Search Results (2,951)

Temporomandibular disorders (TMDs) are the prevalent causes of orofacial pain and dysfunction of the temporomandibular joint (TMJ) and masticatory muscles. Previous studies have revealed that proinflammatory cytokines play a key role in promoting inflammation, pain, and degeneration within the TMJ. In this context, the present systematic review synthesizes current evidence on various cytokines involved in the pathophysiology of TMDs and evaluates their associations with clinical signs and structural TMJ damage. A PRISMA-guided search (PROSPERO: CRD420251163290) was conducted in PubMed/MEDLINE, Embase, Scopus, and the Cochrane Library to identify human-based, in vivo, and in vitro studies (January 2014 to September 2025) that assessed the roles of proinflammatory cytokines in TMDs. The following data were extracted from the identified studies: cytokine profiles, sampling methods, clinical outcomes, and TMJ structural changes. Study quality and risk of bias were systematically evaluated. A total of 15 studies (clinical, animal, and mechanistic) were included in the review. Tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-17 (IL-17) consistently emerged as the major contributors to synovitis, cartilage degradation, nociceptive sensitization, and bone resorption. Human studies showed that high levels of TNF-α, IL-1β, and IL-6 and chemokines such as C-C motif chemokine ligand 2 (CCL2) and regulated on activation, normal T-cell expressed and secreted (RANTES) were associated with TMJ pain, restricted mandibular motion, crepitus, malocclusion, and erosive changes on imaging. An increased ratio of TNF to soluble TNF receptor in synovial fluid correlated with both pain and condylar damage, suggesting that loss of cytokine control contributes to progressive joint destruction. TMDs, particularly inflammatory and degenerative subtypes, are cytokine-driven pathologies rather than purely mechanical disorders. TNF-α, IL-1β, and IL-6 are the promising candidate biomarkers of local inflammation and structural joint pathology. Standardized longitudinal studies are required to validate cytokine-based diagnostics and develop anti-cytokine therapeutics. Full article

Bone health in highly trained female athletes is critical for performance and long-term wellbeing, yet systematic evidence regarding seasonal changes remains limited. The main objective of this systematic review (PROSPERO ID: 420251230393) is to determine changes in bone mineral density (BMD) and bone mineral content (BMC) across the sport macrocycle in highly trained female athletes, encompassing both elite and collegiate (NCAA) populations. Six databases were searched for studies published between 2010 and 2025, with inclusion requiring female athletes, BMD/BMC measurements, and longitudinal assessment across a macrocycle. Fourteen studies involving 522 premenopausal athletes were included, with dual-energy X-ray absorptiometry measurements conducted approximately six months apart. Study quality was assessed using the NIH Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies and indicated a predominantly good quality. Five studies reported no significant change in BMD/BMC, five demonstrated improvements, three reported mixed findings across sports or athlete subgroups, and one reported a significant decline. Only two studies attempted to account for all three primary confounders—menstrual cycle status, dietary intake, and physical activity monitoring—while seven reported no confounding variables. While bone health appears largely maintained across the sport macrocycle in highly trained premenopausal female athletes, these findings should be interpreted cautiously given the inadequate confounder reporting, heterogeneous sport exposures, variability in skeletal sites measured, and inconsistent measurement timing. Future research must comprehensively assess these variables alongside sport-specific skeletal measurements to identify athletes at risk of bone health deterioration. Full article

Phellodendri amurensis Cortex is the dried bark of the cork tree (Phellodendron amurense Rupr.) from the Rutaceae family, and possesses traditional efficacy in clearing heat, drying dampness, purging fire, relieving steaming sensations, detoxifying, and healing sores. Clinically, it is commonly used for treating symptoms such as damp-heat diarrhea and dysentery, jaundice with reddish urine, leukorrhea with vaginal itching, painful and difficult urination due to heat strangury, flaccidity and weakness of the lower limbs, bone-steaming and consumptive fever, night sweats and seminal emission, sores, ulcers, swellings, and toxins, eczema, damp sores, and urinary tract infections. Modern pharmacological studies have further revealed its diverse bioactivities, including antioxidant, antibacterial, anti-inflammatory, immunosuppressive, and anticancer effects. To provide an updated and comprehensive review of the research into Phellodendri amurensis Cortex, this study conducted a thorough literature search and analysis based on databases such as SciFinder, Web of Science, and China National Knowledge Infrastructure. The review integrates information on the plant’s botanical characteristics, geographical distribution, traditional applications, chemical components, quality control methods, and pharmacological effects to present a current and holistic overview of its research status. To date, approximately 170 compounds have been isolated and identified from Phellodendri amurensis Cortex, primarily including alkaloids, phenolics, terpenoids, sterols, lignans, flavonoids, and others. Among these, alkaloids exhibit significant antioxidant and anti-inflammatory activities and demonstrate potential pharmacological value in antibacterial, anticancer, hypoglycemic, and multi-organ protective effects. Although substantial foundational research exists, the mechanisms of action and quality control of Phellodendri amurensis Cortex require further in-depth exploration. Future efforts should focus on clarifying its pharmacodynamic material basis, uncovering new targets and pathways, and improving analytical methods for component analysis and quality control to advance the scientific development and rational utilization of this medicinal material. Full article

Current evidence suggests that achieving the desired level of osseointegration necessitates a hierarchical approach to implant design. This is particularly relevant for osseointegration around implant systems such as those presenting vertical decompression chambers and acid-etched surfaces which could further be augmented by non-thermal plasma (NTP) treatment. Three implant systems were compared in this study: (i) ND (GM Helix Acqua Implant; Neodent^®, Curitiba, PR, Brazil—hybrid, acid-etched thread design treated with isotonic sodium chloride solution), (ii) Sin (Epikut Plus; S.I.N. Implant System, São Paulo, Brazil—V-shaped, acid-etched thread design treated with nano-hydroxyapatite), and (iii) Mp (Maestro; Implacil De Bortoli, São Paulo, Brazil—buttress, acid-etched thread design with decompressing vertical chambers). The ND and Sin implants were used directly as supplied by the manufacturer. For the Mp implants, the manufacturer-supplied surface was subjected to supplemental acid etching with 37% hydrochloric acid followed by Argon-based NTP treatment administered with a pulsed plasma generator prior to implantation into the iliac crest of n = 12 adult female sheep. Histomorphometric analysis was conducted at 3- and 12-week post-implantation (n = 6 sheep per time point) to assess bone-to-implant contact (BIC) and bone area fraction occupancy (BAFO). After 3 weeks in vivo, the healing chambers of all implant groups consisted predominantly of newly forming woven bone. By 12 weeks, bone maturation was observed, with the presence of remodeling sites and some areas of well-organized lamellar structures occupying the healing chambers. At both 3 and 12 weeks, the Mp implants demonstrated significantly higher BAFO values relative to ND (p = 0.015 and p = 0.008, respectively). The combination of vertical healing chambers, acid etching, and NTP treatment promoted early vascular infiltration and sustained bone deposition. Full article

Background: Management of skeletal Class III malocclusion of maxillary origin in late adolescence remains challenging, as conventional tooth-borne orthopedic approaches show reduced effectiveness at advanced stages of skeletal maturation. Minimally invasive, bone-anchored alternatives supported by digital workflows may improve clinical feasibility and patient acceptance. Objective: To describe a digitally guided clinical protocol combining a hybrid maxillary expander and supragingival mandibular miniplates, and to explore skeletal and dentoalveolar outcomes in late adolescents. Methods: This retrospective pilot clinical study included ten late adolescents (mean age 16.0 ± 1.3 years; range 13.8–17.7) in advanced skeletal maturation stages (CS4–CS6) with skeletal Class III malocclusion of maxillary origin. Treatment consisted of a hybrid maxillary expander anchored to palatal miniscrews and custom supragingival mandibular miniplates, placed using a fully digital workflow. Maxillary protraction was performed using a modified Alt-RAMEC protocol followed by continuous intermaxillary elastic traction for 12 months. Pre- and post-treatment cephalometric analyses were conducted. Results: A significant increase in SNA was observed (mean +6.1°, p < 0.001), indicating forward maxillary displacement. The Wits appraisal improved by 3.3 mm (p = 0.007), and the SeMax increased by 2.9 mm (p = 0.0013). No significant changes were found in the SNB or mandibular plane angle. Dentoalveolar effects were limited. Conclusions: Within the limitations of this pilot clinical study, the proposed digitally guided protocol demonstrated clinically relevant maxillary advancement with minimal dentoalveolar side effects and preserved vertical control. This relatively minimally invasive approach compared to conventional subgingival miniplates and orthognathic surgery may represent a feasible treatment option for selected late adolescent patients. Further controlled studies are required to confirm these findings. Full article

The accuracy of static computer-aided implant surgery (s-CAIS) is fundamental for predictable clinical outcomes. The objective of this study was to evaluate the influence of different guide-support modalities on the linear and angular accuracy of implant placement. In this retrospective clinical investigation conducted at a single specialty hospital, a total of 180 implants were analyzed, divided into three equal groups (n = 60) based on the guide support type: tooth-supported, bone-supported, and mucosa-supported. Accuracy was assessed by superimposing preoperative virtual plans with postoperative cone-beam computed tomography (CBCT) scans, measuring linear deviations at the neck and apex of the implant, as well as angular discrepancies. The type of guide support was found to be a significant factor associated with surgical accuracy (p < 0.001). Tooth-supported guides demonstrated the highest level of accuracy, with a mean angular deviation of 1.81° ± 0.45° and linear deviations at the neck and apex of 0.59 ± 0.18 mm and 0.73 ± 0.19 mm, respectively. These were followed by bone-supported guides (2.14° ± 0.48°; 1.04 ± 0.26 mm; 1.61 ± 0.31 mm), while mucosa-supported guides exhibited the greatest deviations (2.95° ± 0.60°; 1.47 ± 0.29 mm; 1.87 ± 0.37 mm). Significant intergroup differences and large effect sizes were observed, particularly regarding angular and horizontal discrepancies. These findings demonstrate a distinct gradient of accuracy based on guide support, establishing tooth-supported guides as the most accurate, followed by bone-supported and, lastly, mucosa-supported guides. While all modalities are clinically applicable, the use of mucosa-supported guides necessitates increased safety margins to account for the increased risk of linear and angular discrepancies inherent to mucosal tissue displacement. Full article

Background: Congenital hearing loss occurs in about 2 of every 1000 newborns, of which half probably have a genetic origin. In syndromic patients, hearing impairment often results from craniofacial malformations affecting the outer and middle ear. Anatomical limitations such as microtia or external auditory canal atresia often preclude conventional air-conduction hearing aids, leaving bone-conduction devices as one viable option. However, surgical intervention in such patients is challenging. This study aimed to evaluate the audiological outcomes, safety, and effectiveness of the Bonebridge BCI 602 implant in 10 patients with genetic syndromes. Methods: The case series was made up of 10 patients aged 6–45 years, each diagnosed with a congenital syndrome affecting the external and/or middle ear. All cases involved surgical implantation of the Bonebridge system. Audiological outcomes were evaluated in free-field conditions on the day of sound processor activation and at 3–6 months follow-up via pure-tone and speech audiometry. Results: All surgical procedures were completed without serious adverse events, and the incidence of postoperative complications was low. Audiological outcomes showed clinically significant hearing improvement in all patients following Bonebridge implantation. Post-implantation hearing thresholds ranged from 25 to 40 dB HL, with notable gains in speech perception in both quiet and noisy environments. Conclusions: The Bonebridge implant appears to be a safe and effective option for auditory rehabilitation in patients with hearing loss associated with various genetic syndromes involving craniofacial malformation. However, this complex patient population requires individual assessment, interdisciplinary evaluation, and careful surgical planning. Full article

Optimization of ridesharing systems poses challenges for the development of solvers due to a nonconvex discrete solution space and complex constraints. Over the past decade, many metaheuristic algorithms have been proposed to solve optimization problems in ridesharing systems. Performance, robustness and efficiency are three important issues in the development of metaheuristic algorithms for ridesharing systems. Cooperative coevolution is a potential approach to improving the performance, robustness, and efficiency of metaheuristic algorithms. However, studies on the application of cooperative coevolution to optimization problems in ridesharing systems remain limited, as most existing work focuses on problems with a continuous solution space. Metaheuristic algorithms can be combined with the cooperative coevolution approach to solve optimization problems. In this paper, we combine particle swarm optimization (PSO) and bare-bones particle swarm optimization (BBPSO) with cooperative coevolution to develop two metaheuristic algorithms for ridesharing systems: discrete cooperative coevolution-based particle swarm optimization (DCCPSO) and discrete cooperative coevolution-based bare-bones particle swarm optimization (DCCBBPSO). We conducted a comparative study to assess their effectiveness in terms of performance, robustness and efficiency based on the experimental results. The results indicate that the cooperative coevolution-based metaheuristic algorithms developed in this study outperform discrete PSO (DPSO), discrete BBPSO (DBBPSO), and many other existing metaheuristic algorithms for ridesharing systems in terms of performance and robustness. The results show that the DCCPSO algorithm and the DCCBBPSO algorithm outperform the other 16 metaheuristic algorithms in convergence speed (measured by the average number of generations to find the best solution) in most cases. However, the DCCPSO and the DCCBBPSO algorithms do not outperform all the other 16 metaheuristic algorithms in terms of runtime. This is due to the inherent complex structure of the CC approach. Full article

Background/Objectives: Several trials have highlighted the importance of PARP inhibitors (PARPi) in the treatment of BRCA-associated breast cancers (BC), initiating changes in practice. However, data on the real-life outcomes of PARPi therapy is limited. In this study, we characterized the clinical characteristics and outcomes of patients with advanced BC and germline BRCA pathogenic variants (PVs) who received PARPi therapy. Methods: We conducted a retrospective single-institution cohort study of patients with advanced BC and germline BRCA1/2 PVs treated with PARPi. Outcomes included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Survival was estimated using Kaplan–Meier methods, and prognostic factors were evaluated using Cox regression analysis. Results: Of the 107 patients treated with PARPi, 48 (44.9%) and 59 (55.1%) had BRCA1 and BRCA2 PVs, respectively. Ninety-seven patients (90.7%) had invasive ductal carcinoma and 42 (39.3%) had triple-negative BC. Nineteen (17.8%) patients had de novo metastatic BC. Sixty-two (57.9%) patients received at least one line of systemic therapy before PARPi; 24 (22.4%) patients received prior platinum. ORR was 62.6%, and the median duration of response (DoR) was 7 months (range, 2.1–96.2). The median PFS was 9 months (95% CI, 6.9–10.5) and median OS was 25.8 months (95% CI, 18.7–31.5). In multivariable models for PFS, bone metastases (HR = 2.25; 95% CI, 1.40–3.61; p = 0.0008) and lung metastases (HR = 2.40; 95% CI, 1.45–3.98; p = 0.0007) were independently associated with increased risk of progression or death. In multivariable models for OS, brain metastases (HR = 3.54; 95% CI, 1.59–7.90; p = 0.0020), bone metastases (HR = 2.22; 95% CI, 1.27–3.88; p = 0.0050), and lung metastases (HR = 2.38; 95% CI, 1.38–4.11; p = 0.0018), were independently associated with increased risk of death. Conclusions: The clinical outcomes of our real-world patients are similar to those reported in previous clinical trials. In addition, metastatic site distribution was independently prognostic for survival outcomes and may support baseline risk stratification at the time of PARPi initiation. Further studies of predictive markers of response and resistance, as well as sequencing with platinums and combinations with other targeted agents, are needed to optimize the benefits of PARPi in this patient population. Full article

Background/Objectives: The guideline targets for blood pressure (BP), hemoglobin A1c (HbA1c), and low-density lipoprotein cholesterol (LDL-C) are frequently unmet, and physicians often misjudge control. This study aimed to characterize the real-world control of BP, HbA1c, and LDL-C in patients with type 2 diabetes (T2D) and hypertension, herein called cardiometabolic multimorbidity (CMM), and to compare guideline-based versus physician-perceived disease control. Methods: We conducted SNAPSHOT–Brazil, a nationwide, multicenter, cross-sectional study to gather real-world data on patients with CMM. The ESC guidelines defined the cardiovascular (CV) risk and control targets. Results: We included 451 patients with hypertension and T2D (median age 65 years; 60% female; 54% White). Most patients (98%) were on pharmacotherapy and reported high adherence (according to the Hill–Bone Medication Adherence Scale). A very high CV risk predominated (78%); 22% of the patients were at a high risk. The guideline-defined control was achieved in 27% for BP, 34% for HbA1c, 13% for LDL-C, and 6% for both BP and LDL-C; only 3% met all three targets simultaneously. The physicians accurately stratified the CV risk in 49% of patients, while 50% had their CV risk underestimated. They systematically overestimated control in 29% of cases for BP, 35% for LDL-C, and 25% for both. The sensitivity ranged from 0.88 to 0.98; the positive predictive values ranged from 0.19 to 0.48, and the positive likelihood ratios ranged from 2.16 to 3.65. Conclusions: The SNAPSHOT–Brazil study revealed a low attainment of BP, HbA1c, and LDL-C targets, despite the widespread pharmacotherapy and the high self-reported adherence. The physicians consistently overestimated disease control and underestimated the CV risk. Full article

Background/Objectives: Myelodysplastic syndromes (MDS) are associated with a significant risk of progression to acute myeloid leukemia (AML), affecting approximately 30% of patients. In high-risk MDS, leukemic transformation may occur within a short time frame, highlighting the need for early and reliable biomarkers of disease progression. Increasing evidence suggests that immune dysregulation and cytotoxic T-cell dysfunction contribute to disease evolution. This study aimed to evaluate PD-1 and CD57 expressions on CD8⁺ T cells and to investigate the CD8⁺PD-1⁺/CD4⁺PD-1⁺ ratio (PERLS) as a potential immunological marker predictive of leukemic transformation. Methods: Thirty-one patients with MDS were prospectively followed over a 12-month period. At baseline, patients underwent routine clinical and laboratory evaluation, including multiparameter flow cytometric assessment of bone marrow blasts. An extended immunophenotypic analysis of bone marrow samples was performed at study entry to assess PD-1 and CD57 expression on CD8⁺ T cells. Cytogenetic and molecular analyses were conducted when clinical findings suggested disease progression. Patients who developed signs of progression were re-evaluated approximately one month later, during the progression phase, to assess dynamic immunological changes. Results: Of the thirty-one patients included, eighteen progressed to AML, whereas thirteen remained clinically stable. Patients who progressed demonstrated a significant increase in PD-1 and CD57 expression on CD8⁺ T cells compared with stable patients. Moreover, a markedly higher CD8⁺PD-1⁺/CD4⁺PD-1⁺ (PERLS) ratio was observed in patients who subsequently developed AML, particularly during the progression phase. Conclusions: Dynamic immunophenotypic monitoring reveals that increased PD-1 on CD8⁺ T cells and an elevated PERLS ratio are associated with imminent leukemic transformation in MDS. These findings support the incorporation of immune-based biomarkers, particularly the CD8⁺PD-1⁺/CD4⁺PD-1⁺ ratio, into routine risk assessment to enable earlier identification of disease progression and timely therapeutic intervention. Full article

Surgical fixation techniques for bone fracture healing are well established and effective; however, opportunities remain to improve both functional outcomes and the patient experience. The Biofiligree^® concept integrates medicine, engineering, and design by reimagining conventional osteosynthesis plates as both therapeutic and aesthetic devices. Inspired by traditional Portuguese filigree, these plates allow patient participation through personalized geometries, patterns, or engravings and may later be transformed into wearable jewellery after removal, preserving them as symbolic artefacts of recovery. This study introduces and biomechanically evaluates a novel calcaneal fixation plate incorporating the biofiligree geometry concept. A biofiligree plate was designed for calcaneus fracture fixation and manufactured in stainless steel 306L. Experimental testing was conducted on synthetic composite calcaneus bone models to simulate anatomical conditions and compare the new design with a standard commercial plate. The biofiligree plate, 2 mm thick, was fixed using five screws and two percutaneous screws positioned at 45° to compress the fracture line. Results demonstrated comparable biomechanical performance between both systems, with similar strain distributions and fracture stabilization. The biofiligree plate showed stresses around 430 MPa and fracture displacement below 0.7 mm. Fixation stiffness values were 1445 N/mm for intact calcaneus, 1065 N/mm for the commercial plate, and 725 N/mm for the biofiligree plate, indicating adequate support for bone healing. Full article

Background: Beckwith–Wiedemann syndrome (BWS) is a rare congenital overgrowth disorder caused by genetic and epigenetic alterations on chromosome 11p15.5. While macroglossia, abdominal wall defects, and tumor predisposition are well recognized, hearing impairment has been sporadically reported. Objectives: The aim of this study is to review audiological features, surgical management, and rehabilitation in BWS, and we additionally present three cases with comprehensive longitudinal audiological follow-up. Methods: A systematic review of PubMed and Scopus was conducted according to PRISMA guidelines, including studies reporting audiological findings in patients with confirmed BWS. Studies without audiological data or reporting only normal-hearing patients were excluded. Data on hearing loss type, severity, genetics, clinical features, imaging, surgical interventions, and outcomes were extracted. A narrative synthesis was conducted; no meta-analysis was performed due to the heterogeneity and limited number of available studies. Data extraction was performed independently by two reviewers who independently screened titles, abstracts, and full texts, with disagreements resolved by discussion. In addition, three original case reports from our institution were included to further illustrate the clinical and rehabilitative variability of hearing impairment in BWS. Results: We identified 40 patients from the review, but only 12 of them reported audiological data (e.g., hearing thresholds, type of hearing loss, or diagnostic tests). Ossicular chain anomalies, particularly stapes fixation, were frequently observed. Surgical management improved hearing in selected cases, while bone conduction devices (BCD) or conventional amplification were effective alternatives when surgery was contraindicated. Genetic analyses revealed CDKN1C mutations or imprinting defects in nine patients. Conclusions: Hearing impairment in BWS is clinically relevant and often conductive, likely related to middle-ear anomalies. Early, multidisciplinary audiological evaluation—including imaging when indicated—and individualized rehabilitation can optimize auditory and communicative outcomes. The evidence is limited by the small number of studies and heterogeneous reporting of audiological outcomes. Full article

Periodontal disease represents a major global health burden, beginning with gingivitis and progressing to periodontitis, which causes connective tissue breakdown, alveolar bone resorption, and eventual tooth loss. Beyond local pathology, periodontitis is a chronic inflammatory condition with systemic associations, including cardiovascular disease, diabetes, and metabolic disorders. Mesenchymal stem cells (MSCs) and their extracellular vesicles (EVs) have emerged as promising candidates for periodontal regeneration. This review aimed to map the current evidence on MSC-derived EVs (MSC-EVs) in periodontal regeneration, focusing on their mechanisms of action, therapeutic potential, and translational challenges. A comprehensive literature search was conducted across a major biomedical database (PubMed) to identify preclinical and clinical studies investigating MSC-EVs in the context of periodontitis. Data were charted on EV cargo composition, biological functions, regenerative outcomes, and reported limitations. Evidence indicates that MSC-EVs encapsulate bioactive molecules—including antimicrobial peptides, proteins, lipids, and microRNAs—that modulate immune responses, suppress pro-inflammatory signaling, and promote angiogenesis and tissue repair. In periodontal models, MSC-EVs attenuate osteoclast activity, enhance fibroblast proliferation, and stimulate extracellular matrix remodeling, supporting regeneration of periodontal ligament and alveolar bone. Exosome-based approaches demonstrate advantages such as reduced immunogenicity, improved safety, and feasibility for storage and standardization. However, most findings remain preclinical, with limited human data available. To bridge the translational gap, well-designed clinical trials are needed to confirm efficacy and safety while addressing regulatory challenges, GMP standards, and outcome measures. Harnessing their regenerative capacity while mitigating side effects may guide precision-targeted therapies, and continued mechanistic studies with standardized production will be key to advancing MSC-EVs into clinical practice. Full article