Search Results (1,378)

Surface functionalization of metallic implants is widely explored to enhance their performance and functionality. In this study, multifunctional hydrogel coatings based on poly(vinylpyrrolidone) and polyethylene glycol were developed and functionalized with a taxifolin (TAX) inclusion complex and collagen to introduce bioactive features. TAX, a naturally occurring flavonoid with antioxidant and anti-inflammatory properties, was incorporated using β-cyclodextrin to improve its stability and enable controlled release. The coatings were applied to titanium-hydroxyapatite composites and titanium sheet substrates to evaluate their applicability across surfaces with varying morphologies, ranging from porous to relatively smooth. The ceramic phase was modified with magnesium ions to enhance its bioactivity and better mimic the composition of natural bone tissue. FTIR and SEM analyses confirmed hydrogel formation and effective surface coverage. Degradation and incubation studies in simulated physiological environments demonstrated the material’s stability, while UV–Vis analysis indicated TAX release, highlighting the system’s potential as a carrier for flavonoid-based compounds. Indirect cytotoxicity studies using MC3T3-E1 preosteoblasts indicated low cytotoxicity and a favorable biological response of collagen- and taxifolin-modified systems. The developed coatings represent a versatile platform for surface modification of titanium-based biomaterials and demonstrate potential for application across substrates with diverse surface characteristics. Further studies are required to assess their biological potential. Full article

Multiple Myeloma (MM) is a hematological malignancy characterized by the clonal proliferation and survival of neoplastic plasma cells (PCs) within the bone marrow (BM), where disease progression is critically supported by interactions with the BM tumor microenvironment (TME). Despite significant advances in therapeutic strategies, MM remains incurable, underscoring the need for improved preclinical models to better understand the disease biology and therapeutic response. This review summarizes current and emerging MM treatment approaches and critically examines the development of models designed to more accurately recapitulate interactions between MM-PCs and the surrounding BM niche. We describe established and emerging modeling platforms, with emphasis on advanced three-dimensional (3D) culture systems and highlight their unique contributions to the preclinical assessment of both existing and novel therapies. The advantages of 3D models, including in vitro and in silico systems, over traditional two-dimensional (2D) models are discussed, alongside a comparative evaluation of scaffold-free and scaffold-based approaches. In addition, the benefits and recent advances in the customization of BM niche simulation using microfluidic technologies and organ-on-a-chip platforms are reviewed. The application of 3D models in MM research is increasingly enabling the study of disease pathogenesis, progression, drug resistance and precision-medicine approaches (informed by biomarker discovery). Although standardized preclinical approaches for evaluating MM therapeutics are currently lacking, the growing imperative to reduce reliance on preclinical animal models highlights the importance of alternate systems. Consequently, the development and adoption of physiologically relevant models that accurately recapitulate MM-PC interactions with the BM TME will be critical for advancing future therapeutic strategies in MM. Full article

Mineralising avian tendon is a widely used experimental model for studying collagen-guided mineralisation. Yet, the three-dimensional organisation and topology of its internal canal system have never been quantitatively characterised. We combined high-resolution micro-computed tomography (micro-CT) and scanning electron microscopy (SEM) to provide the first morphometric and topological analysis of the canalicular network in mineralised turkey gastrocnemius tendon. micro-CT revealed that unmineralised canals occupy approximately 34.6% of the mineralised tissue volume and form a single continuously connected network (99.8% of void volume), with a connectivity density of ~1.3 × 10² mm⁻³, a fractal dimension of 2.58, a degree of anisotropy DA = 0.87 [BoneJ convention, range 0–1], and a closed-loop topology. SEM revealed marked ultrastructural heterogeneity of the mineral phase across fascicle cross-sections, consistent with graded intrafibrillar-to-interfibrillar deposition. These findings establish the first quantitative morphometric framework for physiologically mineralising collagen tissue and support the use of turkey gastrocnemius tendon as a tractable model for studying mineralisation dynamics, enthesis biology, and the design of biomimetic scaffolds with controlled porosity and anisotropy. Full article

Clonal hematopoiesis of indeterminate potential (CHIP) and the gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) are both linked to NLRP3-mediated cardiovascular inflammation, but their interaction has not previously been explored. This work proposes the CHIDT axis (clonal hematopoiesis–dysbiosis–TMAO), a feed-forward mechanism in which TET2 loss-of-function CHIP- and TMAO-generating Gram-negative gut dysbiosis mutually enhance cardiovascular risk. The model proceeds in three nodes. CHIP-associated intestinal immune dysregulation promotes luminal expansion of Gammaproteobacteria, which produce both trimethylamine via CntA/CntB-mediated L-carnitine oxidation and ADP-heptose as an obligate LPS biosynthetic intermediate. TMAO amplifies NLRP3 inflammasome activation through the SIRT3 → SOD2 → mtROS pathway. The evidence base of the CHIDT model is strongest for TET2-CHIP; the proposed extension to DNMT3A-CHIP rests on indirect, associative data and requires dedicated experimental confirmation before it can be considered established. TXNIP cascade, with predicted disproportionate potency in macrophages epigenetically primed by TET2 haploinsufficiency. High concentrations of TMAO have also been shown to suppress TET2 expression in endothelial cells through CYTB promoter hypermethylation, inducing NLRP3–GSDMD-dependent pyroptosis, although it remains unclear whether physiological TMAO levels can trigger this effect. Concurrently, ADP-heptose activates the ALPK1–TIFA–NF-κB pathway in bone marrow progenitors, favoring the expansion of mutant hematopoietic stem and progenitor cells. The model identifies three potential therapeutic strategies: NLRP3 inhibition, microbial TMA lyase inhibition, and microbiome-targeted reduction in Gram-negative bacteria. None has been tested in CHIP carriers stratified by plasma TMAO. Further studies in preclinical models and human cohorts integrating CHIP genotyping and TMAO quantification are needed to validate the CHIDT axis as a target for precision cardiovascular prevention. Full article

Noninvasive light-based measurements have recently been suggested for monitoring fracture healing and for the development of smart implants. The aim of this study was to collect the first exploratory longitudinal in vivo data from human distal fibular fractures. In this prospective observational pilot study, blood flow, oxygen saturation, and relative hemoglobin were noninvasively measured by using combined laser Doppler and white-light spectroscopy at depths of 3 mm and 10 mm. In patients with fibular fractures, measurements were performed at 1–3 days, 2 weeks, 6 weeks, 3 months and 6 months after surgery. Patients with fibular nonunion and healthy control participants underwent a single measurement. Fourteen longitudinal fracture patients, a nonunion patient, and 42 controls were included. In the longitudinal fracture group, oxygen saturation at a depth of 10 mm significantly decreased from baseline to 2 weeks (p < 0.001) and remained at a low plateau significantly below healthy control levels throughout the 6-month period. Blood flow and relative hemoglobin levels did not longitudinally change but remained significantly elevated compared with controls (p < 0.001). A single nonunion case demonstrated a markedly low oxygen saturation value (8.3%) combined with increased blood flow. Fibular fractures treated with plate fixation exhibit a prolonged low-oxygen saturation plateau, in contrast to the rapid recovery observed in tibial shaft fractures, possibly due to differences in anatomy or healing mechanisms. The low oxygen saturation observed in the nonunion requires further investigation, as it may have prognostic potential. Full article

Individuals with Duchenne muscular dystrophy (DMD) are prone to nutritional imbalances, and zinc deficiency may contribute to impaired bone health. This study evaluated serum zinc status and the effects of oral supplementation on bone parameters in DMD. In this quasi-experimental before-and-after study, 34 patients were assessed at three time points over eight months. Eligible participants who met the inclusion criteria and agreed to participate received the proposed interventions during routine follow-up at the Neurology outpatient clinic. Anthropometry, dietary intake, bone mineral density (BMD), bone mineral content (BMC), and serum zinc were measured; supplementation (5–15 mg/day) was provided for four months. Baseline zinc deficiency was observed in 36.7% of participants. No significant overall changes were detected. Stratified analyses revealed a modest increase in total body BMD among individuals with adequate baseline BMD (p = 0.02). As this finding emerged from a subgroup analysis, it should be interpreted cautiously, and the potential contribution of physiological growth to the observed change cannot be excluded. In addition, zinc-deficient participants showed a significant rise in serum zinc levels (p = 0.008). These findings suggest that the response to zinc supplementation may vary according to baseline nutritional and skeletal status and underscore the relevance of micronutrient monitoring in individuals with DMD. Trial registration: The trial was also registered in the Brazilian Registry of Clinical Trials under the code RBR-7cfdxm, approved on 14 June 2018. Full article

[¹⁸F]-PSMA PET/CT is a high-impact modality for the staging and restaging of prostate cancer, but its wide anatomic coverage and tracer biology generate frequent incidental findings on both PET and the accompanying low-dose CT (LDCT). This narrative review is restricted in scope to fluorine-18 PSMA tracers because tracer-specific biodistribution and pitfall profiles shape what is perceived as incidentaloma: how confidently lesions can be categorized, and how often borderline findings trigger downstream testing, particularly for skeletal foci with [¹⁸F]-PSMA-1007. Specifically, [¹⁸F]-PSMA-1007 shows substantially higher rates of focal unspecific bone uptake than [⁶⁸Ga]-PSMA-11—reported in multicenter studies as affecting up to 40–50% of patients—which directly inflates the pool of potential incidentalomas and creates a tracer-specific false-positive problem with no parallel in gallium-68 practice. Additionally, [¹⁸F]-DCFPyL has different urinary clearance kinetics that affect bladder and ureteral uptake patterns, altering what qualifies as physiologic versus incidental in the pelvis. These differences mean that the threshold for Category B versus C classification—and the appropriate cascade-resistant language—must be tuned to the specific tracer in use. A framework built on [⁶⁸Ga]-PSMA-11 data would systematically underestimate bone pitfall frequency in [¹⁸F]-PSMA-1007 practice and could therefore paradoxically increase rather than reduce cascades if applied uncritically across tracers. These biodistribution differences have direct and concrete consequences for reporting behaviour and downstream management. In [¹⁸F]-PSMA-1007 practice, a focal bone uptake without a CT correlate in a mechanically plausible location—such as an anterior rib or vertebral endplate—should trigger Category B language in the report conclusion: the finding is documented in the body with explicit safety netting (“most consistent with unspecific uptake; no routine workup unless interval growth, new pain, or aggressive CT morphology”), and no referral to bone scintigraphy or MRI is generated. Without tracer-specific awareness, the same finding would typically prompt a reflex bone scan or whole-body MRI referral, delaying definitive prostate cancer management by weeks and adding imaging costs without diagnostic gain. By contrast, in [⁶⁸Ga]-PSMA-11 practice, an equivalent focal bone uptake without a CT correlate carries a higher prior probability of true metastatic disease given the lower background rate of unspecific uptake and should more often be reported at Category B with a lower threshold for escalation or more cautious language. For [¹⁸F]-DCFPyL, the higher urinary activity in the pelvis means that ureteral segments can mimic lymph node disease; recognizing this as a physiologic variant (Category C) rather than an equivocal nodal finding (Category B) avoids unnecessary pelvic MRI referrals that would otherwise be triggered by an uncontextualized report. In practical terms, the tracer-specific calibration of the overlay therefore changes not only the category assigned but also the specific safety-netting language and the escalation trigger, which directly modifies the downstream management pathway for each affected finding type. The scanned population—predominantly older men with a high prevalence of degenerative, inflammatory, and vascular abnormalities—creates substantial background noise that can drive low-value diagnostic cascades if incidental findings are communicated without actionability context. We integrate society-endorsed frameworks (EANM/SNMMI procedure guideline 2.0; E-PSMA; PSMA-RADS; and PROMISE/miTNM with miPSMA score) and propose a cascade-aware overlay for incidental findings that can be appended to existing PSMA reporting standards rather than replacing them. The A/B/C actionability overlay is a structured expert-consensus framework informed by existing evidence-based guidelines for specific finding types and by tracer-specific cohort data; it has not yet been prospectively validated as a standalone tool, and its current level of evidence is therefore analogous to a structured expert recommendation rather than an evidence-based clinical guideline. We operationalize a three-tier actionability scheme across PET- and CT-dominant findings, provide cascade-resistant language for conclusions, and clarify why SUVmax-only “probability scales” for lymph nodes are not recommended in routine reports. Three practical tables summarize PET incidental findings, lymph node reporting frameworks, and LDCT incidental findings, and two structured report templates are provided (concise and extended), with the extended version explicitly labelling actionability tiers and escalation triggers. Finally, we outline concrete AI use cases for standardization and triage while emphasizing governance to avoid the amplification of false positives and paradoxical growth of cascades. Full article

Background: Radiology underpins diagnosis and treatment across pediatrics, yet most artificial intelligence (AI) tools are developed for adults and validated on adult datasets only. Of more than 200 AI systems cleared by the United States (U.S.) Food and Drug Administration (FDA), only about 3% include pediatric validation. Because children differ from adults in anatomy, physiology, pathology, epidemiology, and imaging protocols, adult-trained models often perform sub-optimally in pediatric settings. Methods: A narrative review of peer-reviewed literature from 2000 to 2025 was conducted using PubMed, MEDLINE, Google Scholar, and Scopus. Studies involving AI applications in pediatric X-ray, ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), echocardiography, and point-of-care ultrasound with quantitative performance metrics were included. Findings were synthesized by imaging modality, clinical task, and differences between high-income countries (HICs) and low- and middle-income countries (LMICs). Results: AI demonstrated strong performance across multiple pediatric imaging tasks. In X-ray interpretation, AI detected fractures with area under the curve (AUC) values up to 0.96 (sensitivity, 90.8%; specificity, 88.7%). Pneumonia classification achieved 76.5% accuracy, and foreign body aspiration detection showed 95.3% specificity in HICs. In ultrasound, AI improved junior sonographers’ detection of intussusception (AUC 0.857 to 0.966) and reduced scan time by more than 50%. AI-assisted bone age estimation achieved a mean error of 0.39 years. In echocardiography, AI-derived ejection fraction showed excellent agreement with experts’ interclass correlation coefficient (ICC 0.983), and AI support improved atrioventricular septal defect detection (84.4% to 86.5%). In MRI, the use of AI enhanced lesion detection and supported quantitative analysis. Deep-learning models trained on routine T1- and T2-weighted sequences predicted liver stiffness across multi-site datasets, while advanced neuroimaging pipelines improved the identification of subtle epileptogenic lesions that are often missed on conventional pediatric MRI. However, adult-trained models showed limited generalizability to children. Still, excluding children under the age of two years improved the reading accuracy of pediatric chest X-rays (CXRs) by adult-trained models from 88% to 97%. AI faces challenges beyond the development of age-specific models. Substantial heterogeneity, limited pediatric-specific datasets, and unresolved medicolegal responsibility further restrict adoption worldwide. Challenges are amplified in LMICs, where unstable electricity, limited radiology resources, weak digital infrastructure, and scarce pediatric providers limit implementation. Additionally, many large language models underperform and lack inclusive algorithms suitable for pediatric radiology in many LMICs. Conclusions: AI can enhance diagnostic accuracy, efficiency, and access to pediatric imaging, particularly in resource-limited settings, through task-shifting and decision support. However, it cannot replace pediatric radiologists as of today. Safe adoption requires pediatric-specific model development, standardized validation metrics, diverse datasets that include LMIC populations, stronger digital infrastructure, robust radiologist training in AI capabilities, and the establishment of clear guidelines and medicolegal policies. Full article

Background/Objectives: Delayed bone healing remains a relevant complication after polytrauma, where fracture repair occurs in the setting of systemic inflammation and repeated physiologic stress. This study evaluated whether serial changes in interleukin-6 (IL-6), C-reactive protein (CRP), and fibrinogen are associated with delayed union in polytrauma patients with long-bone fractures. Methods: We performed an exploratory retrospective cohort study including 115 adult polytrauma patients with long-bone fractures treated at a single tertiary trauma center between 2 January 2022 and 14 December 2024. Serum IL-6, CRP, and fibrinogen were recorded at 24 h, 72 h, 1 week, 2 weeks, and 4 weeks after injury. IL-6 was measured in the institutional clinical laboratory using routine immunoassay methods, whereas CRP and fibrinogen were measured using standard hospital analytical methods, including an immunoturbidimetric assay for CRP and the Clauss clotting method for fibrinogen. Radiographic healing was assessed at 6, 12, and 24 weeks using an mRUST-based healing score. The primary endpoint was clinician-assigned delayed union at 24 weeks; nonunion at 9 months was assessed secondarily. Complete-case multivariable logistic regression was performed in 86 patients, and exploratory longitudinal biomarker analyses used generalized estimating equations. Results: Delayed union at 24 weeks occurred in 39/115 patients (33.9%), while nonunion at 9 months occurred in 7/115 patients (6.1%). Patients with delayed union had longer time to definitive fixation (35.3 ± 10.2 h vs. 29.0 ± 14.0 h; p = 0.003) and more frequent shock on admission (43.6% vs. 23.7%; p = 0.047). IL-6 was higher in the delayed-union group at 1 week (57.3 ± 30.3 vs. 46.5 ± 29.2 pg/mL; p = 0.043) and 4 weeks (21.2 ± 11.6 vs. 17.1 ± 10.3 pg/mL; p = 0.022), whereas CRP was markedly higher at 4 weeks (29.4 ± 14.2 vs. 16.3 ± 10.6 mg/L; p < 0.001). After false-discovery-rate correction, only CRP at 4 weeks remained significant among serial biomarker comparisons. In multivariable analysis of 86 complete cases, CRP at 4 weeks remained independently associated with delayed union (adjusted OR 2.16 per 10 mg/L, 95% CI 1.36–3.43; p = 0.001). The model showed apparent discrimination with an AUC of 0.80 and acceptable calibration (Hosmer–Lemeshow p = 0.41). In sensitivity analysis excluding deep surgical-site infection cases, the association between CRP and delayed union persisted (adjusted OR 2.02 per 10 mg/L, 95% CI 1.26–3.26; p = 0.004). Conclusions: In this exploratory retrospective cohort of polytrauma patients with long-bone fractures, persistent post-traumatic CRP elevation at 4 weeks was associated with clinician-assigned delayed union, whereas IL-6 findings were weaker and exploratory. Because CRP is a nonspecific inflammatory marker, the observed association may reflect delayed healing, infection, reoperation, and/or persistent postoperative inflammatory burden. These data support association rather than validated prediction and require prospective validation with standardized outcome adjudication. Full article

Background/Objectives: Acceleration of orthodontic tooth movement remains a major challenge in clinical orthodontics. Evidence suggests that increased local blood flow around the alveolar bone is key to bone remodeling and potentially reflects early biological responses associated with accelerated orthodontics. This study aimed to investigate the effects of non-invasive physical stimuli on gingival microcirculation. Methods: Eight healthy adult male volunteers were included in the analysis. Gingival blood flow was assessed using laser Doppler flowmetry under the following conditions: no-stimulation condition (None) and four types of stimuli: thermal stimulation (THM), electric field stimulation (ELF), vibration stimulation (VIB), and far-infrared stimulation (FIR). Gingival blood flow was recorded before and after each stimulation, and the rate of change was calculated. Statistical analysis was performed using a linear mixed-effects model with Type III ANOVA (Satterthwaite approximation), followed by Dunnett-adjusted comparisons. Results: A statistically significant difference was observed between stimulation conditions (p = 0.0087). VIB significantly increased gingival blood flow compared with the no-stimulation condition (p = 0.0041), whereas ELF showed a trend toward increased blood flow (p = 0.0936); THM and FIR showed no statistically significant effects. Conclusions: The findings of this study suggest that non-invasive physical stimuli, particularly vibration stimulation, can enhance gingival microcirculation. Although tooth movement was not directly evaluated, the observed hemodynamic changes may represent short-term physiological responses to non-invasive physical stimulation. Full article

Hypophosphites (also known as phosphinates) are the salts of hypophosphorous acid (also known as phosphinic acid), H₃PO₂. Various hypophosphite salts are known such as calcium hypophosphite (Ca(H₂PO₂)₂) and sodium hypophosphite (Na(H₂PO₂)). Hypophosphites were proposed as a potential treatment for tuberculosis as early as the 1850s; however, they were found to be ineffective against this disease. Following this, there was a period of around 100 years during which no new studies on hypophosphites were published. Subsequent in vitro studies have shown that hypophosphites can be used as potential antibacterial food preservatives. Currently, calcium hypophosphite is used in commercial food supplements for children, as this compound is a suitable source of calcium ions. It also has other advantageous properties, including exceptionally high water solubility (154 g/L at 25 °C), a neutral taste, a high mass fraction of calcium per molecule (23.6%), and an excellent safety profile. Recent studies have shown its potential as an active ingredient in the field of oral care. Since biological mechanisms such as tooth and bone formation and natural remineralization due to saliva rely on calcium ions, calcium hypophosphite can be regarded as a biomimetic agent. Upon contact with phosphate from saliva, calcium hypophosphite forms hydroxyapatite; this imitation of physiological mineralization and crystallization processes in the human body further underlines its biomimetic character. This review summarizes and discusses the available literature on hypophosphites in human health and related fields. Full article

The emergence of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual incretin-based therapies has fundamentally transformed obesity pharmacotherapy, enabling magnitudes of non-surgical weight loss that were previously unattainable. Yet, the clinical success of these treatments cannot be measured in kilograms alone. Total body weight is a composite, tissue-nonspecific endpoint that fails to distinguish between adipose reduction and losses in skeletal muscle mass, strength, and physical function—compartments of direct relevance to metabolic health, functional independence, and long-term resilience. This narrative review builds on and extends existing conceptualizations of weight loss quality by proposing a clinically oriented, multidimensional framework of high-quality weight loss. Within this framework, preferential adiposity reduction is achieved while preserving skeletal muscle mass, neuromuscular function, dietary adequacy, and cardiometabolic health. We examine the physiological and clinical consequences of lean tissue loss during pharmacological energy restriction, with specific attention to phenotypes at greatest risk (i.e., older adults, individuals with sarcopenic obesity, and those with type 2 diabetes). We then evaluate the evidence supporting precision protein nutrition, dietary fiber adequacy, and gastrointestinal tolerability management as nutritional countermeasures, followed by a mechanistic and clinical analysis of resistance training as the primary exercise strategy for preserving lean mass and function. Finally, we discuss body composition monitoring, integrated multidisciplinary care, and unresolved research gaps. The future of obesity treatment lies not in greater weight loss per se, but in achieving better weight loss—defined as metabolically favorable, functionally responsible, and clinically sustainable. Bone health is treated as a further dimension of high-quality weight loss, since pharmacologically driven energy restriction can adversely affect areal bone mineral density and microarchitecture, and adequate protein intake combined with mechanical loading is required to preserve skeletal integrity alongside lean mass. Full article

Healthcare professionals must acquire and maintain both declarative knowledge and fine psychomotor skills across a wide range of clinical procedures. Human working memory is physiologically limited, and the high cognitive demands of clinical environments frequently contribute to medical errors and adverse events. Intra-individual performance variability—driven by fatigue, stress, and motivation—represents a further challenge that conventional medical safety education has not adequately addressed. According to the World Health Organization, patient harm ranks fourteenth in the global burden of disease, with approximately 10% of hospitalised patients in high-income countries experiencing harm within healthcare facilities. This study reports the design, theoretical rationale, and preliminary outcomes of an augmented reality (AR) glasses system for hands-free, self-directed medical procedural training, developed from a human factors and ergonomics (HFE) perspective. The system integrates a see-through head-mounted display (HMD; Epson Moverio BT-40S), bone-conduction earphones (Shokz OpenComm), and an industrial-grade voice recognition application (NEC Solution Innovators), achieving fully hands-free operation compatible with aseptic technique. Content design is grounded in cognitive load theory (CLT) and the cognitive theory of multimedia learning (CTML), extended by neuroscientific evidence on multisensory integration and memory consolidation. More than 40 procedure-specific modules have been developed in-house at Tokyo University of Technology, spanning airway management, vascular access, respiratory therapy, dialysis, and cardiac support. In a four-year longitudinal survey (virtual reality (VR) simulator; n = 286), major satisfaction items consistently exceeded the scale midpoint. In an AR endotracheal suctioning cohort (n = 38/22), procedural flow understanding was rated 3.95/5.0. A peer-reviewed randomised controlled trial (Clinical Simulation in Nursing, n = 36) demonstrated significantly superior skill improvement (p < 0.001) and learning motivation (p = 0.001) in the AR group versus textbook self-practice. Principal ergonomic limitations of current HMD hardware—excessive weight, narrow field of view, and absence of medical-grade certification—are documented, and AI-based real-time procedural assessment is identified as a priority for the next research phase. Full article

Neutrophils are central executors of innate immunity. Yet murine models are inherently limited by low baseline neutrophil counts. NSG mice are among the most widely used models for xenotransplantation and studies on the humanized immune system. Although G-CSF is known to stimulate granulopoiesis, the dose- and schedule-dependent effects of intraperitoneal G-CSF administration have not been systematically characterized in this immunodeficient background. Male NSG mice received intraperitoneal G-CSF according to one of five regimens (n = 6 per group): group 0 served as the saline control, group 1 received a single dose of 250 µg/kg G-CSF administered at 48 h; group 2 received a single dose of 250 µg/kg G-CSF administered at 24 h; group 3 received three doses of 250 µg/kg administered G-CSF at 0 h, 24 h, and 48 h and group 4 received a single dose of 500 µg/kg G-CSF administered at 48 h. All animals were sacrificed at 72 h. Circulating neutrophils were then quantified by flow cytometry, bone marrow neutrophil proportions by panoptic smear analysis, and splenic neutrophil abundance by Ly6G immunofluorescence. Systemic neutrophil activation was assessed via plasma neutrophil elastase (NE) activity and cell-free DNA (cfDNA) levels. Repeated G-CSF administration (Group 3) induced an approximately 13-fold expansion of circulating neutrophils, approaching the human physiological range, with significant increases also observed in bone marrow and a trend towards increased neutrophil abundance in the spleen. A single dose of 250 µg/kg administered at 24 h (group 2), produced significant neutrophil expansion in peripheral blood and bone marrow but not in the spleen, while all other single-dose regimens failed to induce significant expansion in any compartment. NE activity and cfDNA concentrations and a selected cytokine panel remained unaltered across all groups. This systematic comparison establishes repeated intraperitoneal G-CSF administration as a reproducible strategy to achieve human-like neutrophil levels in NSG mice without inducing systemic inflammation. This provides a validated protocol with direct utility in translational models of neutrophil-dependent diseases. Full article

Stress shielding (SS) after cementless total hip arthroplasty arises from the stiffness mismatch between conventional Ti-6Al-4V femoral stems (110 GPa) and cortical bone (10–30 GPa). The β-type Ti-33.6Nb-4Sn (TNS) alloy femoral stem addresses this limitation through a continuous Young’s modulus gradient (~70 GPa proximally to ~40 GPa distally) achieved by localized heat treatment of a single homogeneous alloy. This review synthesizes a translational research program encompassing material characterization, finite element modeling (FEM), preclinical animal studies, and prospective clinical follow-up of up to seven years. FEM demonstrated favorable proximal micromotion well below the osseointegration threshold, with physiological proximal stress concentration concordant with clinical outcomes. At seven years, SS grade distribution was significantly lower in the TNS group than in Ti-6Al-4V controls, with SS frequency reduced in Gruen Zones 2, 3, and 6, and no stem-related failures; however, third-degree SS was still observed in 11 of 34 evaluable cases (32%), indicating that modulus-gradient optimization alone is insufficient to fully prevent SS. TNS alloy is currently the only β-type titanium alloy clinically applied in joint prostheses. Remaining challenges include stem geometry optimization, additive manufacturing-based porous structures, and dual-energy X-ray absorptiometry-based bone density quantification. Future directions encompass long-term follow-up, cyclic fatigue FEM simulations, and expansion to fracture fixation devices and dental implants. Full article