Search Results (275)

Background: Traditional, complementary, and alternative medicine (TCAM) is a promising and increasingly popular approach in managing chronic neck and shoulder pain. Despite recognized benefits for pain relief and well-being, how TCAM facilitates self-care practices is poorly understood. This scoping review maps the existing evidence on TCAM-based self-care strategies for adults with chronic neck and shoulder pain to identify which domains of self-care are addressed and which are overlooked. Methods: We searched five academic databases, including PubMed, Scopus, Embase, Cinahl Complete (EBSCOhost), and Public Health Database (ProQuest). Articles published over a 20-year period that examined the use of TCAM for adults with chronic neck and shoulder pain were included. An analytical framework based on Riegel’s three core components of self-care (maintenance, monitoring, and management) was used to structure and synthesize the findings from included studies. Results: Thirty-three studies met the inclusion criteria. Most research focused on just one or two self-care components, primarily self-care maintenance (e.g., physical activities and treatment adherence) and self-care management (e.g., pain control). However, critical dimensions, such as psychological well-being, social support, work–life balance, and cultural context, were frequently overlooked. Conclusions: To enhance the quality of life for adults with chronic neck and shoulder pain, future TCAM research must adopt a more holistic self-care approach that extends beyond physical symptoms. Our findings highlight the need for integrated research, policy, and clinical services that address the full spectrum of self-care in chronic pain management. Full article

Recognizing emotions accurately in virtual reality (VR) enables adaptive and personalized experiences across gaming, therapy, and other domains. However, most existing facial emotion recognition models rely on acted expressions collected under controlled settings, which differ substantially from the spontaneous and subtle emotions that arise during real VR experiences. To address this challenge, the objective of this study is to develop and evaluate generalizable emotion recognition models that jointly learn from both acted and natural facial expressions in virtual reality. We integrate two complementary datasets collected using the Meta Quest Pro headset, one capturing natural emotional reactions and another containing acted expressions. We evaluate multiple model architectures, including convolutional and domain-adversarial networks, and a mixture-of-experts model that separates natural and acted expressions. Our experiments show that models trained jointly on acted and natural data achieve stronger cross-domain generalization. In particular, the domain-adversarial and mixture-of-experts configurations yield the highest accuracy on natural and mixed-emotion evaluations. Analysis of facial action units (AUs) reveals that natural and acted emotions rely on partially distinct AU patterns, while generalizable models learn a shared representation that integrates salient AUs from both domains. These findings demonstrate that bridging acted and natural expression domains can enable more accurate and robust VR emotion recognition systems. Full article

Conservative management of rotator cuff disorders remains challenging, with no comprehensive, evidence-based framework integrating diagnosis, prognosis, rehabilitation, and biological therapies. Existing recommendations usually address isolated components of care, leading to inconsistent treatment strategies. This article proposes a global, pragmatic protocol for the non-surgical management of rotator cuff lesions, from initial assessment to long-term follow-up. Drawing on clinical expertise supported by recent literature, we outline a stepwise approach that begins with a comprehensive diagnostic process that combines history, clinical examination, and targeted imaging. Based on lesion type, associated shoulder or neurogenic conditions, and patient profile, rotator cuff disorders are stratified into three prognostic categories under conservative care: good, borderline, and poor prognosis, highlighting factors that require treatment adaptation or early surgical consideration. Rehabilitation objectives are structured around four domains: (1) inflammation and pain control, (2) mobility and scapular kinematics, (3) strengthening and motor control with tendon-sparing strategies, and (4) preservation or restoration of anatomy. For each prognostic category, we define a monitoring plan integrating clinical reassessment, ultrasound follow-up, and functional milestones, including return-to-play criteria for athletes. This comprehensive narrative review demonstrates that precise diagnosis and individualized rehabilitation can optimize medical follow-up, active strengthening, and complementary or regenerative therapies. Aligning therapeutic decisions with prognostic and functional goals allows clinicians to optimize patient satisfaction and recovery, providing a clear, evidence-informed roadmap for conservative management of rotator cuff disorders. Full article

Glioblastoma multiforme (GBM) is characterized by aggressive growth, extensive vascularization, high metabolic malleability, and a striking capacity for therapy resistance. Current treatments involve surgical resection and concomitant radiation therapy and chemotherapy, prolonging survival times marginally due to the therapy resistance that is built up by the tumor cells. A growing body of research has identified exosomes as critical enablers of therapy resistance. These nanoscale vesicles enable GBM cells to disseminate oncogenic proteins, nucleic acids, and lipids that collectively promote angiogenesis, maintain autophagy under metabolic pressure, and suppress apoptosis. As interest grows in targeting tumor communication networks, exosome-based therapeutic strategies have emerged as promising avenues for improving therapeutic outcomes in GBM. This review integrates current insights into two complementary therapeutic strategies: inhibiting exosome biogenesis and secretion, and engineering exosomes as precision vehicles for the delivery of anti-tumor molecular cargo. Key molecular regulators of exosome formation—including the endosomal sorting complex required for transport (ESCRT) machinery, tumor susceptibility gene 101 (TSG101) protein, ceramide-driven pathways, and Rab GTPases—govern the sorting and release of factors that enhance GBM survival. Targeting these pathways through pharmacological or genetic means has shown promise in suppressing angiogenic signaling, disrupting autophagic flux via modulation of autophagy-related gene (ATG) proteins, and sensitizing tumor cells to apoptosis by destabilizing mitochondria and associated survival networks. In parallel, advances in exosome engineering—encompassing siRNA loading, miRNA enrichment, and small-molecule drug packaging—offer new routes for delivering therapeutic agents across the blood–brain barrier with high cellular specificity. Engineered exosomes carrying anti-angiogenic, autophagy-inhibiting, or pro-apoptotic molecules can reprogram the tumor microenvironment and activate both the intrinsic mitochondrial and extrinsic ligand-mediated apoptotic pathways. Collectively, current evidence underscores the potential of strategically modulating endogenous exosome biogenesis and harnessing exogenous engineered therapeutic exosomes to interrupt the angiogenic and autophagic circuits that underpin therapy resistance, ultimately leading to the induction of apoptotic cell death in GBM. Full article

Aging is accompanied by progressive gastrointestinal structural and functional decline, increased intestinal permeability, dysbiosis, and impaired mucosal immunity, collectively elevating susceptibility to infections, chronic inflammation, and multimorbidity. These age-related changes are further exacerbated by polypharmacy, metabolic disorders, and lifestyle factors, positioning the gastrointestinal tract as a central driver of systemic physiological decline. Gut-centered interventions have emerged as critical strategies to mitigate these vulnerabilities and support healthy aging. Dietary modulation, prebiotic and probiotic supplementation, and microbiota-targeted approaches have demonstrated efficacy in improving gut microbial diversity, enhancing short-chain fatty acid production, restoring epithelial integrity, and modulating immune signaling in older adults. Beyond nutritional strategies, non-nutritional interventions such as molecular hydrogen and medical ozone offer complementary mechanisms by selectively neutralizing reactive oxygen species, reducing pro-inflammatory signaling, modulating gut microbiota, and promoting mucosal repair. Hydrogen-based therapies, administered via hydrogen-rich water or inhalation, confer antioxidant, anti-inflammatory, and cytoprotective effects, while ozone therapy exhibits broad-spectrum antimicrobial activity, enhances tissue oxygenation, and stimulates epithelial and vascular repair. Economic considerations further differentiate these modalities, with hydrogenated water positioned as a premium wellness product and ozonated water representing a cost-effective, scalable option for geriatric gastrointestinal care. Although preclinical and early clinical studies are promising, evidence in older adults remains limited, emphasizing the need for well-designed, age-specific trials to establish safety, dosing, and efficacy. Integrating dietary, microbiota-targeted, and emerging non-nutritional gut-centered interventions offers a multimodal framework to preserve gut integrity, immune competence, and functional health, potentially mitigating age-related decline and supporting overall health span in older populations. Full article

Photodynamic therapy (PDT) is a minimally invasive therapeutic modality that relies on the activation of photosensitizers (PS) by specific wavelengths of light to generate reactive oxygen species (ROS), resulting in localized cytotoxicity with relative sparing of healthy tissues. Depending on the PS properties, light dose, and intrinsic cellular features, PDT can elicit multiple cell death pathways, including apoptosis, necrosis, and autophagy. Increasing evidence indicates that PDT is also a potent inducer of ferroptosis, an iron-dependent form of regulated cell death driven by excessive lipid peroxidation (LPO), glutathione (GSH) depletion, and inactivation of glutathione peroxidase 4 (GPX4). PDT-derived ROS promote ferroptosis both indirectly by exhausting antioxidant defenses and directly by peroxidizing PUFAs within membrane phospholipids. At the same time, intense oxidative stress generated by PDT can activate adaptive responses such as mitophagy, a selective autophagic process that removes damaged mitochondria to limit ROS production and preserve redox homeostasis. Ferroptosis and mitophagy are therefore tightly interconnected, functioning as opposing yet complementary regulators of cell fate. PDT emerges as a key upstream modulator of the ferroptosis–mitophagy balance, as spatially and temporally confined oxidative stress can shift cellular responses from adaptive mitochondrial quality control to irreversible ferroptotic injury. Despite growing interest in both PDT and ferroptosis, their mechanistic interplay, particularly in relation to mitophagy, remains underexplored. This narrative review provides an integrated overview of current knowledge on how PDT influences ferroptosis and mitophagy, highlighting the molecular mechanisms that connect these pathways and discussing their implications for improving therapeutic efficacy and overcoming resistance. Full article

Background/Objectives: Cancer is a disabling, challenging, and growing global disease. Although early diagnosis and adequate treatment of cancer are developing rapidly, a large part of the population remains without access to specialized services and routinely progresses to uncontrolled pain, poorer quality of life, and suffering. Complementary therapies for pain management and the well-being of patients under palliative care are fundamental tools of integrative oncological medicine. This first version of the protocol was created in August 2023 to structure the aim of this study to investigate the effectiveness of the experimental protocol which uses immersive virtual reality as a meditation tool in patients followed at the Pain Therapy and Palliative Care Service of the CECON Foundation. Methods: This randomized clinical trial, conducted at the Pain Therapy and Palliative Care Service (STDCP) of the FCECON, explores the use of immersive virtual reality to promote regular meditation practice among cancer patients as an effective means of managing pain and improving quality of life. Discussion: The present study has the potential to evaluate the effectiveness of immersive virtual reality as a meditation tool for patients undergoing palliative care, in addition to contributing scientific evidence that supports better decisions in healthcare for the management of cancer pain. Trial registration: Brazilian Registry of Clinical Trials (ReBEC) and ClinicalTrials.gov/NCT06328751/Universal Trial Number (UTN) U1111-1304-3752. Full article

Background: Anxiety is highly prevalent among individuals living with disability, chronic illness, or hospitalisation, yet it often remains insufficiently addressed in healthcare settings. Animal-assisted therapy (AAT) has been proposed as a complementary intervention to reduce anxiety; however, existing evidence is fragmented across populations and methodologies. Methods: A systematic review was conducted following PRISMA 2020 guidelines. The review protocol was registered in PROSPERO (CRD42024494109); no amendments were made to the protocol after registration. Four databases (Scopus, APA PsycInfo, Web of Science, and PubMed) were searched for empirical studies (2013–2023) evaluating AAT delivered by trained professionals using domesticated species and reporting anxiety outcomes in individuals with disability, illness, or hospitalisation. Results: Thirty-one studies met eligibility criteria and were included in the review. Across heterogeneous designs, most interventions—primarily using dogs or horses—reported significant post-intervention reductions in anxiety. Randomised clinical trials consistently showed superior results compared with control conditions. AAT demonstrated beneficial effects across populations including PTSD, paediatric hospitalisation, chronic illness, disability, acute care, and trauma exposure. Long-term outcomes were mixed, and methodological variability limited comparability across studies. Conclusions: AAT appears to be a promising complementary intervention for anxiety management within clinical, psychosocial, and healthcare settings. Evidence supports short-term anxiolytic effects across diverse populations, although standardisation and long-term evaluations remain insufficient. Future research should establish optimal intervention parameters, mechanisms of action, and strategies for integrating AAT into multidisciplinary mental healthcare. Full article

Understanding thrombosis in acute coronary syndromes (ACSs) has evolved through advances in biomarkers, intracoronary imaging, and emerging analytical tools, improving diagnostic accuracy and risk stratification in high-risk patients. This narrative review provides an integrative overview of contemporary evidence from clinical trials, meta-analyses, and international guidelines addressing circulating biomarkers, intracoronary imaging modalities—including optical coherence tomography (OCT), intravascular ultrasound (IVUS), and near-infrared spectroscopy (NIRS)—artificial intelligence–based analytical approaches, and emerging antithrombotic therapies. High-sensitivity cardiac troponins and natriuretic peptides remain the most robust and guideline-supported biomarkers for diagnosis and prognostic assessment in ACS, whereas inflammatory markers and multimarker strategies offer incremental prognostic information but lack definitive validation for routine therapeutic guidance. Intracoronary imaging with IVUS or OCT is supported by current guidelines to guide percutaneous coronary intervention in selected patients with ACS and complex coronary lesions, leading to improved procedural optimization and clinical outcomes compared with angiography-guided strategies. Beyond procedural guidance, OCT enables detailed plaque characterization and mechanistic insights into ACS, while NIRS provides complementary information on lipid-rich plaque burden, primarily for risk stratification based on observational evidence. Artificial intelligence represents a rapidly evolving tool for integrating clinical, laboratory, and imaging data, with promising results in retrospective and observational studies; however, its clinical application in thrombosis management remains investigational due to the lack of outcome-driven randomized trials. In the therapeutic domain, factor XI inhibitors have demonstrated favorable safety profiles with reduced bleeding and preserved antithrombotic efficacy in phase II and early phase III studies, but their definitive role in ACS management awaits confirmation in large, outcome-driven randomized trials. Overall, the integration of biomarkers, intracoronary imaging, and emerging analytical and pharmacological strategies highlights the potential for more individualized cardiovascular care. Nevertheless, careful interpretation of existing evidence, rigorous validation, and alignment with guideline-directed practice remain essential before widespread clinical adoption. Full article

Background and Objectives: Aggressive cancer development is characterized by rapid tumor growth and progressive immune dysfunction. Tumor-derived microRNAs (miRNAs) emerge as master regulators of both malignant transformation and immune evasion, making them promising therapeutic targets. Using the highly aggressive CT-26 peritoneal adenomatosis model, this study explored the potential of selective miRNA inhibition to simultaneously suppress tumor growth and overcome immunosuppression. Methods and Results: Our results revealed that inhibition of miR-155, miR-21, and miR-17 by methylsulfonyl phosphoramidate (mesyl) oligonucleotides exhibited markedly different therapeutic profiles. miR-155 inhibition demonstrated minimal efficacy. miR-21 suppression provided early tumor regression and prevented cancer-associated thymic atrophy, translating into extended survival. miR-17 inhibition displayed delayed but superior tumor growth inhibition, significantly reducing pathologically elevated polymorphonuclear myeloid-derived suppressor cell (MDSC) populations, and nearly doubled animal lifespan. Combination therapy targeting all three miRNAs integrated these complementary mechanisms, maintaining consistent anti-tumor efficacy across early and late stages while providing thymic protection and MDSC reduction. Importantly, therapeutic responses in vivo substantially exceeded predictions based on in vitro tumor cell proliferation and motility measurements, revealing critical contributions of systemic immunomodulation. Conclusions: These findings demonstrate that miRNA inhibition reshapes tumor–immune interactions, positioning anti-miRNA therapeutics as immunomodulatory agents for effective colorectal cancer treatment. Full article

Hereditary ataxias are a heterogeneous group of disorders with overlapping clinical presentations but diverse genetic and molecular etiologies. Biomarkers are increasingly essential to improve diagnosis, refine prognosis, and accelerate the development of targeted therapies. Following PRISMA-ScR guidelines, we conducted a scoping review of PubMed and complementary sources (2010–2025) to map and describe the current landscape of genetic, imaging, fluid, electrophysiological, and digital biomarkers across the most prevalent hereditary ataxias, including SCA1, SCA2, SCA3, SCA6, SCA7, SCA17, SCA27B, dentatorubral–pallidoluysian atrophy (DRPLA), Friedreich’s ataxia (FRDA), RFC1-related ataxia (CANVAS), SPG7, and fragile X-associated tremor/ataxia syndrome (FXTAS). Eligible evidence encompassed observational cohorts, clinical trials, case series, and case reports providing primary biomarker data, with the objective of characterizing evidence breadth and identifying knowledge gaps rather than assessing comparative effectiveness. Across modalities, converging evidence highlights subtype-specific biomarker signatures. MRI volumetry, DTI, and FDG-PET map characteristic neurodegeneration patterns. Fluid biomarkers such as neurofilament light chain are informative across several SCAs and FRDA, while frataxin levels constitute robust endpoints in FRDA trials. Pathology-specific biomarkers such as ataxin-3 are advancing as tools for target engagement and may generalize to future gene-lowering strategies. Electrophysiological and oculographic measures show sensitivity for early disease detection, and wearable technologies are emerging as scalable tools for longitudinal monitoring. This scoping review synthesizes the heterogeneous evidence on hereditary ataxia biomarkers, highlighting multimodal frameworks that link molecular mechanisms with clinical endpoints. Mapping current approaches also reveals substantial variability and gaps across diseases and modalities, underscoring the need for harmonized validation in international multicenter cohorts and systematic integration into future clinical trials to advance precision medicine in hereditary ataxias. Full article

Glioblastoma, isocitrate dehydrogenase (IDH1/2) wild-type (IDH-wildtype), is one of the most aggressive and malignant tumors of the central nervous system, characterized by rapid growth, pronounced cellular heterogeneity, and an exceptionally poor prognosis. The median survival time for patients with glioblastoma, IDH-wildtype, is approximately 15 months after diagnosis, and current multimodal treatment strategies remain largely ineffective. This review focuses on contemporary pharmacotherapeutic approaches used in the management of glioblastoma, IDH-wildtype, including temozolomide-based chemotherapy, corticosteroids for edema control, and antiangiogenic therapy in recurrent disease, with particular emphasis on their clinical efficacy and limitations. In addition, the review discusses emerging targeted therapeutic strategies developed for IDH-mutant diffuse gliomas, which represent a biologically distinct disease entity. Particular attention is given to ivosidenib, a selective inhibitor of mutant IDH1, currently evaluated for the treatment of astrocytoma, IDH-mutant, grade 4. Its epigenetic mechanism of action, involving inhibition of the oncometabolite 2-hydroxyglutarate (2-HG), is outlined, along with preliminary clinical evidence suggesting potential to delay disease progression. Finally, innovative drug-delivery technologies designed to overcome the blood–brain barrier are briefly discussed as complementary strategies that may enhance the efficacy of both conventional and targeted therapies. Overall, future advances in the treatment of diffuse gliomas will likely depend on the integration of molecularly targeted agents, predictive biomarkers, and advanced delivery platforms aimed at improving patient survival and quality of life. Full article

Post-cardiac arrest syndrome (PCAS) remains a major cause of mortality and neurological impairment following successful resuscitation, yet the mechanisms linking global ischemia–reperfusion injury to microvascular and systemic dysfunction are not yet completely understood. While prior work has focused on inflammation, endothelial injury, and circulatory collapse, the central role of platelets in coordinating these pathological processes has not been comprehensively examined. This review provides the first integrated framework positioning platelets as core modulators, rather than secondary participants, in PCAS pathophysiology. We synthesize emerging evidence demonstrating that ischemia and reperfusion transform platelets into potent thromboinflammatory effectors through oxidative stress, DAMP-mediated pattern recognition signaling, and mitochondrial dysfunction. Hyperactivated platelets drive cerebral microthrombus formation, coronary no-reflow, and peripheral organ hypoperfusion, while platelet–leukocyte aggregates, neutrophil extracellular traps, and platelet-derived microparticles amplify systemic inflammation and endothelial injury. We further highlight the clinical significance of dynamic platelet dysfunction in coagulopathy, prognostication, and responses to post-arrest therapies including targeted temperature management and ECMO. Finally, we outline a novel, platelet-centered therapeutic paradigm, emphasizing selective interventions, such as GPVI inhibition, P-selectin blockade, FXI/XIa inhibition, and NETosis modulation, that target pathological platelet activity while preserving essential hemostatic function. In this review, by reframing platelets as the central determinants of PCAS, we report new mechanistic insights and therapeutic opportunities that are complementary to the existing post-arrest strategies and have the potential to improve survival and neurological outcomes after cardiac arrest. Full article

Transanal Irrigation (TAI) and Colon Hydrotherapy (CHT) represent emerging therapeutic options that may complement first-line interventions or serve as rescue treatments for chronic constipation and fecal incontinence. Their clinical utility depends on patient characteristics, specific therapeutic goals, device features, and probe type, as well as the procedural setting. This review presents the various pathophysiological contexts in which these techniques can be applied, analyzing their specific characteristics and potential pros and cons. Moreover, these interventions are also considered within a Psycho-Neuro-Endocrino-Immunological (PNEI) framework, given the potential influence of intestinal function and microbiota modulation on the bidirectional communication pathways linking the enteric nervous system, neuroendocrine regulation, immune activity, and global patient well-being. Since there is not yet enough scientific data on this topic, future research should prioritize randomized controlled trials comparing these techniques with other standard treatments (e.g., laxatives or dietary fiber) in defined patient populations. Longitudinal studies will also be essential to clarify long-term safety, potential effects on microbiota, and both risks and benefits. Standardization of technical procedures also remains a critical need, especially regarding professional competencies, operating parameters (e.g., instilled volumes and pressure ranges), and reproducible protocols. Moreover, future investigations should incorporate objective outcome measures, as colonic transit time, stool form and frequency, indices of inflammation or intestinal wall integrity, and changes to microbiome composition. In conclusion, TAI and CHT have the potential to serve as important interventions for the treatment and prevention of chronic constipation and intestinal dysbiosis, as well as their broader systemic correlates, in the setting of bio-integrated medicine. Full article

Background and Clinical Significance: Cutaneous Rosai-Dorfman disease (CRDD) is a rare, benign histiocytic proliferative disorder, accounting for approximately 3% of all Rosai-Dorfman disease (RDD) cases. Currently, the diagnosis of CRDD relies on invasive pathological examination due to the absence of reliable non-invasive alternatives. This case series evaluates the potential utility of high-frequency ultrasound (HFUS) as an adjunctive diagnostic tool for CRDD. Case Presentation: We present three CRDD cases, correlating HFUS features with histopathology. All cases showed hypoechoic lesions with varying infiltration depths and morphologies, though no specific diagnostic features were identified. HFUS clearly delineated involvement of the dermal and subcutaneous layers, assessed morphological characteristics like contour regularity and border definition, and evaluated vascularity. This information is crucial for clinical decision-making. HFUS also demonstrated value in therapeutic follow-up. In Case 1, it objectively showed a reduction in lesion size and decreased internal vascularity, providing clear evidence of treatment response. Conclusions: Although HFUS cannot independently diagnose CRDD and histopathology remains the gold standard, it serves as a valuable complementary tool. HFUS allows evaluation of deeper tissue structures, infiltration depth, and vascularity. As a non-invasive modality, it is useful for treatment monitoring, therapy guidance, and prognosis assessment. Integrating HFUS into the CRDD workflow enables more comprehensive and precise management. Full article