Search Results (3,103)

Since 2014, the Paleoanthropology Group of the National Museum of Natural Sciences (CSIC), in collaboration with Equatoguinean researchers, has been conducting archeo-paleontological fieldwork in Equatorial Guinea, continuing a longstanding Spanish naturalist tradition in this region of West Central Africa. These multidisciplinary investigations, framed within an archeo-paleo-anthropological approach, aim primarily to identify early human occupation in the Central African rainforests. To date, robust evidence of Pleistocene human presence has been documented, particularly through lithic assemblages. Although the scarcity and fragmentation of well-dated sites in Central Africa complicate chronological placement, technological traits observed in the lithic industries recorded in Equatorial Guinea show clear affinities with the African Middle Stone Age (MSA). Complementary taphonomic analyses of faunal remains have been undertaken to better understand bone preservation and fossilization processes under tropical rainforest conditions, thereby contributing to the interpretation of archeological contexts. In parallel, ongoing primatological research within the project—focused on extant primates in their natural habitats—seeks to provide ethological models relevant to the study of hominin locomotor evolution. Notably, the project has led to the ecogeographic characterization of the Engong chimpanzee group in Monte Alén National Park, one of the country’s most pristine protected areas. Full article

Background: Central precocious puberty (CPP), defined as the onset of secondary sexual characteristics before age 8 in girls, is increasingly prevalent worldwide. CPP is often caused by early activation of the HPG axis, leading to accelerated growth and bone maturation. However, the diagnostic accuracy of standard bone age (BA) methods remains uncertain in this context. Objective: To compare the diagnostic accuracy of the Greulich–Pyle atlas (GPA) and Tanner–Whitehouse 3 (TW3) methods in estimating skeletal age in girls with CPP and to assess the predictive value of serum hormone levels for estimating chronological age (CA). Methods: An observational, cross-sectional diagnostic study was conducted, involving n = 109 girls aged 6–12 years with confirmed CPP (Ethics Committee approval: CHUC_2023_86; 13 July 2023). Left posteroanterior hand–wrist (PA–HW) radiographs were assessed using the GPA and TW3 methods. Anthropometric measurements were recorded, and serum concentrations of estradiol, LH, FSH, DHEA-S, cortisol, TSH, and free T4 were obtained. Comparisons between CA and BA estimates were conducted using repeated-measures ANOVA, and ANCOVA was applied to examine the hormonal predictors of CA. Results: Both GPA and TW3 overestimated CA between 7 and 12 years, with the GPA showing larger deviations (up to 4.8 months). The TW3 method provided more accurate estimations, particularly at advanced pubertal stages. Estradiol (η²_p = 0.188–0.197), LH (η²_p = 0.061–0.068), and FSH (η²_p = 0.008–0.023) emerged as the strongest endocrine predictors of CA, significantly enhancing the explanatory power of both radiological methods. Conclusions: The TW3 method demonstrated superior diagnostic accuracy over GPA in girls with CPP, especially between 7 and 12 years. Integrating estradiol, LH, and FSH into BA assessment significantly improved the accuracy, supporting a more individualized and physiologically grounded diagnostic approach. Full article

Clozapine, a second-generation antipsychotic known for its effectiveness in treating resistant schizophrenia, is often linked with serious hematological side effects, particularly neutropenia and agranulocytosis. This review investigates the underlying pathophysiological mechanisms of clozapine-induced neutropenia (CIN) and agranulocytosis (CIA), outlines associated risk factors, and evaluates current clinical management strategies. Clozapine’s pharmacological profile, marked by its antagonism of dopamine D4 and serotonin receptors, contributes to both its therapeutic advantages and hematological toxicity. Epidemiological data show a prevalence of CIN and CIA at approximately 3.8% and 0.9%, respectively, with onset typically occurring within the first six months of treatment. Key risk factors include older age, Asian and African American ethnicity, female sex, and certain genetic predispositions. The development of CIN and CIA may involve bone marrow suppression and autoimmune mechanisms, although the exact processes remain partially understood. Clinical presentation often includes nonspecific symptoms such as fever and signs of infection, necessitating regular hematological monitoring in accordance with established guidelines. Management strategies include dosage adjustments, cessation of clozapine, and the administration of granulocyte colony-stimulating factors (G-CSF). Advances in pharmacogenomics show promise for predicting susceptibility to CIN and CIA, potentially improving patient safety. This review emphasizes the importance of vigilant monitoring and personalized treatment approaches to reduce the risks associated with clozapine therapy. Full article

Cadmium (Cd) is a toxic environmental heavy metal that exerts harmful effects on multiple tissues, including the kidney, liver, lung, and bone, and is also associated with the development of anemia. However, the precise molecular mechanisms underlying Cd-induced toxicity remain incompletely understood. In this paper, we review the recent molecular mechanisms of Cd-induced toxicity and its modification, with a particular emphasis on our recent findings. Using a combination of DNA microarray analysis, protein–DNA binding assays, and siRNA-mediated gene silencing, we identified several transcription factors, YY1, FOXF1, ARNT, and MEF2A, as novel molecular targets of Cd. The downregulation of their downstream genes, including UBE2D2, UBE2D4, BIRC3, and SLC2A4, was directly associated with the expression of cytotoxicity. In addition, PPARδ plays a pivotal role in modulating cellular susceptibility to Cd-induced renal toxicity, potentially by regulating apoptosis-related signaling pathways. In addition to apoptosis pathways, Cd toxicity through ROS generation, ferroptosis and pyroptosis were summarized. Furthermore, it has been revealed that Cd suppresses the expression of iron transport-related genes in duodenal epithelial cells leading to impaired intestinal iron absorption as well as decreased hepatic iron levels. These findings provide a mechanistic basis for Cd-induced iron deficiency anemia, implicating disrupted iron homeostasis as a contributing factor. Full article

Background and Clinical Significance: Hemophagocytic lymphohistiocytosis (HLH) and autoimmune hemolytic anemia (AIHA) are both life-threatening hematologic syndromes that rarely present together outside of malignancy. Advanced acquired immunodeficiency syndrome (AIDS) creates a milieu of profound immune dysregulation and hyperinflammation, predisposing patients to atypical overlaps of these disorders. Case Presentation: A 30-year-old woman with poorly controlled AIDS presented with three weeks of jaundice, fever, and fatigue. Initial labs revealed pancytopenia, hyperbilirubinemia, and elevated ferritin level. Direct anti-globulin testing confirmed warm AIHA (IgG⁺/C3d⁺) with transient cold agglutinins. Despite intravenous immunoglobulin (IVIG), rituximab, and transfusions, she developed hepatosplenomegaly, extreme hyperferritinemia, and sIL-2R > 10,000 pg/mL, meeting HLH-2004 criteria. Bone marrow biopsy excluded malignancy; further work-up revealed Epstein–Barr virus (EBV) viremia and cytomegalovirus (CMV) reactivation. Dexamethasone plus reduced-dose etoposide transiently reduced soluble interleukin-2 receptor (sIL-2R) but precipitated profound pancytopenia, Acute respiratory distress syndrome (ARDS) from CMV/parainfluenza pneumonia, bilateral deep vein thrombosis (DVT), and an ST-elevation myocardial infarction (STEMI). She ultimately died of hemorrhagic shock after anticoagulation despite maximal supportive measures. Conclusions: This case underscores the diagnostic challenges of HLH-AIHA overlap in AIDS, where cytopenias and hyperferritinemia mask the underlying cytokine storm. Pathogenesis likely involved IL-6/IFN-γ overproduction, impaired cytotoxic T-cell function, and molecular mimicry. While etoposide remains a cornerstone of HLH therapy, its myelotoxicity proved catastrophic in this immunocompromised host, highlighting the urgent need for cytokine-targeted agents to mitigate treatment-related mortality. Full article

Background: Patients with mastocytosis may present with exacerbated respiratory symptoms and lung diseases resulting from mast cell mediator release. However, their prevalence and severity level remain under debate. The study aims to analyze the prevalence of respiratory symptoms and the usefulness of lung function tests like spirometry, diffusing capacity of the lung for carbon monoxide (DLCO), and high-resolution computed tomography (HRCT) of the chest in mastocytosis patients presenting with dyspnea, cough, and exercise intolerance. Methods: We included 104 patients with mastocytosis and 71 healthy controls. Data collection encompassed patient interview, clinical examination, spirometry, DLCO, and chest HRCT. Diagnosis of mastocytosis included bone marrow biopsies and serum tryptase measurements. Results: Compared to controls, patients with mastocytosis exhibited significantly lower values in FEV1/VC ratio, absolute DLCO/VA, predicted DLCO/VA, absolute DLCOcSB, and predicted DLCOcSB (p < 0.001). Commonly reported respiratory symptoms included dyspnea (36.5%), chest tightness (22.1%), and wheezing (9.6%). Airway obstruction was identified in 7.7% of patients; however, it appeared to be independent of the mastocytosis subtype. A decreased DLCO/VA ratio was observed in 4.8% of patients, but HRCT did not reveal any evidence of underlying lung disease. Conclusions: Mastocytosis appears to be a risk factor for the occurrence and exacerbation of respiratory symptoms. However, airway obstruction and impairment of the alveolar–capillary membrane seem to occur independently of the clinical subtype of mastocytosis. Additionally, the causal relationship between pulmonary involvement, mast cell infiltration of the alveolar–capillary membrane, and the systemic circulation of mast cell mediators remains unclear and requires further research. Full article

Background and Objective: This study presents a combined osteometric and biomechanical analysis of a Korean female cadaver exhibiting bilateral lower limb bone asymmetry with abnormal curvature and callus formation on the left femoral midshaft. Methods: To investigate bilateral bone length differences, osteometric measurements were conducted at standardized landmarks. Additionally, we developed three gait models using Meta Motivo, an open-source reinforcement learning platform, to analyze how skeletal asymmetry influences stride dynamics and directional control. Results: Detailed measurements revealed that the left lower limb bones were consistently shorter and narrower than their right counterparts. The calculated lower limb lengths showed a bilateral discrepancy ranging from 39 mm to 42 mm—specifically a 6 mm difference in the femur, 33 mm in the tibia, and 36 mm in the fibula. In the gait pattern analysis, the normal model exhibited a straight-line gait without lateral deviation. In contrast, the unbalanced, non-learned model demonstrated compensatory overuse and increased stride length of the left lower limb and a tendency to veer leftward. The unbalanced, learned model showed partial gait normalization, characterized by reduced limb dominance and improved right stride, although directional control remained compromised. Conclusions: This integrative approach highlights the biomechanical consequences of lower limb bone discrepancy and demonstrates the utility of virtual agent-based modeling in elucidating compensatory gait adaptations. Full article

Background/Objectives: Malnutrition is an imbalance of nutrients required for growth, development, and organ function. Its impact on bone development is known, but its effects on cartilage remain unclear. This study aimed to evaluate the femoral cartilage thickness in children with primary malnutrition. Methods: In this cross-sectional observational study, 83 children with primary malnutrition and 62 age- and sex-matched healthy controls were included. Patients with primary malnutrition were classified as mild, moderate and severe. Femoral cartilage thickness measurements of all children were taken by ultrasound from the femoral lateral condyle, femoral medial condyle and intercondylar area for both knees with the patient in a supine position with the knees flexed 90 degrees. Results: The right lateral, right medial, left lateral, and left medial femoral cartilages were significantly thicker in patients with malnutrition compared to those without malnutrition (p = 0.002, 0.004, <0.001, and 0.001, respectively). A significant negative correlation was found between age, weight Z-score, and height Z-score and triceps skinfold thickness. Conclusions: Distal femoral cartilage thickness is significantly greater in children with primary malnutrition. This demonstrates the effect of nutritional factors on cartilage tissue and suggests that children with chronic malnutrition are at risk for both knee joint problems and short stature later in life. Full article

Background: Inflammatory bowel diseases (IBD), such as Crohn’s disease (CD) and ulcerative colitis (UC), may impair bone metabolism, particularly in children. The RANKL/OPG axis, as a key regulator of bone turnover, may contribute to these disturbances. However, data in the pediatric population remain limited. Methods: A single-center, prospective observational study included 100 children aged 4–18 years, with a comparable number of girls and boys. Among them, 72 had IBD (27 CD, 45 UC) and 28 were healthy controls. Anthropometric, biochemical, and densitometric assessments were performed, including serum levels of RANKL and OPG, and markers of inflammation and bone turnover. Results: Children with CD had significantly lower height and weight percentiles compared to UC and controls. Serum RANKL and the RANKL/OPG ratio were significantly elevated in IBD patients, particularly in CD (p < 0.01). Total body BMD Z-scores were lower in IBD compared to controls (p = 0.03). Low BMD was found in 14.7% of UC and 26.3% of CD patients. In both groups, over 30% had values in the “gray zone” (−1.0 to −2.0). A positive correlation was observed between height and weight and bone density (p < 0.01). Higher OPG was associated with lower body weight (p < 0.001), while increased RANKL correlated with osteocalcin (p = 0.03). Patients receiving biological therapy had significantly lower BMD. Conclusions: Pediatric IBD is associated with significant alterations in the RANKL/OPG axis and reduced bone density. These findings support early screening and suggest RANKL/OPG as a potential biomarker of skeletal health. Full article

Background/Objectives: Tamoxifen, a selective estrogen receptor modulator widely used as an adjunct in the treatment of breast cancer, has known effects on bone metabolism, although its impact on osseointegration and cellular responses during early bone healing remains unclear. Understanding these effects is essential given the increasing use of dental implants in cancer survivors. The study aimed to observe the influence of tamoxifen on human osteosarcoma (SAOS-2) cells lines, as well on the osseointegration of titanium implants in ovariectomized female rats. Methods: SAOS-2 cells were incubated with Dulbecco’s modified growth medium. Six titanium (Ti) disks were used at each time point. The samples were divided into groups with the presence (TAM, n = 36) or not (CTR, n = 36) of tamoxifen in a concentration of 2 μM. In vivo, 72 animals were divided in groups with bilateral ovariectomy or SHAM and tamoxifen administration or not (15 mg/kg). Cell viability, mineralization rate, and collagen synthesis were assessed, as well as bone/implant contact (BIC) and bone ingrowth (BIN). Results: Tamoxifen caused a decrease in SAOS-2 viability, although an increase in the mineralization rate was observed. In vivo, the TAM groups presented higher BIC and BIN when compared to their control, but a lower percentage of mature collagen cells. Conclusions: Based on our findings, in vitro, the therapy with TAM slightly reduced the viability of SAOS-2 cells while significantly increasing the mineralization rate. In vivo, the therapy positively influenced BIC and BIN during the osseointegration phase. Full article

Background/Objectives: This study aimed to assess the long-term clinical performance of full-arch fixed restorations made of fiber-reinforced composite (FRC) supported by four ultra-short implants (4.0 × 5.0 mm) in patients with edentulous, atrophic mandibles. Methods: Ten patients were treated at Sapienza University of Rome and monitored over a 10-year period. Each case involved the placement of four plateau-design implants with a pure conometric connection and a calcium phosphate-treated surface. The final prostheses were fabricated using CAD/CAM-milled Trinia^® fiber-reinforced composite frameworks. Clinical parameters included implant and prosthesis survival, marginal bone level (MBL), peri-implant probing depth (PPD), and patient-reported outcome measures (PROMs). Results: Implant and prosthesis survival reached 100% over the 10-year follow-up. MBL data showed a minor bone gain of approximately 0.11 mm per 5 years (p < 0.0001). PPD remained stable under 3 mm, with a minimal increase of 0.16 mm over the same period (p < 0.0001). PROMs reflected sustained high patient satisfaction. No technical complications, such as chipping or framework fracture, were observed. Conclusions: Rehabilitation of the edentulous mandible with ultra-short implants and metal-free FRC prostheses proved to be a minimally invasive and long-lasting treatment option. The 10-year follow-up confirmed excellent implant and prosthetic outcomes, favorable peri-implant tissue health, and strong patient satisfaction. Nonetheless, further studies with larger sample sizes are needed to confirm these encouraging results and strengthen the clinical evidence. Full article

The influence of soft tissue structures, including ligaments spanning one or more intervertebral junctions and the nuchal ligament, on motion of the equine cervical joints remains unclear. The present study addressed this using four post-mortem horse specimens extending from head to withers with all ligaments intact. Three-dimensional kinematics was obtained from markers on the head and bone-anchored markers on each cervical and the first thoracic vertebra during rotation, lateral bending, flexion and extension of the whole head, and neck segment. Yaw, pitch, and roll angles in 8 cervical joints (total 32) were calculated. Flexion and extension were expressed mainly as pitch in 27 and 22 joints, respectively. Rotation appeared as predominantly roll in 13 joints, whereas lateral bending was represented as predominantly yaw in 1 and as roll or pitch in all other joints. Significant correlations between yaw, pitch, and roll were observed at individual cervical joints in 97% of all measurements, with the atlanto-occipital joint showing complete (100%) correlation. Most non-significant correlations occurred at the C5–C6 joint, while C6–C7 exhibited significantly lower correlation coefficients compared to other levels. The overall movement of the head and neck is not replicated at individual cervical joint levels and should be considered when evaluating equine necks in vivo. Full article

Introduction: The optimal management of hallux sesamoid fracture nonunions remains a subject of ongoing debate, particularly in the context of personalized medicine. This systematic review aimed to synthesize current evidence regarding surgical strategies for this rare but disabling condition. Methods: A comprehensive literature search was conducted in accordance with the PRISMA guidelines. Results: Six studies met the inclusion criteria, encompassing a total of 80 patients. Surgical techniques varied and included open and arthroscopic sesamoidectomy, autologous bone grafting (alone or combined with screw fixation), and percutaneous screw fixation. When reported, outcomes were generally favorable, with union rates ranging from 90.5% to 100% and with consistent postoperative improvements in clinical function. Complication and reoperation rates were both 6.5%. The most frequent reoperation was sesamoidectomy for persistent pain or nonunion, followed by hardware removal. Conclusions: Despite the limited and low-quality evidence, available data suggest that individualized surgical planning can lead to favorable outcomes with low complication rates. Sesamoidectomy remains the most reliable salvage procedure in refractory cases. These findings support a personalized, stepwise approach to treatment—prioritizing sesamoid preservation, when feasible, while reserving excision for symptomatic nonunions. Further studies are needed to validate tailored algorithms and refine patient-specific decision-making in this challenging clinical scenario. Full article

Background: The role of collagen membrane fixation during guided bone regeneration (GBR) remains debatable, particularly in post-extraction sockets with buccal defects and concomitant immediate implant placement. This study evaluated whether or not fixation with titanium pins improved regenerative outcomes. Methods: Six adult Beagle dogs received bilateral extractions of the fourth mandibular premolars. An implant was immediately placed in both the distal alveoli, and standardized buccal bone defects (5 mm height, 3–2 mm width) were prepared. All defects were filled with a slowly resorbing equine xenograft and covered by a resorbable pericardium membrane. At the test sites, the membrane was apically fixed with pins, while no fixation was applied to the control sites. After 3 months of healing, histomorphometric analyses were performed. Results: The vertical bone gain of the buccal crest was 3.2 mm in the test sites (pin group) and 2.9 mm in the control sites (no-pin) (p > 0.754). No significant difference was found in terms of bone-to-implant contact (BIC). However, residual graft particles were located significantly more coronally in the pin group compared to the no-pin group (p = 0.021). Morphometric analyses revealed similar new bone formation within the groups, but with higher amounts of residual xenograft and soft tissue in the pin group. Conclusions: Membrane fixation did not significantly enhance vertical bone gain, and although the slightly higher regeneration in the pin group (3.2 mm vs. 2.9 mm) may hold clinical relevance in esthetically sensitive areas and osseointegration, it appeared to limit coronal migration of the grafting material. Full article

Compared with biocompatibility, osteoconductivity, and mechanical properties, the poor injectability of calcium phosphate bone cements (CPCs) is always ignored, which actually hinders the development of CPC clinical transfer in minimally invasive orthopedic surgeries. Moreover, currently, CPC preparation in the clinic is labor-intensive and requires well-trained technicists, which might also result in the unstable quality of CPCs. In this work, we focused on three research objectives: (i) introducing a standardized preparation method for CPCs; (ii) studying the effects of preparation parameters on CPC injectability and compressive strength; and (iii) studying the injecting condition effects on CPC injectability, aiming to overcome CPCs’ disadvantages in minimally invasive surgeries. Firstly, two strategies, named “variable mixing barrel control (VMBC)” and the “nested blade–baffle stirring rod (NBBSR)”, were proposed in this study to solve the problems in the preparation of CPCs, which involved blending CPC powder and an agent to generate a paste, by enhancing the mixing performance and mimicking human manual stirring actions. Secondly, although the grinding parameter could significantly generate differences in the microstructure of CPCs, the compressive strength remained relatively stable. However, it was found to significantly affect the injectability of CPCs, leading to the inefficient injection of CPCs. Finally, the effects of syringe design, dimensions, and injecting conditions on CPC injectability were studied, and the results showed that the optimization of these factors enables the injection of CPCs, which has otherwise always been infeasible to implement in minimally invasive orthopedic surgeries. Full article