Same-day multimodal aesthetic treatments may optimize patient convenience, but concerns remain regarding possible thermal degradation of botulinum toxin type A (BoNT-A) when combined with energy-based devices. To preliminarily evaluate the feasibility and clinical outcomes of a single-session protocol combining Q-switched (QS) 1064 nm laser, incobotulinumtoxinA, and laser-assisted drug delivery (LADD) of polydeoxyribonucleotide (PDRN) and retinoic acid. This pilot case series included five patients. The protocol consisted of carbon-assisted QS 1064 nm laser treatment (2 J/cm), immediately followed by intramuscular BoNT-A injections and topical application of 5% PDRN and 10% retinoic acid. Outcomes were assessed 15 days post-treatment using the Modified Fitzpatrick Wrinkle Scale (MFWS) and Global Aesthetic Improvement Scale (GAIS). Clinical follow-up was performed for up to 6 months. Mean MFWS scores improved from 1.96 ± 0.46 to 0.88 ± 0.39 (p < .001). All patients were rated as "Much Improved" or "Very Much Improved" on GAIS. No serious adverse events occurred. BoNT-A efficacy was clinically preserved throughout follow-up. This multimodal protocol appears to be a feasible and well-tolerated strategy for same-session facial rejuvenation without clinically compromising BoNT-A efficacy.
Puerperal uterine inversion is a rare and life-threatening obstetric emergency that occurs during the third stage of labor. We report the case of a 27-year-old primigravida who developed an acute third-degree uterine inversion immediately after a vaginal delivery, with partial placental tissue remaining in situ. The patient presented with severe postpartum hemorrhage, hemodynamic shock, and intense pelvic pain. The diagnosis was made clinically, and prompt resuscitative measures (including arrangement of O-negative blood at midnight) followed by uterine reduction via the modified Johnson method were initiated. Early recognition and immediate management are crucial to reduce maternal morbidity and mortality associated with this condition.
This study examines clinician and patient experiences and concerns regarding the use of digital technology platforms, particularly artificial intelligence (AI) chatbots, for clinical care. We conducted focus groups with clinicians and patients across two disciplines - young adult mental health and prenatal care - to explore these themes. While clinicians and patients both recognized the benefits of AI chatbots, they also noted the potential for misuse and inability to consider the clinical context among other concerns. We call for AI chatbots to provide clear, culturally sensitive communication, transparent attribution of sources, disclaimers for follow-up with health care professionals, and a form of regulation to avoid bias and misuse.
Armed conflict and inequitable access to public services are increasingly understood as interconnected public health and policy challenges. Recent scholarship has argued that equitable allocation of services across rural and urban regions may reduce conflict risk by mitigating deprivation and group grievance. While this perspective advances conflict-sensitive public health policy, it leaves the place of mental health within allocation frameworks. This commentary extends that debate by arguing that mental health should be understood as a central, rather than peripheral, domain of conflict health allocation. Using Yemen as a critical case, the commentary highlights how protracted conflict exposes limitations in prevailing allocation models and demonstrates the need to move beyond geographic distribution toward a broader conception of mental health equity in conflict policy. It is argued that integrating mental health into allocation debates strengthens both distributive justice frameworks and public health approaches to conflict prevention and recovery.
Pig production is a vital source of livelihood for many smallholder farmers in Uganda, contributing significantly to food security and livelihoods. However, farmers face numerous challenges that hinder pig productivity and profitability. A critical aspect of disease control is the availability and accessibility of effective vaccines. This study aimed to identify barriers to the uptake of pig vaccines by practitioners and farmers in Uganda. We employed a systematic literature review with qualitative investigation, including focus group discussions (FGDs) and key informant interviews (KIIs) to characterise the pig vaccine supply chain, identify actors involved, barriers and challenges faced, and propose possible solutions. The study identified a supply chain involving multiple actors, including vaccine importers, wholesalers, retailers, and end users. Key barriers identified were policy weaknesses, incoordination, structural (poor staffing and funding of veterinary services), technical (knowledge gaps), logistical (limited infrastructure), and socio-economic (high costs).Contribution: This study highlights key barriers to farmers' uptake of pig vaccines. It highlights a need for the Ugandan government to strengthen the regulation, control, and monitoring of pig vaccines. Given that policy and structural, technical, logistical, and socio-economic barriers exist at different nodes of the value chain, specific interventions are needed to address them. There is a need for capacity building of value chain actors - especially veterinary practitioners and farmers on the safe use and benefits of vaccines. The vaccine supply chain actors would benefit from increased investments in infrastructure, such as cold chain facilities, by public and private sector players. Future studies on the epidemiology of important diseases, vaccine efficacy, and socio-cultural barriers to vaccine uptake are recommended.
Affective dysregulation (AD) in children is characterized by irritability, anger, and frequent intense temper outbursts. Considerable evidence implies altered processing of frustration about missed rewards, but few studies investigated the preceding and thus potentially predictive reward anticipation and initial delivery processing in children with AD. A total of 103 children aged 8-12 years (50 with AD and 53 without AD) were examined during a monetary reward anticipation task with event-related potential (ERP) components resolving reward anticipation (cue-CNV [Contingent Negative Variation]) and reward delivery phases (Reward Positivity and Feedback-Related Negativity). All components were analyzed by repeated measures analysis of variance. Regression analyses also evaluated the associations between those ERP components and dimensional AD symptoms. Children with AD showed attenuated anticipatory reward processing compared to No-ADs. The CNV at fronto-central site (FCz) showed a significant group effect (No-AD > AD, p = 0.017). Post-hoc test showed that this group difference was stronger for the cue monetary condition (monetary cue: p = 0.007, d = 0.56, verbal cue: p = 0.901, d = 0.16), and that only the No-AD group showed a significant difference between conditions (p < 0.001). No significant effects were obtained for the delivery phase. Regression analysis showed that a reduced anticipatory CNV at FCz significantly explained AD symptoms, and that anger/irritability and anxiety/depressive symptoms predicted a reduced anticipatory CNV at FCz. This neurophysiological characterization of reward anticipation and delivery in children with AD demonstrates altered neural activity in AD during anticipation of reward rather than following the delivery (or omission) of the reward itself. Our results highlight that altered reward anticipation in AD can occur outside frustration-prone tasks or settings, and underline the important role of both anger/irritability and anxiety/depressive symptoms in the pathophysiology of AD for atypical reward anticipation.
Dilapan-S, a synthetic osmotic dilator used for pre-induction cervical ripening, has proven to be as effective as the Foley balloon in terms of vaginal versus cesarean delivery and has been associated with increased patient satisfaction. Nevertheless, its ability to lower cesarean rates and its cost-effectiveness remain poorly studied. To estimate the likelihood that synthetic osmotic dilators reduce cesarean deliveries and to evaluate their health system costs (2026 US$) and incremental cost-effectiveness compared to the Foley balloon during cervical ripening. Secondary Bayesian analyses were conducted using data from the single-center DILAFOL randomized controlled trial, which enrolled 419 parturients at ≥37 weeks' gestation with singleton pregnancies undergoing labor induction with an unfavorable cervix. Participants were randomized to receive synthetic osmotic dilators (n = 208) or a Foley balloon (n = 209) for cervical ripening. A Bayesian logistic regression model was used to estimate the probability of a reduced cesarean delivery rate with synthetic osmotic dilators. Health system costs were evaluated using Bayesian generalized linear models. The incremental cost-effectiveness ratio (ICER) was derived from these models using neutral priors, assuming no treatment effect. In intent-to-treat analysis, synthetic osmotic dilators had an 89% probability of reducing cesarean delivery compared to the Foley balloon (mean absolute risk difference, -5.0% (95% credible interval [CrI], [-12.8 to 2.7). Mean total obstetric cost per patient was $10,198 for synthetic osmotic dilators and $10,176 for Foley (RR, 1.00; 95% CrI, 0.94 - 1.06). Although synthetic osmotic dilators cost $399 per patient, this was largely offset by an 85% probability of reduced hospital costs ($8,771 vs. $9,081; RR, 0.97; 95% CrI, 0.90-1.03) and 99% probability of reduced physician costs ($1,028 vs. $1,094; RR, 0.94; 95% CrI, 0.89-0.99). The ICER of synthetic osmotic dilators versus Foley was $439 per cesarean delivery prevented (95% CrI, -$51,813 to $57, 697]), with 42% of posterior draws falling in the dominant quadrant (cost-saving and more effective). The probability of cost-effectiveness rose from 47% at $0 willingness-to-pay threshold to 85% at $15,000 per cesarean delivery prevented. Subgroup analyses suggested that economic benefits were most favorable among patients aged <35 years and nulliparous parturients, in whom the posterior probability of dominance was 52% and 39%, respectively. Despite its higher material cost, synthetic osmotic dilators likely reduced cesarean delivery rates with minimal impact on total health system costs and a favorable cost-effectiveness profile. These findings, which do not account for neonatal costs or future pregnancy outcomes, suggest that osmotic dilators represent good value in obstetric care, particularly among younger and nulliparous patients. Further validation across obstetric settings is warranted.
Digital health technologies are increasingly recognised as important tools for strengthening healthcare delivery across African health systems. Despite rapid growth in digital health innovation, the implementation-oriented research landscape remains fragmented, with limited synthesis of the field's thematic structure, collaboration patterns, and evolving research priorities. This study maps the intellectual structure and thematic evolution of implementation-focused digital health research across selected African countries (South Africa, Kenya, Uganda, Nigeria, Ethiopia, Ghana, Tanzania and Rwanda). A bibliometric analysis was conducted on peer-reviewed publications indexed in Web of Science, Scopus, and PubMed between 2015 and 2025. Records were retrieved using a structured Boolean search strategy combining digital health, implementation, geographic, clinical-domain, care-setting, and outcome-related terms. The search captured implementation-oriented publications with explicit references to selected African countries. Following screening and deduplication, 440 publications were included. Analyses were performed using the Bibliometrix R package and included performance analysis, co-word analysis, thematic mapping, collaboration-network analysis, and temporal trend analysis. Digital health research across the selected African countries expanded substantially during the study period, particularly after 2020. Research activity was strongly dominated by mobile-health-supported interventions targeting maternal health, HIV care, tuberculosis adherence, and primary healthcare delivery. Thematic mapping identified "mobile health-antenatal care-mobile phone" as a motor theme, while "mHealth-HIV-Kenya" emerged as a broadly connected but conceptually fragmented basic theme. Telemedicine-related research appeared as a specialised niche theme, whereas tuberculosis-focused digital adherence interventions occupied an emerging-or-declining thematic position. Keyword trend analyses further indicated a transition from feasibility-oriented studies toward implementation-focused and system-oriented digital health research. Precision medicine and rare-disease terminology did not form distinct thematic clusters within the retrieved corpus. Implementation-oriented digital health research across the selected African countries is undergoing rapid expansion, with increasing emphasis on scalable mobile health systems and integrated healthcare delivery. However, thematic fragmentation, limited interoperability, and the absence of longitudinal system-level evaluation remain important challenges.
N-butyl cyanoacrylate (NBCA) embolisation is an effective technique for rapid haemostasis and tumour devascularisation. However, selection of a single glue dilution requires balancing distal penetration against proximal control, often relying heavily on operator experience. Achieving both deep distribution and stable proximal occlusion can be challenging, particularly in complex lesions. We describe a sequential dual-dilution NBCA embolisation technique ("Nitoryu" technique), in which a dilute NBCA-lipiodol mixture is first administered to achieve flow-directed distal penetration, followed by injection of a more concentrated mixture to achieve rapid proximal occlusion and stabilisation of the embolic cast. The technique was applied in two cases. In a patient with ruptured hepatocellular carcinoma and coagulopathy, multiple small tumour-feeding arteries and a poorly visualised culprit pseudoaneurysm required deep penetration of dilute glue, followed by proximal occlusion to ensure durable haemostasis. In a second case of bronchial artery pseudoaneurysm causing haemoptysis, a tiny tortuous feeder necessitated very dilute glue for distal delivery, while subsequent proximal embolisation with a more concentrated mixture reduced the risk of reflux and non-target embolisation. In both cases, the sequential approach allowed controlled embolisation with effective distal penetration of glue and stable proximal occlusion. The sequential dual-dilution NBCA embolisation (Nitoryu technique) enables controlled distal penetration and proximal stabilisation, and may improve safety and efficacy in selected cases requiring precise glue delivery.
In Japan, declining birth rates and concentration of pediatric cases in fewer high-volume children's hospitals have reduced anesthesiologists' opportunities, particularly during training, to gain experience in pediatric anesthesia. There is no standardized national curriculum, and training relies largely on workplace-based learning. The Safer Anaesthesia From Education (SAFE) Paediatrics Course is a structured program originally developed for low- and middle-income countries; whether it can be contextually adapted and disseminated in a high-income country facing different training challenges has not been established. To describe the translation, contextual adaptation, early implementation, and initial national dissemination of the SAFE Paediatrics Course in Japan, including preliminary educational outcomes from a single-center resident training program. We conducted a two-phase descriptive educational project. Phase 1 comprised course translation, contextual adaptation, pilot testing of a multiple-choice question (MCQ) examination, and pilot delivery. Phase 2 comprised single-center implementation and evaluation at Saitama Children's Medical Center among anesthesia residents (October 2021-March 2023). Participants completed pre- and post-course MCQ tests and confidence ratings; a post-course survey assessed satisfaction. National dissemination was described using aggregated course-level data. Thirty residents participated in the single-center evaluation. MCQ scores increased from 37.87 to 41.67 out of 50 (mean increase 3.80; 95% CI: 2.64-4.96; p < 0.001), and self-rated confidence increased. Satisfaction was high (17/20 respondents rated the course 4 or 5). Between October 2021 and January 2026, 28 courses were delivered across four geographical areas and national meeting-affiliated sessions, accounting for 359 participant attendances; many used condensed one-day or half-day formats. The SAFE Paediatrics Course was translated, contextually adapted, and implemented in Japan, with early dissemination across multiple geographical areas and flexible delivery formats. Preliminary single-center outcomes support its suitability as a structured pediatric anesthesia educational program in this setting. Further multicenter and longitudinal evaluation is warranted.
Labor pain is among the most intense forms of pain, and neuraxial analgesia, including epidural, spinal, and combined spinal-epidural techniques, is considered the gold standard for its management. Despite its effectiveness, persistent misconceptions, cultural barriers, and disparities in awareness contribute to underuse among certain populations. Educational interventions have been developed to address these gaps, yet a comprehensive synthesis of such efforts in the United States is lacking. This scoping review aims to map the extent, range, and nature of current literature describing educational interventions designed to improve knowledge, awareness, and acceptance of neuraxial analgesia during labor among pregnant women. Following the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) framework, peer-reviewed studies published in English were identified through PubMed, Embase, and Scopus from inception to August 2025. Eligible studies include those focusing on pregnant individuals eligible for neuraxial analgesia who received educational or counseling interventions during prenatal or perinatal care. Extracted data include study design, intervention type, delivery method, timing, and outcomes of interest, including patient understanding of risks and benefits, awareness of neuraxial analgesia options, acceptance of or preference for neuraxial analgesia, satisfaction with education, and uptake during labor. Data will be synthesized descriptively using summary tables and figures, with a narrative synthesis to categorize interventions by type, timing, and delivery method and identify patterns and gaps across studies. This project was conceived in August 2024, and the protocol was registered in the Open Science Framework in January 2025. The database search was conducted in August 2025. As of protocol submission in October 2025, full-text screening and data extraction are pending and are scheduled for May 2026 to June 2026. Data synthesis and drafting of the results will be completed in September 2026. The manuscript will be submitted in October 2026. This scoping review will map existing educational interventions related to neuraxial labor analgesia and identify gaps in the current literature. The findings may help inform future research and the development of more consistent and accessible patient education approaches.
Gestational psittacosis is a rare but high-risk infection caused by Chlamydia psittaci, often leading to severe maternal complications and adverse fetal outcomes. We report a unique case of a 30-year-old woman at 22 + 5 weeks of gestation who presented with acute high fever and respiratory failure following bird exposure. The diagnosis of C. psittaci infection was rapidly confirmed via blood metagenomic next-generation sequencing (mNGS). Following multidisciplinary consultation involving obstetricians, infectious disease specialists, intensivists, respiratory physicians, clinical pharmacists, and neonatologists, an individualized management plan was established to balance maternal infection control, respiratory support, fetal monitoring, and medication safety during pregnancy. The patient was treated with intravenous azithromycin combined with corticosteroids, and her clinical condition stabilized within 2 weeks. Notably, the pregnancy continued to term, resulting in the delivery of a healthy male infant. To our knowledge, this represents the first reported case worldwide of a successful full-term delivery following gestational psittacosis. This case underscores the critical importance of early mNGS-based diagnosis, multidisciplinary collaboration, and appropriate antimicrobial therapy in optimizing maternal and neonatal outcomes, providing a valuable clinical reference for managing this life-threatening zoonosis during pregnancy.
Though informal healthcare providers (IHPs), often defined as unregistered and not formally trained, are heavily utilised by low-income urban residents and present an opportunity to address the urban primary care gap, these providers are rarely prioritized or integrated into health systems. This paper explores IHPs' role in urban settings across four rapidly urbanizing low- and middle-income countries: Bangladesh, Nepal, Nigeria, and Ghana, to enhance understanding of their potential within health systems and promote their integration to improve access and quality of care for the urban poor. We studied published and unpublished articles and policy documents to compare informal provider types, roles, services, and target populations in each country. We then present case studies illustrating how these providers support healthcare for urban poor. A narrative synthesis was applied to describe the included documents/literature and results, while quantitative data were analyzed using STATA version 16. OpenStreetMap basemaps were employed to illustrate informal providers' locations within urban areas. Our findings show that across the four countries, there is substantial evidence that informal providers contribute significantly to health service delivery by bridging the care gap, particularly for socially and economically disadvantaged urban populations. They serve as the first point of contact, offering a wide range of health services, including preventive, curative, and restorative services. However, they are loosely defined and lack robust standards, protocols, professional training and accreditation. Informal providers play a critical, though varied, role in the delivery of healthcare across the countries studied, facilitating access to care where it might otherwise be unavailable or unaffordable. Initiatives to strengthen the informal sector, for example, linking or integrating with the formal sector, have the potential to improve healthcare access and quality for the urban poor.
The escalating crisis of antimicrobial resistance, driven by pathogens such as methicillin-resistant Staphylococcus aureus (MRSA), underscores the urgent demand for innovative therapeutic strategies that outperform conventional antibiotic regimens. In this study, we developed a versatile targeted celastrol nanoassembly (CDPG) that integrates site-specific antibacterial delivery with coordinated immunomodulation to effectively address MRSA infections and prevent their recurrence. The nanoassembly consists of a celastrol-dextran antibacterial core encapsulated by a polyethylene glycol (PEG) shell, which is linked via pH-sensitive boronate ester bonds and stabilized through the reconstitution of the β-glucan triple-helix structure. This design enables prolonged systemic circulation under physiological conditions. Upon reaching the acidic microenvironment of the bacterial infection site, the nanoassembly undergoes PEG layer dissociation, exposing dextran moieties that enhance pathogen targeting through lectin-mediated recognition, while simultaneously releasing β-glucan to activate both innate and adaptive immune responses. In murine models of MRSA infection, CDPG demonstrated precise accumulation at lesion sites, potent bactericidal efficacy, modulation of inflammatory responses, and induction of systemic immune activation upon rechallenge. This study presents a natural product-derived, rationally designed nanomedicine strategy that integrates stimulus-responsive structural transformation, pathogen-targeted drug delivery, and modulation of the host immune system, offering a hopeful therapeutic approach to combat multidrug-resistant bacterial infections.
The obligate parasitic plant Cuscuta campestris delivers trans-species microRNAs (miRNAs) into host plants that silence host mRNAs. Here, the genetic requirements for biogenesis, movement, and function of these miRNAs were investigated. Primary miRNA transcript accumulation precedes mature miRNA accumulation by 24 to 48 h. Trans-species miRNAs accumulate in host tissues a short distance from the site of parasite attachment. Trans-species miRNAs require C. campestris but not host Dicer-Like 1 (DCL1) for accumulation. These miRNAs specifically avoid Argonaute (AGO) loading in C. campestris tissue where they instead accumulate as miRNA/miRNA* duplexes. After arrival and short-distance spreading in host tissues, they are loaded onto host AGO proteins, including AGO1 and AGO2. This study clarifies the transcription, dicing, delivery, and function of C. campestris trans-species miRNAs. We propose that selective avoidance of self-AGO loading is a mechanism to facilitate high rates of delivery of these "export only" miRNAs to host tissues.
Although cancer vaccines have been proposed for decades, their clinical outcomes have remained largely unsatisfactory. Over the past decade, progress in deciphering the interaction between the immune system and cancer, along with widespread adoption of high-throughput sequencing technologies and improved MHC-peptide binding affinity prediction, have revitalized interest in cancer vaccine development. Nanomaterials benefit from the integration of tunable composition, modular architecture, and immunologically relevant dimensions, which collectively enable the rational design of immunomodulatory strategies tailored on demand, ensuring the reliable induction of antitumor immune responses. Given the spatiotemporal nature of immune responses, multifunctional nanomaterials can be further engineered to enable multivalent antigen presentation and controlled vaccine trafficking, thereby confining antitumor immune activation to desired contexts and minimizing off-target immune-related toxicities. Beyond conventional discussions of antigen delivery, this review emphasizes how rational nanomaterial design can be leveraged to regulate multiple stages of the cancer-immunity cycle, providing an updated perspective on the development of next-generation cancer vaccines. This Review will systematically summarize recent advances in nanomaterial-based cancer vaccines and discuss the key challenges and future directions in this rapidly evolving field.
The therapeutic potential of Cannabis sativa has attracted growing interest in oncology. Its diverse phytochemicals, including cannabinoids, flavonoids, and terpenes, interact with oncogenic signaling pathways and the endocannabinoid system influencing tumour progression and therapeutic responses. This review critically evaluates the molecular mechanisms by which Cannabis sativa phytochemicals modulate cancer pathways, with emphasis on apoptosis, oxidative stress regulation, autophagy, angiogenesis, and metastasis. It also explores synergistic and additive interactions among cannabinoids and flavonoids, highlighting their translational relevance. Cannabinoids such as Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabigerol (CBG) exhibit pathway-specific effects, including induction of apoptosis, modulation of oxidative stress, and inhibition of angiogenesis. Flavonoids such as cannflavin A, genistein, daidzein, hesperetin, and naringenin exhibit selective cytotoxicity across bladder, breast, melanoma, and pancreatic cancers, often sparing normal tissue. Importantly, phytochemical interactions are not uniformly synergistic; while combinations such as THC and CBD amplify apoptotic signaling, others act additively or antagonistically. Clinical formulations such as Nabiximols provide translational evidence of cannabinoid synergy, although outcomes remain context-dependent. The disconnect between preclinical efficacy and clinical outcomes underscores critical gaps in dosing strategies, patient selection, and combination regimens. Future research should prioritize mechanistic studies, rational phytochemical combinations, and innovative drug delivery systems. Taken together, Cannabis sativa phytochemicals emerge as promising molecular entities with the potential to reshape integrative oncology, provided their therapeutic promise is matched with rigorous, evidence-based evaluation.
Colorectal cancer is one of the leading causes of cancer-related mortality worldwide, and its progression is strongly associated with oxidative stress, chronic inflammation, dysregulated apoptosis, and impaired autophagy. Although honokiol (HNK) possesses promising anticancer properties, its therapeutic application is limited by poor bioavailability and low aqueous solubility. Therefore, this study investigated the potential of liposomal honokiol nanoparticles (HNK-LNPs) as an advanced nanotherapeutic strategy to enhance the chemoprotective efficacy of HNK against dimethylhydrazine (DMH)-induced colon carcinogenesis in Wistar rats. Sixty rats were randomly allocated into six groups (n = 10): normal control, HNK, HNK-LNPs, DMH, DMH + HNK, and DMH + HNK-LNPs. Experimental treatments were continued for 10 weeks. DMH administration markedly increased serum tumor markers, including AFP, CEA, CA19-9, CA125, and CA15-3, as well as vascular endothelial growth factor (VEGF) levels. DMH exposure also induced severe oxidative stress, evidenced by elevated malondialdehyde (MDA) levels and depletion of total antioxidant capacity (TAC), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Moreover, DMH suppressed the NRF2/HO-1 antioxidant signaling pathway and significantly increased inflammatory mediators, including NF-κB, COX-2, TNF-α, IL-6, IL-1β, and nitric oxide (NO). In addition, DMH disrupted autophagic activity through downregulation of LC3-II and Beclin-1 and activated the PI3K/AKT/mTOR/SREBP-1c signaling pathway, leading to increased expression of fatty acid synthase (FASN) and acetyl-CoA carboxylase 1 (ACC1). DMH also inhibited apoptosis, as demonstrated by reduced expression of BAX, caspase-3, and TP53, along with increased BCL-2 expression. Histopathological and ultrastructural analyses confirmed marked colonic tissue injury and cellular abnormalities in DMH-treated rats. Co-administration of HNK partially ameliorated these alterations, whereas HNK-LNPs produced substantially greater protective effects. Treatment with HNK-LNPs restored antioxidant defenses, suppressed inflammatory and lipogenic signaling pathways, enhanced autophagy and apoptosis-related markers, and markedly improved histological architecture. Overall, HNK-LNPs demonstrated superior chemoprotective efficacy compared with free HNK, suggesting that liposomal delivery enhances the therapeutic potential of honokiol against DMH-induced colon carcinogenesis.
Cellular senescence has emerged as a central mechanism driving cutaneous aging, impaired regeneration, and numerous dermatologic pathologies. Initially evolved as a protective mechanism to prevent malignant transformation and facilitate wound repair, senescence becomes maladaptive when senescent cells persist. Senescent keratinocytes, fibroblasts, and melanocytes can secrete pro-inflammatory mediators and other factors, collectively termed the senescence-associated secretory phenotype (SASP), which may degrade extracellular matrix components, disrupt pigmentary balance, and impair barrier function. Senescent cells are resistant to conditions that cause death of non-senescent cells and are generally removed by the immune system. Persisting senescent cells can become increasingly pro-inflammatory and fibrotic, perhaps due to accumulating DNA damage within these cells. Two primary geroscience-based therapeutic paradigms (gerotherapeutics) have been proposed: senolytics, which selectively eliminate senescent cells, and senomorphics, which modulate or suppress SASP activity without inducing senescent cell death. In dermatology, these approaches are particularly relevant given skin's accessibility, visible aging markers, and ability to serve as a translational platform for systemic gerotherapeutic interventions. Interfering with the development of senescent cells, for example by interfering with such regulators of senescent cell formation as p16, retinoblastoma protein (pRB), p53, or p21, can be detrimental due to the protective roles of transient senescence in wound healing and cancer suppression. However, senolytics, which do not prevent senescent cells from developing but rather act by clearing already formed persisting and tissue-damaging senescent cells, offer the potential to delay, prevent, alleviate, or treat aged or fibrotic skin. Because of the days to weeks for senescent cells to form fully and their inability to divide, senolytics can be administered intermittently, for example for brief intervals every 2 weeks or once a month. Senomorphics, conversely, can modulate the detrimental effects of the SASP and generally need to be administered continuously or more frequently than senolytics. Some agents are both senolytic and senomorphic. This review considers the mechanistic underpinnings of senescence in skin, the evidence for both therapeutic approaches, and the future directions for integrating senotherapeutics into regenerative and aesthetic dermatology. Advances in cutaneous biomarkers, topical delivery systems, and AI-assisted patient stratification are expected to accelerate translation into clinical practice.
BackgroundEvidence on the feasibility of integrating music therapy into routine post-stroke aphasia rehabilitation in real-world settings remains limited.ObjectiveTo examine the feasibility of integrating a structured music therapy protocol into conventional speech-language therapy for post-stroke aphasia and explore preliminary outcomes.MethodsThis quasi-experimental study was conducted in an outpatient speech-language clinic in Thailand. Participants received standard speech-language therapy or therapy combined with a manualised music therapy protocol. The intervention represents a dose-augmented feasibility design, as the experimental group received increased overall therapeutic contact time. Language performance was assessed using the Thai Adaptation of the Western Aphasia Battery, and anxiety using the State-Trait Anxiety Inventory, Form Y-2. Pre-post changes were examined using descriptive statistics and exploratory analyses, including paired tests for within-group comparisons and independent tests for between-group differences.ResultsThe intervention was feasible, with complete delivery and assessment. Within-group improvements in language performance were observed in both groups, with greater gains in the music therapy-augmented group; however, between-group differences were not statistically significant. Anxiety scores decreased in both groups, with no significant differences. Interpretation of anxiety outcomes is limited by the use of a trait-based measure, which may reflect the limited sensitivity of trait-based measure to short-term changes.ConclusionsIntegrating music therapy into routine speech-language rehabilitation for post-stroke aphasia is feasible in a real-world outpatient setting. Findings should be interpreted as exploratory and reflective of increased therapeutic exposure rather than modality-specific effectiveness. These results inform the design of future dose-matched and methodologically rigorous trials.