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Noncommunicable diseases (NCDs) account for the majority of morbidity, mortality, and health expenditures, yet progress toward international reduction targets remains limited. Although evidence-based strategies for prevention and long-term management are well-established, health systems predominantly remain biomedical and fragmented across clinical, public health, and community sectors. This structural misalignment constrains the ability to scale prevention and deliver coordinated chronic disease management. This paper proposes "Operation Whole Health" as a framework for a paradigm shift in the health care system. Drawing on lessons from the coordinated mobilization observed in the United States during the COVID-19 response, the framework emphasizes the importance of mission clarity, cross-sector workforce integration, and sustained financing to achieve significant and scalable change. Whole health models-person-centered, interprofessional, and prevention-oriented-offer a mechanism for aligning clinical care with behavioral, social, and community determinants of health. Expanding prevention capacity includes systematic integration of traditional, complementary, and integrative medicine professionals, whose competencies align with chronic disease prevention but remain underutilized within publicly financed systems. Because effective whole health interventions for NCDs are known, a key constraint in widespread implementation may be policy prioritization rather than scientific uncertainty. A structural redesign of health care anchored in the whole health paradigm may be needed to alter NCD trajectories and stabilize long-term health expenditures.

Low-density lipoprotein cholesterol (LDL-C) is an established therapeutic target for atherosclerotic cardiovascular diseases (ASCVD), particularly in high-risk individuals. In 2022, the Japan Atherosclerosis Society Guidelines (JAS-GL) for Prevention of Atherosclerotic Cardiovascular Diseases introduced more stringent LDL-C targets to reduce ASCVD. We evaluated the non-achievement rates of the LDL-C goals across risk groups using a nationwide real-world dataset, which included a broad range of ASCVD patients. This retrospective, cross-sectional study included 200,607 adults (aged ≥18 years) with dyslipidemia. Patients were stratified according to the JAS-GL 2022 into a high-risk primary prevention population (Groups I, II, and familial hypercholesterolemia [FH]: no history of coronary artery disease [CAD] or stroke, classified by comorbidities such as diabetes), and a secondary prevention population (Groups III and IV: history of CAD or stroke, with Group IV having additional conditions such as diabetes). The primary endpoint was the proportion of patients who did not achieve their target LDL-C goals. Non-achievement rates were 28.2% (Group I), 46.7% (Group II), 64.3% (Group FH), 30.0% (Group III), and 65.6% (Group IV). Importantly, these rates remained high and showed little change before and after the revision of the guidelines across all studied risk groups. Non-achievement of LDL-C targets remained high despite updated recommendations. These findings highlight a need for more effective implementation strategies and sustained efforts to improve lipid management.

Early childhood caries (ECC) remains one of the most prevalent chronic diseases affecting children worldwide and represents a major public health challenge in many African settings. Understanding its determinants is essential for developing oral health promotion strategies and preventive policies aimed at improving child oral health and reducing inequalities. This umbrella review followed PRISMA guidelines and was registered in PROSPERO (CRD420261379153). Systematic reviews and meta-analyses published between January 2000 and May 2026 were identified through searches of MEDLINE, Scopus, Web of Science, and Embase. Methodological quality was assessed using AMSTAR 2, risk of bias using ROBIS, overlap using a citation matrix and corrected covered area (CCA), and certainty of evidence using a narrative GRADE approach. Findings were synthesized narratively. Seven systematic reviews and meta-analyses were included. Methodological quality ranged from high to critically low, while ROBIS identified predominantly low overall risk of bias, although two reviews were judged to be at high risk of bias. The corrected covered area (CCA) was 4.7%, indicating a low degree of overlap among reviews. ECC prevalence ranged from 17% to 57%, with higher estimates reported in North and Southern Africa. The most consistently reported determinants were dietary, oral hygiene-related, sociodemographic, and breastfeeding and bottle-feeding-related factors, whereas maternal/caregiver-related, biological, health-related, and contextual determinants were supported by a smaller body of evidence. Certainty of evidence was moderate for ECC prevalence and the most consistently reported determinants, but low for maternal/caregiver-related, health-related, biological, and contextual determinants. These findings support evidence-informed oral health promotion and prevention strategies across African settings. ECC remains a substantial oral health burden in Africa and is influenced by interacting behavioral, sociodemographic, caregiver-related, biological, health-related, and healthcare access determinants. Comprehensive oral health promotion strategies should strengthen caregiver education, support healthy dietary and oral hygiene behaviors, improve access to preventive services, and integrate oral health into maternal and child health programs. Such approaches may help reduce ECC burden and oral health inequalities among vulnerable populations. PROSPERO, identifier CRD420261379153, http://www.crd.york.ac.uk/PROSPERO/view/CRD420261379153.

Ultrafine particles (≤100 nm) and other environmental nanoparticles have emerged as biologically active pollutants that can cross biological barriers, including the blood-brain barrier and the placenta. Growing evidence implicates ultrafine particles in a wide range of neuropsychiatric conditions, yet their effects remain poorly integrated into clinical and public health frameworks. In this review, we distinguish between size-defined ultrafine particles (UFPs, ≤100 nm), composition-defined environmental nanoparticles originating from combustion and secondary formation processes, and engineered nanomaterials (ENPs), which differ in physicochemical properties, exposure scenarios, and regulatory status. This narrative systematic review synthesizes findings from human and experimental studies on the neuropsychiatric and neurodevelopmental effects of environmental nanopollutants. A structured search was conducted in PubMed, Web of Science, Scopus, and Google Scholar up to November 2025, following explicit inclusion and exclusion criteria. Eligible studies included peer-reviewed human and animal research assessing mental health or neurological outcomes of nanopollutant exposure. Epidemiological studiesprimarily involving traffic-related air pollution and mixed combustion-derived ultrafine particle exposuressuggest associations with increased risk of cognitive impairment, autism spectrum disorder, depression, schizophrenia, and neurodegenerative diseases, including Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis. Prenatal and early life exposures were linked to cortical thinning, altered neurodevelopmental trajectories, and early proteinopathies. Underlying mechanisms include neuroinflammation, oxidative stress, and protein aggregation. Despite methodological heterogeneity, the evidence supports the urgent need for regulation and prevention. Environmental nanopollutants constitute an under-recognized, modifiable risk factor for neuropsychiatric and neurodegenerative conditions. A paradigm shift is needed to incorporate environmental exposure history into mental health research, risk assessment, and prevention strategies. Regulatory action targeting nanopollutant emission and exposure, particularly in vulnerable populations, is critical to mitigating long-term neurological consequences.

Coronary heart disease (CHD) is a major cause of morbidity and mortality worldwide. Regular physical activity (PA) is a vital component of secondary prevention, yet adherence among patients remains low. The study aimed to gain a deeper understanding of barriers to PA among Jordanian patients with CHD. A qualitative descriptive design was used. Semi-structured interviews were conducted with 22 patients recruited from outpatient medical clinics, and data were analyzed thematically. The main theme of the findings was "Barriers to PA of CHD." Five sub-themes were identified: Psychological and Health-Related Barriers, Motivational Barriers, Lack of knowledge regarding PA, Perceived external obstacles,and Healthcare System-Related Barriers. Patients with CHD encountered psychological, educational, social, and system-level barriers to PA. Addressing these barriers required culturally tailored active and consistent healthcare counseling, appropriate education, and improved rehabilitation accessibility to increase adherence to PA and promote better secondary prevention outcomes.

Osteoporosis (OP) persists as the principal contributor to the global disease burden. OP is defined by reduced bone mass and impaired bone microarchitecture, thereby weakening bone strength and elevating fracture risk. Imbalanced bone remodeling is the major pathological mechanism of OP, in which osteoclast-mediated bone resorption exceeds osteoblast-mediated bone formation. Iron serves as a vital micronutrient for numerous biochemical activities and is essential for many cellular processes. Ferroptosis is an iron-dependent form of modulated cell death with unique traits, including disrupted iron balance, compromised antioxidant defenses, and aberrant lipid peroxidation. Ferroptosis participates in various physiological and pathological processes, and its role in bone-related diseases, particularly OP, is increasingly being explored. Hence, a systematic examination of the mechanisms modulating ferroptosis in OP is imperative to pinpoint potential therapeutic targets and innovate novel therapeutic and/or preventive strategies. The agents currently used to treat OP have numerous side effects, prompting increased research on natural compounds for OP treatment. This review systematically summarizes the key features and modulation mechanisms of ferroptosis based on the latest research advances, and explores its pathogenic implications and therapeutic opportunities in OP. Additionally, we also discussed investigations of natural products in vitro and in vivo to prevent OP by interfering with ferroptosis.

Coal, as a porous medium, exhibits a strong adsorption capacity for gas. The laws governing gas adsorption and transport are critical research topics for gas disaster prevention and control, as well as for coalbed methane (CBM) extraction. This study takes coal samples from the Guobei Mine as the research subject. Isothermal adsorption experiments under constant pressure conditions were conducted on coal particles of different sizes to investigate the influence of particle size and initial pressure on gas adsorption capacity and adsorption rate. Based on the density gradient diffusion theory, mathematical models for gas adsorption in both cylindrical and spherical coal particles were established. These models were nondimensionalized, solved using the finite difference method for simulation analysis, and subsequently validated against experimental results. The research indicates that under the same initial pressure, smaller coal particle sizes result in a larger cumulative adsorption capacity and a faster adsorption rate. For particles of the same size, a higher initial pressure leads to a greater saturated adsorption capacity and a shorter time to reach adsorption equilibrium. The cumulative gas adsorption capacity conforms to an empirical model where ″the reciprocal of adsorption capacity shows a linear relationship with 1/t0.65″. The simulation results for cylindrical and spherical particles show a high degree of agreement. Under different initial pressures, the nondimensional pressure for both shapes follows a consistent pattern: "rapid surface response → internal gradient transmission → overall trend toward equilibrium". The equilibrium nondimensional time is approximately 0.08982 at 4.0 MPa, and ranges between 0.3 and 0.45 at 0.5 MPa, with the radial pressure gradient decay rate being consistent. The initial slope, equilibrium time, and saturated adsorption capacity of the nondimensional cumulative adsorption curves are essentially identical. For 50-60 mesh coal samples at 2 MPa, the deviation in the adsorption cycle is less than 0.05 cm3/g, confirming that particle shape has no significant effect on gas adsorption and transport. The established model accurately captures the dynamic characteristics of gas transport. The fit between simulated and experimental values is excellent, with R 2 > 0.99 and an average relative error of only 3.2%. This work breaks through the limitation of the "single spherical particle" assumption, enhances the applicability of the density gradient diffusion theory, and provides reliable theoretical support for the optimization of CBM extraction and gas disaster prevention and control.

Adverse childhood experiences (ACEs) may accelerate early menopause and influence neurodegenerative processes, contributing to sex-specific dementia risk. This study examined associations with cognitive decline and incident dementia in ACEs and early menopause. We studied 6093 women and 5784 men aged &#x2265;50 years from the Health and Retirement Study, a US cohort spanning between 2010 and 2022. Incident dementia was based on self-report of physician-diagnosed dementia. Cognition was measured using a composite score of immediate and delayed recall, serial sevens subtraction, and counting backwards (range, 0-27). ACEs were assessed using seven items and classified into none, 1, 2, and &#x2265;3 ACEs. Age at menopause was classified into <47, 47 to 52, and &#x2265;53 years. We included men and defined the four categories of sex and age at menopause, assessing varying levels of female hormones with age at menopause serving as the proxy indicator of those differences. Covariates included lifestyle risk factors for dementia. We used a longitudinal panel design with each observation containing baseline covariates and 2-year follow-up outcomes. We applied a random-effects model to survival analysis for incident dementia and to linear regression analysis for cognition. Here we show that experiencing 2 (hazard ratio: 1.32 [95% CI: 1.07-1.62]) or &#x2265;3 ACEs (1.32 [1.03-1.68]) is associated with higher dementia risk compared with no ACEs. Dementia risk does not differ by sex and age at menopause in women. Women with early menopause (&#x3b2;&#x2009;=&#x2009;-0.22 [95%CI: -0.41 to -0.03]) and men (-0.92 [-1.06 to -0.78]) have worse cognition than women with late menopause. ACE level is not associated with cognition. No mediation by early menopause is observed between multiple ACEs, dementia, or cognition in women. Mechanisms linking ACEs and early menopause to dementia risk may differ. Risk reduction strategies should consider preventing and addressing ACEs and early menopause, respectively.

Anthracyclines play a crucial role in the chemotherapy of various malignant tumors; however, they may cause myocardial injury, which limits their clinical application. Therefore, it is of great importance to investigate drugs for the prevention and treatment of anthracycline-induced myocardial injury. The aim of this study is to evaluate the cardioprotective effects of Apelin-13 in a murine model of doxorubicin (DOX)-induced myocardial injury and to elucidate its potential underlying mechanisms. Male C57BL/6 mice (8 weeks old) were randomly assigned to four groups, with all mice received intraperitoneal injections: Control (normal saline), DOX (with a cumulative dose of 20 mg), Apelin-13 (Apelin-13 0.1 &#x3bc;mol/kg/d), and Apelin-13 + DOX (Apelin-13 0.1 &#x3bc;mol/kg/d; with a cumulative dose of 20 mg). Cardiac function was assessed using echocardiography. Histopathological changes were assessed via hematoxylin and eosin (HE) staining, and myocardial fibrosis was evaluated with Masson's trichrome staining. Immunohistochemical analysis and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining were conducted to assess protein expression and cardiomyocyte apoptosis, respectively. Protein expression levels were further validated by western blotting (WB). In vitro, rat H9C2 cardiomyocytes were cultured and divided into four groups. Control, Apelin-13 (Apelin-13 1 &#x3bc;M), DOX (DOX 2 &#x3bc;M), and Apelin-13 + DOX group (first treated with Apelin-13 1 &#x3bc;M, followed by DOX 2 &#x3bc;M after 1-2 hours). Cell viability was measured using the Cell Counting Kit-8 (CCK-8) assay. Flow cytometry was employed to quantify apoptosis, and WB was used to analyze signaling pathway components. In mice studies, no mice died during or after the drug intervention period. It was found that Apelin-13 could significantly increase left ventricular ejection fraction (LVEF) and fractional shortening (FS) (P<0.05) and decrease left ventricular end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD) (P<0.05) in mice with DOX-induced cardiomyopathy, as well as alleviate the disordered arrangement of myocardial cells and alleviate the reduction in cross-sectional area (CSA) induced by DOX. Masson staining and immunohistochemistry showed that Apelin-13 could alleviate myocardial fibrosis. WB indicated that Apelin-13 could reduce apoptosis induced by DOX and change the effects of DOX on the transforming growth factor-&#x3b2; (TGF-&#x3b2;)/mothers against decapentaplegic homolog (Smad) proteins. Further research confirmed that the protective effect of Apelin-13 on DOX-induced cardiomyopathy was related to the upregulation of P-ERK and P-AKT. Similarly, in H9C2 studies, it was found that Apelin-13 could reduce DOX-induced apoptosis, increase cell survival rate, and alleviate the decrease in P-ERK and P-AKT induced by DOX. Apelin-13 exerted a protective effect against DOX-induced myocardial injury in both C57BL/6 mice and H9C2 cardiomyocytes. This cardio protection was mediated, at least in part, through modulation of the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) and extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signaling pathways.

Numerous liver diseases are characterized by late diagnosis, rapid progression and high incidence, seriously threatening public health. Though widely used, traditional treatments such as drug therapy, resection and transplantation have substantial limitations. Therefore, developing novel preventive strategies and specialized therapies is crucial. As Chinese medicine continues to modernize, increasing evidence suggests that certain Chinese medicine ingredients can protect the liver. Astragaloside IV (AS&#x2011;IV) is a natural saponin extracted from the root of the traditional herb Astragalus membranaceous. It exhibits diverse pharmacological activities, including anti&#x2011;inflammatory, antioxidant, antiapoptotic and anticancer properties, and is recognized for treating neurological, cardiovascular and metabolic disorders, and cancer. These discoveries indicate its substantial promise for the treatment of liver diseases. Therapeutic trials revealed its hepatoprotective effects for the treatment of various liver diseases, such as non&#x2011;alcoholic fatty liver disease, liver fibrosis, hepatocellular carcinoma and liver injury induced by heavy metals, drugs, or alcohol and involve various signaling pathways such as nuclear factor erythroid 2&#x2011;related factor 2, toll&#x2011;like receptor 4, acetyl&#x2011;CoA carboxylase, protein kinase B, nuclear factor &#x3ba;B and adenosine monophosphate&#x2011;activated protein kinase. The present study presents a narrative review that comprehensively summarizes existing evidence regarding the therapeutic influence of AS&#x2011;IV on diverse liver disorders and deeply analyzes the molecular mechanisms underlying its action in liver disease. The objective is to comprehensively offer insights and references for relevant scientific research and clinical drug development to improve nutritional supplements for liver health.

Accurate molecular diagnosis is essential for thalassemia prevention and carrier screening, particularly in high-prevalence regions. Conventional PCR-based methods are widely used in clinical practice but have limited ability to detect rare variants, homologous recombination events, and large structural rearrangements. This study evaluated the clinical performance of combined SNPscan/CNVplex assay for comprehensive thalassemia screening. A total of 1,026 hematologic testing-positive individuals from Hunan Province, China, were analyzed using routine PCR and SNPscan/CNVplex assay in parallel. The SNPscan assay targeted 48 single-nucleotide variants and indels, while CNVplex targeted 28 deletional mutations and homologous recombination events in HBA1/HBA2 and HBB. All positive results and discordant results were confirmed by Sanger sequencing or specially designed PCR. SNPscan/CNVplex assay identified thalassemia-associated variants in 302 individuals (29.43%), compared with 283 correctly detected by routine PCR, representing a 6.71% increase in diagnostic yield. Concordant results between the two methods were observed in 98.15% of cases, while 19 cases showed discordant findings. Additional variants detected by SNPscan/CNVplex assay included 14 &#x3b1;-globin gene triplications, one HK&#x3b1;&#x3b1; rearrangement, two rare SNVs/indels, and two large fragment copy number variants involving the &#x3b1;-globin gene cluster. The most common &#x3b1;-thalassemia mutation was--SEA, whereas HBB:c.316-197C>T was the most frequent &#x3b2;-thalassemia variant. Three individuals carried both &#x3b1;-globin gene triplications and &#x3b2;-thalassemia mutations, indicating potential risk for aggravated globin chain imbalance. CNVplex assay also successfully identified large deletions and duplications encompassing the &#x3b1;-globin gene cluster that were missed by routine PCR. Combined SNPscan/CNVplex assay demonstrated broader mutation coverage and higher diagnostic yield than routine PCR, particularly for detecting homologous recombination events and large structural variants. This integrated strategy may improve carrier detection and genetic risk assessment in thalassemia screening programs.

Burnout affects many medical students, yet the role of positive childhood experiences (PCEs) remains largely unexplored. Sense of belonging protects against burnout, but whether it mediates the link between PCEs and burnout is unknown. To test whether sense of belonging mediates the association between PCEs and burnout in medical students. This cross-sectional survey study examined medical students (N&#x202f;=&#x202f;132) at a U. S. medical school using validated measures of PCEs, sense of belonging, and burnout. Mediation was tested using PROCESS Model 4 with 5,000 bias-corrected bootstrap confidence intervals. Year of training, age, and gender were covariates. All primary bivariate correlations were significant (p&#x202f;<&#x202f;0.001). PCEs predicted belonging (B&#x202f;=&#x202f;1.389, &#x3b2;&#x202f;=&#x202f;0.353, p <&#x202f;0.001), and belonging predicted lower burnout controlling for PCEs and covariates (B&#x202f;=&#x202f;-0.490, &#x3b2;&#x202f;=&#x202f;-0.555, p&#x202f;<&#x202f;0.001). The indirect effect was significant (B&#x202f;=&#x202f;-0.680, &#x3b2;&#x202f;=&#x202f;-0.205, 95% BootCI [-1.124, -0.297]). The direct effect remained significant (B&#x202f;=&#x202f;-0.806, p&#x202f;=&#x202f;0.001), indicating partial mediation. The model explained 51.1% of burnout variance; belonging accounted for 45.8% of the total PCE&#x202f;-&#x202f;burnout association. Age was significant (p&#x202f;=&#x202f;0.026); year of training showed a marginal trend toward higher burnout in more advanced students (p&#x202f;=&#x202f;0.065). Findings are consistent with a partial mediation model in which belonging explains a substantial portion of the PCE&#x202f;-&#x202f;burnout association. Since belonging is institutionally modifiable, fostering belonging-oriented environments offers an evidence-informed burnout prevention strategy, especially for students with fewer nurturing childhood experiences.

Coronary obstruction (CO) is a catastrophic complication of transcatheter aortic valve implantation (TAVI). Chimney stenting (CS) is one of the direct preventive measures for CO; however, data on its clinical course and characteristics are limited. We evaluated mid- to long-term outcomes of prophylactic CS during TAVI using supra-annular self-expanding bioprostheses. Among 315 consecutive TAVI procedures with supra-annular self-expanding valves between November 2015 and April 2022, 14 patients at high risk for CO underwent prophylactic CS. The clinical outcomes of the CS group were investigated using a non-CS group (n=301) as a comparison reference. High-risk anatomy was identified by preprocedural computed tomography assessing the sinotubular junction, sinus of Valsalva, coronary height, and annular calcification. CS was performed when balloon aortic valvuloplasty with simultaneous aortography demonstrated absent coronary opacification or impending obstruction. Patients in the CS group were predominantly female with a smaller body size, smaller aortic root dimensions, and low left coronary height (9.6 vs. 12.5 mm; P<0.001). Dual antiplatelet therapy was administered in 93% of CS patients for a mean duration of 7.4 months. During a mean follow up of 4.3 years, mortality was similar to that of non-CS patients (log-rank P=0.756). The clinical outcomes of prophylactic chimney stenting were comparable with the conventional TAVI cohort; therefore, it may be considered a therapeutic option for patients at high risk of CO during supra-annular self-expanding TAVI.

The effectiveness of free cancer screening programs in reducing long-term healthcare expenditures remains debated, yet quasi-experimental evidence is scarce. This study evaluates the impact of a large-scale, government-led free cancer screening program, available to citizens aged 65 and above, on the medical expenditures of urban retirees in Jiangsu Province, China. We employed a sharp regression discontinuity design (RDD). Our analysis included a cross-sectional sample of 1,503 retired individuals aged 60-70 from Jiangsu Province, China, who participated in free physical examinations in 2021. The treatment group (aged &#x2265;65) was eligible for free cancer screening, while the control group (aged 60-64) was not. The primary outcome was self-reported annual medical expenditure. We estimated local average treatment effects using local linear regression with a triangular kernel and conducted robustness checks using alternative bandwidths and polynomial orders. A significant discontinuity in annual medical expenditure was observed at the eligibility threshold. The free screening policy led to an immediate increase in medical spending at age 65 (RD estimate&#x202f;=&#x202f;CNY 1968, 95% CI [1,042, 2,894], *p*&#x202f;<&#x202f;0.001). This short-term surge (ages 65-67) was primarily driven by increased health information-seeking and subsequent medical consultations. Cross-sectional trend analysis revealed different expenditure patterns across age cohorts, with those aged 68 and above showing slower growth rates in medical spending compared to younger cohorts. Subgroup analyses indicated that the policy's impact was more pronounced among men and residents of developed regions. Free cancer screening acts as a double-edged sword for medical expenditures among older adults. It induces a short-term cost surge likely due to initial information shock and elevated risk perception. Policymakers should anticipate and manage the initial demand shock while considering the differentiated patterns across age groups. Strategies to optimize information delivery and mitigate gender and regional disparities are crucial for enhancing the equity and cost-effectiveness of such large-scale preventive health programs.

Osteosarcoma is the most common primary malignant bone tumor in dogs, characterized by aggressive local invasion and early metastatic potential, most frequently affecting the appendicular skeleton of large and giant breeds. This report describes a rare case of proximal radioulnar osteosarcoma in a 3.5-year-old intact male Great Dane that presented with progressive left forelimb lameness, swelling distal to the elbow, and weight loss. Radiographic examination revealed an aggressive mixed lytic-proliferative lesion involving the proximal radius and ulna, with distinct margins and no radiographic evidence of pulmonary metastasis. A definitive diagnosis of proximal radioulnar osteosarcoma was established by histopathological examination following forelimb amputation with scapulectomy. The dog underwent surgery and showed good postoperative recovery, with no evidence of recurrence during a 6-month follow-up period. Adjuvant chemotherapy was recommended to prevent metastasis, but the owner's financial constraints did not allow for this treatment. This case highlights the importance of early recognition, comprehensive diagnostic evaluation, and timely surgical intervention in managing canine osteosarcoma, particularly at uncommon anatomical sites.

As interest in non-pharmacologic treatments for migraine prevention increases, there is an urgent need to evaluate these treatments in well-designed randomized trials. However, designing a "control" for non-pharmacologic treatments is complex. One possible solution is to design credible educational programs to use as comparators which partially control for natural history, patient engagement, attention and positive expectancy. To develop and validate through a modified Delphi process a "Headache Health Education" (HHE) program to be used as the control arm in a pilot study of multimodal chiropractic care for episodic migraine. Leveraging existing patient educational materials, we drafted an initial HHE program with 14 modules, each covering a different migraine-related topic. Designed to be delivered by research personnel in a one-on-one video conference, each module provides education using a slide deck and guided conversation that is grounded in adult learning theory. Furthermore, to engage participants, the script-based sessions are informed by the psychological implications of polyvagal theory and motivational interviewing. The program was validated using a modified Delphi process. Modifications were made to the program based on the ratings and feedback, and a second round of review was then performed. Initial endorsement of the HHE program was generally supportive but included considerable variability. After program refinement, endorsement improved with much lower score variability. Key improvements included the addition of 2 topics, selection of new videos, and training for research assistants/associates in how to use conversational style and specific prompts to engage participants. Initial development and validation of an HHE program to use as a comparator in trials of a non-pharmacological treatment for migraine has been completed. Future analysis will examine the fidelity and acceptability of the HHE program when used as a comparator in a randomized controlled trial of multimodal care for migraine.

Cytokines represent a diverse group of soluble proteins that play crucial roles in mediating cellular communication in order to regulate cell fate, particularly in the context of the immune system. Because of their critical roles in controlling cell differentiation, proliferation, migration, activation, and survival, cytokines are heavily implicated in the development and progression, as well as in the prevention and clearance, of cancer. Using both native cytokines and engineered versions thereof, ongoing research in the cancer field endeavors to harness the antitumor activities of cytokines to develop targeted immunotherapies. This review surveys the biology of cytokines and their use in cancer treatment, covering several categories of cytokines, including interleukins, interferons, chemokines, growth factors, and hormones. Preclinical and clinical efforts with natural and engineered cytokines along with efforts to combine these molecules with other anticancer modalities are discussed, highlighting both the triumphs and challenges for these essential proteins in oncology applications.