Background: Skeletal muscle is increasingly recognized as an endocrine organ that releases bioactive factors, termed myokines, capable of mediating inter-organ communication, including signaling to the brain. Aim: To summarize current evidence on key myokines involved in muscle–brain crosstalk and their potential roles in neuroplasticity, cognition, and neurodegenerative diseases. Methods: This narrative review synthesizes findings from experimental and clinical studies addressing exercise-induced myokines, their interaction with the blood–brain barrier, and associated intracellular signaling pathways relevant to central nervous system function. Results: Multiple myokines, including fibronectin type III domain-containing protein 5 (irisin), cathepsin B, insulin-like growth factor-1, interleukin-6, interleukin-1, leukemia inhibitory factor, and lactate, have been implicated in muscle–brain communication. These factors may influence brain function by crossing or modulating the blood–brain barrier and activating signaling pathways such as protein kinase B, extracellular signal-regulated kinases, and cAMP response element-binding protein. Evidence suggests that these mechanisms contribute to increased brain-derived neurotrophic factor expression, promoting neurogenesis, synaptic plasticity, and neuroprotection. Additionally, creatine, although not a myokine, may support brain function through its role in cellular energy homeostasis. Conclusion: Myokines represent key mediators linking physical exercise to brain health, with potential implications for the prevention and management of neurodegenerative conditions. However, further studies are required to clarify their mechanisms and clinical applicability. Relevance for Patients: Understanding how exercise-induced factors influence brain function may support the development of non-pharmacological and adjunct therapeutic strategies to preserve cognitive function and reduce the risk of neurodegenerative diseases.
Background: Pancreatic metastases (PM) account for 2%–5% of pancreatic neoplasms diagnosed clinically, while autopsy series report a 3%–12% prevalence, reaching 43% in advanced malignancy. This statistic suggests underdiagnosis of silent lesions mimicking primary pancreatic tumors, representing a major diagnostic challenge. Aim: This study aims to summarize evidence on PM etiology, diagnosis, and management, as illustrated by an exceptional case of acute pancreatitis (AP) secondary to pulmonary artery intimal sarcoma (PAIS). Methods: A narrative review of the medical literature was conducted in June 2026 using PubMed/MEDLINE. Publications available up to January 2026 were reviewed, including electronic ahead-of-print publications. Relevant original studies, systematic reviews, pooled analyses, and clinical guidelines were reviewed, synthesized, and integrated with the case. Results: Renal cell carcinoma (RCC), which accounts for 30%–70% of reported PM in clinical and surgical series, is characterized by indolent biology and latency periods exceeding ten years. Sarcomas, which represent 4.3%–7.2% of reported PM, are biologically aggressive sources of PM. AP presentation is exceptionally uncommon and is a result of mechanical pancreatic duct obstruction. Endoscopic ultrasound-guided fine-needle biopsy is considered the diagnostic standard, with a 97.9% accuracy. Metastasectomy achieves a 76.6% five-year survival rate in RCC cases. In PAIS cases, AP has been reported to resolve following systemic chemotherapy; however, this temporal association should not be interpreted as evidence confirming the proposed pathogenic mechanism. Conclusion: PM should be considered in any pancreatic mass or AP of uncertain origin in patients with cancer. The oligometastatic disease model (≤5 lesions) supports curative-intent or prolonged systemic disease-control strategies. Relevance for patients: Accurate diagnosis prevents staging errors, preserves pancreatic function, and supports prolonged radiological surveillance in tumors with pancreatic tropism.
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is becoming a growing public health concern. MASLD often coexists with abnormal glucose metabolism. Currently, there is no standard treatment for MASLD. Aim: To elucidate the influence of ursodeoxycholic acid (UDCA) on hepatic lipid deposition, blood glucose, and insulin levels in high-fat diet-induced Sprague–Dawley (SD) rats. Methods: SD rats were randomly assigned to three groups: Group A, which comprised a normal-diet control group; Group B, which comprised a high-fat-fed group; and Group C, which comprised rats treated with UDCA combined with a high-fat diet. At the end of week 4, we performed oral glucose tolerance tests, measured liver enzymes, triglyceride (TG) and total cholesterol (TC) contents, identified morphological changes of the liver, and quantified the expression of major genes in fatty acid, glucose, and bile acid metabolic pathways using real-time polymerase chain reaction. Results: In comparison to Group A, Group B had higher postprandial glucose, insulin, C-peptide, and hepatic TG and TC concentrations (all p < 0.05); metabolism-related genes were differentially expressed in Group B. In comparison to Group B, the values of these indices were all decreased in Group C (all p < 0.05); UDCA reversed the mRNA expression of metabolism-related genes in Group C (all p < 0.05). Conclusion: UDCA administration decreased hepatic lipid content, blood glucose, and insulin levels in SD rats. Relevance for patients: UDCA may be helpful in the treatment of MASLD and its related comorbidities in clinical practice.
Background: Early detection of neurodegenerative diseases is an important and unmet clinical need because traditional assays are not sensitive enough to detect low concentrations of biomarkers at the prodromal stages. Objective: This study presents a novel biosensing system based on quantum measurement principles and biomolecular recognition to achieve ultrasensitive detection of biomarkers for Alzheimer’s disease (AD) and Parkinson’s disease (PD) in patient samples. Methods: We developed a hybrid sensor that uses antibody-functionalized nanostructures for selective biomarker capture and nitrogen-vacancy centers in diamond for quantum spin-based readout. The performance was evaluated against standard fluorescence immunoassays of cerebrospinal fluid (CSF) and plasma collected from a clinical cohort (n = 120; 60 AD/PD, 60 controls) in endogenous amyloid-β42 (Aβ42), phosphorylated tau (p-tau181), and α-synuclein. Results: The quantum-enhanced platform detection limits of 12.6 fM for Aβ42, 15.8 fM for p-tau181, and 18.2 fM for α-synuclein are 150–300-fold better than enzyme-linked immunosorbent assay (ELISA). The signal-to-noise ratio increased by ~22 dB, within the quantum-limited scaling. Diagnostic accuracy was high, with an area under the receiver operating characteristic curve ranging from 0.94 to 0.96, superior to ELISA (0.72–0.81). In addition to sensitivity, analytical validation has excellent reproducibility (intra-assay coefficient of variation [CV] ≤ 7.5%, inter-assay CV ≤ 10.8%), high recovery in patients’ plasma and CSF (92–105%), low cross-reactivity (<3%), and a stable sensor performance of seven days of storage. Multiplexed detection reduced the sample volume by 60% and the assay turnaround time by more than threefold compared to ELISA. Conclusion: Quantum-enhanced biosensing is a powerful diagnostic method for detecting biomarkers at clinically relevant concentrations, providing a scalable, noninvasive approach to early diagnosis of neurodegenerative diseases in affected populations. Relevance for patients: Clinical implementation of quantum biosensing has the potential to enable pre-symptomatic disease detection, facilitating earlier therapeutic intervention and improved disease management.
Background: Atherosclerotic cardiovascular disease (ASCVD) leaves substantial residual risk despite intensive low-density lipoprotein-cholesterol lowering and anti-inflammatory therapy. Reactive oxygen species (ROS) have long been implicated, yet neutral broad-antioxidant trials left unclear which dimensions of ROS imbalance are causal, clinically informative, and therapeutically tractable. Aim: To critically appraise ROS imbalance in atherosclerosis through a plausibility–association–utility hierarchy and to propose a staged framework for precision cardiovascular prevention. Methods: We synthesized mechanistic, biomarker, and translational evidence from targeted PubMed/MEDLINE, Embase, and Cochrane searches (January 2000–February 2026), combining terms for ROS, oxidative stress, atherosclerosis, oxidative biomarkers, and residual cardiovascular risk, with citation chaining. Mass-spectrometry biomarker work, prospective cohorts, and randomized trials received greater interpretive weight. Systematic-review procedures were not applied. Results: Compartmentalized, source-specific ROS imbalance contributes to endothelial dysfunction, lipoprotein oxidation, inflammatory amplification, and plaque progression, particularly in high-risk cardiometabolic phenotypes. Human biomarker data are predominantly observational, assay standardization is incomplete, and risk-reclassification evidence is limited. F2-isoprostanes are a relatively mature lipid-peroxidation marker better suited to trial enrichment than treatment selection. Conclusion: Oxidative biomarkers are defensibly used for trial enrichment but not individual treatment selection. A staged precision-prevention agenda should test source-selective interventions in biomarker-enriched cohorts using vascular and mechanistic endpoints before large outcome trials. Relevance for Patients: Adults whose cardiovascular risk remains high despite cholesterol-lowering and anti-inflammatory treatment—including those with diabetes, kidney disease, smoking, obesity, or recurrent events—may eventually benefit if oxidative stress tests can identify who remains vulnerable and guide targeted prevention.
Background: Brush biopsy is a minimally invasive method for early detection of oral squamous cell carcinoma (OSCC). Enhanced accuracy for clinical utility depends on analysis of the whole cell population and automated cohort classifications. Aim: This study aims to delineate OSCC, high-grade dysplasia (HGD), and low-risk lesions (LRLs) by profiling single-cell level alterations using multiplexed flow cytometry. Methods: Brush-biopsy samples were analyzed from patients with LRL, HGD, and OSCC. Flow cytometry analysis was standardized to ascertain cell distribution, heterogeneity, and epithelial cell content. Markers were used for epithelial cell (Pan-Cytokeratin [Pan-CK]/ propidium iodide [PI]) and atypical cell (Sambucus–Nigra–Agglutinin-1 [SNA-1]/ polyadenosine diphosphate-ribose polymerase inhibitor [PARPi-FL]) delineation. In addition, scatter properties and molecular-equivalence fluorescence (MEF) values of markers were analyzed for cohort classification. Results: Brush-biopsy samples from OSCC/HGD patients showed heterogeneity in the percentage of Pan-CK+ve/PI+ve cells. Significant variation in MEF values of SNA-1/PARPi-FL/PI delineated the OSCC cohort (area under the curve > 0.85). Furthermore, the markers in combination with scatter properties delineated OSCC (multivariate logistic regression; sensitivity: 90%, specificity: 82%). The analysis of the forward-scatter height-to-area ratio delineated HGD from low-risk lesions by capturing the morphology-based cellular differences. Conclusions: These results suggest that a flow cytometry-based analysis of brushbiopsy samples may serve as an adjunct tool for risk stratification of oral lesions. Relevance for patients: This study provides evidence towards the application of flow cytometry as an objective, quantitative adjunct to conventional cytology, and improves early detection and risk stratification of oral lesions using a minimally invasive sampling method, thereby supporting timely clinical decision-making and patient management.
Background: Cardiac disorders are either inherited or acquired, reflecting deformities in their structural or functional characteristics. Despite significant advances in cardiovascular drugs and surgical procedures, no breakthroughs have been achieved. The cervicothoracic ganglia, also known as stellate ganglia, located within the paravertebral chain, are known to innervate myocardial tissues in a heterogeneous manner; however, their therapeutic potential for managing myocardial diseases is not yet fully understood. Methods: Our single-cell sequencing transcriptomic data from wild-type stellate ganglia demonstrated that cardiac-innervating Npy2r-expressing neuronal subpopulations consistently innervate the myocardium. To investigate whether these neuronal subpopulations influence cardiac functions, we used the Npy2r-IRES-Cre crossed with the Ai32-(ChR2(H134R)/EYFP) strain. The offspring with genotypes Npy2r+/-::ChR2+/-, 6 to 8 weeks old littermates, were selected for optical stimulation via an optical fibre connected to the OptoEngine (473 nm, 400 mW, OptoEngine). Results: We observed a significant increase in heart rate among Npy2r+/-::Ai32+/- heterozygous mice compared to control Ai32+/- mice following optical stimulation at various frequencies: 1Hz, 5Hz, 10Hz, 15Hz, and 20Hz. Stellate ganglia isolated from Npy2r+/-::Ai9+/- heterozygote mice showed positive neuronal staining for tdTomato expression. Conclusion: These findings clearly indicate that Npy2r-expressing neuronal subpopulations in the cervicothoracic ganglia influence heart rates during in vivo optical stimulation of stellate ganglia. Relevance for Patients: The study provides novel targets for devising anti-adrenergic therapies against refractory ventricular arrhythmia. These novel targets should be used as the combinatorial therapies along with β-blockers and surgical interventions.
Background: Alzheimer’s disease (AD) is a debilitating neurodegenerative disease and the main cause of age-related dementia. The incidence and financial burden of this brain disorder are expected to increase significantly in the coming decades. Establishing a definitive diagnosis of AD is a long and costly process involving multiple clinical assessments and a range of imaging and laboratory tests. Aim: This review investigates the potential application of Fourier-transform infrared (FTIR) spectroscopy in the diagnosis and screening of AD in the elderly, highlighting the advantages and limitations of this optical diagnostic method compared with those currently used in clinical practice. Additionally, this review examines the utility of FTIR spectroscopy in the differential diagnosis between AD and closely related neurodegenerative diseases. Conclusion: FTIR spectroscopy-based analysis of blood plasma possesses attractive properties to qualify as a promising screening and diagnostic test for AD. It can also be a potential tool for differentiating between AD and dementia with Lewy bodies with relatively high accuracy. This vibrational spectroscopic technique overcomes many, if not most, of the limitations associated with the laboratory and imaging methods used for AD diagnosis. Relevance for patients: Early detection of AD can be of immense benefit to patients, their caregivers, and society as a whole. It enables patients to plan their lives while retaining full decision-making capacity. It also allows patients to start appropriate treatment early in the disease course, which can delay their need for healthcare services.
Guillain–Barré syndrome (GBS) causes acute flaccid paralysis and long-term motor and functional deficits, often necessitating prolonged, multidisciplinary rehabilitation. In recent years, rapid advances in biomedical and digital technologies have broadened the therapeutic landscape for neurorehabilitation; however, their use and methodological quality in GBS have not yet been comprehensively reviewed. Objective: This scoping review systematically maps and synthesizes emerging rehabilitation technologies in GBS, grouping them into five clusters: robotics, electrical/biofeedback therapies, virtual and telerehabilitation, augmented reality/sensor-based systems, and hybrid/interactive platforms. It integrates both primary studies (n = 18) and systematic reviews (n = 3) to assess outcome trends (motor recovery, functional independence, and secondary measures such as quality of life, usability, and engagement) and to evaluate methodological quality using the Joanna Briggs Institute’s critical appraisal tools. Relevance for patients: The mapping of technologies demonstrated consistent improvements in motor recovery and functional outcomes among GBS survivors, especially with robotic and electrical/biofeedback therapies. High-quality evidence (≥80% “Yes”) predominated in this area, supporting the safe and effective integration of technology-based rehabilitation. The review highlights the clinical relevance of engineering-assisted, interactive strategies that foster adaptive, personalized recovery and enhance patient engagement throughout long-term neurorehabilitation.
Background: Pulmonary embolism (PE) is a major global health concern and the third leading cause of cardiovascular mortality in the U.S. There are various treatment options available for the treatment of intermediate-to-high risk acute PE, including catheter-based treatments, surgical embolectomy, and systemic thrombolysis. Objective: To perform a systematic review and Bayesian network meta-analysis (NMA) comparing the safety and efficacy of advanced therapies in patients with intermediate-to-high risk acute PE. Methods: We searched PubMed/Medline, Embase, and Scopus for relevant studies published until August 30, 2024, and performed a Bayesian NMA to synthesize direct and indirect evidence using the Bayesian inference Using Gibbs Sampling to conduct a Network meta-analysis package in R. Results: Of 1,586 studies, 47 met the inclusion criteria, of which 45 were non-randomized. A total of 267,695 acute intermediate-to-high risk PE patients were included in the analysis, receiving one of five advanced interventions: ultrasound-assisted thrombolysis (USAT), standard catheter-directed thrombolysis (sCDT), catheter-based embolectomy, surgical pulmonary embolectomy (SE), or systemic thrombolysis. USAT had the lowest risk of short-term (94.11), long-term mortality (94.67), major bleeding (90.38), and risk of blood transfusions (91); sCDT had the lowest risk of intracranial hemorrhage (86.2), and SE had the lowest risk of any bleeding (99.37) and gastrointestinal bleeding (87.46) based on Surface Under the Cumulative Ranking values. Conclusion: In our study, USAT offers significant short- and long-term mortality benefits with the lowest risk of major bleeding and transfusion requirements, while sCDT is ideal for patients at high-risk for intracranial hemorrhage. Relevance for patients: Among catheter-based therapies for acute intermediate-to-high-risk PE, USAT offered the best clinical and safety outcomes.
Background: Historically, intervertebral fusion required bone bridging for stability. Bioactive interbody devices enable bone integration at the endplate–implant interface, prompting an updated radiographic assessment and classification system that recognizes implant adhesion as contributing to fusion. Aim: This study aims to develop and evaluate a reliable computed tomography (CT)-based grading system for assessing spinal fusion and stability associated with interbody devices, including factors such as osseointegration, implant type, and bone connectivity. Methods: A novel fusion grading system was developed, incorporating both bone and fusion consolidation through and around the device and the apposition of bone to the implants. A total of 10 cases with one-year postoperative CT scans were provided for the survey. Surveys were administered twice, more than two weeks apart and in a different order. Inter- and intra-rater reliability were assessed using the intraclass correlation coefficient (ICC). Results: A total of 51 spine surgeons participated, of whom 37 completed both survey rounds. For all 51 participants, the ICC was 0.618 (95% confidence interval = 0.435–0.834; p < 0.001), and the mean intra-rater reliability was 0.778 (standard deviation = 0.211). Four raters had outlier intra-rater scores, with an average of 0.259. After removing these four raters (10.8% of the cohort) and analyzing the remaining 89.2% of raters, the ICC was 0.628 (95% confidence interval = 0.445–0.841; p < 0.001), and the mean intra-rater reliability was 0.831 (standard deviation = 0.125; p ≤ 0.015). Conclusions: The novel CT-based classification system showed moderate-to-good inter-rater and good-to-excellent intra-rater reliability in clinical cases. Future work should use it to assess the relative contributions of on-growth, in-growth, and bone healing around bioactive interbody devices. Relevance for patients: This new classification system may be utilized to account for the stabilizing effects of bone in-growth at the implant interface when studying fusion with bioactive implants.
Background: Semaglutide is a long-acting glucagon-like peptide-1 receptor agonist used in the management of type 2 diabetes mellitus. Broader access to semaglutide therapy may be supported by clinically suitable alternative formulations if pharmacokinetic comparability with the reference product is established. Aim: To evaluate the pharmacokinetic bioequivalence of semaglutide 0.5 mg solution for injection developed by Dr. Reddy’s Laboratories Limited, India, compared with Ozempic® (semaglutide) 0.5 mg solution for injection in a pre-filled pen under fasting conditions in healthy adult subjects. Methods: This was an open-label, balanced, randomized, two-treatment, single-dose, parallel-group bioequivalence study. Eighty healthy volunteers were enrolled, 78 were dosed, and 74 were included in the pharmacokinetic and statistical analyses. Plasma semaglutide concentrations were measured using a validated liquid chromatography–tandem mass spectrometry method across 31 sampling time points up to 816 hours after dosing. Primary pharmacokinetic endpoints were Cmax, area under the curve (AUC)0–t, and AUC0–∞. Bioequivalence was concluded if the 90% confidence intervals for the test/reference ratio were within 80% to 125%. Results: The 90% confidence intervals were 93.11%–107.22% for Cmax, 93.76%–112.65% for AUC0–t, and 91.48%–104.47% for AUC0–∞, meeting bioequivalence criteria for all primary parameters. Forty-six non-serious adverse events were reported in 28 subjects. No serious adverse events or deaths occurred. Conclusion: The test semaglutide formulation was bioequivalent to the reference product and was generally well tolerated in healthy adult subjects under fasting conditions. Relevance for patients: A pharmacokinetically comparable semaglutide injection may help expand access to long-term semaglutide treatment where innovator product cost or availability may limit patient use.
Background: Randomized controlled feeding trials are ideal for studying diet-disease relationships, but interpreting results requires accurate dietary adherence measures. Aim: This study assesses dietary adherence using self-reported measures and estimates from predictive equations in the National Institute of Diabetes and Digestive and Kidney Diseases Body Weight Planner and evaluates differences in adherence across diet treatments and study periods in a feeding trial. Methods: In a randomized, counterbalanced, crossover trial, 12 African American adults with prediabetes or early, untreated type 2 diabetes received either a plant-based diet (PBD) or an isocaloric control diet for eight weeks, followed by a washout period and the alternate diet. Primary measures included self-reported dietary adherence and estimates of actual caloric intake using predictive equations. T-tests evaluated differences by treatment and period. Results: Nine participants completed the study. Study completers (n = 9) consumed a greater caloric excess beyond the kilocalories provided by the study diets during the control treatment (480.6 ± 525.9 kcal/day) versus the PBD treatment (126.0 ± 585.4 kcal/day; p = 0.025) and in the second period (464.8 ± 592.4 kcal/day) versus the first period (141.8 ± 529.5 kcal/day; p = 0.033). Participants also reported omitting more kilocalories from the study diets during the PBD treatment (422.4 ± 289.1 kcal/day) versus the control treatment (276.4 ± 185.0 kcal/day; p = 0.015). Conclusion: Predictive equations showed significant differences in dietary adherence by treatment and period, underscoring the limitations of self-reported intake and highlighting the need for more objective measures. Relevance for patients: Variable adherence to study diets suggests the original study should be viewed as an effectiveness study, not an efficacy study.
Background: Type 2 diabetes mellitus (T2DM) is a progressive cardiometabolic disease in which many patients require treatment intensification despite lifestyle intervention and evidence-based pharmacotherapy. Oleanolic acid (OA), a pentacyclic triterpenoid found in olives and other plants, has shown insulin-sensitizing, antioxidant, anti-inflammatory, and hepatometabolic effects in experimental models. Aim: This narrative translational review evaluates OA as a potential investigational adjunct in T2DM, with emphasis on formulation-dependent bioavailability, translational limitations, clinical endpoints, safety, and patient relevance. Methods: We synthesized mechanistic, preclinical, pharmacokinetic, clinical, regulatory, and trial-registry evidence. As this was not a systematic review or meta-analysis, the evidence was interpreted narratively, with attention to study design, formulation, dose, model validity, comparator use, and potential sources of bias. Results: Preclinical studies suggest that OA may influence insulin signaling, hepatic glucose production, oxidative stress, inflammatory pathways, lipid metabolism, and β-cell stress. However, most mechanistic data derive from cell or animal models, often using high doses, short treatment durations, or models with limited human predictability. Human evidence remains limited. PREDIABOLE reported reduced progression from prediabetes to T2DM after long-term intake of OA-enriched olive oil, while BIO-OLTRAD demonstrated measurable systemic exposure after a 30 mg OA dose in functional olive oil. OLTRAD is testing this formulation as an adjunct to metformin-based therapy. Conclusion: OA is a plausible investigational adjunct, but clinical efficacy in established T2DM has not been established. Its future value depends on reproducible exposure, clinically meaningful outcomes, long-term safety, compatibility with contemporary therapies, and avoidance of disease-treatment claims unsupported by human trials. Relevance for Patients: OA-enriched functional foods may eventually complement, but should not replace, evidence-based diabetes treatment.
Background: Hemifacial spasm (HFS) is a chronic and disabling movement disorder commonly affecting older adults. Although botulinum toxin (BoNT) is an established treatment, standardized and multidimensional assessments of severity remain limited. Aim: This study evaluates the therapeutic efficacy of the HFS Severity Score (HFSS), a newly developed scale incorporating five symptom domains, and compares its responsiveness with that of the Jankovic Rating Scale (JRS). Methods: This retrospective study included 18 patients aged 65 years or older who were treated with 10 units of BoNT. HFSS and JRS were assessed at baseline and 4 weeks post-injection by two blinded neurosurgeons. Inter-rater reliability (intraclass correlation coefficient [ICC]) and internal consistency (Cronbach’s α) were calculated. Pre–post differences were evaluated using the Wilcoxon signed-rank test. Convergent validity was examined using Spearman correlation between baseline HFSS and JRS. Responsiveness was assessed using change–score correlations and standardized response means (SRMs). Scatter plots were generated to visualize relationships between the scales. Results: Mean HFSS improved significantly from 9.39 to 3.72 (p<0.001), with all subdomains showing improvement. Baseline HFSS and JRS demonstrated a strong correlation (ρ = 0.82, p<0.001), while ΔHFSS and ΔJRS showed a weaker association (ρ = 0.32), reflecting a floor effect in post-treatment JRS scores. SRM scores indicated high responsiveness for HFSS (1.73) and JRS (1.54), while the ICC (0.91) and Cronbach’s α (0.85) confirmed excellent reliability. No adverse events were observed. Conclusion: BoNT treatment is effective and well-tolerated in older adults with HFS. HFSS is a reliable, multidimensional, and highly responsive tool that complements existing scales and enhances clinical assessment. Relevance for Patients: Older adults with HFS may achieve symptom relief with BoNT. HFSS provides a comprehensive metric that can enhance personalized care and reduce reliance on medication.
Background: The blood-brain barrier (BBB) is an intricate structure of the vascular endothelium that regulates trafficking required for cerebral homeostasis via tightly regulated influx and efflux transport mechanisms. It also performs a critical function in mediating communication between the periphery and the central nervous system (CNS). The BBB is designed to maintain a precisely regulated microenvironment conducive to normal neuronal activity. The development of in vitro BBB models has been driven by the need for a fast, reliable, and cost-effective tool to study the complexities of the BBB and to screen potential CNS drugs. Aim: This review provides readers with a concise yet comprehensive introduction to the fundamental histology of the BBB. This background is essential for interpreting model design constraints and limitations in BBB simulation. Following that, we thoroughly examine in vitro models, providing a comprehensive analysis of their applications and the equations used to assess specific BBB parameters. Relevance for patients: From a translational and clinical perspective, in vitro models of the BBB have the potential to provide novel insights into brain pathophysiology under adverse conditions, including brain tumors, traumatic injuries, strokes, and neurodegenerative disorders, and ultimately aid in the discovery of effective treatment strategies.
Background: Macular edema secondary to retinal vein occlusion (RVO-ME) impairs vision. Intravitreal ranibizumab is commonly used, but the adjunctive value of acupuncture remains unclear. Objective: To evaluate the clinical efficacy and safety of acupuncture combined with intravitreal ranibizumab injection for RVO-ME. Methods: Patients with RVO-ME (n = 45) were randomized into a control group (ranibizumab monotherapy) and an acupuncture group (ranibizumab and acupuncture). Both groups received monthly intravitreal ranibizumab (0.5 mg/0.05 mL) for 3 months, with a total follow-up of 6 months. Best-corrected visual acuity (BCVA), central macular thickness (CMT), macular vessel density (MVD) of superficial vascular complex (SVC), and deep vascular complex (DVC), foveal avascular zone (FAZ) area, and safety outcomes were assessed. Results: At 3 and 6 months post-treatment, BCVA, CMT, SVC-MVD, and DVC-MVD improved significantly in both groups (p<0.05). The acupuncture group showed significant reductions in SVC-FAZ and DVC-FAZ at 6 months (p<0.05), whereas the control group showed no such changes. Between-group differences at 6 months were significant for BCVA, CMT, DVC-MVD, and DVC-FAZ (p<0.05), with DVC-MVD differing significantly at 3 months (p<0.05). Adverse events (subconjunctival hemorrhage, elevated intraocular pressure, subcutaneous hemorrhage) were mild and comparable between groups (p>0.05). Conclusion: Acupuncture combined with ranibizumab effectively reduces RVO-ME, improves the microvascular structure of the macula, and is safe and reliable, with no serious adverse reactions. Relevance for patients: Patients with vision loss from RVO-ME may benefit from this combined treatment, which improves visual acuity, reduces retinal edema, and supports better long-term macular health with a favorable safety profile.
Background: Viral elements, such as human papillomavirus (HPV), Epstein–Barr virus (EBV), endogenous retroviruses (e.g., human endogenous retrovirus K), and bacteriophages, are known to regulate oncogenic signaling. To assess the ability of patient-level virome activity and host-pathway disruption to predict patient survival, we developed a Trans-Kingdom Signaling Index (TKSI). Methods: We examined 320 patients with HPV-positive head and neck squamous cell carcinoma, HPV-positive cervical cancer, and EBV-positive stomach adenocarcinoma. Viral features, including HPV E6/E7, virome modules, phage CpG DNA, phage structural proteins, and viral double-stranded RNA, along with tumor RNA sequencing data, were analyzed using single-sample Gene Set Enrichment Analysis on six host pathways: nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB), cGAS–STING, p53, MYC, EMT, and PD-L1. A coupling matrix (K) was constructed to connect viral modules to host pathways, and TKSI was calculated, normalized, and dichotomized into TKSI-high and TKSI-low. Results: TKSI values followed an approximately normal distribution and stratified survival independent of tumor type. Patients with high TKSI exhibited lower overall survival (median overall survival 18.2 vs. 29.4 months) and an adjusted hazard ratio of 1.6 (log-rank p=0.018). TKSI–survival associations were robust, with bootstrapped 95% confidence intervals supporting these findings. Observed virome–host interactions corresponded to known mechanisms, including HPV-mediated suppression of p53, EBV microRNA-mediated PD-L1 expression, human endogenous retrovirus K-mediated activation of MYC, and phage CpG–TLR9–NF-κB. Conclusion: Virome–host interactions significantly influence cancer prognosis and signaling. TKSI integrates viral and host mechanisms to improve risk stratification. Relevance for patients: TKSI-derived virome–human quantification enhances patient stratification and may guide the development of virome-responsive biomarkers for precision oncology.
