Laxatives are the primary treatment for functional constipation (FC), but they are not always effective and well-tolerated. Dietary fiber can represent a valid alternative. This study aimed to determine whether combining dietary fibers from different origins could be a valuable strategy for FC. Thus, the efficacy of a fiber-based formulation (MNS-36), composed of resistant dextrin from wheat starch (Triticum aestivum L.), pectin, and insoluble fibers from Citrus spp., and oat fibers (Avena sativa L.) was tested in a monocentric, double-blind, randomized, placebo-controlled clinical trial with 54 adults with FC. Participants received two sachets of MNS-36 or a placebo daily for 28 days, with weekly visits and a follow-up. Compared to the placebo group, bowel movements, used as the primary outcome of the study, increased significantly between baseline and week 4 (β = 2.43 ± 0.23, p < 0.001). Similarly, Bristol Stool Form Scale scores significantly improved in the treatment group (p < 0.001), being normalized from week 2 onwards (p ≤ 0.008). In the treatment group, significant reductions were also observed in abdominal bloating (β = 1.21 ± 0.17, p < 0.001), abdominal distension (β = 1.66 ± 0.18, p < 0.001), heaviness (β = 1.39 ± 0.21, p < 0.001), and flatulence (β = 1.51 ± 0.26, p < 0.001), whereas abdominal pain did not differ significantly between groups. No adverse events were reported, and treatment adherence was high. These findings highlight the efficacy of combining soluble and insoluble fibers from different food origins in improving gut function, addressing both symptoms and tolerability, and underscore this strategy as a natural alternative approach to laxatives for managing FC.
Roasting profoundly influences the phytochemical composition of pistachio (Pistacia vera L.) kernels, yet the interaction between processing and geographical origin remains poorly understood. This study evaluated the impact of a dry roasting-like treatment at 140°C for 45 min on the bioactive profile, pigments, and antioxidant capacity of pistachios from Iran, Spain, the USA, and Turkey. Raw and roasted samples subjected to a dry roasting-like treatment were analyzed for total phenolic content (TPC), individual (poly)phenols by HPLC-DAD, antioxidant capacity using ABTS and DPPH assays, and pigments including chlorophylls and carotenoids. Results showed that geographical origin influenced all parameters. Among raw samples, Turkish pistachios exhibited the highest antioxidant capacity, with ABTS and DPPH values of 1.05 and 3.73 mg TE/g dw, respectively, whereas Iranian samples showed the highest TPC, at 2.5 mg GAE/g dw. The dry roasting-like treatment induced marked compositional shifts, particularly in Turkish samples, with increases of 105% in ABTS, 255% in DPPH, and 255% in TPC. HPLC-DAD identified p-hydroxybenzoic acid as the predominant phenolic compound. The treatment affected individual (poly)phenol concentrations differently depending on origin: total quantified levels increased in USA samples from 140 to 156 μg/g dw but decreased markedly in Turkish samples, from 665 to 241 μg/g dw. Specifically, gallic acid increased across all origins, likely due to the thermal hydrolysis of complex phenolic structures, whereas protocatechuic acid decreased. In terms of pigments, chlorophylls underwent extensive degradation, while carotenoids remained relatively thermally stable. Overall, the dry roasting-like treatment triggered a compositional reconfiguration in which the degradation of thermolabile compounds may have been counterbalanced by the formation of Maillard reaction products, resulting in a net enhancement of functional quality. These findings elucidate the dynamic interaction between geographical origin and thermal processing and provide a scientific basis for promoting pistachios subjected to a dry roasting-like treatment as a functional food contributing to the dietary intake of bioactive phytochemicals.
Home to a lake around 4 billion years ago, Jezero Crater is a unique location to study the interplay between igneous processes and aqueous alteration on ancient Mars. The Máaz formation, rich in basaltic rock, is the highest stratigraphic unit on the crater floor and hosts a diversity of alteration phases that indicate multiple aqueous episodes affected the crater floor rocks. Using data from the Planetary Instrument for X-ray Lithochemistry aboard the Perseverance rover, we investigated manganese enrichments across the crater floor. We report on multiple distinct types of Mn-rich materials. The first, in the Guillaumes abrasion low in the Máaz formation, has been tentatively identified as the rare mineral despujolsite (Ca3Mn4+(SO4)2(OH)6·3H2O), which forms on Earth in hydrothermal and lacustrine deposits. In the Alfalfa abrasion patch, high in the Máaz formation, we find Mn-enriched magnetite spatially associated with a Ca-dominant sulfate that may contain minor Mn, which suggests a history of serpentinization followed by exposure to oxidizing acidic fluids. These findings underscore the complexity of aqueous alteration over the course of Jezero history. Future sample return missions could refine mineralogical interpretations and provide more information to improve our understanding of aqueous conditions and habitability in the crater.
Apoptosis is a tightly regulated form of programmed cell death that enables the controlled elimination of damaged or infected cells without eliciting deleterious inflammatory responses. Beyond its fundamental roles in embryogenesis, tissue homeostasis, and cellular turnover, the molecular architecture of apoptosis reflects deep evolutionary origins shaped by mitochondrial quality control, the emergence of intercellular communication, and immune surveillance mechanisms. Apoptotic signaling is initiated through three principal pathways, the extrinsic (death receptor-mediated), perforin/granzyme-mediated, and intrinsic (mitochondrial) pathways, which converge on caspase activation as the final execution step. Accumulating evidence indicates that persistent interactions with intracellular pathogens have profoundly influenced the evolution and diversification of these pathways. Viruses, bacteria, fungi, and protozoan parasites have independently evolved convergent strategies to suppress, delay, redirect, or exploit apoptosis by targeting conserved regulatory nodes, including mitochondrial outer membrane permeabilization, Bcl-2 family proteins, Bid-mediated pathway integration, Apaf-1-dependent caspase activation, and inhibitors of apoptosis proteins. These pathogen-driven pressures have not only shaped infection outcomes but have also contributed to the expansion, redundancy, and regulatory complexity of host apoptotic machinery. Here, we synthesize recent advances in the understanding of pathogen-mediated modulation of apoptosis and propose that programmed cell death operates as part of an integrated, evolutionarily conserved network of host defense. In this framework, apoptosis emerges as a central battleground in host-pathogen coevolution, linking cellular homeostasis to immune protection.
Effective management of infectious disease relies not only on biomedical interventions but also on the circulation and interpretation of health-related information. Narratives, whether accurate or misleading, influence public perceptions, adherence to protective measures, and policy debates, as illustrated during COVID-19, measles resurgences, and vaccine controversies. YouTube, as a global platform combining an information repository and interactive discussion space, exerts persuasive influence through its audiovisual formats. Avian influenza, a recurrent zoonotic threat with episodic media attention, provides a valuable case for analyzing evolving health narratives. We analyzed 11,465 YouTube videos and associated comments related to avian influenza published between 2020 and 2025. Thematic structures were identified using an MPNet-based topic modeling approach, and sentiment analysis was conducted with XLM-RoBERTa to assess emotional tone across content and audience interactions. Temporal patterns of narrative clusters were also examined. Video content predominantly conveyed factual health information aligned with epidemiological updates and preventive measures. In contrast, user comments displayed substantial interpretive activity, including contestation, speculation, and the adoption of controversial frames concerning virus origins, institutional trust, public health interventions, and alternative treatments. These discussions were characterized by predominantly negative sentiment, indicating that audiences frequently recontextualize online information, potentially fostering ambiguity and misinformation. YouTube serves as both a disseminator of factual health information and a forum for audience reinterpretation, highlighting the platform's dual role in digital health communication. Understanding these dynamics is crucial for public health authorities seeking to design interventions that mitigate misinformation and promote effective protective behaviors during emerging infectious disease threats.
Hybridization is a major driver of fungal evolution, yet knowledge of the molecular mechanisms underpinning hybridization and its genomic impact remain limited. Here, we analyse 197 Cryptococcus neoformans genomic sequences, including 13 newly sequenced strains, identifying three genetically clustered and distinct hybrid groups (H1, H2 and H3) each with unique parental origins and ecological associations. Using phylogenomics, population structure analyses, and long-read genome assemblies, we identified hybrid genomes with chromosome-wide loss of heterozygosity (LOH), inheritance of large intact parental haplotype blocks and widespread aneuploidy within and across genomes. These patterns are also observed when progeny were generated with spo11 Δ parents, indicating these features are a result of a meiotic-independent process such as parasex. This is further underscored by discovery of haploid and near-haploid recombinants in both spo11 Δ mutant progeny and reanalysed the wild-type hybrid progeny. We hypothesise these haploid and near-haploid recombinants are generated through ploidy reduction via independent chromosome assortment because of concerted chromosomal loss, which is a key feature of the parasexual cycle. Phenotypic assays demonstrated that several hybrid isolates have diverse growth and virulence patterns, underscoring functional consequences of genome plasticity. Together, our work suggests a non-meiotic reproductive process contributes to shape the genotypic and phenotypic diversity of Cryptococcus neoformans . Hybridisation in fungal pathogens has been linked to novel genotypes, some of which have enhanced virulence. Cryptococcus is a human pathogen responsible for approximately 180,000 deaths annually worldwide. However, the mechanisms by which Cryptococcus generates genotypic diversity remains understudied. By analysing 197 C. neoformans genome sequences, we identified three distinct groups of hybrids, defined by their ancestral inheritance. In each of these 3 groups, we discovered novel features of hybrid isolates including uneven chromosome numbers in most but not all hybrids, chromosome-wide loss of heterozygosity consistent with whole chromosome inheritance from a single parent, and whole-chromosome-wide haplotype inheritance. These genomic features are consistent with a parasexual form of reproduction, which is a non-meiotic process involving cell and nuclear fusion, followed by gradual chromosome loss and sometimes mitotic recombination. Surprisingly, similar genomic patterns were observed in spo11 Δ mutant crosses, supporting the hypothesis that a non-canonical process such as parasex is facilitating cryptococcal hybridisation. Our results expand our understanding of fungal reproduction and highlight new routes for the emergence of virulence and antifungal resistance.
Low-pressure systems, such as extratropical cyclones (ETCs), are a key component of mid-latitude climate variability and frequent drivers of extreme weather in North America. This study evaluates 27 CMIP6 global climate models (GCMs) and the Canadian Regional Climate Model (CRCM6), driven by ERA5 reanalysis or three CMIP6 GCMs, in reproducing surface pressure anomalies and near-surface humidity during intense cyclonic events over 1980-2014. We introduce a novel Eulerian approach that identifies the strongest low-pressure systems at each grid point and characterizes their local temporal evolution using a three-parameter decomposition: [Formula: see text] intensity, mean [Formula: see text], and [Formula: see text]. This decomposition effectively captures key regional differences and provides a new approach to assess model biases in simulating local dynamical and thermodynamical conditions associated with intense systems. Results indicate that GCMs share systematic biases in characterizing local environmental changes, though the origins vary regionally. Model resolution influences error magnitude but is less critical over continental areas. In high track density regions or areas affected by explosive cyclones, higher resolution reduces pressure anomaly errors, while near-surface humidity shows no clear resolution-related pattern. CRCM6 simulations exhibit the smallest errors domain-wide and perform consistently regardless of driving data. They show particular added value north of [Formula: see text]N and over oceans, especially where GCM errors are large, although some substantial errors persist in certain regions. This study underscores the challenges in simulating intense extratropical and tropical cyclones, highlights the importance of accurately representing synoptic and regional surface conditions, and provides a framework for evaluating model performance, informing improved dynamical downscaling and climate projections. The online version contains supplementary material available at 10.1007/s00382-026-08260-7.
Cyanobacteria, among the most ancient and versatile microorganisms on Earth, thrive across different aquatic ecosystems, ranging from freshwater to marine environments. In addition to being important producers of structurally diverse secondary metabolites, these photosynthetic prokaryotes are crucial to the global cycling of carbon and nitrogen. With their wide range of biological activities, such as antibacterial, antiviral, anticancer, and anti-inflammatory properties, cyanobacterial metabolites are attractive options for use in biotechnology and medicine. In addition, some cyanometabolites have toxic properties that affect aquatic ecosystems and present problems for human health and water quality. This dual significance for ecology and biomedicine emphasizes how crucial it is to do systematic research on cyanobacterial metabolites. The chemical diversity, biological roles, and biosynthetic origins of cyanobacterial secondary metabolites are summarized in this review, with a focus on their translational potential and ecological responsibilities. Innovative approaches for accelerating metabolite discovery and characterization are also covered, including recent developments in metabolite profiling, genome mining, and artificial intelligence (AI)-assisted biosynthetic gene cluster prediction. The present review integrate ecological, biochemical, and computational perspectives emphasizes the cyanobacteria is ongoing significance as sources of bioactive chemicals for environmental sustainability, pharmaceutical research, and biotechnology.
Background: Pupil size variability (PSV) has emerged as a potential non-contact indicator of autonomic nervous system (ANS) function; however, its physiological origins remain unclear. This study aims to develop a computational model to investigate the physiological foundations of PSV and assess how frequency-domain indices reflect cardiovascular autonomic balance. Methods: We integrated a well-established cardiovascular regulation model with a biomechanical pupillary muscle plant. The model simulates PSV alongside heart rate variability (HRV) by transmitting respiratory and baroreflex inputs through an indirect neural pathway to the pupillary muscles. Frequency-domain analyses were conducted to compare simulated PSV and HRV across different autonomic states. Results: Simulations suggest that PSV arises from respiratory and baroreceptor inputs, with its classical range-nonlinearity (RNL) property emerging naturally from iris biomechanics. The model reproduces key physiological behaviors, including inspiration-linked dilation and parasympathetic modulation. Frequency-domain analyses reveal low- and high-frequency components in PSV that are similar to those found in HRV. However, the magnitudes of these PSV components depend heavily on the underlying autonomic state and the mean pupil size. Conclusion: These findings provide a mechanistic framework for interpreting PSV as a cardiovascular autonomic biomarker. This ultimately supports the development of non-invasive, wearable, and eye-based ANS monitoring systems.
Oral squamous cell carcinoma (OSCC), being the most common malignancy of head and neck origin, corelates with genomic instability (GI) through increased consumption of carcino-genotoxic substances. Elevated consumption of tobacco, betel quid, araca nut, alcohol, pipe and cigarette smoking predispose the cells to persistent DNA damage and chromosomal abnormalities. GI leads to tumor immune evasion by suppression of immune signaling pathways (PI3K/AKT/mTOR, RAS/RAF/MAPK, cGAS-STING), upregulation of exhaustion markers (PD-1, CTLA-4), and T-regs (FOXP3) followed by downregulation of cytokine secretion (SOC3) and Major Histocompatibility Complex-1 (MHC-I). Cytokinesis block micronucleus (CBMN) assay is a cost-effective cytogenetic test that efficiently quantifies various metrices of GIg (micronucleus, nuclear buds, nucleoplasmic bridge frequency and chromosomal abrasions), cell proliferation/stasis (replication index, cytokinesis block proliferation index, cytostasis percentage, nuclear division index, nuclear division cytotoxicity index and disturbed ana-telophase) and cell death (apoptotic and necrotic percentage). Therefore, the utilization of CBMN assay for the cytogenetic assessment of peripheral blood mononuclear cells could offer promising results for the accurate quantification tumor immune evasion. Additionally, the review aims to deliver a novel insight into GI-TIE axis and a proposed GI-TIE index to relate GI with TIE severity in OSCC patients. The precise quantification of various cytogenetic metrices for the quantification of tumor immune evasion usingCBMN assay has translational potential to enhance personalized medicine and precision oncology.
Understanding how the introduction of functional groups influences the interaction between metal-organic frameworks and small organic molecules is essential for designing materials capable of mitigating the effects of psychoactive substances. In this study, a set of UiO-66-type zirconium frameworks modified with distinct linker substituents was examined to determine how these variations alter their response toward mephedrone (4-MMC). The selected functional groups introduced changes in polarity and acidity that significantly affected the behaviour of the materials in media of different composition. The framework bearing a sulfonic acid group rapidly removed nearly all detectable 4-MMC from aqueous solution, whereas derivatives containing amino-based functionalities performed more effectively under conditions resembling physiological fluids. These findings emphasise the combined influence of linker chemistry and medium composition on the uptake process. Electronic-structure calculations were used to gain deeper insight into the origin of these trends. The analysis showed that frameworks containing sulphur-based substituents form particularly stable host-guest configurations through cooperative contributions from dispersive, electrostatic, and partially covalent interactions. Aromatic stacking interactions were present but contributed less significantly than charge-related interactions. Biological evaluation confirmed that the modified frameworks exhibit minimal intrinsic toxicity and can attenuate several harmful effects produced by 4-MMC in both cell models and zebrafish larvae. Among the studied materials, the amino-functionalized derivative provided the clearest protective effect, reducing behavioural disturbances and developmental abnormalities triggered by the drug. This work demonstrates that rational modification of UiO-66 linkers offers an effective route to control the bioavailable fraction of 4-MMC, highlighting the potential of such materials for future detoxification strategies involving synthetic cathinones.
This study assessed the utility of baseline 18F-FDG PET/CT radiomics by integrating tumor habitat analysis with both intra- and peritumoral features to predict EGFR mutation status in lung adenocarcinoma. A total of 724 patients from two centers were allocated to training, validation, and test cohorts. Peritumoral regions were delineated with 2-8 mm radial expansions using LIFEx, while tumor habitat subregions were identified via k-means clustering. Multiple machine learning algorithms were employed to develop clinical-metabolic, intratumoral, peritumoral, habitat, and combined models. Model performance was assessed using AUC, calibration curves, DCA, and DeLong tests, and SHAP analysis was applied to interpret critical predictive features. In the test cohort, the combined model achieved the highest and most favorable predictive performance for EGFR mutation (AUC = 0.862, 95% CI: 0.80-0.93), followed by the habitat model (AUC = 0.831, 95% CI: 0.76-0.90). Both models significantly outperformed all other models across datasets (all P < 0.05). Among peritumoral models, the 6 mm expansion version demonstrated the highest AUC. SHAP analysis indicated that 16 of the 17 key features in the habitat model originated from Habitat 1 and 2 subregions, and approximately two-thirds of the top predictive features were CT-based. Baseline 18F-FDG PET/CT radiomics provides reliable prediction of EGFR mutation. Both the habitat and combined models show comparable and strong predictive performance to guide image-informed personalized treatment, while SHAP analysis enhances interpretability for clinical implementation.
This study aimed to compare the microbial profiles between hospital wastewater and river water to assess the dissemination of clinical isolates into the environment. Two types of water samples were collected from sampling sites which were geographically close (wastewater from the University Hospital of Larissa and river water from the Pineios River). Gram-negative bacteria isolated from both sample types were identified using MALDI-TOF. Furthermore, the minimum inhibitory concentration (MIC) of antibiotics were evaluated. A total of 54 Gram-negative isolates, belonging to diverse species, were collected from wastewater sample and river sample. All isolates were classified as MDR, exhibiting resistance to at least one agent from more than three different antibiotic classes. Based on species identification and susceptibility profiles, 27 isolates (19 from wastewater and 8 from river-water) were selected to be further characterized by whole-genome sequencing (WGS). Analysis of WGS data, revealed the presence of different STs, even in isolates belonging to the same bacterial species. Additionally, WGS data showed that carbapenemase-encoding genes were identified in the majority of isolates. PlasmidFinder identified a huge variety of plasmid replicons among the isolates studied. In conclusion, both hospital wastewater and river water contained isolates carrying clinically relevant resistance determinants, such as carbapenemase-encoding genes. The presence of these pathogenic bacteria in the river poses a significant public health concern. Although we could not identify the origin of MDR bacteria in the river sample, these findings highlight the growing threat of antimicrobial resistance in the environment and underscore the urgent need for improved treatment methods and stricter surveillance to control its spread.
Ureteral metastasis is an exceptionally rare manifestation of malignant disease, with pancreatic cancer as the primary source being particularly uncommon. Because ureteral involvement typically reflects advanced systemic disease and is associated with poor prognosis, early and accurate diagnosis is essential for appropriate clinical management. A 74-year-old man with a history of surgically treated gastric, colorectal, and pancreatic cancers was under routine follow-up after curative resection of pancreatic cancer. Surveillance computed tomography revealed a periureteral mass accompanied by left-sided hydronephrosis. Subsequently, serum tumor marker levels increased, and 18F-fluorodeoxyglucose positron emission tomography/computed tomography demonstrated increased metabolic uptake confined to the periureteral lesion. As imaging findings alone were insufficient to determine the primary origin, surgical resection was performed. Histopathological and immunohistochemical analyses revealed features consistent with pancreaticobiliary adenocarcinoma, confirming periureteral metastasis from recurrent pancreatic cancer. Postoperatively, systemic chemotherapy with gemcitabine plus nab-paclitaxel was initiated. This case highlights that pancreatic cancer can cause isolated ureteral metastasis even several years after curative surgery. In patients with a history of multiple malignancies, newly identified periureteral lesions should raise suspicion for metastatic disease, and histopathological confirmation is essential to establish the primary origin and guide optimal systemic therapy.
Movement disorders associated with neuromuscular diseases are often underrecognized, yet they represent a distinct clinical entity. Abnormalities in areas of the peripheral nervous system, i.e., nerves and muscles, can stem from dysfunction of ion channels and proteins involved in membrane excitability. Hyperexcitability of peripheral motor nerves presents as cramps, stiffness, abnormal posture and gait, as well as changes in motor unit potentials during electromyography studies; hence, it may be classified as a movement problem. Etiologies range from hereditary, immune-mediated, or may be secondary to structural changes. This review focuses on peripheral nervous system and muscle-derived movement disorders associated with autoantibodies. It aims to highlight immune-mediated peripheral nerve hyperexcitability syndromes, stiff-person spectrum disorders, and immune-mediated rippling muscle disease (a movement disorder of muscular origin). It also discusses pathophysiology, diagnosis (particularly immunologic markers), and therapeutics.
Catheter ablation is an effective treatment for premature ventricular contractions (PVCs). Mapping typically relies on bipolar (bip-EGMs) and unipolar electrograms (uni-EGMs). Recently, catheters equipped with microbipolar electrodes have become available. This study aimed to investigate the value of microbipolar EGMs (micro-EGMs) in PVCs mapping. We performed a multicenter retrospective study including patients who underwent successful outflow tract PVC ablation using QDOT catheters. 2 groups were identified based on the superficial or intramural origin of the PVC. EGMs-bip-, uni-, and micro-EGMs-were assessed at the successful ablation sites. The primary outcome was the ability of micro-EGM to discriminate between superficial and intramural PVCs. The secondary outcome was signal amplitude. Among 81 patients (mean age 54 ± 11 years; 59.3% male), 51 had superficial and 30 had intramural PVCs. In superficial PVC, micro-EGM preceded both uni-EGM and bip-EGM in 90% of cases. In particular, when the earliest bip-EGM preceded the earliest micro-EGM by >10 ms (Δbip-micro >10 ms), there was a high probability (sensitivity 0.94; specificity 0.75) of requiring ablation in both the right ventricular outflow tract and left ventricular outflow tract for successful PVC suppression. Micro-EGMs had higher initial deflection amplitude (1.5 vs 2.8 mV; P = .025). Micro-EGMs allow more accurate PVC mapping, improving depth estimation. Micro-EGMs seem to be valuable for local activation time annotation with important implications on automated annotation algorithms within existing electroanatomic mapping systems.
Esophageal cancer is a highly aggressive malignancy associated with a generally poor clinical prognosis. While distant metastases are common, the metastasis of esophageal squamous cell carcinoma (ESCC) to the pancreas and stomach is extremely rare. We report the case of a 62-year-old male with a history of ESCC who presented with an incidentally discovered pancreatic mass on imaging 37 months after the completion of radiotherapy. The patient subsequently underwent radical surgical resection. Postoperative histopathological and immunohistochemical analyses confirmed the presence of pancreatic and gastric metastases originating from the primary ESCC. For subsequent disease management, the patient received a systemic regimen comprising immune checkpoint inhibitors combined with platinum-based chemotherapy. This case underscores the importance of considering rare metastases in the differential diagnosis of new pancreatic lesions in patients with a history of ESCC, even following a prolonged disease-free interval. Furthermore, it suggests that aggressive surgical resection combined with postoperative immunochemotherapy may represent a viable multidisciplinary therapeutic strategy for managing such atypical metastatic presentations.
Tracing the propagation of high-frequency oscillations (HFOs) aids in localizing epileptogenic regions and improving surgical outcomes. We examined how hippocampal epileptogenicity influences the propagation properties of the HFOs it generates. We analyzed non-REM sleep stereo-EEG from 49 patients (68 hemispheres) with verified hippocampal contacts. Hippocampi were stratified by excitability: 28 seizure onset zone (SOZ), 22 more-irritative non-SOZ (>6 interictal epileptiform discharges [IED]/min), and 18 less-irritative non-SOZ (<6 IED/min). To isolate significant HFO propagation pathways, we constructed empirical temporal networks (maximum latency 150 ms) and validated them against 1,000 permutation-generated surrogates. We then compared the proportion of statistically significant propagating HFOs originating from hippocampal contacts across these groups. We examined ripples on oscillation (RonO, 80-250 Hz) and fast ripples on oscillation (FRonO, 250-600 Hz). FRonO, but not RonO, rates were significantly elevated in hippocampal SOZ versus non-SOZ contacts (p<1e-9). Intrahippocampal RonO propagation proportion was highest in less-irritative non-SOZ compared to more-irritative non-SOZ (p<0.05) and SOZ (p<0.001). Across groups, we found no other differences in RonO or FRonO propagation proportions, including spread to other mesial-temporal structures or the neocortex. Intrahippocampal RonO propagation is proportionally greater in less-irritative non-SOZ tissue than in the epileptogenic hippocampus. Distinguishing physiological from pathological RonO using signal features alone remains challenging. Our work suggests these categories are not distinct; rather, RonO signals and their underlying hippocampal substrates likely exist on a continuous physiological-to-pathological spectrum. Furthermore, RonO propagation may serve as a novel metric to quantify hippocampal epileptogenicity. Intrahippocampal propagation of ripples on oscillations (RonO, 80-250 Hz) is highest in the less-irritative hippocampus along the epileptogenicity spectrum despite their rates were similar.The proportions of hippocampal-to-mesial-temporal and hippocampal-to-neocortical RonO propagation remain constant across varying degrees of hippocampal epileptogenicity.Propagation proportions for fast RonO (fRonO, 250-600 Hz) do not differ significantly across the hippocampal epileptogenicity spectrum despite that their rates differ. The hippocampus is a part of the brain that is crucial for memory. Sometimes, injured parts of the hippocampus create fast electrical brainwaves, called high-frequency oscillations (HFOs), which are linked to seizures. However, healthy parts of the hippocampus also create HFOs, and these are important for learning and memory. In this study, we wanted to know: do the brainwaves from an injured hippocampus spread differently through the brain than the brainwaves from a healthy one?
Fungal diseases constitute a rapidly escalating global health threat, causing an estimated 1.5-2 million deaths annually and affecting more than one billion individuals worldwide, particularly immunocompromised patient populations. The increasing incidence of severe systemic infections, severely limited therapeutic options, prolonged treatment regimens, and the rapid emergence of antimycotic resistance collectively underscore the urgent clinical need for innovative treatment strategies. Consequently, the World Health Organization (WHO) has highlighted sustainable investment in antifungal research and the targeted development of novel therapeutics as a primary global priority. Nanotechnology-based drug delivery systems, particularly advanced lipid-based nanocarriers, offer highly promising solutions to overcome current therapeutic limitations. Sophisticated vesicular systems have successfully demonstrated improved target-site accumulation, highly controlled drug release, enhanced tissue penetration (including deep ocular and cutaneous applications), and drastically reduced systemic toxicity in both preclinical and selected clinical settings. Furthermore, PEGylated and ligand-functionalized liposomes, such as DC-SIGN targeted amphotericin B formulations, significantly improve pathogen-specific binding and overall antifungal activity in rigorous experimental models. Emerging formulation strategies, including pH-responsive stealth liposomes and stimuli-sensitive systems adapted directly from oncological applications, suggest immense potential for maximizing antifungal selectivity and clinical efficacy. Additionally, advanced liposome-in-hydrogel hybrid matrices enable sustained therapeutic release, remarkably enhancing formulation stability while minimizing off-target systemic exposure. This comprehensive review provides an integrative analysis of nanostructured lipid carriers in antifungal therapy, detailing fundamental mechanistic principles, advanced formulation strategies, scalable preparation methodologies, and diverse clinical applications. Particular emphasis is strategically placed on highly deformable liposomal platforms explicitly engineered to overcome the structural limitations of conventional delivery systems. Ultimately, successfully bridging the formidable translational gap between experimental benchtop innovation and routine clinical implementation requires harmonized regulatory frameworks, scalable and reproducible manufacturing protocols, rigorous quality control, and substantially enhanced public and private sector collaboration. By synthesizing mechanistic pharmacological insights with realistic translational and regulatory perspectives, this work aims to advance the fundamental understanding of lipid-based antifungal delivery platforms and directly support the development of highly effective, clinically viable therapeutic approaches.
Acinetobacter baumannii is a Gram-negative opportunistic pathogen increasingly implicated in severe hospital and community-acquired infections. In Nigeria, widespread antibiotic use across human, animal and environmental sectors contributes to antibiotic selection pressures that drive the emergence and spread of high-risk multidrug-resistant lineages. This One Health genomic surveillance study investigated the prevalence, resistance mechanisms, genomic characteristics and reservoirs of A. baumannii across multiple sources in Kano, Nigeria. A total of 3,235 samples were collected from clinical samples, hospital environments, non-hospital environments and poultry droppings. A. baumannii isolates were identified by growth on MacConkey/CHROMagar and confirmed by bla OXA-51-like amplification. Antimicrobial susceptibility was assessed using the Kirby-Bauer disc diffusion method. Of all samples, 62 isolates were confirmed as A. baumannii, originating from clinical samples (n=24), hospital environments (n=33), non-hospital environments (n=2) and poultry droppings (n=3). Whole-genome sequencing of 27 select isolates was performed to characterize resistance and virulence genes, sequence types (STs), mobile genetic elements, genomic islands and SNP-based relatedness. Thirteen bla OXA-51-like and one bla OXA-58-like variants were detected. MLST revealed 21 STs using the Pasteur scheme and 14 using the Oxford scheme, many of which were susceptible to most antibiotics tested. In contrast, isolates N9, N13 and N16 (ST821) and N19 (ST625) were resistant to all tested antibiotics, including carbapenems. The highly resistant ST821 clones were isolated from a municipal dumpsite, hospital floors and a hospital bedside surface and separated by only 5-17 SNPs, indicating close relatedness and clonality. Previously reported ST821 strains from the UK, Pakistan, Germany and Nigeria were highly susceptible to antimicrobials. Although no plasmids were detected, complementary genomic islands were identified in N9, N13 and N16 containing blaNDM-1, tetA/tetR, folP, aac, aphA, dinB, cueR and trxC and therefore likely to confer resistance to antimicrobials. In conclusion, this study provides the first broad One Health genomic overview of A. baumannii circulating across human, environmental and poultry sources in northern Nigeria, revealing substantial genomic diversity and the identification of a closely related extreme drug-resistant ST821 lineage spanning hospital and community environments.