Search Results (48,685)

Background/Objectives: Mentoring is defined as a supportive relationship between an experienced professional (mentor) and a less experienced individual (mentee), influencing skill development, professional confidence, and psychological well-being. This systematic review addresses the question: “Can support from a senior colleague positively impact junior healthcare workers?” Methods: Following PRISMA 2020 guidelines, a systematic literature search was performed (January 2004–December 2024) in Web of Science, PubMed, and Scopus databases, yielding 399 studies. Results: After rigorous screening and quality assessment using the QuADS checklist, 74 studies were included in the final analysis. The reviewed articles span various healthcare fields, including nursing, medicine, and midwifery, utilizing qualitative, quantitative, observational, and mixed-methods approaches. Key findings highlight the mentor’s role in academic and emotional support; fostering clinical and transversal skills such as communication, collaboration, and problem-solving; and enhancing self-efficacy, resilience, and autonomy, particularly during transitional or emotionally demanding periods. Challenges identified include the need for inclusive environments and standardized mentoring models. Conclusions: Overall, mentoring supports the professional and personal growth of junior healthcare professionals and contributes positively to training quality and clinical work. However, issues regarding equitable access, program standardization, and the need for further research to establish consolidated guidelines remain. Full article

Background: Plasma fibrinogen (FIB) levels exhibit a significant elevation during the acute phase of ischemic stroke (IS), and their dynamic fluctuations serve as important biomarkers for stroke onset, disease progression, and long-term prognosis. Tong-Qiao-Huo-Xue Decoction (TQHXD) is highly effective in treating blood stasis syndromes affecting the head and face. Nevertheless, the association between TQHXD and FIB in the underlying mechanism of treating IS warrants further investigation. Methods: Proteomics analysis predicted the potential therapeutic targets of TQHXD for IS. An in vivo model of middle cerebral artery occlusion followed by reperfusion (MCAO/R) was created in mice. To explore the interaction between FIB and NLRP3, as well as to verify the particular healing outcomes of TQHXD. Results: An increased blood–brain barrier (BBB) permeability was observed after MCAO/R, accompanied by substantial accumulation of FIB in the brain. In vivo experiments demonstrated that FIB triggered the activation of the NLRP3 inflammasome in microglia. Proteomic analysis revealed a significant increase in FIB levels following model induction, which were markedly reduced after treatment with TQHXD; KEGG pathway enrichment analysis indicated that these changes were primarily associated with the NOD-like receptor signaling pathway. Laser speckle contrast imaging showed that TQHXD treatment significantly improved cerebral blood flow and attenuated brain injury in mice. Fluorescence imaging, ELISA, and Western blotting results collectively demonstrated that TQHXD effectively reduced FIB accumulation and suppressed NLRP3 inflammasome activation. MD and pull-down experiments further demonstrated a strong interaction strength between FIB and NLRP3. Conclusions: FIB accumulates in the ischemic penumbra following CIRI, while TQHXD can effectively down-regulate FIB expression and inhibit NLRP3 inflammasome activation to mitigate CIRI. These findings provide a novel theoretical foundation and treatment direction for stroke management in clinical settings. Full article

Aging is the strongest independent risk factor for cerebrovascular diseases, profoundly influencing vascular structure, immune responses, and regenerative capacity of the brain. Traditional therapeutic strategies, largely developed in younger populations, often show reduced efficacy and increased risk in elderly patients, underscoring the need for age-adapted interventions. Advances in the understanding of cerebrovascular aging have revealed key mechanisms such as vascular senescence, chronic low-grade inflammation, blood–brain barrier dysfunction, mitochondrial impairment, and circadian dysregulation as central drivers of disease progression and poor recovery. This narrative review summarizes emerging therapeutic strategies targeting the molecular and cellular hallmarks of aging-related cerebrovascular disease. These include immunomodulatory and anti-inflammatory approaches, senescence-targeted therapies, stem cell and extracellular vesicle-based regenerative strategies, RNA-based interventions, and metabolic and mitochondrial modulation. Particular emphasis is placed on therapies aimed at restoring neurovascular unit integrity and promoting brain repair in the aged microenvironment. Additionally, this review highlights the growing role of chronobiology and precision medicine, integrating biomarkers and multi-omics approaches to tailor treatments for elderly patients. Collectively, these emerging therapies represent a paradigm shift from symptom-oriented management toward mechanism-based and personalized interventions. Addressing age-specific pathophysiology will be critical for improving outcomes in cerebrovascular diseases in the aging population and for translating experimental advances into effective clinical therapies. Full article

Background/Objective: Long COVID is an important cause of disability following SARS-CoV-2 infection; yet, its underlying mechanisms are not completely understood. One proposed mechanism is the long-lasting dysregulation of the immune complement system. This systematic review is the first to summarize the current evidence and evaluate the potential role of long-lasting complement activation in people with long COVID. Methods: A systematic electronic search on PubMed, MEDLINE, CINAHL, and Embase was conducted up to 15 October 2025, to identify studies investigating complement activation in people with the post-COVID-19 condition. The Newcastle–Ottawa Scale was used to evaluate the risk of bias and methodological quality. Results: Among the 247 studies initially identified, eleven met the inclusion criteria, comprising 1435 individuals (age: 48.5 years, 70% females) with long COVID and 1124 controls (age: 43.6 years, 60% females). All studies were of a high quality, with scores ranging from 7 to 8 stars (mean: 7.6 ± 0.5). The activation of the classical complement pathway was investigated in nine studies, whereas the lectin, alternative, and terminal complement pathways were each assessed in three studies. Multiple studies investigated several complement pathways. The results were heterogeneous since several markers of complement activation spanning the classical (C2, C4a, C4b, and C1s-C1INH), alternative (Ba, iC3b, and Factor D), and terminal (C5bC6, C5a, C9, and TCC) pathways were elevated, whereas other markers were not significantly different (C3, C4, and C4d) between patients with/without long COVID. In addition, markers spanning the lectin complement pathway (MBL, and MASP1-C1INH) were not significantly different between individuals with and without long COVID. Conclusions: The current evidence suggests potential long-lasting complement system dysregulation in individuals with long COVID, although the clinical significance remains controversial, due to heterogenous findings. Specific post-COVID symptom clusters, such as fatigue, dyspnea, or brain fog, have been linked to a distinct pattern of complement dysregulation. Substantial methodological heterogeneity, including differences in follow-up periods, complement markers, assessment methods, and control groups, along with the small number of available studies, underscores the need for further research to clarify the mechanisms linking complement dysregulation to long COVID. Full article

Burnout syndrome is increasingly recognized as a significant occupational health issue, characterized by emotional exhaustion, depersonalization, and a reduced sense of personal accomplishment. It predominantly arises from chronic work-related stress, but recent research has highlighted the role of genetic and epigenetic factors in determining individual vulnerability to burnout. This review aims to synthesize findings regarding the genetic footprints of burnout, focusing on genes related to stress regulation, including the 5-HTT (serotonin transporter) gene, BDNF (brain-derived neurotrophic factor) gene, and NR3C1 (glucocorticoid receptor) gene. Twin studies reveal that burnout is moderately heritable, with genetic factors accounting for 33–36% of the variability in burnout-related traits, such as emotional exhaustion and performance-based self-esteem. However, burnout risk seems highly driven by non-shared environmental factors, such as work stress, lack of social support, and personal coping mechanisms. Specific genetic polymorphisms in the serotonergic system (5-HTT) and HPA axis genes (NR3C1, FKBP5) have been linked to increased burnout susceptibility, particularly in individuals exposed to chronic job strain or early-life stressful situations. Variations in 5-HTT rs6354 and HTR2A rs6313 are associated with altered stress reactivity, while polymorphisms in NR3C1 and FKBP5 contribute to dysregulation of the HPA axis, which influences cortisol secretion patterns in response to stress. Increased methylation in genes like BDNF and SLC6A4 has been observed in individuals with burnout, suggesting that environmental stressors may lead to lasting changes in gene expression, contributing to the syndrome’s development. Studies on telomere length have shown that burnout is associated with accelerated cellular aging, with individuals exhibiting shorter telomeres, particularly during high-stress periods. These findings hold particular relevance for professionals within the forensic and justice systems, including law enforcement, the judiciary, and forensic experts, who operate under chronic, high-stakes stress. We examine how understanding the biological basis of burnout can inform more objective ‘fitness-for-duty’ evaluations and provide a scientific framework for distinguishing physiological exhaustion from professional negligence in legal contexts. Full article

Background: The relationship between inflammatory markers and cerebral small vessel disease (CSVD) in patients with acute ischaemic stroke (AIS) remains unclear. This study aimed to investigate the association between simplified inflammatory biomarkers and neuroimaging markers of CSVD. Methods: This retrospective cohort study included patients with AIS who had symptom onset within 72 h and underwent MRI brain between January 2019 and December 2023. The associations between tertiles (T) of the neutrophil-to-lymphocyte ratio (NLR) and CSVD markers were studied using multinomial logistic regression. Functional outcomes at discharge and 90 days, as measured by the modified Rankin Scale (mRS), were also evaluated. Results: A total of 299 eligible patients were included, with a mean age of 65.7 ± 13.8 years and 55.5% (166/299) were male, and categorised into three tertiles of NLR (T1: 101, T2: 101, T3: 97). Patients with a higher NLR tertile had more admission NIHSS (T3 vs. T1: 3 (2, 5) vs. 2 (1, 3), p = 0.005). NLR was associated with an increased risk of ≥5 lobar cerebral microbleeds (CMBs) in an unadjusted model (T3 vs. T1: relative risk ratio (RRR), 5.69 (95% confidence interval (CI) 1.21–26.68); p = 0.03); however, this was not significant when adjusted for potential confounders (RRR 3.86; 95% CI 0.79–18.89; p = 0.10). No significant associations were observed in the remaining neuroimaging markers of CSVD. Patients in the T2 of NLR had a higher likelihood of achieving an mRS of 0–1 at 90 days (RRR 2.16; 95% CI 1.05–4.44; p = 0.04) compared to those in T1. Conclusions: In AIS, admission NLR showed a possible association with higher lobar CMB burden in unadjusted analyses, but this was not robust after adjustment, and no consistent relationships were observed with other CSVD markers. Associations with functional outcomes were not uniform across tertiles, and the apparent benefit in the middle NLR tertile should be interpreted cautiously as a potentially non-linear or chance finding, indicating that NLR is not a reliable independent imaging or prognostic marker in this cohort. Full article

Pain empathy plays an important role in both social bonding and defensive mechanisms, yet previous studies have mostly used non-predictive paradigms and rarely examined the effects of expectation. Using event-related potentials (ERPs), this study explored how pain expectation temporally modulates empathic responses and proposed an avoidance–approach dual-drive model. Behaviorally, participants responded faster and more accurately under pain-expectation conditions. At the neural level, greater N2 amplitudes were elicited by pain expectation, reflecting avoidance reactions driven by self-protection. In the P3 stage, two concurrent effects emerged: (1) overall P3 amplitudes decreased under pain expectation, suggesting reduced cognitive resource allocation due to avoidance; and (2) painful stimuli still evoked larger P3 amplitudes than neutral stimuli, indicating empathic engagement associated with approach motivation. These results suggest that pain empathy is not governed by a single mechanism but by a dynamic interplay between avoidance and approach motivations at different temporal stages, providing a neurophysiological framework that integrates defensive and affiliative needs in pain empathy. Full article

The scientific activity and outputs of the neurosciences are fascinating and, for the most part, uncontroversial. However, there have been sustained claims that neuroscientific findings represent a powerful challenge to historic, orthodox Christian teaching concerning human ontology. While philosophers had long debated the “mind/brain” problem, the rise of “eliminative materialism” (in the specific form of “neurophilosophy”) in the last quarter of the 20th century evoked various responses to the proposition that a mature neuroscience would forever banish familiar “folk science” entities like beliefs and desires as well as immaterial souls or minds. These would all be shown to play no role in a thoroughly materialistic, mature, neuroscientific understanding of ourselves. One aspect of the response to such claims within Christian scholarship was a turn to non-reductive physicalism and theological monism prompting a reassessment of biblical teaching concerning human ontology, seeking a position that would be consistent both with neuroscience (or its alleged implications) and Christian teaching. The aim of this paper is to review neuroscientific, philosophical and theological developments in order to establish where theological anthropology currently stands. In part this requires an assessment of contemporary neuroscience (including the subfield of “consciousness studies”) because while the science continues to generate intriguing hypotheses and data, it has fallen some way short of the eliminative materialists’ hopes of forty years ago. Additionally, important methodological criticisms of the science have emerged concerning such issues as reproducibility and participant selection. This may have contributed to the twenty-first century resurgence of interest in the sort of dualism long a key component of theological orthodoxy, as well as highlighting the need for a reassertion of theological values, methods and perspectives. The apparent non-elimination of theology indicates a need to rebalance theological and neuroscientific perspectives in developing our understanding of the person. Full article

Luteolin (Ltn), a natural flavonoid, effectively inhibits microglial activation in Alzheimer’s disease (AD) with promising therapeutic potential, but its efficacy is severely limited by the blood–brain barrier (BBB). To overcome this obstacle, this study prepared poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs)—designated as TGN/RAP12-RBC-NPs@Ltn—which were coated with red blood cell membranes (RBCm) functionalized with two peptides, TGN (TGNYKALHPHN) and RAP12 (EAKIEKHNHYQK). The results demonstrated that TGN significantly enhanced BBB permeability, while RAP12 enabled effective targeting and delivery of TGN/RAP12-RBC-NPs@Ltn to microglial mitochondria in the brain. In addition, the presence of RBCm significantly inhibited the phagocytosis of NPs by macrophages, exerting a notable role in immune evasion. Meanwhile, the study confirmed that encapsulating Ltn within NPs significantly enhanced cognitive function in APP/PS1 mice, modulated the expression of key mitochondrial metabolic enzymes—pyruvate dehydrogenase (PDH) and its phosphorylated forms (pS232PDH, pS293PDH, pS300PDH)—in microglia, thereby ameliorating mitochondrial dysfunction and effectively regulating the neuroinflammatory environment in the mouse brain, and ultimately contributed to therapeutic efficacy. From this, it could be seen that TGN/RAP12-RBC-NPs@Ltn could significantly enhance the therapeutic effect of Ltn on AD, providing an effective treatment strategy for delaying the progression of AD. Full article

Background and Objectives: Glioblastoma (GBM), defined as IDH-wildtype CNS WHO grade 4, remains the most common and aggressive primary malignant brain tumor in adults. Although the extent of resection (EOR), particularly gross total resection (GTR), is considered a potentially modifiable factor, survival comparisons across surgical groups are vulnerable to selection bias and unmeasured biological confounding. We evaluated the association between GTR and survival outcomes in patients with newly diagnosed IDH-wildtype GBM in a dual-center, real-world cohort. Materials and Methods: We conducted a retrospective, dual-center cohort study of 100 adult patients with histopathologically confirmed GBM who underwent primary surgical resection between 2015 and 2021. GTR was defined as no measurable residual contrast-enhancing tumor on early postoperative MRI (≤72 h). All patients received adjuvant chemoradiotherapy according to the Stupp protocol. Survival was analyzed using Kaplan–Meier methods with log-rank tests and explored using univariable Cox regression analysis. Given the missing key prognostic covariates (notably MGMT promoter methylation) and the retrospective design, the analyses were reported as unadjusted and descriptive. Results: Of the 100 patients, 63 (63%) underwent GTR and 37 (37%) non-GTR. The GTR group had a significantly higher rate of radiologic complete response (42.9% vs. 10.8%, p = 0.001). However, no significant differences were observed in overall survival (OS; median 13 vs. 12 months, p = 0.847) or progression-free survival (PFS; 8 vs. 8 months, p = 0.963) between the groups in unadjusted analyses. Long-term Kaplan–Meier estimates (e.g., 5-year OS) should be interpreted cautiously due to the small number of patients at risk and potential selection and biological confounding. Conclusions: In this dual-center cohort, GTR was associated with improved radiologic response but not with longer OS or PFS in unadjusted analyses. These results should be considered hypothesis-generating and not interpreted as evidence against maximal safe resection. The absence of MGMT promoter methylation status, lack of volumetric EOR quantification (including non-contrast-enhancing/FLAIR disease), and lack of standardized functional outcome data substantially limited causal inference. Prospective studies integrating molecular stratification, volumetric resection metrics, and functional outcome assessments are warranted. Full article

The increasing production and accumulation of plastic waste, coupled with insufficient recycling practices, contribute to the growing presence of plastic in the environment. Nanoplastic particles are of particular concern, as they pose greater (health and environmental) risks and exhibit wider dispersion compared to macroplastics. The blood–brain barrier may be exposed to nanoplastics present in the blood, which could affect its functionality or even pass through and damage the central nervous system. This study examined the effects of polystyrene (PS) nanoparticles with different chemical surface modifications (pristine, carboxylated, aminated) and sizes (50 nm and 100 nm) on cells of the neurovascular unit (NVU): human brain endothelial cells, astrocytes, and pericytes. Results indicated that only high concentrations of nanoparticles (100 μg/mL and 300 μg/mL) applied for 48 h decreased cell viability and barrier integrity significantly. Specifically, 50 nm carboxylated PS particles reduced barrier integrity and altered tight junction gene expression substantially. Fluorescent labelling of the investigated particles enabled to confirm their uptake by all tested cell types of the NVU, but also highlighted that the labelling changes the particles’ properties. Furthermore, cell culture medium-dependent particle agglomeration and increase of size were inversely correlated with cellular internalisation, which has to be considered for future risk assessments. Full article

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by a wide range of symptoms and severity, posing significant challenges for accurate diagnosis. Approaches that rely on a single data source, or unimodal data, often fail to capture the disorder’s inherent heterogeneity. A multimodal approach, which integrates diverse data types, can create a more holistic and precise understanding of ASD. This paper introduces the Multimodal ASD (MMASD) framework, a novel predictive model for ASD. The MMASD framework is built upon two distinct input modalities: structural magnetic resonance imaging (sMRI) and corresponding phenotype data. The sMRI data provides detailed neuroanatomical metrics, including brain tissue segmentation, volumetric measurements, and cortical thickness. Complementing this, the phenotype data encompasses the clinical and behavioral characteristics of each individual. In the proposed framework, latent features are independently extracted from both modalities and then fused to generate a comprehensive representation of the multimodal information. These fused features are then used to predict ASD by leveraging the outputs of various classifiers. A majority voting ensemble is employed to determine the final prediction. The MMASD framework achieves a high accuracy of 97.27%, surpassing the performance of current state-of-the-art approaches and demonstrating the efficacy of integrating neuroimaging and clinical data for ASD prediction. Full article

Background and Objectives: The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is a key innate immune complex, and its aberrant activation contributes to metabolic and neurodegenerative diseases. Brain-derived neurotrophic factor (BDNF) is a neurotrophin with anti-inflammatory and metabolic regulatory functions, but its role in NLRP3 inflammasome activation and gasdermin D (GSDMD)-mediated pyroptosis remains unclear. The aim of this study was to investigate the effects of BDNF deficiency on LPS- and nigericin-induced NLRP3 inflammasome activation and GSDMD-mediated pyroptosis in vivo, and to elucidate the involvement of NF-κB signaling, autophagy, and ESCRT-III-dependent plasma membrane repair in this process. Materials and Methods: In this in vivo study, male Bdnf ^+/+ and Bdnf ^+/− mice were subjected to lipopolysaccharide (LPS) plus nigericin-induced NLRP3 inflammasome activation. Serum and hippocampus, cortex, liver, epididymal adipose, and muscle tissues were collected 24 h after stimulation for analysis of inflammasome-related, autophagy-related, and membrane repair-related proteins by Western blotting and of serum BDNF, interleukin-1β (IL-1β), and interleukin-18 (IL-18) by ELISA. Results: Bdnf ^+/− mice displayed significantly reduced circulating BDNF levels and exhibited exaggerated LPS plus nigericin-induced increases in IL-1β and IL-18 compared with Bdnf ^+/+ mice. Across all tissues, BDNF deficiency enhanced NF-κB p65, NLRP3, active caspase-1 p20, and GSDMD expression, indicating amplified inflammasome activation and pyroptosis. Conversely, LC3B and SQSTM1/p62 levels were decreased, and VPS4A expression, a key component of the ESCRT-III membrane repair machinery, was suppressed in Bdnf ^+/− mice, suggesting impaired selective autophagy, autophagosome formation, and plasma membrane repair. Conclusions: Together, these findings indicate that BDNF restrains NLRP3 inflammasome activation and GSDMD-mediated pyroptosis through inhibition of NF-κB signaling and coordinated activation of autophagy and ESCRT-III-dependent membrane repair. BDNF thus emerges as an endogenous negative regulator of inflammasome activity and a potential therapeutic target for conditions characterized by aberrant NLRP3-driven inflammation. Full article

The genus Calliandra (Leguminosae: Mimosoideae) encompasses over 200 species, many of which hold significant ethnobotanical value. However, a critical and comprehensive review consolidating their phytochemical and pharmacological knowledge is currently lacking. This article aims to provide a detailed and analytical overview of the traditional uses, phytochemistry, and pharmacological properties of the most studied Calliandra species, identifying trends, gaps, and future research priorities. A systematic literature search was conducted using Google Scholar, Scopus, Web of Science, and PubMed from 1986 to 2025. The review focuses on Calliandra portoricensis, Calliandra haematocephala, and Calliandra surinamensis due to the relative abundance of scientific literature concerning their medicinal applications. These species produce a diverse array of secondary metabolites, including distinctive galloylated flavonoids, phenolic acids, and triterpenes. Extracts and isolated compounds demonstrate a wide range of pharmacological activities, such as antioxidant, antimicrobial, anti-inflammatory, antidiabetic, and anticancer effects, providing a scientific basis for their traditional uses. The genus Calliandra represents a promising source of bioactive compounds. However, future research must focus on compound isolation, mechanistic studies, rigorous toxicological profiling, and clinical trials to fully realize its therapeutic potential. Full article

The kynurenine pathway (KP) is the primary route of tryptophan metabolism and a key interface linking immune activation, metabolic state, and neurochemical signaling. Although KP biomarkers are widely studied in psychiatric disorders, their interpretation remains inconsistent, in part due to biological context and compartmentalization. In this narrative review, we integrate evidence across peripheral and central systems to clarify how age, sex hormones, metabolic health, inflammation, and behavioral factors systematically bias KP flux and shape biomarker readouts. We re-examine the interpretation of the kynurenine/tryptophan ratio in light of differential IDO1 and TDO2 regulation, blood–brain barrier constraints, and cell-specific downstream metabolism that governs neuroprotective and neurotoxic outputs. We further synthesize clinical evidence linking KP alterations to symptom severity, cognitive dysfunction, treatment resistance, and suicidality, highlighting quinolinic acid as a mechanistic node connecting immune activation to glutamatergic dysregulation. Together, this framework reframes the kynurenine pathway not as a static biomarker of disease, but as a context-sensitive metabolic system with direct implications for study design, risk stratification, and personalized approaches in psychiatry. Full article