrófico Ciliar/metabolismo , Factor Neurotrófico Ciliar/farmacología , Menopausia/efectos de los fármacos , Menopausia/metabolismo , Menopausia/psicología , Modelos Animales de EnfermedadRESUMEN
INTRODUCTION: Dementia risk reduction through lifestyle modification has much potential but is not yet implemented in routine clinical care. Currently, there are no preventive interventions available for memory clinic patients. Therefore, the aim of The Lifestyle Intervention in the memory clinics of General and academic Hospitals Trial (LIGHT) is to examine the (cost)effectiveness of a multidomain intervention combining lifestyle coaching with risk self-management for patients with subjective cognitive decline (SCD) and mild cognitive impairment (MCI). METHODS: LIGHT is a 1-year multi-center randomized controlled trial for dementia risk reduction by improving brain health through lifestyle modifications in memory clinic patients without dementia. Starting early 2025, the trial aims to include 300 older adults (≥ 50 years) with SCD or MCI, with presence of ≥ 2 modifiable dementia risk factors, recruited via the memory clinics of Dutch hospitals. Participants are randomized 1:1 to either the intervention group or control group. The intervention consists of three components: (1) three individual sessions with a certified lifestyle coach to set and work on personal goals, (2) vouchers for access to brain-healthy services from local providers, and (3) access to an online self-management platform (www.breinzorg.nl) providing psychoeducation on dementia risk reduction through lifestyle. The control group receives general health advice. The primary outcome is 1-year change in modifiable dementia risk captured by the LIfestyle for BRAin Health 2 (LIBRA2) index consisting of coronary heart disease, diabetes, hypercholesterolemia, hypertension, depression, obesity, smoking, high physical activity, and chronic kidney disease, high alcohol intake, high cognitive activity, healthy diet, hearing impairment, sleep disturbances, and social participation. Secondary outcomes include cognitive functioning, health-related quality of life, activities of daily living, self-efficacy, care use, as well as change in individual risk factors. CONCLUSION: LIGHT will provide insight into the implementation and (cost-)effectiveness of a lifestyle intervention for indicated prevention in a memory clinic setting. TRIAL REGISTRATION: Clinicaltrials.gov: NCT06832761 (date 2025-02-18), OMON: 57,198.
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BACKGROUND: Myasthenia Gravis, traditionally known as a purely motor disease, has been recently associated also with non-motor symptoms, including psychological and cognitive symptoms. However, the presence of cognitive impairment in Myasthenia Gravis remains unclear due to limited and heterogeneous findings. This systematic review and meta-analysis aims to clarify the relationship between Myasthenia Gravis and cognitive performances. METHODS: Following PRISMA guidelines, we systematically searched PubMed, Web of Science, and SCOPUS for original researches published between January 2000 and December 2024 assessing cognitive functioning in people with MG compared to healthy controls. Pooled standardized mean differences and 95% confidence intervals were calculated for each cognitive domain using random-effects meta-analysis. RESULTS: Six studies comprising 242 Myasthenia Gravis patients and 166 healthy controls met inclusion criteria. Compared to healthy controls, people with Myasthenia Gravis showed significantly lower performance in processing speed (Symbol Digit Modalities Test), phonemic and animal verbal fluency, visuo-spatial memory (visual reproduction), and verbal learning (California Verbal Learning Test). Heterogeneity was low to moderate across most outcomes. CONCLUSIONS: This meta-analysis supports the presence of selective cognitive impairments in individuals with Myasthenia Gravis. These findings underscore the need for a multidimensional approach to care in Myasthenia Gravis, that includes cognitive and psychological health.
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Cognición , Disfunción Cognitiva , Miastenia Gravis , Humanos , Miastenia Gravis/complicaciones , Miastenia Gravis/psicología , Disfunción Cognitiva/etiología , Disfunción Cognitiva/fisiopatología , Cognición/fisiologíaRESUMEN
BACKGROUND: Bipolar disorder (BD) is a chronic mental illness characterized by high relapse rates and mood instability, which significantly impair neuropsychological functioning, sleep patterns, relationships, and occupational performance. This study explores the effects of accelerated aging on diverse domains of neuropsychological functions in adulthood BD patients. METHODS: A total of 264 BD patients (ages 18-65) were recruited from both inpatient and outpatient settings, all in remission (Hamilton Depression Rating Scale [HDRS] ≤ 12; Young Mania Rating Scale [YMRS] ≤ 10). Additionally, 218 healthy controls (HCs) were included. All participants underwent a series of neuropsychological assessments, including the Wisconsin Card Sorting Test (WCST), Trail Making Test (TMT), Continuous Performance Test (CPT), and working memory tasks. RESULTS: The results showed that BD patients exhibited overall deficits in neuropsychological performance compared to HC (ps < 0.0001), as expectedly. When divided into age groups (young and middle-to-old adulthood), young adulthood BD patients showed accelerated aging in cognitive domains, including psychomotor speed, impulsivity, and executive function, compared to the HC. The findings suggest an accelerated aging effect in BD patients, particularly in psychomotor, impulsivity, and cognitive flexibility. CONCLUSIONS: These results highlight the importance of understanding the relationship between aging and neuropsychological decline in BD to improve treatment strategies and enhance patients' quality of life. The implications suggest that targeted interventions may consider age-related cognitive changes to optimize long-term outcomes for individuals with BD.
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Trastorno Bipolar , Disfunción Cognitiva , Humanos , Trastorno Bipolar/psicología , Trastorno Bipolar/complicaciones , Trastorno Bipolar/diagnóstico , Adulto , Masculino , Femenino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Adulto Joven , Adolescente , Función Ejecutiva/fisiología , Anciano , Memoria a Corto Plazo , Desempeño PsicomotorRESUMEN
BackgroundSubjective memory complaints (SMC) are common in older adults and may indicate an increased risk of cognitive decline. Polypharmacy and anticholinergic burden have been associated with cognitive impairment, but their specific contribution to SMC remains unclear. The aim of this study was to investigate the association between polypharmacy, anticholinergic burden and SMC in community-dwelling older adults.MethodsThis cross-sectional study included 652 participants aged 65 years and older from geriatric outpatient clinics. SMC was assessed via a structured clinician-administered question, and cognitive function was evaluated using the Mini-Mental State Examination (MMSE). Polypharmacy was defined as the concomitant use of five or more medications, while anticholinergic burden was determined using the Anticholinergic Burden Classification (ABC). Logistic regression models were used to examine the independent effects of polypharmacy and anticholinergic burden on SMC, adjusting for demographic variables, comorbidities and depressive symptoms.ResultsSMC was reported by 48% of participants. Polypharmacy (OR = 2.10, 95% CI: 1.43-3.08, P < 0.001) and higher anticholinergic burden (OR = 2.39, 95% CI: 1.72-3.32, P < 0.001) were independently associated with increased SMC. Chronic obstructive pulmonary disease (COPD) was also identified as a significant predictor (OR = 2.90, 95% CI: 1.41-5.98, P = 0.004).ConclusionPolypharmacy and anticholinergic burden are significant risk factors for SMC in older adults. Reducing unnecessary medication use and minimizing anticholinergic burden may help to alleviate cognitive complaints. Future longitudinal studies are needed to determine causal relationships and possible interventions.
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Antagonistas Colinérgicos , Disfunción Cognitiva , Trastornos de la Memoria , Polifarmacia , Humanos , Anciano , Masculino , Femenino , Antagonistas Colinérgicos/efectos adversos , Estudios Transversales , Anciano de 80 o más Años , Trastornos de la Memoria/inducido químicamente , Trastornos de la Memoria/epidemiología , Disfunción Cognitiva/inducido químicamente , Disfunción Cognitiva/epidemiologíaRESUMEN
Respiratory pathogens pose a significant risk to public health and are responsible for burdening health care by causing worldwide morbidity and mortality. The immune environment in the airway is critical for protection from respiratory pathogens and comprises several specialist subsets of resident lymphocytes and myeloid cells. Tissue resident-memory B cells (BRM) are a subset of memory B cell which reside in mucosal tissues, including the airways. Although, BRM have only recently been characterised, they have a crucial role in generating robust and localised immune responses to respiratory infections, particularly secondary responses, by rapidly differentiating into antibody-secreting cells. A greater understanding of their role in protecting the airways from respiratory pathogens will enable the development of immunisation strategies against respiratory disease. This mini-review aims to summarise the current knowledge of BRM and highlight areas for future research.