Search Results (22,320)

Background/Objectives: Renal denervation (RDN) has re-emerged as an adjunctive treatment option for patients with uncontrolled or resistant hypertension, with contemporary sham-controlled trials showing a modest but reproducible reduction in out-of-office blood pressure. However, in routine practice, apparent treatment resistance often reflects pseudoresistance caused by the white-coat effect, poor measurement quality, therapeutic inertia, or nonadherence. This review aimed to summarize the contemporary evidence on renal denervation in uncontrolled or resistant hypertension and to propose a pragmatic, measurement-first framework for patient selection, integration into routine care, and a structured post-procedural response assessment. Methods: This article is a narrative, implementation-focused review. A structured search of PubMed, Embase, Cochrane CENTRAL, and Web of Science was performed from database inception through January 2026. We prioritized the randomized sham-controlled RDN trials, major meta-analyses, guidelines, consensus documents, and studies addressing ABPM, HBPM, medication adherence, and telemonitoring. Results: The contemporary sham-controlled trials support RDN as an adjunctive option with a modest blood pressure-lowering effect, which is best assessed by out-of-office measurements. The placebo-adjusted reductions in ambulatory systolic blood pressure were generally in the 4–6 mmHg range. Appropriate use requires the confirmation of sustained uncontrolled hypertension, the exclusion of pseudoresistance, the optimization of treatment, and an adherence assessment. We identified three phenotypes most likely to benefit and proposed a three-axis framework for a response assessment at 3 and 6 months. Conclusions: RDN should be viewed not as a substitute for antihypertensive therapy but as a program-based adjunct for carefully selected patients. The measurement-first care pathway presented here should be interpreted as a pragmatic clinical model intended to operationalize the available trial and guideline evidence in routine care, rather than as a prospectively validated algorithm or formal consensus recommendation. Full article

Animal-assisted services (AASs) are increasingly integrated into healthcare, education, and social support settings. However, empirical evidence on the emotional well-being of participating dogs remains limited. This study investigates how dog, session, handler, and client factors influence dogs’ affective states during animal-assisted activities (AAAs), education (AAE), coaching (AAC), and therapy (AAT). A total of 837 sessions involving 63 dogs and 30 handlers were observed, with behavioural scoring and statistical analyses used to analyse the data. Principal Component Analysis then identified key affective components, including playfulness, comfort, anxiety, and uncertainty, which explained 45–61% of the variance. Session circumstances, as well as the characteristics of handlers, clients, and individual dogs—including age, experience, and gender—significantly influenced dogs’ responses. Specifically, older dogs were less playful but more settled, while experience was linked to positive affect in AAAs and AAT, but not in AAC. Female dogs demonstrated increased uncertainty and arousal in AAAs and AAE. The impact of session length varied by context. In AAC, unfamiliar handlers increased tension. Additionally, younger clients were associated with heightened uncertainty or tension in dogs across AAAs, AAC, and AAE. In light of these findings, optimising dog welfare requires matching dogs to suitable roles, attentive session planning, and managing workload. Full article

Malignant gliomas remain highly treatment-resistant brain tumors despite surgery and adjuvant therapies. Targeted toxin therapies represent a unique strategy that exploits receptor-mediated cellular internalization to deliver cytotoxic components that result in the irreversible inhibition of protein synthesis independent of DNA damage or cell-cycle status. Advances in molecular profiling, toxin engineering, and delivery development have refined components targeting IL4Rα, IL13Rα2, EGFR/EGFRvIII, uPAR, and the transferrin receptor. Early clinical studies demonstrated biological activity, acceptable safety, and durable responses in subsets of patients, validating the fundamental mechanism of this approach. However, late-phase trials failed to demonstrate a population-level survival benefit, largely due to variability in delivery, receptor heterogeneity, and limitations in trial design rather than insufficient cytotoxic potency. Recent progress has focused on multiple receptor-targeting and delivery systems capable of achieving reliable intratumoral distribution. MRI-guided convection-enhanced delivery, vector-mediated toxin expression, and blood–brain barrier penetrant nanocarriers now enable more precise tumor targeting. Emerging evidence also reveals that toxin-mediated cytotoxicity can enhance antitumor immune responses, supporting their integration with immunotherapy. These advances position targeted toxins as precision cytotoxic compounds whose success depends on coordinated molecular targeting, delivery optimization, and biologically stratified patient selection, establishing a translational pathway for future glioma therapy. Full article

Background/Objectives: Diffuse large B-cell lymphoma (DLBCL) and high-grade follicular lymphoma (FL) are aggressive B-cell malignancies predominantly affecting older adults. R-CHOP remains the frontline standard of care, with frail and elderly patients requiring attenuated regimens such as R-mini-CHOP. Real-world comparative data in elderly and Hispanic populations remain limited. We aimed to evaluate outcomes of R-mini-CHOP versus R-CHOP in elderly patients and to explore potential differences by ethnicity. Methods: Single-center retrospective analysis of adult patients older than 70 years with DLBCL and high-grade FL, treated between January 2014 and June 2025. Clinical characteristics, treatment responses, and survival outcomes were analyzed. The overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan–Meier method. Results: A total of 136 patients were included (72 R-mini-CHOP; 64 R-CHOP). Patients receiving R-mini-CHOP were older (median 82 vs. 74 years) and had higher-risk features. Overall response rates were 88.7% and 92.6% in the R-mini-CHOP and R-CHOP groups, respectively. Two-year OS was 79.3% for R-mini-CHOP and 76.7% for R-CHOP. Median OS and PFS were not reached in either group. Elevated lactate dehydrogenase (LDH) was associated with an inferior response. We identified a trend toward better response with R-CHOP in Hispanic patients, although this was not statistically significant. Conclusions: In this real-world cohort, R-mini-CHOP achieved response and survival outcomes comparable to R-CHOP despite worse baseline characteristics. These findings support the use of dose-attenuated therapy in frail and elderly patients and suggest that equitable access to care may mitigate ethnic disparities in outcomes. Full article

Gastrointestinal malignancies remain among the leading causes of cancer-related morbidity and mortality worldwide, largely due to late diagnosis, aggressive tumor progression, and resistance to conventional therapies. Tumor angiogenesis and the tumor microenvironment (TME) play crucial roles in the initiation, growth, and metastatic dissemination of gastrointestinal cancers. Hypoxia-driven signaling pathways, including hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β), and inflammatory mediators such as NF-κB and MAPK, are key regulators of these processes. Increasing evidence suggests that natural products derived from medicinal plants and other biological sources may modulate these pathways and exhibit anti-angiogenic, anti-inflammatory, and anti-fibrotic properties. This review summarizes recent findings on natural compounds that influence angiogenesis and tumor microenvironment dynamics through the regulation of molecular pathways involved in hypoxia signaling, extracellular matrix remodeling, fibroblast activation, and inflammatory responses. Compounds such as neotuberostemonine, aloperine, silymarin derivatives, tanshinone IIA, berberine, asiatic acid, and phloretin demonstrate promising biological activities in experimental models by targeting pathways including HIF-1α, PI3K/AKT/mTOR, TGF-β/Smad, and NF-κB signaling. However, further studies focusing on gastrointestinal cancer models and clinical validation are required to translate these preclinical observations into effective therapeutic strategies. Full article

The sodium/iodide symporter (NIS/SLC5A5) is a major determinant of radioiodine therapy efficacy in differentiated thyroid cancer (DTC). This narrative review examines the molecular mechanisms underlying NIS dysregulation and radioiodine refractoriness in DTC. Reduced NIS expression or function in radioiodine-refractory DTC is associated with multiple mechanisms, including transcriptional suppression linked to MAPK/ERK and PI3K/AKT pathway activation and disruption of thyroid differentiation programs; epigenetic silencing involving SLC5A5 regulatory regions; impaired protein trafficking and membrane localization; and post-transcriptional regulation by microRNAs such as miR-221-3p, miR-222-3p, miR-146b-3p, and miR-204-5p. Genetic alterations including BRAF V600E and TERT promoter mutations are associated with dedifferentiated tumor phenotypes and poor radioiodine response. Redifferentiation approaches using MAPK pathway inhibitors such as selumetinib and dabrafenib can restore iodine uptake in selected patients, although the overall clinical applicability of these strategies remains under evaluation. A better understanding of these mechanisms may support improved biologic stratification and more selective therapeutic decision-making in radioiodine-refractory DTC. Full article

Brain metastases represent a heterogenous group of tumors, with distinct characteristics and prognosis, depending on the primary malignancy and on the patient performance status. In up to 28% of cases, neurological symptoms from a brain metastasis are the initial clinical manifestation of the primary cancer. If the primary neoplasm remains unidentified, patients are diagnosed with Brain Metastases for Cancer of Unknown Primary (BM-CUP). While brain metastases are far more common than primary brain tumors, CUP represents a rare malignancy, accounting for 2–5% of all cancer cases. It is characterized by an aggressive clinical course, rapid metastatic spread, low response rate to chemotherapy, and poor prognosis. Understanding BM-CUP remains a challenge, and being such a rare disease, there is still a significant lack of consensus regarding the management of these patients. Nevertheless, recent progression in diagnostic techniques, immunohistochemistry, and genomic sequencing open a new horizon to personalized therapies in selected cases. However, limitations persist, including biological heterogeneity and limited access to genomic sequencing, often leading to the use of empirical treatment. This review synthesizes recent advancements in the diagnosis and management of BM-CUP, highlighting the importance of a structured therapeutic approach for optimizing survival outcomes and preserving quality of life in this challenging patient population. Full article

Thyroid eye disease (TED) is an autoimmune inflammatory disorder primarily affecting orbital tissues, but ocular surface and adnexal involvement represent a frequent and clinically significant component of disease burden. Beyond mechanical exposure resulting from eyelid retraction and proptosis, TED-associated ocular surface disease arises from complex interactions between immune activation, epithelial stress, glandular dysfunction, and altered neuro-epithelial signaling. Increasing use of systemic immunomodulatory therapies, biologics, and orbital radiotherapy has improved control of orbital inflammation; however, their molecular and cellular effects on ocular surface homeostasis remain incompletely defined. This review summarizes current evidence on the cellular and molecular mechanisms underlying ocular surface dysfunction in TED and examines how disease-modifying therapies influence epithelial integrity, tear film stability, meibomian and lacrimal gland function, and local immune signaling. Key pathways discussed include cytokine-mediated inflammation, thyroid-stimulating hormone receptor and insulin-like growth factor-1 receptor crosstalk, pro-fibrotic signaling, neuro-inflammatory mechanisms, and epithelial stress responses involving mitogen-activated protein kinase and nuclear factor kappa B pathways. We further highlight the challenge of disentangling therapy-induced molecular effects from persistent exposure-related mechanical stress. Understanding how TED therapies modulate ocular surface and adnexal homeostasis is essential for optimizing integrated management strategies that address both orbital inflammation and long-term ocular surface stability. Full article

Background: An increasing number of reports showed patients with bulky tumors after lattice radiation therapy (LRT) treatment achieved good local control. However, in these reports, LRT was previously used primarily for palliation. We reported a case that LRT plays a synergistic role in the radical treatment of locally advanced bulky cervical cancer (LABCC) combined with INTERLACE study protocol. Methods: The patient was a 54-year-old female with LABCC and treated with LRT combined with the INTERLACE study protocol. She received three fractions of 3 Gy each to the gross tumor volume (GTV) and three fractions of 9 Gy each to the lattice therapy volume (LTV), on an emergent basis, using volumetric modulated arc therapy (VMAT). Subsequently, according to the INTERLACE study protocol, chemotherapy and radiotherapy were carried out and the standard follow-up examinations were conducted. Adverse events (AEs) were assessed according to the Common Terminology Criteria for AEs (CTCAE) version 5.0. Results: The patient initially received LRT, which reduced the tumor burden and controlled bleeding. After this was combined with the INTERLACE study protocol, the complete clinical response (cCR) was achieved and they maintained this status for 13 months after the completion of concurrent chemoradiotherapy (CCRT), with only manageable grade IV hematological toxicity observed after the completion of CCRT. During this period, only manageable grade IV hematological toxicity (platelet count 16 × 10⁹/L, white blood cell count 0.33 × 10⁹/L) was observed. Conclusions: In this case, LRT combined with INTERLACE study protocol appears to be a safe and effective for the treatment of LABCC which improved the patient’s quality of life without uncontrolled treatment-related toxicity. Full article

Background: Episodic ataxia type 2 (EA2) is the most common subtype of episodic ataxia and is primarily caused by pathogenic variants in the CACNA1A gene. Although classically characterized by paroxysmal ataxia, CACNA1A-related disorders are increasingly recognized as an age-dependent phenotypic continuum that extends beyond episodic cerebellar dysfunction to include fluctuating weakness, persistent neurological signs, and neurodevelopmental impairments. Case report: A 12-year-old boy presented with episodic vertigo. His medical history was notable for infantile paroxysmal tonic upward gaze beginning at 6 months of age. From the age of 7 years, he developed frequent episodes of vertigo and ataxia lasting 2 to 3 h. At 10 years of age, he experienced an episode of acute lower limb weakness with diminished deep tendon reflexes, without prominent ataxia. Guillain–Barré syndrome was initially suspected, and he received two courses of intravenous immunoglobulin, with only transient improvement. Neurophysiological studies were largely unremarkable, except for an isolated decremental response on repetitive nerve stimulation. In addition to paroxysmal events, he exhibited persistent interictal cerebellar signs, including dysmetria, dysdiadochokinesia, and downbeat nystagmus. Neuropsychological testing revealed mild intellectual disability with prominent visuospatial deficits. Trio-based whole-exome sequencing identified a de novo CACNA1A splice donor variant (c.978 + 1G > A), confirming the diagnosis of EA2. Treatment with acetazolamide resulted in marked improvement in episodic ataxic events. Conclusions: This case highlights EA2 as part of a broader CACNA1A-related phenotypic continuum rather than a purely paroxysmal disorder. Awareness of atypical and age-dependent manifestations is crucial to avoid diagnostic pitfalls and to facilitate the timely initiation of targeted therapy and appropriate developmental support. Full article

Background/Objectives: Uterine serous carcinoma (USC) is an aggressive subtype of endometrial cancer characterized by high recurrence rates and poor response to conventional therapies, resulting in unfavorable clinical outcomes. Eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid, has demonstrated anti-cancer activity in multiple malignancies. Methods: This study used two USC cell lines, ARK1 and SPEC2, to evaluate the effects of EPA on cell proliferation, invasion, cell cycle profile, stress response, and apoptosis. The potential synergistic effects of EPA combined with carboplatin were also examined. Western blotting was used to examine EPA’s effects on downstream pathways related to cellular stress, inflammation, and epithelial–mesenchymal transition (EMT). Results: EPA treatment markedly reduced cell proliferation and colony formation, with IC₅₀ values of 28.96 µM for ARK-1 cells and 14.96 µM for SPEC-2 cells compared with control groups. It also induced G1 phase cell cycle arrest, increased cellular stress, triggered caspase-dependent apoptotic cell death, and suppressed invasive capacity. Moreover, EPA effectively counteracted TNF-α-stimulated upregulation of COX-2 and phosphorylated NF-κB. The combined treatment with EPA and carboplatin resulted in synergistic inhibition of cell viability and migration. Western blotting analysis showed that EPA attenuates the NF-κB and AKT/mTOR signaling pathways, promotes the expression of cellular stress-related proteins, and inhibits the expression of EMT-related proteins in both cell lines. Conclusions: EPA exhibits potent anti-tumor activity against USC cells and enhances the efficacy of carboplatin. These data indicate that EPA has potential as a low-toxicity, multi-target adjuvant treatment for USC, necessitating additional pre-clinical and clinical investigation. Full article

Silk fibroin (SF) is an ideal biomaterial for next-generation clinical wound dressings due to its biocompatibility and tunable mechanical properties. Cell therapies for wound healing have explored using SF as the base for delivering beneficial cargo; however, retention is poor due to exudate “wash out.” To address concerns with the premature release of cargo from SF-fabricated wound dressings, we utilized amine-reactive chemistry to conjugate SF mats with azido-reactive dibenzocyclooctyne (DBCO) that can then attach complementary azido-tagged cargo through chemoselective immobilization. SF mats were made using electrospinning of a 1:1 SF/PCL solution and were then conjugated with N-Hydroxysuccinimide-dibenzocyclooctyne ester (DBCO). PBS soaking was used for control SF mats. SF mats were then imaged and characterized using the following metrics: pore size, fiber alignment, fiber distribution, fiber diameter, ultimate tensile strength, tangent modulus, proteolytic degradation, absorption, and retention. Successful DBCO conjugation of SF mats was confirmed through the presence of the Az-Cy5 dye while exhibiting no significant changes to the DBCO SF mats in any of the tested metrics compared to controls. Our results provide evidence that the amine chemistry responsible for the DBCO conjugation does not alter important SF mat properties. This confirms that DBCO augmentation paired with Az-Cy5 tags may be a viable approach for immobilizing different therapeutic cargoes to aid wound healing efforts. Full article

Viral hemorrhagic fevers (VHFs) comprise a heterogeneous group of severe infectious diseases that continue to represent a major global health concern. Although many VHFs remain endemic to regions of Africa, Asia, and the Americas, their wide geographic distribution, together with increasing international travel and global trade, facilitates the importation of cases into non-endemic areas and raises the risk of secondary transmission under favorable ecological and epidemiological conditions. These infections are frequently associated with high case-fatality rates and impose a substantial social and economic burden, including pressure on healthcare systems, disruption of essential services, and long-term physical and psychological sequelae among survivors. Despite notable advances in recent years, therapeutic options for VHFs remain limited. Supportive care continues to represent the cornerstone of clinical management for most infections, while pathogen-targeted therapies are available only for a restricted number of diseases. Monoclonal antibody-based therapies have achieved the most significant regulatory success to date, particularly for Ebola virus disease. In parallel, several small-molecule antivirals have been investigated in preclinical and clinical settings, including during outbreak responses, although inconsistent efficacy and safety concerns have limited widespread approval. Vaccine development has progressed further, with licensed vaccines available for selected VHFs, including Ebola, yellow fever, and dengue, and multiple candidates based on diverse technological platforms advancing through clinical evaluation. In addition to summarizing current therapeutic and vaccine strategies, this review highlights pharmaceutical development considerations relevant to biologic therapeutics and selected vaccine platforms, including formulation stability, pharmacokinetic behavior, delivery routes, storage requirements, and logistical constraints affecting deployment during outbreak responses. Using a comparative cross-pathogen framework, the review synthesizes recent literature to identify translational gaps, regulatory challenges, and future priorities for the development of safer and more effective medical countermeasures against VHFs. Full article

Raman spectroscopy offers unique molecular fingerprinting capability for cancer diagnosis and monitoring, yet its biomedical application is fundamentally limited by weak intrinsic signals and complex biological backgrounds. Composite Raman probes, particularly surface-enhanced Raman scattering (SERS)—based systems, overcome these limitations through synergistic electromagnetic and chemical enhancement combined with functional integration. By engineering plasmonic nanostructures, interfacial electronic states, and molecular architectures, composite Raman probes achieve synergistic electromagnetic and chemical enhancement while incorporating biorecognition units, reporter molecules, and protective coatings to improve stability, specificity, and biocompatibility. In recent years, these probes have evolved from simple signal tags into multifunctional platforms capable of ultrasensitive tumor biomarker detection, high-contrast imaging, surgical guidance, therapy monitoring, and dynamic analysis of the tumor microenvironment (TME). This review systematically summarizes recent advances in composite Raman probes for oncological applications, with an emphasis on material design strategies, enhancement mechanisms, and stimulus-responsive regulation. Representative applications at both molecular and tissue levels are highlighted, including nucleic acid, protein, and exosome detection, as well as in vivo imaging and microenvironmental sensing. Finally, current challenges and future perspectives toward clinical translation are discussed, aiming to provide guidance for the rational design of next-generation Raman probes for precision oncology. Full article

Background: Non-invasive intrauterine resuscitation measures, such as maternal repositioning and intravenous fluid therapy, are used in the presence of suspicious or pathological cardiotocographic (CTG) patterns during labor. However, evidence regarding their link with CTG abnormalities, amniotic fluid color, and immediate neonatal outcomes is limited. Objectives: To analyze the link between maternal repositioning and intravenous fluid therapy and the occurrence of suspicious or pathological intrapartum CTG patterns, as well as their relationship with amniotic fluid color and immediate neonatal effects. Methods: An analytical, observational, prospective study was conducted in women in labor with continuous monitoring. Changes in maternal position, administration of intravenous fluid therapy, CTG patterns, amniotic fluid color, and immediate neonatal outcomes were analyzed. Links were evaluated using appropriate statistical tests, considering maternal positions in isolation and in combination. Results: Maternal repositioning, both alone and in combination, was associated with the presence of suspicious or pathological CTG and with statistically significant differences in the 5 min Apgar score when analyzed as a continuous variable. No significant association was observed between intravenous fluid therapy and CTG patterns or neonatal outcomes. The presence of meconium-stained amniotic fluid was associated with a higher frequency of suspicious or pathological CTG. Conclusions: Maternal repositioning was most frequently applied as a clinical response to a suspicious CTG. Intravenous fluid therapy showed no link with CTG abnormalities or adverse neonatal outcomes. These findings reinforce the need to interpret intrapartum CTG in an integrated manner with the overall clinical context and support the use of maternal repositioning as a non-invasive measure in intrapartum management. Full article