Search Results (1,442)

Background and Objectives: Transcatheter aortic valve implantation (TAVI) has become the mainstay of treatment for symptomatic aortic stenosis (AS) in patients over 70 years of age. It is also indicated for younger patients with significant comorbidities, for valve-in-valve interventions, and in selected patients with severe aortic insufficiency. We aimed to evaluate procedural and clinical outcomes of transfemoral TAVI performed over the course of 12 years by the same operators using different bioprosthetic valves. Materials and Methods: Between 2012 and 2023, 375 patients underwent TAVI in our clinic, with six types of bioprosthetic valves (Edwards Sapien XT, Medtronic Valves [CoreValve and Evolut R], Portico, Myval, Acurate Neo, and Direct Flow Medical). A transfemoral approach was used in all patients. The procedural and clinical outcomes were defined according to Valve Academic Research Consortium-3 (VARC-3) criteria. Results: The mean age of the patients was 78.4 ± 7.3, and their median STS score was 4.2 (2.9–5.9). Of the 375 patients, 361 had severe AS, 4 had severe aortic insufficiency, 5 were valve-in-valve, and 5 were valve-in-TAVI. Seven patients required a second valve implantation: four due to embolization of the prosthetic valve and three due to deep implantation of the prosthetic valve. Based on the VARC-3 criteria, the rates of technical success and device success were 90.4% and 85.3%, respectively. Major vascular complications were observed in 18 (4.8%) patients. Also, 42 (11.2%) patients required permanent pacemaker implantation. The incidence of moderate or worse paravalvular leak was 2.9%. The peri-procedural, 30-day, 1-year, and 5-year mortality rates were 5.1%, 4.3%, 15.2%, and 45.6%, respectively. STS scores (HR:1.129, 95%CI: 1.068–1.192, p < 0.001) and post-TAVI acute kidney injury (HR:3.993, 95%CI:1.629–9.785, p = 0.002) were detected as independent predictors of mortality in Cox regression analysis. Conclusions: This registry demonstrated the evolution of TAVI procedures at a single center over 12 years. A high level of collaboration between experienced operators and innovations in devices seem to be the key features for achieving high procedural success and low complication rates. Full article

Background/Objectives: Inter-individual variability in injury severity represents a major barrier to reproducibility in neonatal hypoxia–ischemia (HI) models. Objective early postoperative stratification of animals is therefore essential for standardized group allocation and reliable assessment of experimental outcomes. This study aimed to evaluate whether laser speckle contrast imaging (LSCI) can be used as a rapid, noninvasive tool for early post hoc stratification of ischemic brain damage severity in neonatal mice following HI. Methods: Neonatal CD-1 mice (postnatal day 9; n = 60) underwent hypoxia–ischemia using a modified Rice–Vannucci protocol. Cerebral perfusion was assessed by laser speckle contrast imaging at baseline, 3 h, and 7 days after HI. The difference in mean perfusion between ipsilateral and contralateral hemispheres at 3 h (Δ perfusion) was used to stratify animals into severity groups. Brain injury was quantified by 2,3,5-triphenyltetrazolium chloride (TTC) staining at 24 h and 7 days. Survival was monitored for 7 days and analyzed using Kaplan–Meier curves and the log-rank (Mantel–Cox) test. Results: LSCI-derived Δ perfusion at 3 h enabled the formation of distinct injury-severity groups (no visible damage, mild, moderate, and severe) with significant between-group differences (p < 0.0001). TTC-based lesion area increased stepwise across severity groups, and Δ perfusion correlated with lesion size when all animals were analyzed together (r = 0.688, p = 0.0011). No significant correlations were observed within individual severity groups, indicating that the overall association was driven primarily by between-group differences. Survival analysis revealed 75% mortality in the severe injury group (p < 0.0001). Conclusions: LSCI represents a robust and practical approach for early, objective, group-level stratification of neonatal mice by HI injury severity, thereby improving reproducibility and statistical validity in preclinical studies. However, its ability to predict outcomes within individual severity categories is limited, and repeated long-term measurements may pose technical challenges. Full article

Background: Patient-reported outcome measures (PROMs) provide important insights into recovery after anterior cruciate ligament reconstruction (ACLR). Previous research suggests that males and females recover differently after ACLR, with females reporting greater pain, slower functional gains, and lower psychological readiness at later stages of rehabilitation. However, it is unknown if patient-reported outcomes differ by sex early after ACLR. To address this gap, we conducted a cross-sectional analysis comparing patient-reported outcome measures between sexes three months after ACLR. We hypothesized that females would report worse PROMs compared to males. Methods: This cross-sectional analysis used data from a prospectively maintained ACL reconstruction cohort. Fifty-six individuals (female: 23 and male: 33) with primary, unilateral ACLR completed PROMs three months after surgery. These PROMs included the Knee Injury and Osteoarthritis Outcome Score (KOOS; Symptoms, Pain, Activities of Daily Living, Sport and Recreation, Quality of Life), International Knee Documentation Committee (IKDC) subjective score, Knee Outcome Survey–Activities of Daily Living Scale (KOS-ADLS), Anterior Cruciate Ligament–Return to Sport After Injury (ACL-RSI), and the Tampa Scale of Kinesiophobia (TSK). All outcomes were expressed on a 0 to 100 percent scale, with higher scores indicating better outcomes, except for TSK, where lower scores indicated better outcomes. Normality was assessed within sex, using the Shapiro–Wilk test. Two-tailed independent-samples t-tests with Welch correction were used for approximately normal variables; otherwise, Mann–Whitney U tests were utilized (α = 0.05). Several outcomes had limited statistical power to detect MCID-sized differences, and findings for these measures should be interpreted cautiously. Results: No significant differences between sexes were found for any of the PROMs. Males trended towards having better KOOS Sport and Recreation and IKDC, but these were not statistically significant, and the effect sizes were small-to-moderate. Conclusions: No statistically significant sex-based differences were detected in PROMs at approximately 3 months after ACLR, indicating that any sex-related divergences between these measures may not occur until later in recovery. Full article

As cold-sensitive fruits, loquats easily develop chilling injury (CI) during cold storage, which leads to quality deterioration and economic losses. Our prior research indicated that exogenous melatonin (MT) treatment can mitigate CI in postharvest loquats by regulating reactive oxygen species (ROS) metabolism, but the underlying molecular mechanism remains unclear. The primary objective of this study is to decipher the molecular regulatory pathway by which MT alleviates CI in postharvest loquats, focusing on the role of MYB transcription factors (TFs) in modulating antioxidant enzyme genes. Here, MT treatment remarkably reduced CI severity in loquat fruits, as reflected by lower CI index, reduced cell membrane permeability, decreased firmness, lower a* and b* values, and higher L* value, compared with the control group. Moreover, a cold-induced MYB TF, designated EjMYB15, was identified. Compared to non-treated fruits, the expression level of EjMYB15 was maintained at higher levels in MT-treated loquats. Subcellular localization and transactivation assays demonstrated that EjMYB15 is a nuclear-localized transcriptional activator. Electrophoretic mobility shift assay (EMSA) and dual-luciferase reporter (DLR) assays showed that EjMYB15 binds the MYB-binding sites (MBS) in the promoters of four antioxidant enzyme genes (EjCAT1, EjCAT2, EjGST1, and EjGST2), thereby activating their transcription. Taken together, these findings indicate that EjMYB15 positively regulates cold tolerance of loquat fruits by improving ROS scavenging capacity. These results elucidate the regulatory pathway by which MYB TFs mitigate CI and provide new theoretical support for the application of MT in alleviating CI in postharvest fruits. Full article

Hair loss disorders, particularly androgenetic alopecia (AGA), are common conditions that carry significant psychosocial impact. Current standard therapies, including minoxidil, finasteride, and hair transplantation, primarily slow progression or re-distribute existing follicles and do not regenerate lost follicular structures. In recent years, regenerative medicine has been associated with a gradual shift toward approaches that aim to restore follicular function and architecture. Stem cell-derived conditioned media and exosomes have shown the ability to activate Wnt/β-catenin signaling, enhance angiogenesis, modulate inflammation, and promote dermal papilla cell survival, resulting in improved hair density and shaft thickness with favorable safety profiles. Autologous cell-based therapies, including adipose-derived stem cells and dermal sheath cup cells, have demonstrated the potential to rescue miniaturized follicles, although durability and standardization remain challenges. Adjunctive interventions such as microneedling and platelet-rich plasma (PRP) further augment follicular regeneration by inducing controlled micro-injury and releasing growth and neurotrophic factors. In parallel, machine learning-based diagnostic tools and deep hair phenotyping offer improved severity scoring, treatment monitoring, and personalized therapeutic planning, while robotic Follicular Unit Excision (FUE) platforms enhance surgical precision and graft preservation. Advances in tissue engineering and 3D follicle organoid culture suggest progress toward producing transplantable follicle units, though large-scale clinical translation is still in early development. Collectively, these emerging biological and technological strategies indicate movement beyond symptomatic management toward more targeted, multimodal approaches. Future progress will depend on standardized protocols, regulatory clarity, and long-term clinical trials to define which regenerative approaches can reliably achieve sustainable follicle renewal in routine cosmetic dermatology practice. Full article

Preeclampsia (PE) is the onset of hypertension in pregnancy with systemic involvement; PE poses significant risks of cerebral complications, including eclampsia and long-term cognitive impairment. This review explores the potential of neurological biomarkers—neurofilament light chain (NfL), neuron-specific enolase (NSE), S100 Calcium Binding Protein B (S100B), and tau—as indicators of cerebral injury in PE. A literature search identified studies comparing biomarker levels in preeclamptic and healthy pregnancies. Findings reveal elevated plasma levels of NfL, NSE, S100B, and Tau in PE, with NfL showing the strongest association with blood–brain barrier dysfunction, cognitive symptoms, and disease severity. Variations between plasma and cerebrospinal fluid levels suggest impaired BBB integrity rather than increased central nervous system production. Despite promising correlations, limitations include small sample sizes, lack of standardized thresholds, and limited CSF data. While NfL emerges as a particularly promising marker for risk stratification, further research is needed to validate the clinical utility of these biomarkers in routine PE management. Full article

This review explores the interplay between SARS-CoV-2 and HIV-1 infections within the human brain, highlighting the significant neurological implications of these viral infections. SARS-CoV-2 can infect the central nervous system (CNS), with evidence of the virus detected in various brain regions, including the hypothalamus, cerebellum, and olfactory bulb. This infection is linked to microglial activation and neuroinflammation, which can lead to severe neurological outcomes in affected individuals. Autopsy studies revealed microglial changes, including downregulation of the P2RY12 receptor, indicating a shift from homeostatic to inflammatory phenotype. Similar changes in microglia are found in the brains of people with HIV-1 (PWH). In SARS-CoV-2, the correlation between inflammatory cytokines, such as IL-1, IL-6, and MCP-1, found in cerebrospinal fluid and brain tissues, indicates significant neurovascular inflammation. Astrogliosis and microglial nodules were observed, further emphasizing the inflammatory response triggered by the viral infections, again in parallel to those found in the brains of PWH. Epidemiologic data indicate that although SARS-CoV-2 infection rates in PWH mirror those in People without HIV (PWoH) populations, Long-COVID prevalence is markedly higher among PWH. Evidence of overlapping cognitive impairment, mental health burden, and persistent neuroinflammation highlights diagnostic complexity and therapeutic gaps. Despite plausible mechanistic synergy, direct neuropathological confirmation remains scarce, warranting longitudinal, biomarker-driven studies. Understanding these interactions is critical for developing targeted interventions to mitigate CNS injury and improve outcomes. Full article

Background and Objectives: Neutrophil extracellular traps (NETs) have been linked to hypercoagulability, immunothrombosis, and organ injury in COVID-19. Digital morphology of peripheral blood smears enables the identification of NET-compatible appearances (NET-like) in circulation, and associations between NET-like derived indices and clinical outcomes have been reported. However, evidence at hospital admission that relates smear NET-like burden to systemic inflammation and clinical severity remains limited. We therefore aimed to compare the burden of NET-like structures on admission smears according to disease severity and systemic inflammatory markers. Materials and Methods: We included 50 consecutively enrolled adults hospitalized for COVID-19; samples were obtained within 24 h of admission. Severity was defined by the World Health Organization Clinical Progression Scale and grouped as moderate or severe. C-reactive protein (CRP), ferritin, and complete blood counts were measured; the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were calculated. Digital morphology assessed 200 leukocytes per patient; the presence of morphological abnormalities, including NET-like events per patient, was recorded. We additionally quantified NET-like events per 100 white blood cells (NET-like/100 WBC) and the neutrophil extracellular trap–segmented neutrophil ratio (NNSR). Results: At admission, CRP, ferritin, NLR, and PLR of patients were above method-specific reference intervals. NET-like events were identified in 66% of patients. NET-like/100 WBC correlated positively with NLR (r = 0.312; p < 0.05). Patients with severe COVID-19 had higher NET-like/100 WBC than those with moderate disease (5.8 ± 7.34 vs. 14.14 ± 15.12; p = 0.0294). Conclusions: Digital morphological identification of NET-like structures on peripheral blood smears is frequent at admission and is associated with systemic inflammatory burden and with greater COVID-19 severity. These findings support the potential complementary value of reporting NET-like events for initial risk stratification in the clinical laboratory. Full article

The development of RNA-based drugs for MAFLD-related fibrosis is severely hampered by the poor oral bioavailability of nucleic acids. This study employed a novel, patent-protected LNP formulation to orally deliver plant-derived miR-55 and investigate its therapeutic potential, focusing on its novel mechanism of action via the CK2α/SMO interaction. In a rat model established with a methionine-choline-deficient diet, orally administered miR-55 markedly improved liver injury, lipid dysregulation, oxidative stress, and pathological collagen deposition. The anti-fibrotic efficacy was quantitatively confirmed by a significant reduction in hepatic hydroxyproline content and downregulation of key fibrogenic genes (Col1a1, Col3a1, TIMP-1, TGF-β1, CTGF) and pro-inflammatory cytokines (TNF-α, IL-6), achieving effects comparable to the full Ge Xia Zhu Yu Decoction. Mechanistically, both bioinformatic prediction and in vivo validation indicated that miR-55 is predicted to target CK2α. This targeting suppressed CK2α expression and disrupted the endogenous CK2α-SMO complex, thereby promoting the ubiquitin-mediated degradation of SMO—a previously unreported mechanism. This cascade inhibited the downstream Gli1 pathway and downregulated pro-fibrotic and pro-angiogenic factors (VEGF, PDGF), thereby providing a comprehensive mechanistic basis for the therapeutic effects. This study is the first to provide evidence that orally delivered, plant-derived miR-55 may act as a natural modulator that potentially through disrupting the CK2α/SMO interaction via a unique complex disruption-promoted degradation mechanism, attenuating Hedgehog signaling and alleviating liver fibrosis. These findings offer important insights into cross-kingdom regulation and highlight miR-55 as a potential targeted therapeutic candidate. Full article

Metabolic acidosis is common after kidney transplantation and has been linked to adverse renal outcomes. However, its relationship with histological injury in kidney allografts remains poorly characterized. We aimed to explore the association between metabolic acidosis and histopathological features in kidney allograft biopsies. This single-center, cross-sectional observational study included 63 adult kidney transplant recipients who underwent clinically indicated allograft biopsies. Metabolic acidosis was defined as a serum bicarbonate level < 22 mmol/L at the time of biopsy. Histological lesions were assessed according to the Banff classification. Lesion severity was evaluated using descriptive statistics, nonparametric comparisons, ordinal logistic regression, and multivariable logistic regression models adjusted for renal function, proteinuria, and time from transplantation. Sensitivity analyses additionally adjusted for hemoglobin and donor-related variables. Patients with metabolic acidosis exhibited numerically higher severity scores for both acute inflammatory lesions and chronic histological changes, including total inflammation and interstitial fibrosis/tubular atrophy (IFTA). Across ordinal analyses and multivariable regression models, consistent directional trends toward a greater histological injury burden were observed among acidotic patients; however, none of these associations reached statistical significance, and confidence intervals were wide. Sensitivity analyses yielded directionally consistent effect estimates. In this biopsy-based analysis, metabolic acidosis showed consistent directional trends toward a higher burden of inflammatory and chronic histological lesions, although these findings did not reach statistical significance. Full article

Objective: Pain is among the most common and debilitating symptoms experienced by oncology patients and has been associated with adverse mental health outcomes, including depression and suicide. Nevertheless, the relationship between pain and suicide in oncology populations remains insufficiently characterized. A clearer understanding of this interplay is essential to guide personalized approaches aimed at reducing cancer-related burden and improving quality of life. Methods: We searched PubMed and PsycInfo without imposing limits regarding publication date using pain* AND (suicid* OR “self-harm” OR “self-injurious behavior” OR “self-inflicted injury” or “self-killing”) AND (cancer* OR oncolog* OR tumor* OR neoplasm* OR metasta*). A total of 832 articles were identified, and 15 of them were included in our review. Results: Inadequately managed pain in cancer patients is associated with a significantly elevated risk of suicidal ideation. This association is further exacerbated in individuals presenting with depressive symptoms, advanced-stage disease, or limited access to timely psychological support. These factors may interact synergistically, intensifying the emotional and cognitive burden of pain, thereby increasing vulnerability in cancer patients. Conclusions: Cancer-related pain should be conceptualized as a highly variable indicator of psychological vulnerability. Factors influencing this variability include cancer type and severity, as well as the presence of past psychopathology. These findings support the need for a personalized medicine approach, whereby pain management and psychosocial interventions are tailored to patient-specific factors such as disease stage, psychological comorbidity, and access to supportive care. Full article

Background/Objectives: Post-traumatic epileptogenesis is a frequent and clinically relevant consequence of traumatic brain injury (TBI), often contributing to worsened neurological and functional outcomes. In patients experiencing early post-injury seizures, rehabilitative strategies that support recovery while considering increased epileptogenic risk are needed. This case study explores the potential benefits of combining neurofeedback (NFB) with motor therapy on cognitive and motor recovery. Methods: A patient hospitalized for severe TBI who experienced an acute symptomatic seizure in the early post-injury phase underwent baseline quantitative EEG (qEEG), neuromotor, functional, and neuropsychological assessments. The patient then completed a three-week rehabilitation program (five days/week) including 30 sensorimotor rhythm (SMR) NFB sessions (35 min each) combined with daily one-hour motor therapy. qEEG and clinical assessments were repeated post-intervention and at 6-month follow-up. Results: Post-intervention qEEG showed significant reductions in Delta and Theta power, reflecting decreased cortical slowing and enhanced neural activation. Relative power analysis indicated reduced Theta activity and Alpha normalization, suggesting improved cortical stability. Increases were observed in Beta and High-beta activity, alongside significant reductions in the Theta/Beta ratio, consistent with improved attentional regulation. Neuropsychological outcomes revealed reliable improvements in global cognition, memory, and visuospatial abilities, mostly maintained or enhanced at follow-up. Depressive and anxiety symptoms decreased markedly. Motor and functional assessments demonstrated meaningful improvements in motor performance, coordination, and functional independence. Conclusions: Findings suggest that integrating NFB with motor therapy may support recovery processes and be associated with sustained neuroplastic changes in the early post-injury phase after TBI, a condition associated with elevated risk for post-traumatic epilepsy. Full article

Background: Neuromuscular blockade (NMB) is frequently used in moderate-to-severe acute respiratory distress syndrome (ARDS) to optimize ventilatory synchrony and minimize ventilator-induced lung injury. However, comparative real-world data on different NMB strategies remain limited. Objective: To describe patterns of neuromuscular blockade use in ARDS and describe clinical outcomes across four NMB strategies: intermittent rocuronium, continuous cisatracurium, escalation from rocuronium to cisatracurium, and de-escalation from cisatracurium to rocuronium. Methods: A retrospective chart review was conducted in an 18-bed tertiary ICU at Hôpital Montfort (Ottawa, Canada) between November 2021 and March 2025. Adult ARDS patients who received NMB for >24 h were included. Continuous variables (age, ventilation time, ICU stay) were summarized as means ± SD and median [IQR]; categorical variables (sex, ARDS etiology, mortality) as counts and percentages. Inferential testing was limited to baseline characteristics; clinical outcomes were summarized descriptively. Results: Fifty-one patients met inclusion criteria: rocuronium (n = 20), cisatracurium (n = 14), rocuronium→cisatracurium (n = 8), and cisatracurium→rocuronium (n = 9). Mean ventilation durations were 280, 195, 272, and 262 h, respectively; corresponding ICU stays were 245, 237, 380, and 299 h. Mortality ranged from 25% to 56%. Escalation from rocuronium to cisatracurium typically reflected persistent dyssynchrony or worsening oxygenation, whereas de-escalation occurred in improving patients with residual ventilatory drive. Variability in corticosteroid use, adjunctive proning, and epoprostenol were potential confounders. Conclusions: Distinct NMB use patterns in ARDS reflect bedside clinical judgment rather than predefined thresholds. Patient trajectory and dyssynchrony severity appear to drive NMBA escalation decisions more than oxygenation indices alone. These findings highlight the need for prospective studies defining standardized criteria for NMB initiation, escalation, and weaning in ARDS. Full article

Background: Sex-based variations in brain structure, hormonal balance, and neurochemistry may influence symptom presentation and recovery after mild traumatic brain injury (mTBI). This systematic review investigated sex-related differences in mTBI severity, symptoms, and recovery outcomes across different injury mechanisms. Methods: This review followed PRISMA 2020 guidelines and was registered with PROSPERO (CRD420251011379). Searches were conducted in PubMed, SPORTDiscus, Web of Science, and Scopus for articles published between 2000 and 2024. Eligible studies included adults (≥18 years) diagnosed with mTBI or concussion (Glasgow Coma Scale 13–15) with quantifiable outcome data for both sexes. Data extraction and quality assessment followed the JBI critical appraisal tools. Results: Forty-one studies involving 15,656 participants (8671 males; 6985 females) met the inclusion criteria. Female participants reported a greater symptom burden, higher pain intensity, and longer recovery times for gait abnormalities and return to activity compared with males. Neuroimaging studies showed more extensive white matter alterations in females, whereas males displayed greater reductions in cerebral blood flow. Cognitive and neurosensory outcomes revealed poorer cognitive performance, slower reaction times, and higher rates of vestibular–ocular and visual abnormalities in females. A limited number of studies explored electrophysiological measures, indicating sex-based differences in early brain responses to emotional stimuli. Conclusions: Sex plays an important role in symptom presentation and recovery after mTBI. Female patients demonstrate heightened vulnerability across several clinical domains, likely due to biological and neurochemical differences. Recognising these sex-specific patterns can support more targeted diagnostic and rehabilitation strategies. Future research should further explore the structural and biochemical mechanisms underlying these differences to improve precision in mTBI management. Full article

Creutzfeldt–Jakob disease (CJD) is a rare but devastating neurodegenerative disorder characterized by the pathological misfolding of the cellular prion protein (PrP^C) into the pathogenic isoform-scrapie prion protein (PrP^Sc), ultimately leading to fatal outcomes. Cerebrospinal fluid (CSF) biomarkers play a pivotal role in early diagnosis, longitudinal monitoring, and prognostic assessment, thereby enhancing the clinical management of this challenging disease. This review summarizes the established CSF biomarkers, 14-3-3 protein, tau protein (total tau), phosphorylated tau isoforms, α-synuclein, neurofilament light chain (Nfl), S100B, neuron-specific enolase (NSE), and phosphorylated neurofilament heavy chain (pNFH), highlighting typical sensitivity ranges (14-3-3 ~70–85%; RT-QuIC > 90%) and subtype-dependent performance variation. We further dissect limitations related to assay variability, inter-laboratory cut-off inconsistencies, and reduced specificity in non-prion dementias. Looking ahead, we discuss emerging multi-omics discovery, integration of CSF with blood-based biomarkers and imaging signatures, and AI-enabled diagnostic modeling. We propose a three-tier biomarker framework combining Real-Time Quaking-Induced Conversion (RT-QuIC) as a confirmatory assay, tau/NfL/pNFH as injury-severity indicators, and multi-omics-derived signatures for early detection and prognosis stratification. Full article