Ankle osteoarthritis (AOA) is a progressive condition that impairs mobility and reduces quality of life. Conservative treatments like rocker bottom (RB) shoes and ankle-foot orthoses (AFOs) are commonly prescribed, but their effectiveness in managing AOA is not well understood, and patient preferences are underexplored. This is a pilot study aimed to evaluate the effect of RB shoes and AFOs in managing AOA and to identify factors influencing patient preferences for these conservative treatments. This was a cross-over telehealth study involving 10 participants with doctor-diagnosed AOA. Each participant wore three footwear conditions: control shoes, RB shoes, and AFOs, each for 3 weeks. Participants completed baseline pain ratings and functional assessments using PROMIS and FAAM questionnaires. After each 3-week footwear session, participants reported pain levels and provided feedback on their preferred footwear. Younger participants (aged 56-63) preferred AFOs for pain relief and improved mobility, while older (aged 66-75) and taller participants preferred RB shoes for their comfort. No significant differences were found in pain or function across footwear conditions, but AFO-preferred participants experienced significant reductions in maximum pain compared to the RB group. Footwear preferences were influenced by age and activity level. Younger participants preferred AFOs for functional benefits, while older participants prioritized comfort and selected RB shoes. These findings emphasize the need for personalized conservative treatment strategies in managing AOA. This pilot study highlights the importance of tailoring conservative treatments for AOA based on age and activity level. Understanding patient preferences can help guide clinical decisions and improve patient outcomes.
Partial foot amputation (PFA) is increasingly performed due to rising prevalence of diabetes and peripheral vascular disease. While PFA may preserve gait and reduce energy expenditure compared with transtibial amputation, biomechanical deficits are common. This review aimed to evaluate biomechanical outcomes during baref following PFA. A systematic review was conducted. MEDLINE, Embase, CINAHL, SCOPUS and Web of Science databases were searched for studies reporting biomechanical outcomes in adults with PFA without prosthesis. Eligible outcomes included spatiotemporal metrics, joint kinematics and kinetics, plantar pressures, and ground reaction forces. Twelve studies including a total of 101 participants met inclusion criteria. Across studies, PFA was associated with impaired barefoot gait. This included spatiotemporal changes, such as reduced walking speed and shorter step length, and kinetic changes, such as reduced ankle power. Elevated plantar pressures were commonly reported, particularly in the forefoot and midfoot, highlighting loading abnormalities in the residuum. Several studies also described proximal compensatory strategies at the knee and hip, suggesting that biomechanical consequences extend beyond the foot and ankle. However, the evidence base was limited by small sample sizes, inconsistent protocols, and substantial heterogeneity. Barefoot walking is impaired after partial foot amputation and the degree of dysfunction may vary by amputation level. Abnormal loading and compensatory changes may extend beyond the foot and ankle to the knee and hip. Given the limited and methodologically heterogeneous evidence, larger prospective studies with standardised biomechanical outcomes are needed to clarify the effects of amputation level and aetiology. This standardisation is important to inform surgical planning, rehabilitation, and prosthetic device design.
Off-road activities such as trail running and hiking have undergone a significant surge in global popularity over the last 2 decades, but this engagement also raises the potential for musculoskeletal injuries, which are prevalent and comparable to rates reported in road running. Footwear is critical in these dynamic environments, incorporating features such as aggressive outsole patterns and structural stability elements to accommodate varied and rugged terrain. Given the limited synthesis and fragmented nature of the literature, this scoping review systematically mapped and summarised existing research on the influence of footwear in hiking and trail running. The review was guided by three research questions that examined key outcome domains and methodological approaches, using the Arksey and O'Malley framework, and was reported in accordance with PRISMA-ScR guidelines. A search across four databases identified 16 eligible studies. Thirteen studies (81%) focused on trail running, exploring various footwear types, including advanced footwear technology, minimalist designs, and specific midsole characteristics. Biomechanical outcomes were the most frequently investigated (62% of studies), while physiological outcomes, performance, injury, and comfort were addressed in 25%-31% of studies each. Although methodological strengths include an increasing commitment to ecological validity by leveraging wearable sensors in combined lab and field protocols, persistent limitations include frequent use of small sample sizes and the underrepresentation of female participants in many controlled trials. A significant evidence gap remains regarding the chronic effects of prolonged footwear use and the interaction of footwear with fatigue. Future research requires methodological standardisation and longitudinal studies to advance toward individualised, evidence-based footwear solutions.
Patients increasingly turn to AI chatbots for medical information, including before complex orthopaedic procedures such as progressive collapsing foot deformity (PCFD) surgery. Whether these tools deliver content of sufficient quality and accessibility for preoperative patient education remains unclear, particularly across competing platforms. This study addressed three questions: (1) Do ChatGPT, Perplexity AI and Google Gemini differ in the accuracy, comprehensiveness and clarity of their responses to PCFD-related patient questions? (2) Do these platforms produce content meeting recommended readability thresholds for patient education? (3) Does the level of agreement among blinded foot and ankle surgeons rating the quality of chatbot responses vary depending on the platform used? The three AI chatbot platforms produce responses of comparable accuracy but differ significantly in readability, with none reaching the recommended readability thresholds for patient education materials. Cross-sectional comparative study. Twenty frequently asked questions regarding PCFD, covering disease understanding, conservative management, surgical planning and postoperative recovery, were submitted verbatim to ChatGPT (GPT-4o mini), Perplexity AI and Google Gemini (free versions, March 25, 2026). The 60 resulting responses were rated by three blinded foot and ankle surgeons on three 5-point Likert scales (accuracy, comprehensiveness, clarity). Readability was assessed using the Flesch Reading Ease (FRE) and Flesch-Kincaid Grade Level (FKGL). Inter-rater agreement used Kendall's W; differences between platforms were analysed using Kruskal-Wallis tests with Bonferroni-corrected pairwise comparisons. All platforms produced responses rated accurate to very accurate. Perplexity achieved significantly higher accuracy than ChatGPT (p = 0.0003) and higher accuracy and clarity than Gemini (p = 0.0065 and p = 0.0075). No platform reached the recommended FRE ≥ 60 or FKGL ≤ 6 thresholds: median FKGL ranged from 13.1 (ChatGPT) to 21.4 (Perplexity), with ChatGPT producing the most readable and Perplexity the least readable content (p < 0.001). Inter-rater agreement was fair to substantial across platforms, lowest for Perplexity. AI chatbots produce generally accurate baseline information on PCFD surgery, with Perplexity showing significantly higher expert-rated accuracy and clarity than the other platforms-contrary to our hypothesis of comparable accuracy-while readability remains uniformly inadequate for all platforms, as hypothesized. These tools may serve as a supplementary source of information, but their inadequate readability suggests they are not yet suited to replace tailored, surgeon-led patient education. III; cross-sectional comparative study.
Foot-and-mouth disease (FMD) is a highly contagious infectious disease caused by foot-and-mouth disease virus (FMDV). FMDV replicates not only in epithelial cells, where it induces vesicular lesions, but also in myocardial and skeletal muscle tissues, leading to myocarditis and even fatal outcomes in infected animals. RIPK3/MLKL-mediated necroptosis is a proinflammatory cell death process that plays a significant role in viral infections. However, whether FMDV infection can trigger necroptosis in host cells remains unclear. We assessed necroptosis induced by FMDV infection through activation of the RIPK3/MLKL pathway in PK-15 and BHK-21 cells. Specific inhibitors GSK'872 (targeting RIPK3 phosphorylation) and NSA (targeting MLKL phosphorylation) were applied to examine the impact of this pathway on viral replication. Additionally, Co-immunoprecipitation (Co-IP) was used to analyze the interactions between FMDV-encoded proteins and RIPK3/MLKL, and AlphaFold3 was used to predict the interaction interface between the 3D protein and the RHIM-containing region of RIPK3. FMDV infection activated the RIPK3/MLKL pathway and induced necroptosis in both PK-15 and BHK-21 cells. Inhibitor assays revealed that blocking RIPK3 or MLKL phosphorylation significantly reduced FMDV VP1 expression and viral titers, indicating that the necroptosis pathway favors FMDV replication. Further investigation revealed that the FMDV non-structural protein 3D is the key protein responsible for activating RIPK3/MLKL pathway. Moreover, we confirmed that the 3D protein interacts and colocalizes with RIPK3. AlphaFold3 structural prediction suggested that 3D can directly associate with the RHIM-containing region of RIPK3, with residues R320, H322, E324, and Y346 of 3D interacting with residues N466, V469, and K471 of RIPK3 at the interface. Our results demonstrate that FMDV infection induces necroptosis in host cells. This finding expands the modes of host cell death caused by FMDV infection, advances the understanding of the role of necroptosis in viral infections, and may help elucidate the pathogenic mechanisms of FMDV.
Falls are a serious health problem among older adults. This study aimed to evaluate the feasibility and preliminary efficacy of a nurse-delivered foot health program for individuals aged 65 years or older. A sample of 58 individuals participated in a 12-session program. The program included plantar massage, group postural workshops focusing on foot and ankle strengthening and stretching, and the use of minimalist footwear. The program was completed by 51 participants from five different nursing homes. The participation rate was 77.3%, and participant satisfaction was rated at 8.7/10. Participants improved in all physical and psychological outcomes, such as Timed Up and Go (TUG), foot pain, and fear of falling (FoF). However, only changes in TUG and pain when wearing shoes were statistically significant. High attendance rates and positive participant feedback indicated high program feasibility. The study provides preliminary evidence of potential positive effects on fall risk factors over time.
Falling is a concern for both older persons and transtibial prosthesis users (TTPUs), with older TTPUs potentially facing compounded risk. Older adults and TTPUs display foot clearance (FC) behavior that may contribute to increased tripping risk. Further, a person's knowledge of their leg orientation in space (ie proprioception) plays a role in managing FC and is affected by age and prosthesis use. To examine the effect of walking speed on FC of older TTPUs and the relationship between FC and leg proprioception. Twelve unilateral TTPUs and 10 age-matched able-bodied controls participated in this observational study. Proprioception was assessed through knee joint angle replication ability. FC was recorded with optical motion capture while participants walked at self-selected normal and fast speeds. Average FC between groups was assessed using an independent t-test. A repeated-measures ANOVA assessed the effects of speed by limb on FC for each group separately. Linear regression controlling for speed assessed the association between FC and proprioception. At both speeds, older TTPUs showed no difference in FC on their prosthetic limb compared with the nondominant limbs of controls. Both groups exhibited reduced FC when walking faster. Worse proprioception on the prosthetic side of TTPUs was associated with lower sound limb FC. These behaviors may reflect a protective strategy of TTPUs to avoid foot collision during swing, including a desire to keep the sound limb close to the ground with poorer prosthetic limb position awareness.
India is rapidly becoming the diabetes capital of the world, with diabetic foot ulcers (DFUs) emerging as one of the most common and debilitating complications. They significantly impair quality of life and, if untreated, may lead to lower limb amputation in up to 12% of cases. Various treatment methods are available, and this study aimed to evaluate the efficacy and clinical outcomes of diperoxochloric acid (DPA) in the management of DFUs at a tertiary care center. A prospective study was conducted from September 2022 to September 2024, involving 50 patients with Wagner's Grade 1 and 2 DFUs. DPA solution was applied topically during daily dressings. Wound size was measured at 2-, 4-, 6-, and 10-week intervals. A 40%-50% reduction in wound size by the 4-week mark was considered a positive healing response. Among the 50 patients, the most common age group was 51-60 years, with a mean age of 51.96 years. The male-to-female ratio was 4.56:1. Wagner's Grade 1 ulcers were more frequently observed. At the 4-week interval, 84% of patients showed ≥40% wound contraction, and 28% achieved complete wound healing by the end of the study period. Notably, 82% of patients were successfully managed in the outpatient setting without the need for hospital admission. Diperoxochloric acid is an effective, safe, and cost-efficient adjunct in the management of DFUs. It promotes faster wound contraction, reduces the risk of complications, lowers the need for hospitalization, and improves overall patient outcomes and quality of life. Résumé Contexte:L’Inde devient rapidement la capitale mondiale du diabète, les ulcères du pied diabétique (UPD) représentant l’une des complications les plus fréquentes et les plus invalidantes. Ils altèrent considérablement la qualité de vie et, en l’absence de traitement, peuvent conduire à une amputation du membre inférieur dans jusqu’à 12 % des cas. Diverses modalités thérapeutiques sont disponibles, et cette étude avait pour objectif d’évaluer l’efficacité et les résultats cliniques de l’acide diperoxochlorique (DPA) dans la prise en charge des UPD dans un centre de soins tertiaires.Sujets et Méthodes:Une étude prospective a été menée de septembre 2022 à septembre 2024, incluant 50 patients présentant des UPD de grade 1 et 2 selon la classification de Wagner. Une solution de DPA a été appliquée localement lors des pansements quotidiens. La taille des plaies a été mesurée aux intervalles de 2, 4, 6 et 10 semaines. Une réduction de 40 % à 50 % de la taille de la plaie à la quatrième semaine était considérée comme une réponse positive à la cicatrisation.Résultats:Parmi les 50 patients, la tranche d’âge la plus représentée était celle de 51 à 60 ans, avec un âge moyen de 51,96 ans. Le ratio hommes/femmes était de 4,56:1. Les ulcères de grade 1 selon Wagner étaient les plus fréquemment observés. À la quatrième semaine, 84 % des patients présentaient une contraction de la plaie ≥40 %, et 28 % ont obtenu une cicatrisation complète à la fin de la période d’étude. Il est à noter que 82 % des patients ont pu être pris en charge avec succès en consultation externe, sans nécessité d’hospitalisation.Conclusion:L’acide diperoxochlorique constitue un adjuvant efficace, sûr et rentable dans la prise en charge des UPD. Il favorise une contraction plus rapide des plaies, réduit le risque de complications, diminue le besoin d’hospitalisation et améliore les résultats globaux ainsi que la qualité de vie des patients.
This methodological study was conducted to evaluate the Turkish validity and reliability of the "Instrument of Self-care for Prevention of Diabetic Foot" developed by Herrera-Guerra and Bautista-Arellano. This research is of methodological type. The study was conducted with 202 diabetic individuals followed up at a university hospital in Türkiye. Translation-back translation was used to assess linguistic validity, and the opinions of 11 experts were consulted for content validity. Confirmatory Factor Analysis (CFA) was applied to assess construct validity, and the Diagonally Weighted Least Squares (DWLS) estimator was used in the analyses. For reliability analysis, internal consistency coefficients (Cronbach's alpha and McDonald's omega) were calculated, and a test-retest reliability test was performed on 26 patients at four-week intervals. The content validity index was found to be 0.98. CFA results showed that the three-factor structure of the scale (Self-Care Monitoring, Self-Care Maintenance, and Self-Care Management) is suitable for the Turkish sample and that the model fit indices are at an excellent level (GFI = 0.989, CFI = 0.995, RMSEA = 0.055, SRMR = 0.061). Cronbach's alpha coefficients for the sub-dimensions of the scale were found to be in the range of 0.859-0.885, and McDonald's omega coefficients were in the range of 0.869-0.887. In the test-retest analysis, it was determined that there was no systematic deviation between the measurements in the Bland-Altman plots and that there was a very high level of positive correlation between test and retest scores (r = 0.992-0.994). As a result of the research, it was determined that the Instrument of Self-care for Prevention of Diabetic Foot is a valid and reliable scale in Turkish. This tool can be used as a guide in nursing care in terms of preventing diabetic foot ulcers and monitoring self-care of patients with diabetes in the Turkish population.
The pathology of diabetic foot ulcer (DFU) is characterized by keratinocyte dysfunction, non-resolving inflammation, and oxidative stress. We aim to investigate the effects and mechanisms of piroxicam on DFU healing through regulating mitochondrial function and suppressing inflammation. DFU was established in male C57BL/6 J mice and ovariectomized female mice. Piroxicam (1% or 0.33%) solution or saline was then applied for 9 days. HaCaT cells were induced with high glucose (HG) and subsequently incubated with piroxicam (0, 1.2, 3.7, 11, 33, 100 nM). Piroxicam significantly promoted DFU healing and inhibited the fibrosis in male diabetic mice at a low dose. Consistently, piroxicam enhanced proliferation and migration, and inhibited inflammation, fibrosis, and cellular senescence in HG-induced HaCaT cells. Mechanistically, piroxicam alleviated HG-induced mitochondrial dysfunction by stabilizing the mitochondrial respiratory chain, increasing biogenesis, and enhancing mitophagy. These effects further attenuated oxidative stress and inhibited the cGAS-STING-NF-κB inflammatory pathway, thereby reducing the release of pro-inflammatory factors. Furthermore, molecular docking revealed that piroxicam bound to ERα, a finding further confirmed by a cellular thermal shift assay. HG induced a significant decrease in nuclear ERα protein levels, which was reversed by piroxicam, especially at 11 and 33 nM. Additionally, piroxicam's pro-healing and anti-inflammation effects were attenuated in ovariectomized female DFU mice. Piroxicam's protection of mitochondrial function and suppression of oxidative stress was also abolished upon blocking ERα by tamoxifen. In conclusion, piroxicam alleviates mitochondrial dysfunction and suppresses inflammatory responses by binding to ERα, which ultimately promotes DFU healing at low doses.
Recalcitrant diabetic foot ulcers (DFUs) remain difficult to heal and impose substantial clinical and economic burdens. This exploratory, four-arm, parallel-group randomized pilot trial aimed to evaluate whether combining platelet-rich plasma-fibrin glue (PRP‑FG) with a novel repairing gel enhances healing outcomes in DFUs compared with standard care and single‑agent therapies. In this study, twenty patients with DFUs unresponsive to at least four weeks of standard treatment were randomized using computer-generated blocks with allocation concealment to receive PRP‑FG alone, repairing gel alone, the combination therapy, or standard care. Allogeneic PRP‑FG was prepared by gradient‑density centrifugation. The repairing gel contained multiple active components, including vitamins A, B3, and C, collagen, glycine, organic acids, sodium alginate, carboxymethyl cellulose, benzoic acid, gentian violet, methylene blue, triethanolamine, bromelain, allantoin, and dimethyl sulfoxide. Wound healing rate over 12 weeks served as the primary outcome, assessed weekly by a blinded evaluator. Nineteen patients completed the 12‑week follow‑up. Complete epithelialization occurred in 100% (5/5) of participants receiving the combined therapy, 20% (1/5) of those receiving the repairing gel alone, and 0% (0/5) in the PRP‑FG alone and standard care groups. The combined therapy significantly accelerated ulcer healing compared with all other groups (p < 0.05). These findings are preliminary and derived from a small pilot sample. No serious adverse events were observed. This exploratory pilot trial suggests that combined PRP‑FG and repairing gel therapy may promote superior healing of recalcitrant DFUs compared with standard care or single‑agent treatments. Larger, multicenter clinical trials are warranted to validate these preliminary findings.
The pathogenesis of early-stage skin lesions in diabetic foot (DF) remains poorly understood, and cannot be fully explained by conventional theories. Skin microbiota dysbiosis has recently emerged as a critical factor, but the underlying mechanisms remain unclear. In this study, we integrated metabolomics and metagenomics analyses of skin samples to investigate metabolic dysregulation driven by microbial dysbiosis. We identified elevated serine as a key metabolic alteration strongly correlated with a dysbiotic microbiota structure. Functionally, we demonstrate that abnormal serine accumulation contributes to the dysregulation of the early skin immune microenvironment in the diabetic foot. Mechanistically, our results reveal that excess serine synergizes with lipopolysaccharide (LPS) to stimulate the release of eHsp90α from keratinocytes, which was strictly dependent on the Akt/mTOR/HIF-1α pathway. This released eHsp90α then acts as a damage-associated molecular pattern, promoting both the migration and subsequent pyroptotic cell death of macrophages. Collectively, our findings suggest a novel pathogenic axis where a microbiota-host derived metabolite collaborates with a bacterial endotoxin to promote inflammatory cell death, which is closely associated with early skin lesions in DF. This work not only elucidates a new mechanism for DF pathogenesis but also suggests that the serine-eHsp90α-pyroptosis axis may serve as a potential candidate for future therapeutic exploration.
This study aimed to identify the prognostic markers for Diabetic Foot Ulcer (DFU) healing using routinely collected clinical data. A prospective cohort study of 1075 (M/F: 664/411) patients who attended the foot clinic with a DFU was conducted. At baseline, detailed clinical data were collected and ulcer characteristics were systematically assessed and classified. During 167 ± 408 days follow-up, ulcers of 1039 patients healed and 36 did not. Ulcers with SINBAD classifications 4, 5 and 6 (compared to SINBAD-3) showed 50%, 60% and 70% increase in the risk of not healing and 2.2, 2.8 and 3.3 folds increase in healing duration respectively. Also, deeper ulcer and having previous ulcer history showed 68% and 47% increase in the risk of ulcer not healing and 57% and 20% increase in healing duration respectively. Each day delay in presentation increased the risk of ulcer not healing by 0.5%. The duration of healing was 2.4 times longer for bigger ulcers (> 1 cm2) and 24% longer in patients with peripheral arterial disease. SINBAD score was the strongest predictor of ulcer healing. Among SINBAD constitutive components, ulcer depth (deep-vs-shallow) was the strongest predictor of risk of ulcer not healing, while ulcer size (bigger-vs-smaller than 1 cm2) was the strongest predictor of ulcer healing duration.
To evaluate the utility of the Small Artery Disease (SAD) score as a predictor of clinical outcomes and major adverse limb events in patients with chronic limb-threatening ischemia (CLTI), using lateral digital subtraction angiography images. A retrospective study was conducted with 183 patients with Fontaine 3 or 4 (mean age 72,2 ± 12,1 years old, 132 male) that underwent lateral DSA of the foot between 2020 and 2022. Three independent observers assessed all lateral projections of the foot using the SAD score. Outcomes included wound healing, amputation, repeat revascularisation, major adverse limb events (MALE) and survival. Patients with a SAD score ≥1 had a significantly increased risk for MALE (HR 2,22, p = 0,011) and death (HR 2,06, p = 0,025). There was no significant risk for impaired wound healing (HR 1,15, p= 0,669) and amputation (HR 1,48, p = 0,157) in patients with SAD ≥ 1. Interobserver agreement between the three observers for presence of SAD was substantial with an intra-class correlation coefficient of 0,61 (95% CI 0,53-0,68). Presence of SAD increases the risk of MALE and death in patients with chronic limb-threatening ischemia (CLTI), but had no relation with wound healing or amputation.
Diabetes-related foot ulceration (DFU) is a serious complication, serving as a leading cause of amputation, disability, hospitalisation and a significant contributor to healthcare costs. Deficiencies in vitamin C and other micronutrients are common in DFU. Emerging evidence suggests vitamin C supplementation may enhance wound healing; however, high-quality randomised controlled trials are lacking. Therefore, the aim of this study is to investigate the efficacy of oral vitamin C supplementation (1 g/day) for 8 weeks on wound healing in people with DFU. This is a multi-site, parallel group, randomised, placebo-controlled, double-blind trial. Eighty adults with DFU will be recruited and randomly assigned to either placebo or vitamin C supplementation (500 mg twice daily). Ulcer measurements will be obtained at baseline, 2, 4, 6 and 8 weeks with all other measures collected at baseline and 8 weeks. The primary outcome measure is the percentage reduction in ulcer size (ulcer volume in mm3) at 8 weeks, compared to baseline. Secondary outcomes are changes in plasma vitamin C, time to 50% ulcer healing, time to complete ulcer healing, rate of healing of ulcers and adverse events. Exploratory outcomes include changes to glycaemic status, blood lipids, blood pressure, peripheral arterial perfusion, mental health and well-being, scurvy signs and symptoms and oxidative stress. The findings from this research will provide high-quality evidence on the efficacy of vitamin C for wound healing in people with DFU and help to inform clinical practice regarding vitamin C supplementation alongside current standard care to aid in the healing of DFUs. Australian and New Zealand Clinical Trials Registry (ACTRN12624000675527). Universal Trial Number (UTN) U1111-1308-1050.
Diabetic foot ulcers (DFUs) are a leading cause of lower-limb amputation, with oxidative stress and ferroptosis playing critical roles in impaired wound healing. This study aimed to evaluate the therapeutic potential of luteolin (LU), a naturally occurring plant-derived flavonoid, in DFU repair and to elucidate its underlying molecular mechanisms. A DFU rat model was established using a high-fat/high-glucose diet combined with streptozotocin injection, followed by full-thickness skin wounding. LU was topically administered at different concentrations. Wound closure was monitored macroscopically, while histopathological changes, inflammatory cytokines, and growth factor levels were assessed by microscopy and ELISA. Network pharmacology and molecular docking analyses were performed to identify potential targets and signaling pathways, which were subsequently validated in vitro using human umbilical vein endothelial cells (HUVECs). LU significantly accelerated wound closure in a dose-dependent manner, accompanied by reduced oxidative stress and pro-inflammatory cytokine production, enhanced collagen deposition, increased angiogenesis, and upregulated expression of key growth factors. Bioinformatics analysis identified ferroptosis inhibition and activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway as central mechanisms, which were confirmed experimentally. LU reduced intracellular reactive oxygen species levels and lipid peroxidation and promoted HUVEC migration and viability. Notably, pharmacological inhibition of Nrf2 with ML385 markedly reversed the protective effects of LU, indicating a pivotal role for Nrf2 signaling. Collectively, these findings demonstrate that LU promotes DFU healing through activation of Nrf2 signaling and suppression of ferroptosis, supporting its potential as a therapeutic candidate for the management of diabetic wounds.
Stroke is a leading cause of severe long-term disability, and foot drop is a common post-stroke gait impairment that may reduce toe clearance, increasing the risk of toe contacts and, in turn, trip-related falls. This case series evaluated the novel combination of transcranial direct current stimulation (tDCS), functional electrical stimulation (FES) to the tibialis anterior, and physical therapy training to improve minimum toe clearance (MTC) in individuals with chronic stroke. The rationale for this combined approach was that tDCS may prime the motor cortex and enhance neuroplastic responsiveness, while FES provides task-specific peripheral stimulation to the dorsiflexors during gait-related training, potentially increasing MTC and minimizing toe drag. Four individuals with chronic stroke participated in an 8-week treatment program with sessions twice a week. Assessments were conducted at baseline, 4 weeks, and 8 weeks. Participant 1 started with tDCS alone for 4 weeks, then added FES for the remaining 4 weeks. Participant 2 began with FES for the first 4 weeks, and tDCS was added for the remaining 4 weeks. Participants 3 and 4 received both tDCS and FES throughout the entire 8-week program. Participants 1 (58-year-old female) and 4 (42-year-old male) showed no active ankle dorsiflexion at baseline, while participants 2 (66-year-old male) and 3 (36-year-old male) had a grade of 2 out of 5 for ankle dorsiflexion strength at baseline. Toe clearance and functional outcomes were collected at each assessment. Participants 1 and 4 demonstrated no meaningful change in MTC, whereas participants 2 and 3 both showed modest improvements. Among these responders, MTC increased by an average of 0.63 cm. These findings suggest that combining cortical neuromodulation with localized FES and physical therapy may improve toe clearance in select individuals with chronic stroke. However, because tibialis anterior activation was not directly measured, it remains unclear whether the observed changes were due to improved dorsiflexor activation or other compensatory gait strategies.
To develop a wound-healing prediction algorithm and validate the effect of platelet-rich plasma (PRP) gel for treating elderly diabetic foot ulcer (DFU) patients. From April 2020 to April 2022, 68 patients with Wagner Grade II-III DFU were consecutively enrolled, and their demographic, clinical, laboratory, and follow-up data were collected. A multiple regression model was used to develop a wound-healing algorithm with subsequent graphic model-fitting analysis. In the subgroup analysis, this study further compared the hemoglobin levels, inflammation indicators, and cytokines between the PRP treatment group (N = 31) and the non-PRP treatment group (N = 37). A wound healing prediction algorithm was developed as follows: Wound Healing Time (WHT) = -1.38 - 1.799 × PRP treatment + 0.813 × IL-6 - 0.158 × HbA1C + 0.559 × previous ulcer duration. In this prediction algorithm, the application of PRP treatment was identified as a significant parameter influencing WHT. In further subgroup analysis, the PRP treatment group showed superior results in terms of white blood cells, blood sedimentation, C-reactive protein, VEGF, and ENA-78 levels (all P-value < 0.01) compared with the non-PRP treatment group. PRP treatment promoted wound healing in elderly DFU patients by modulating inflammation and enhancing tissue regeneration, and the proposed algorithm offered predictive utility for healing time.
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Diabetic peripheral neuropathy (DPN) is a multifactorial complication in which metabolic dysregulation, altered body composition, and neuromuscular impairment may contribute to structural foot alterations and ulceration risk. These domains are often studied separately, limiting understanding of their combined relationship with digital deformities and diabetic-foot risk. To evaluate exploratory associations between digital deformities, diabetic-foot risk, and integrated anthropometric, metabolic, bioimpedance-derived, functional, and neuromuscular markers. This single-center case-control study included 65 adults: 28 with type 2 diabetes and 37 non-diabetic controls. Assessments included anthropometry, bioimpedance-derived parameters - phase angle (PhA), ECW/TBW ratio, and muscle quality - handgrip dynamometry, HbA1c, and the triglyceride-glucose (TyG) index. Diabetic-foot risk was classified according to IWGDF criteria in participants with type 2 diabetes. Analyses included Shapiro-Wilk tests, Student's t-test or Mann-Whitney U test, Pearson or Spearman correlations, and one-way ANOVA with Tukey post-hoc tests. Missing data were below 5% and were imputed. Diabetic-foot risk correlated with waist circumference (r = 0.443, p < 0.001), BMI (r = 0.333, p = 0.005), HbA1c (r = 0.560, p < 0.001), and TyG index (r = 0.454, p < 0.001). Digital deformities were associated with fasting glucose (r = 0.573, p < 0.001), HbA1c (r = 0.560, p < 0.001), and TyG index (r = 0.565, p < 0.001). Inverse associations were observed for handgrip strength (r = -0.340, p = 0.004), muscle quality (r = -0.311, p = 0.009), and PhA (r = -0.285, p = 0.018). Exploratory subgroup analyses showed differences across analytical risk strata for PhA (F = 6.99, p = 0.002), muscle quality (F = 6.99, p = 0.002), and handgrip strength (F = 4.04, p = 0.022). Digital deformities and diabetic-foot risk in DPN were associated with combined metabolic, bioimpedance-derived, and systemic neuromuscular alterations. Handgrip strength and bioimpedance-derived parameters showed exploratory associations with risk and deformities; however, their role as complementary assessment measures requires confirmation in larger longitudinal studies with adjusted models.