The aim of this study was to evaluate the effects of autologous microfragmented adipose tissue (MFAT), obtained by mechanical fragmentation, on radiographic bone healing in dogs subjected to tibial plateau levelling osteotomy (TPLO). Twenty dogs with unilateral cranial cruciate disease were enrolled and randomly assigned to the treatment group (MFAT) or the control group (NT). The MFAT group underwent TPLO and autologous MFAT intra-articular administration while the NT group underwent TPLO alone. The adipose tissue was collected from the thigh region and MFAT was obtained by mechanical fragmentation at the end of the surgery. The patients were subjected to X-ray exam preoperatively, immediately postoperatively (T0) and at 4 (T1) and 8 (T2) weeks postoperatively. Two radiographic scores that had previously been described for the evaluation of bone healing after TPLO were used. A 12-point scoring system (from 0 = no healing to 12= complete remodelling) was used at T0, T1 and T2, while a 5-point scoring system (from 0 = no healing to 4 = 76%–100% of healing) was used at T1 and T2. The median healing scores were significantly higher at T1 and T2 for the MFAT group compared with the NT group for the 12-point (p < 0.05) and 5-point (p < 0.05) scoring systems. The intra-articular injection of autologous microfragmented adipose tissue can accelerate bone healing after TPLO without complications.

Osteoconductive granulated biopolymers (OGB) are used to restore the lost volume of the jaw bone. OGB is employed as a loose fraction and exhibits physical traits common to bulk mixtures. By removing air bubbles and industrial dust from the OGB fraction through special processing, more accessible spaces are left over for the adsorption of bone growth factors. The recipient site's biological environment alters the OGB fraction's physical characteristics. This is the cause of the OGB fraction's volume changing uncontrollably during the first three weeks following surgery. Predictive indicators for describing the physical processes of osteoconduction include the compaction coefficient and adsorption capacity. Taking into account the prognostic indicators of the dynamics of changes in the physical properties of the OGB fraction in the postoperative period, 3D planning of the bioengineered structure should be done. The OGB fraction's adsorption and drainage properties are optimized by raising the purity of OGB production and preparing the biopolymer for clinical studies.

When bone substitutes materials are used, the increased risk of infection due to the none-autogenic graft is often discussed. The treatment of large bone defects in geriatric patients, often with osteoporotic bone, often presents major challenges to surgery. Bone substitutes materials are available indefinitely without the risk of additional surgery in each patient. Can bone substitutes materials be used without hesitation in the geriatric patient?Eighty-three patients suffered traumatic fractures of the distal radius, proximal humerus, and proximal tibia. The defect zones were filled with bone substitute material based on nanocrystalline hydroxyapatite (NHA) or calcium phosphate (CP). For comparison, a reference group without the void filling with a bone graft substitute (void defects, ED) was studied. All patients over the age of 64 years were retrospectively evaluated for complications and radiological outcomes. Results: 106 patients sustained traumatic fractures of the distal radius (68.9%), proximal humerus (5.7%), and proximal tibia (22.6%). No differences in infections were found when comparing the groups (p=1.0). retrospectively evaluated. The KEM group had a nonsignificantly lower rate of pseudarthrosis (p=0.09). A relative risk (RR) reduction of complications of 32.64% was observed when bone grafting material was used. The NNT for the prevention of complications was 5.99. When bone healing was assessed by radiological images, some follow-up studies showed significant differences in fracture bridging (p<0.001).Conclusions: In contrast to previous studies, bone substitutes materials can support the healing process in geriatric patients without relevant disadvantages. With an NNT of 6 regarding complications, many patients could benefit from bone graft augmentation. No increased infection rate was observed.

When bone substitutes materials are used, the increased risk of infection due to the none-autogenic graft is often discussed. The treatment of large bone defects in geriatric patients, often with osteoporotic bone, often presents major challenges to surgery. Bone substitutes materials are available indefinitely without the risk of additional surgery in each patient. Can bone substitutes materials be used without hesitation in the geriatric patient? Eighty-three patients suffered traumatic fractures of the distal radius, proximal humerus, and proximal tibia. The defect zones were filled with bone substitute material based on nanocrystalline hydroxyapatite (NHA) or calcium phosphate (CP). For comparison, a reference group without the void filling with a bone graft substitute (void defects, ED) was studied. All patients over the age of 64 years were retrospectively evaluated for complications and radiological outcomes. Results: 106 patients sustained traumatic fractures of the distal radius (68.9%), proximal humerus (5.7%), and proximal tibia (22.6%). No differences in infections were found when comparing the groups (p=1.0). retrospectively evaluated. The KEM group had a nonsignificantly lower rate of pseudarthrosis (p=0.09). A relative risk (RR) reduction of complications of 32.64% was observed when bone grafting material was used. The NNT for the prevention of complications was 5.99. When bone healing was assessed by radiological images, some follow-up studies showed significant differences in fracture bridging (p<0.001). Conclusions: In contrast to previous studies, bone substitutes materials can support the healing process in geriatric patients without relevant disadvantages. With an NNT of 6 regarding complications, many patients could benefit from bone graft augmentation. No increased infection rate was observed.

Age-related disorders of the musculoskeletal system including sarcopenia, osteoporosis and arthritis represent some of the most common chronic conditions worldwide, for which there remains a great clinical need to develop safer and more efficacious pharmacological treatments. Collectively, these conditions involve multiple tissues, including skeletal muscle, bone, articular cartilage and the synovium within the joint lining. In this review, we discuss the potential for oligonucleotide therapies to combat the unmet clinical need in musculoskeletal disorders by evaluating the successes of oligonucleotides to modify candidate pathological gene targets and cellular processes in relevant tissues and cells of the musculoskeletal system. Further, we discuss the challenges that remain for the clinical development of oligonucleotides therapies for musculoskeletal disorders and evaluate some of the current approaches to overcome these.

Celiac disease (CD) is an autoimmune disorder triggered by gluten ingestion in genetically predisposed individuals. In addition to the typical gastrointestinal symptoms such as diarrhea, bloating, or chronic abdominal pain, CD may also present a wide spectrum of manifestations, including low bone mineral density (BMD) and osteoporosis. This review aims to describe the role of CD in the development of skeletal alterations, underlying important clinical aspects and therapeutic implications. The etiopathology of bone lesions in CD is multifactorial and their management is challenging. Here, we provide gastroenterologists and orthopedics with an up-to-date overview on the link between CD and osteoporosis to improve the management of the CD condition.

In previous studies regarding the osseointegration of zirconia (ZrO2) implants, a lack of consistency was observed in the surface topographies of the ZrO2 and Ti samples because of the difficult processability of ZrO2 surfaces. To resolve this problem, we used the molecular precursor method (wet process), which is a surface-modifying technique that can easily change the surface chemistry without changing the surface topography. A roughened Ti surface was prepared using sandblasting (large-grit) and acid treatment. We were able to create ZrO2-coated Ti implants with the same topography as that of roughened Ti substrates using the molecular precursor method, which solution contained a Zr complex. The uniform presence of tetragonal Zr was confirmed, and the apparent zeta potential of the surface of the ZrO2-coated Ti implant was higher than that of Ti. In animal experiments, ZrO2-coated Ti implants showed an equivalent or higher bone-to-implant contact ratio compared to that of the non-coated implants inserted into the femur bone defects of the rats. ZrO2 with the same surface topography as that of roughened Ti exhibits a promotion of osteogenesis equivalent to or better than that of Ti in the early stages of bone formation.

Ciliopathies are genetic syndromes that link skeletal dysplasias to dysfunction of primary cilia. Primary cilia are sensory organelles synthesized by intraflagellar transport (IFT) - A and B complexes, which traffic protein cargo along a microtubular core. We have reported that deletion of IFT-A gene, Thm2, together with a null allele of its paralog, Thm1, causes a small skeleton with small mandible or micrognathia in juvenile mice. Using micro-computed tomography, here we quantify the craniofacial defects of Thm2^-/-;Thm1^aln/- triple allele mutant mice. At postnatal day 14, triple allele mutant mice exhibit micrognathia, maxillary hypoplasia, and a decreased facial angle due to shortened maxilla, premaxilla, and nasal bones, reflecting altered development of facial anterior-posterior elements. In contrast, other ciliopathy-related craniofacial defects, such as cleft lip and/or palate, hypo-/hypertelorism, broad nasal bridge, craniosynostosis, and facial asymmetry, were not observed, suggesting development of the facial transverse dimension is intact. Calvarial-derived osteoblasts of triple allele mutant mice showed reduced bone formation in vitro that was ameliorated by Hedgehog agonist, SAG. Together, these data indicate that Thm2 and Thm1 genetically interact to regulate bone formation and sculpting of the postnatal face. The triple allele mutant mice present as a novel model to study craniofacial bone development.

It is very difficult to repair large bone defects, especially when they have a complex shape. We have developed a new technique to make a desired copy of rabbit bones. A rabbit distal femur was scanned by computed tomography (CT), and a rectangular-shaped beta-tricalcium phosphate (β-TCP) block with 75% porosity was automatically machined using milling tools into a half-scale copy of the distal femur based on the CT data. The β-TCP block was seeded with bone morphogenetic protein-2 and bone marrow cells obtained from the femur and implanted on the periosteum of the femur. At 10 weeks after implantation, most of the β-TCP block had been replaced by bone and a complete copy of the distal femur was reconstructed. Our findings indicate that this technique will be useful in the clinical setting. We also report the representative clinical results of treatment with β-TCP graft in patients with bone defects since 1989.

Chimeric Antigen Receptor (CAR) T-cell therapy has demonstrated high rates of response in recurrent B-cell Acute Lymphoblastic Leukemia in children and young adults. Despite this success, a fraction of patients experience relapse after treatment. Relapse is often preceded by recovery of healthy B cells, which suggests loss or dysfunction of CAR T cells in bone marrow. This site is harder to access, and thus is not monitored as frequently as peripheral blood. Understanding the interplay between B cells, leukemic cells and CAR T cells in bone marrow is paramount in ascertaining the causes of lack of response. In this paper, we put forward a mathematical model representing the interaction between constantly renewing B cells, CAR T cells and leukemic cells in the bone marrow. Our model accounts for the maturation dynamics of B cells and incorporates effector and memory CAR T cells. The model provides a plausible description of the dynamics of the various cellular compartments in bone marrow after CAR T infusion. After exploration of the parameter space, we found that the dynamics of CAR T product and disease were independent of the dose injected, initial B-cell load and tumor burden. We also show theoretically the importance of CAR T product attributes in determining therapy outcome, and have studied a variety of possible response scenarios, including second dosage schemes. We conclude by setting out ideas for the refinement of the model.

Porous tantalum (Ta) is a promising biomaterial and has been applied in orthopedics and dentistry for nearly two decades. The high porosity and interconnected pore structure of porous Ta promise fine bone ingrowth and new bone formation within the inner space, which further guarantee rapid osteointegration and bone-implant stability in long term. Porous Ta has high wettability and surface energy that can facilitate adherence, proliferation and mineralization of osteoblasts. Meanwhile, low elastic modulus and high friction coefficient of porous Ta can effectively avoid stress shield effect, minimize marginal bone loss and ensure primary stability. Accordingly, the satisfactory clinical application of porous Ta based implants or prostheses are mainly derived from its excellent biological and mechanical properties. With the advent of additive manufacturing, personalized porous Ta based implants or prostheses have shown their clinical value in the treatment of individual patient who need specially designed implant or prosthesis. In addition, many modification methods have been introduced to enhance the bioactivity and antibacterial property of porous Ta with promising in vitro and in vivo research results. In any case, choosing suitable patients is of great importance to guarantee surgical success after porous Ta insertion.

Denosumab is a human monoclonal antibody that neutralizes RANKL, a cytokine able to interact with the RANK receptor on preosteoclasts and osteoclasts, decreasing their recruitment and differentiation, leading to a decreased bone resorption. The aim of this observational real-life study was to analyze adherence to denosumab therapy, its effectiveness in increasing bone mineral density (BMD) and in modulating biochemical skeletal markers upon previous treatments with bisphosphonates in a group of post-menopausal women affected by osteoporosis. Women were recruited in the specialized center from March 2012 to September 2019. Biochemical markers were recorded at baseline and every six months prior to subsequent drug injection. Dual X-ray Absorptiometry was requested at baseline and after 18/24 months. Comparing BMD at baseline and after denosumab therapy in naive patients and in those previously treated with bisphosphonates, a positive therapeutic effect was observed in both groups. The results of our real-life study demonstrate, as expected, that BMD values significantly increased upon denosumab treatment. Interestingly, denosumab showed an increased effectiveness in patients previously treated with bisphosphonates. Moreover, biochemical markers data indicate that osteoporotic patients, without other concomitant unstable health conditions, could be evaluated once a year, decreasing the number of specialistic center access.

Astronauts are at risk of losing 1.0 to 1.5% of their bone mass for every month they spend in space despite their adherence to high impact exercise training programs and dietary regimens designed to preserve their musculoskeletal system. This loss is the result of microgravity-related impairment of osteocyte and osteoblast function and the consequent upregulation of osteoclast-mediated bone resorption. This review describes the ontogeny of osteoclast hematopoietic stem cells, the contributions of macrophage colony stimulating factor, activator of NFkB and the calcineurin pathways make in osteoclast differentiation, and provides details of bone formation, the osteoclast cytoskeleton, the immune regulation of osteoclasts, and osteoclast mechanotransduction on Earth, in the microgravity of space, and in conditions of simulated microgravity. The article discusses the need to better understand how osteoclasts are able to function in zero gravity and reviews current and prospective therapies that may be used to treat osteoclast-mediated bone disease.

Malignant gliomas are heterogeneous neoplasms. Glioma stem-like cells (GSCs) are undifferentiated and self-renewing cells that develop and maintain these tumors. These cells are the main population that resist current therapies. Genomic and epigenomic analyses has identified various molecular subtypes. Bone morphogenetic protein 4 (BMP4) reduces the number of GSCs through differentiation and induction of apoptosis, thus increasing therapeutic sensitivity. However, the short half-life of BMP4 impedes its clinical application. We have previously reviewed BMP4 signaling in central nervous system development and glioma tumorigenesis and its’ potential as a treatment target in human gliomas. Recent advances in understanding both adult and pediatric malignant gliomas highlight critical roles of BMP4 signaling pathways in the regulation of tumor biology, and indicate its’ potential as a therapeutic molecule. Furthermore, significant progress has been made on synthesizing BMP4 biocompatible delivery materials, which can bind to and markedly extend BMP4 half-life. Here, we review current research associated with BMP4 in brain tumors, especially in pediatric malignant gliomas. We also summarize BMP4 delivery strategies, with a focus on biocompatible BMP4 binding peptide amphiphile nanostructures as promising novel delivery platforms for treatment of these devastating tumors.

Purpose: The aim of the present experimental 3D-finite element study was to evaluate the influence of an augmented sinus lift with an additional inserted bone graft block. The bone graft block stabilizes the implant in addition to conventional augmented bone. We placed the block in three different positions. The implants were loaded with axial force and forces secondary to laterotrusion and protrusion. Material and Methods: A simplified U-shaped 3D finite element model of the upper jaw and a more complex anatomical model of the left maxilla were created. The bone graft block was placed in three positions: in the lower third in contact with the sinus floor, the middle, and the upper third of the implant. Van Mises’ stress distribution was calculated and analyzed for the different models. We also compared the complex anatomical model with the simplified one. Results: The position of the bone graft block significantly influences the magnitude of stress distribution. A bone graft block positioned in the upper third or middle of the implant reduces the quantity of stress compared to the reference model without a bone graft block. The low bone graft block position is clearly associated with lower stress distribution in compact bone. We registered no significant differences in stress in compact bone with regard to laterotrusion or protrusion. Conclusions: Maximum values of von Mises stresses in compact bone can be reduced significantly by using a bone graft block. The reduction of stress is nearly the same for positions in the upper third and the middle of the implant. It is much more pronounced when the bone graft block is in the lower third of the implant near the sinus floor, which appeared to be the best position in the present study.

Preterm infants are at significant risk to develop reduced bone mineralization based on inadequate supply of calcium and phosphorus (Ca-P). Biochemical parameters can be used to evaluate the nutritional intake. The direct effect of nutritional intake on changes in biochemical parameters has not been studied. Our objective was to evaluate the effect of Ca-P supplementation on biochemical markers as serum (s)/urinary (u) Ca and P; alkaline phosphatase (ALP); tubular reabsorption of P (TrP) and urinary ratios for Ca/creatinin and P/creatinin in Very-Low-Birth-Weight infants on postnatal day 1, 3, 5, 7, 10, and 14. This observational study compared two groups with High (n = 30) and Low (n = 40) intake of Ca-P. Birth weight: median (IRQ) 948 (772-1225) vs. 939 (776-1163) grams; Gestational age: 28.2 (26.5-29.6) vs. 27.8 (26.1-29.4) weeks. Daily median concentrations of biochemical parameter were not different between the groups but linear regression mixed model analyses showed that Ca intake increased the uCa and TrP (p = 0.04) and decreased ALP (p = 0.00). Phosphorus intake increased sP, uP and uP/creat ratio and ALP (p ≤ 0.02) and caused decrease in TrP (p = 0.00). Protein intake decreased sP (p = 0.000), while low gestational age and male gender increased renal excretion of P (p < 0.03). Standardized repeated measurements showed that biochemical parameters were affected by nutritional intake, gestational age and gender.

In recent times, the application areas of unmanned aerial vehicles (UAVs) are expanding, and autonomous functions are becoming increasingly prominent, eliminating the need for remote pilot control. Certain applications require the drone to use a docking station autonomously, even for wireless charging. This involves performing autonomous takeoff and landing, where high preci-sion is demanded. These maneuvers can be significantly influenced by environmental factors. The effectiveness of the precision landing function of the DJI Mavic 2 Pro UAV in strong winds is in-vestigated in this article based on experimental measurements conducted outdoors. New findings on the precision landing capabilities of the DJI Mavic 2 Pro UAV are presented in this paper, par-ticularly under windy conditions. The efficiency of precision landing is compared in cases when the precision landing function is enabled versus when it is disabled. It is investigated whether there is a statistically significant difference between the two landing modes in strong winds and it is examined whether the DJI Mavic 2 Pro can perform precision landing on a surface of a specific size in windy conditions. This helps to predict the suitability of the DJI Mavic 2 Pro for precise landing and wireless charging at a docking station in strong winds and high gusts.

Overhydration (OH) is a prevalent medical problem occuring in patients with kidney failure, but a specific marker has still not been found. Currently, clinicians employ techniques such as bioimpedance spectroscopy (BIS), ultrasound (US) markers of fluid overload or markers of heart and kidney function such as NT-pro-BNP, GFR or creatinine levels. New serum markers, including but not limited to Ca-125, Galectin-3 (Gal-3), Adrenomedullin (AMD) and Urocortin-2 (UCN-2), are presently under research, displaying promising results. The necessity to ascertain a more precise marker of overhydration is urgent mainly because physical examination is exceptionally imprecise. Signs and symptoms of fluid overload, like edema or gradual increase of body mass, are not always present, notably in patients with chronic kidney disease. This review paper summarizes actual knowledge of a patient's hydration status estimation, focusing specifically on kidney diseases.

(1) Background: Factors reported in literature associated with inappropriate prescribing of antimicrobials, such as physicians with less experience, uncertain diagnosis, and patient caregiver influences on physicians' decisions. Monitoring antimicrobial resistance is critical for identifying emerging resistance patterns, developing, and assessing the effectiveness of mitigation strategies. Improvement in prescribing `antimicrobials would minimize the risk of resistance and, consequently, improve patients' clinical and health outcomes. The purpose of the study is to delineate factors associated with antimicrobial resistance, describe the factors influencing prescriber’s choice during prescribing of antimicrobial, and examine factors related to consequences of inappropriate prescribing of antimicrobial. (2) Methods: Cross-sectional study conducted among healthcare providers (190) in six tertiary hospitals in the Eastern province of Saudi Arabia. The research panel has developed validated and piloted survey specific with closed-ended questions. A value of P &lt;0.05 was considered for statistical significance. All data analysis was performed using Statistical Package for Social Sciences (IBM SPSS version 23.0). (3) Results: 72.7% of the respondents have agreed that poor skills and knowledge are key factors that contribute to the inappropriate prescribing of antimicrobials. All the respondents acknowledged effectiveness and previous experience with the antimicrobial, and reading scientific materials (such as books, articles, and the internet) were key factors influencing physicians’ choice during antimicrobial prescribing. (4) Conclusion: The current study has identified comprehensive education and training needs for healthcare providers about antimicrobial resistance. Using antimicrobials unnecessarily, insufficient duration of antimicrobial use, and using broad spectrum antimicrobials, were reported to be common practices. Further, poor skills and knowledge were a key factor that contributed to the inappropriate use and overuse of antimicrobials and using antimicrobials without physician prescription (self-medication) were the key factors which contribute to AMR from participants’ perspectives. Furthermore, internal policy and guidelines are needed to ensure that the antimicrobials are prescribed in accordance with standard protocols and clinical guidelines.

Bone age assessment is essential for evaluating skeletal maturity, especially in cases where chronological age is uncertain, such as in unaccompanied foreign minors. Traditional methods, such as the Greulich-Pyle atlas and the Tanner-Whitehouse system, while effective, often result in variability due to manual interpretation and are not fully adapted to ethnically diverse populations. Although automated systems are available, they are typically proprietary, expensive, and require programming expertise, which limits their accessibility. This paper introduces an open-source domain-specific language specifically designed for bone age estimation, offering a balance between flexibility and ease of use. The system provides a straightforward, user-friendly syntax, allowing healthcare professionals without programming knowledge to perform accurate bone age assessments. It integrates well-established bone age methodologies, such as the Greulich-Pyle and Tanner-Whitehouse systems, ensuring flexibility in its application. The system is developed using a test-driven development approach, which guarantees both accuracy and reproducibility in bone age assessments. By offering a customizable, open-source solution, this system reduces costs and eliminates the reliance on proprietary software. Its ability to simplify the bone age estimation process makes it a valuable tool in clinical and forensic settings, particularly for professionals involved in the assessment of unaccompanied foreign minors and other populations where accurate bone age determination is crucial.

Osteoporosis is considered a serious public health problem, particularly affecting the postmenopausal period. In 2018, in the Republic of Kazakhstan the total and primary incidence was 10 and 3.7 cases per 100,000 adults, respectively. The objective is to study osteoporosis prevalence and indicate main factors affecting low bone mineral density by screening adult population of Abay region, Kazakhstan. The target group were 641 respondents aged between 18 and 65 years old, Kazakh population living in Abay region since birth. All participants filled out questionnaire and had a bone mineral density measurement by dual energy X-ray absorptiometry (DXA) between July 15, 2023 and February 29, 2024. Logistic regression analysis was conducted to assess the association between low bone mineral density and key demographic characteristics, aforementioned lifestyle factors and nutrition habits. We identified the prevalence of low bone density and osteoporosis at the level of 34.1% with the highest prevalence in the older population group (50+ years) - 48.3%. Regression analysis revealed a number of indicators associated with the likelihood of bone sparing. However, only 4 of these showed significance in the final multivariate model (R2=22.4%). These included age (AOR 1.05), body mass index (AOR 0.92), fracture history (AOR 1.64), consumption of nuts and dried fruits were associated with lower prevalence of osteoporosis (AOR 0.48). Our study was the first in Kazakhstan that investigates the association of key demographic, behavior and anamnestic factors with low mineral density.

Background Popular movement-based injury risk screens have been shown to lack predictive precision, leading to interest in multifactorial models. Furthermore, there is a lack of research regarding injury risk assessment for those currently or planning to be recreationally active. This study aims to provide injury risk insights by analyzing multifactorial injury risk models and as-sociated clinical measures in the U.S. population. Methods Data related to injury, inflammatory markers, physical functioning, body composition, physical activity, and other variables from 21,033 respondents were extracted from NHANES. Odds ratios for self-reported injury were calculated for single predictors and risk models. Case-control and principal component analyses (PCA) were conducted to elucidate confounders and identify risk factor clusters, respectively. Receiver operating characteristic analysis was used to test the precision of a risk factor cluster to identify pain points and functional difficulties. Results Sociodemographic, individual, and lifestyle factors were strongly associated with higher odds of injury. Increases in fibrinogen and C-reactive protein were significantly associated with all risk groups. Membership to the high-risk group (age over 40, obesity, no muscle-strengthening activities, sedentary lifestyle, and low back pain) predicted at least one functional difficulty with 67.4% sensitivity and 87.2% specificity. In the injury group, bone turnover markers were higher, yet confounded by age and there was a significantly higher prevalence of self-reported osteoporosis compared to the control. In males, low testosterone was associated with injury, and higher estradiol was associated with pain and functional difficulties. In females, higher levels of follicle-stimulating hormone were associated with functional difficulties. PCA revealed four high-risk profiles, with markers and activities showing distinct loadings. Conclusion A comprehensive approach to injury risk assessment should consider the nexus of aging, lifestyle, and chronic disease to enhance tailored injury prevention strategies, fostering safe and effective physical activity participation and reducing the burden of musculoskeletal disorders.

This study investigates the effect of scaffold architecture on bone regeneration, focusing on 3D-printed polylactic acid-bioceramic calcium phosphate (PLA-bioCaP) composite scaffolds in rabbit femoral condyle critical defects. To assess their influence on bone healing and scaffold performance, we explored two distinct scaffold designs, alternate and helical laydown patterns. The scaffolds were meticulously characterized for pore size, strut thickness, porosity, pore accessibility, and mechanical properties. The in vivo efficacy of these scaffolds was evaluated using a rabbit femoral condyle critical defect model. Our findings indicate that both scaffold architectures are biocompatible and support bone formation. The helical scaffolds, characterized by larger pore sizes and higher porosity, demonstrated significantly greater bone regeneration than the alternate structures. However, their lower mechanical strength presented limitations for use in load-bearing sites. This study highlights the importance of scaffold architecture in bone tissue engineering and underscores the need to balance porosity and mechanical strength for optimal bone regeneration. The findings provide crucial insights for the design of 3D- printed scaffolds in clinical applications, particularly in the context of critical-sized bone defects. The study also outlines potential areas for future research, including exploring hybrid scaffold designs to achieve optimal porosity without compromising mechanical integrity.

Our previous study demonstrated that mesenchymal stem/stromal cells (MSCs) induced the differentiation of myeloid-derived suppressor cells (MDSCs) in the bone marrow (BM) under inflammatory conditions. In the present study, we aimed to explore the signaling pathway in BM cells responsible for MDSC generation. RNA-seq revealed that the mitogen-activated protein kinase (MAPK) pathways, among biochemical pathways, exhibited the highest number of differentially expressed genes in BM cells with MSC coculture relative to those without. Western blot confirmed strong phosphorylation of c-Jun N-terminal kinase (JNK) in BM cells cocultured with MSCs under GM-CSF stimulation, whereas p38 kinase activation remained unaltered by MSCs. Inhibition of JNK by SP600125 significantly abolished the expression of Arg1 and Nos2, the hallmark genes of MDSCs, as well as Hif1α, a molecule mediating monocyte functional re-programming into suppressive phenotype, in MSC-cocultured BM cells, while increasing TNF-α in response to lipopolysaccharides stimulation. Furthermore, JNK inhibition markedly abrogated the effect of MSCs on the production of TGF-β1, TGF-β2 and IL-10 in BM cells. These results suggest that MSCs induce MDSC differentiation in BM during inflammation, at least in part, through the activation of the JNK MAPK signaling pathway.

Scaffolds for tissue engineering are expected to respond to a challenging combination of physical and mechanical requirements, guiding the research towards the development of novel hybrid materials. This study introduces innovative three-dimensional bioresorbable scaffolds, in which a stiff poly(lactic acid) lattice structure is meant to ensure temporary mechanical support, while a bioactive gelatin-chitosan hydrogel is incorporated to provide a better environment for cell adhesion and proliferation. The scaffolds present a core-shell structure, in which the lattice core is realized by additive manufacturing, while the shell is nested throughout the core by grafting and crosslinking a hydrogel forming solution. After subsequent freeze-drying, the hydrogel network forms a highly interconnected porous structure that completely envelops the poly(lactic acid) core. Thanks to this strategy, it is easy to tailor the scaffold properties for a specific target application, by properly designing the lattice geometry and the core/shell ratio, which are found to significantly affect the scaffold mechanical performance and its bioresorption. Compression stiffness and strength provided by poly(lactic acid) lattices are overall within the range of values displayed by human bone tissue and remain stable after prolonged immersion in water at body temperature for several weeks. On the other hand, the hydrogel undergoes gradual and homogeneous degradation over time, but the core-shell integrity and structural stability are nevertheless maintained during at least 7-week hydrolytic degradation tests. In vitro experiments with human mesenchymal stromal cells reveal that the core-shell scaffolds are biocompatible and their physical-mechanical properties and architecture are suitable to support cell growth and osteogenic differentiation, as demonstrated by hydroxyapatite formation. These results suggest that the bioresorbable core-shell scaffolds can be considered, and further studied, in view of clinically relevant endpoints in bone regenerative medicine.

Background: Glycogen storage diseases (GSDs), known as glycogenoses, belong to inborn metabolic defects in the glycogen metabolism pathway. Several types of GSDs are distinguished, including Ia, Ib, III, VI, and IX. GSDs manifest as excessive glycogen deposition in the liver and muscles, resulting in the dysfunction of these organs. Therefore, the treatment of choice is multitherapy that, due to dietary restrictions, may lead to nutritional deficiencies and organ complications. This study aims to assess anthropometric, body composition, skeletal status, results of selected laboratory tests, dietary, lifestyle and physical capacity analyses in patients with glycogenoses and compare the results between GSD I and GSD III-VI-IX groups. Results: The results indicate that GSD patients were overweight or obese (44% of patients had BMI +1SD or +2SD) with high percentage of fat tissue (50% of patients had above 30% of body fat) and inadequate bone mineralisation (total body less head: median z-score -0.9, L2-L4 segment: median z-score -1.65). GSD I patients had the highest risk of developing obesity (67% of them had above 30% of body fat) and osteoporosis (total body less head: median z-score -1.0, L2-L4 segment: median -1.7). Conclusions: Special attention should be paid to appropriate diet and supplementation in patients with glycogenoses.

Tissue bioengineering has been assuming a pivotal role in implementing alternatives to conven-tional ossicular middle ear replacement prostheses to overcome extrusion while preserving acoustic properties. This in vitro study aims to explore for the first time in current literature the feasibility of a biohybrid middle ear prosthesis composed of titanium surrounded by bone ex-tracellular matrix as bio-coating. We have hereby studied the adhesion and proliferation of human adipose-derived mesenchymal stem cells (hASC) on titanium scaffolds in vitro. Moreover, we identified the osteogenic differentiation of hASC using immunofluorescence assay to analyze osteoblasts gene expression profile (Alp, Runx2, Col1a1, Osx, and Bglap) and we accounted the presence of collagen as a marker of hASC ability to secrete extracellular matrix. We utilized scanning electron microscopy to evaluate the presence of extracellular matrix on the scaffolds. Our preliminary data demonstrated the titanium ability to support human adipose-derived mesenchymal stem cell colonization, proliferation, and osteoblastic differentiation, to obtain a biohybrid device. Our experience seems encouraging, we advocate further in vivo research to corroborate our results towards bone transplantation.

nutrition, macro and micronutrients, bone health, exercise, exogenous and endogenous microRNA, epigenetics

Bone fractures are very common in the geriatric population and poses a great economic burden worldwide. While traditional methods for repairing bone defects have primarily been autografts, there are several drawbacks limiting its use. Bone graft substitutes have been used as alternative strategies to improve bone healing. However, there remains several impediments to achieving the desired healing outcomes. Injectable hydrogels have become attractive scaffold materials for bone regeneration given their high performance in filling irregularly sized bone defects, ability to encapsulate cells and bioactive molecules, and mimic the native ECM of bone. We investigated the use of an injectable chitosan-based hydrogel scaffold to promote differentiation of preosteoblasts in vitro. The hydrogels were characterized by evaluating cell homogeneity, cell viability, rheological and mechanical properties, and differentiation ability of preosteoblasts in hydrogel scaffolds. Cell-laden hydrogel scaffolds exhibited shear thinning behavior and the ability to maintain shape fidelity after injection. The CNC-CS hydrogels exhibited higher mechanical strength and significantly upregulated the osteogenic activity and differentiation of preosteoblasts as shown by ALP activity assays and histological analysis of hydrogel scaffolds. These results suggest that this injectable hydrogel is suitable for cell survival, can promote osteogenic differentiation of preosteoblasts, and structurally support new bone growth.

There was no significant difference in bacterial adhesion between the 3 bone graft types tested, regardless of the bacterial strain used (p &gt; 0.22). After 72 hours of culture, there was no significant difference between the Fresh and Frozen bone groups, while the number of CFU in the Decellularised group was significantly lower (p &lt; 0.01), averaging -0.72 +/- 0.08 lg, -0.20 +/- 0.01 lg and -0.78 +/- 0.48 lg with S. epidermidis, S. aureus and E. coli respectively. Absolute values differences are low, and considering fresh bone (equivalent to autograft) as the gold standard due to its low infection rates in clinical studies, we can conclude that adhesion and biolfilm development characteristics are similar between Fresh, Frozen and Decellularised bone grafts..

This review article deals with the design of bioactive calcium phosphate coatings deposited on metallic substrates to produce bone implants. The bioceramic coating properties are used to create a strong bonding between the bone implants and the surrounding bone tissue. They provide a fast response after implantation and increase the lifespan of the implant in the body environment. The first part of the article describes the different compounds belonging to the calcium phosphate family and their main properties for applications in biomaterials science. The calcium to phosphorus atomic ratio (Ca/P)at. and the solubility (Ks) of these compounds define their behavior in a physiological environment. Hydroxyapatite is the gold standard among calcium phosphate materials, but other chemical compositions/stoichiometries have also been studied for their interesting properties. The second part reviews the most usual deposition processes to produce bioactive calcium phosphate coatings for bone implant applications. Plasma spraying is the main industrial process, but magnetron sputtering, pulsed laser deposition, electrospray deposition, electrophoretic deposition, and electrodeposition are also widely studied in academic and industrial research. The last part describes the main physicochemical properties of calcium phosphate coatings and their impact on the bioactivity of bone implants in a physiological environment.

Total Hip Arthroplasty is one of the most successful surgery. However, due to the worldwide growing population life expectancy and the related incidence of age-dependent bone diseases, a growing number of cases of intra-operative fractures lead to revision surgery with high rates of morbidity and mortality. Surgeons choose the type of the implant, either cemented or cementless prosthesis, on the basis of the age, the quality of the bone and the general medical conditions of the patients. Generally, no quantitative measures are available to assess the intra-operative fracture risk. Consequently, the decision-making process is mainly based on medical operators’ expertise and qualitative information obtained by imaging. Motivated by this scenario, we here propose a mechanical-supported strategy to assist surgeons in their decisions, by giving intelligible maps of the risk fracture which take into account the interplay between actual strength distribution inside the bone tissue and its response to the forces exerted by the implant. To this end, we produce charts and patient-specific synthetic “traffic-light” indicators of fracture risk, by making use of ad hoc analytical solutions to predict the stress levels in the bone by means of CT-based mechanical and geometrical parameters of the patient. We felt that, if implemented in a friendly software or proposed as an app, the strategy could constitute a practical tool to help the medical decision-making process, in particular with respect to the choice of adopting cemented or cementless implant

Bioimpedance measurements are used increasingly in health applications because bioelectric parameters have been associated with anatomical and physiological properties, thus enabling to distinguish medical conditions. For bone fracture diagnostics, nevertheless, there is no established non-invasive method. Ex vivo studies and In vivo bioimpedance procedures, both invasive and non-invasive, on mammalians long bones are associated with promising results. In this work, out of a total of 568 papers, we reviewd 59 articles that mention long bone integrity by electric properties, be it Bioimpedance Analysis, Electrical Impedance Spectroscopy or Electrical Impedance Tomography. The papers are described in three sections, “Ex vivo measurements”, “In vivo invasive measurements” and “In vivo non-invasive measurements”. This review allows to establish the basics to planning the development of new technology to detect bone fracture via bioimpedance measurements.

Osteoporosis is an abnormal bone remodeling condition characterized by decreased bone density, which leads to high risks of broken bones. Previous studies have demonstrated that Lycii Radicis Cortex (LRC) extract inhibits bone loss in ovariectomized (OVX) mice by enhancing the osteoblast differentiation. A bioactive compound, Kukoamine B (KB), was identified from a fractionation of LRC extract as a candidate component responsible for an anti-osteoporotic effect. This study investigated the anti-osteoporotic effects of KB using in vitro and in vivo osteoporosis models. KB treatment significantly increased the osteoblastic differentiation and mineralized nodule formation of osteoblastic MC3T3-E1 cells, while it significantly decreased the osteoclast differentiation of primary-cultured monocytes derived from mouse bone marrow. The effects of KB on osteoblastic and osteoclastic differentiations under more physiological conditions were also examined. In the co-culture of MC3T3-E1 cells and monocytes, KB promoted osteoblast differentiation but did not affect osteoclast differentiation. For the in vivo experiments, KB significantly inhibited OVX-induced bone mineral density loss and restored the impaired bone structural properties in osteoporosis model mice. These results suggest that KB may be a potential therapeutic candidate for the treatment of osteoporosis.

Although fragility fractures, osteoporosis, sarcopenia and frailty are becoming more prevalent in our aging society the treatment options are limited and preventative strategies are needed. Despite magnesium being integral bone and muscle physiology the relationship between dietary magnesium and skeletal muscle and bone health has not been investigated concurrently before. We analysed cross-sectional associations between dietary magnesium and skeletal muscle mass (as fat free mass – FFM), grip strength and bone density (BMD) in 156,575 men and women aged 39-72 years from the UK Biobank cohort. FFM was measured with bioelectrical impedance and expressed as the percentage of body weight (FFM%) or divided by body mass index (FFM_BMI). Adjusted mean grip strength, FFM%, FFM_BMI, and BMD were calculated according quintiles of dietary magnesium, correcting for covariates. Significant inter-quintile differences across intakes of magnesium existed in men and women respectively of 1.1% and 2.4% for grip strength, 3.0% and 3.6% for FFM%, 5.1% and 5.5% for FFM_BMI, and 2.9% and 0.9% for BMD. These associations are as great or greater than annual measured losses of these musculoskeletal outcomes indicating potential clinical significance. Our study suggests that dietary magnesium may play a role in musculoskeletal health and have relevance for population prevention strategies for sarcopenia, osteoporosis and fractures.

Segmental bone defects caused by trauma, infection, tumor resection or osteoporotic fractures present significant surgical treatment challenges. Host bone autograft is considered the gold standard to restore function but comes with the cost of harvest site comorbidity. Allograft bone is a secondary option but has its own limitations in incorporation with host bone as well as cost. Therefore, developing new bone tissue engineering strategies to treat bone defects is critically needed. In the past three decades, the use of stem cells delivered with different scaffolds or growth factors for bone tissue engineering has made tremendous progress. Many varieties of stem cells have been isolated from different tissues for use in bone tissue engineering. This review summarizes the progress in using different postnatal stem cells including bone marrow mesenchymal stem cells, muscle-derived stem cells, adipose-derived stem cells, dental pulp stem cells/periodontal ligament stem cells, periosteum stem cells, umbilical cord-derived stem cells, peripheral blood stem cells and urine-derived stem cells for bone tissue engineering and repair. This review also summarizes the progress using exosomes or extracellular vesicles delivered with various scaffolds for bone repair. The advantages and disadvantages of each type of stem cell are also discussed and explained in detail. It is hopeful in the future that these preclinical results will translate into new therapies for bone defect repair.

Celiac disease is an autoimmune disease triggered by oral ingestion of gluten, with certain gluten residues resistant to digestive tract enzymes. Within the duodenum, the remaining peptides incite immunogenic responses, including the generation of autoantibodies and inflammation, leading to irreversible damage. Our previous exploration unveiled a glutenase called Bga1903 derived from the Gram-negative bacterium Burkholderia gladioli. The cleavage pattern of Bga1903 indicated its moderate ability to mitigate the toxicity of pro-immunogenic peptides. The crystal structure of Bga1903, along with the identification of subsites within its active site, was determined. To improve its substrate specificity toward prevalent motifs like QPQ within gluten peptides, the active site of Bga1903 underwent site-directed mutagenesis according to structural insights and enzymatic kinetics. Among the double-site mutants, E380Q/S387L exhibits an approximately 38-fold increase in its specificity constant toward the QPQ sequence, favoring glutamines at the P1 and P3 positions compared to the wild type. Not only does the heightened specificity of E380Q/S387L improve the hydrolytic activity against pro-immunogenic peptides, but also holds this version of the enzyme as a promising candidate as an oral therapy enzyme for celiac disease.

Background. Type 2 diabetes mellitus (T2DM) is becoming a major global health concern, especially in poorer nations. The high prevalence of obesity and the ensuing diabetes I attributed to rapid economic progress, physical inactivity, consumption of high-calorie foods, and changing lifestyles. Objectives. We investigated the role of interleukins-10 , 19 and 22 with varying levels of obesity in T2DM in the Asir region of Saudi Arabia. Materials and methods. 170 confirmed T2DM patients and a control group were enrolled. The demographic data, serum levels of IL-10, IL-19, and IL-22, and biochemical indices were assessed in patients and control groups by standard procedures. Results. T2DM patients were divided into four groups: A (normal body weight), B (Overweight), C (obese), and D (highly obese). Both male and female T2DM subjects in Group A showed significant decreases in IL-10 levels as compared to controls; however, there were insignificant changes in IL-10 levels in Groups C and D. T2DM patients in groups C and D, in both males and females, depicted very significant (p 0.001) increases in IL-19 levels as compared to controls and group A. Patient groups A to D displayed a progressive elevation of Il-22 levels irrespective of gender, although significant alterations were seen only in groups B to D, with p 0.05 for group B and p 0.01 for groups C and D respectively, as compared to healthy controls. Conclusions. IL-10 showed a strong relationship with T2DM in males with varying degrees of obesity, but females depicted relatively higher IL-10 levels in obese and highly obese groups, pointing to a protective phenomenon. IL-19 levels showed significant increases in all four groups, irrespective of gender. IL-22 appears to be unrelated to T2DM per se but shows an association with varying degrees of obesity.

Climate changes challenges people’s life and sustainability. Environmental problems seem to derive from human behavior. Dentistry has a high environmental footprint that needs to be controlled worldwide. Thus, the change of behavior of dentists is a necessary condition to improve the environmental situation. In this study we use a system dynamics approach to analyze pro-environmental behavior in dentists. Systemic modelling in this case, allow us to make a clear prediction of how the population of non-eco dentists will change in the future if certain factors will be affected and how much time will be needed by the system of a group of dental professionals to become eco- dentists. The ECODENT model was designed with Vensim software. It was based on the influence of WOM (word of mouth) spread of information among colleagues and stakeholders (e.g. patients, auxiliary staff and community) and other factors such as dental income, state support, CaPex and OpEx, education hours, level of urbanization and time to react. By changing each one of them we can observe the changes in the groups of non-eco and eco dentists as well as the flow of the phenomenon. It is tested that by augmenting WOM parameter, state economic support or education hours, while diminishing CaPex and OpEx, changes in pro-environmental behaviors of dentist will be reported in a shorter time. The ECODENT model can be used to further study pro-environmentalism in different dental groups and associations and design relevant eco-friendly educational programs.

Stress Granules formation is a pro-survival mechanism helping cells to cope with environmental challenges. Stress Granules have been studied for two decades in fundamental research, and are now being examined in the context of human pathogenesis. Here, we review studies highlighting stress granules’ involvement in cancer development through translational pattern modification.

Background: Bone marrow aspiration concentrate (BMAC) has garnered increasing interest due to its potential for healing musculoskeletal injuries. While the iliac crest remains a common harvest site, the aspiration technique’s efficacy in offering the highest yield and prevalence of mesen-chymal stem cells (MSCs) is controversial. This study aimed to compare two different techniques of bone marrow aspiration over the anterior iliac crest from a single level (SL) versus multiple level (ML). Methods: Anterior iliac crests were selected in 9 adult patients (aged between 31 and 59 years old). Aspiration was achieved using an 11-gauge needle (length: 100 mm; diameter: 2.3 mm) specifically manufactured for bone marrow collection (BD, Becton, US) connected to a 10-mL syringe. On one side, 4cc of bone marrow was aspirated at an SL to a depth of 7cm without changing the needle direction. On the other side, over the same portion of the iliac crest, 1 cc of bone marrow was obtained from ML of different depths during needle retrieval, maintaining a distance of 1cm and changing the tip direction. The samples were blindly sent to the laboratory without indicating whether they came from an SL or ML. Fluorescence-activated cell sorting (FACS) and osteoblast differentiation were analyzed and compared. Results: In the FACS analysis, the SL resulted in a higher population of MSCs that were positive for CD105, CD73, and CD90 and negative for CD34, compared to the ML method. In the process of osteoblast differentiation, it was observed that MSCs exhibited more advanced features of en-hanced osteoblastic abilities in the SL method rather than the ML method. Conclusion: An SL aspiration technique at the anterior iliac crest may produce a high-quality bone marrow aspirate. This technique may help obtain specific populations of MSCs with the desired characteristics for use in regenerative therapies for musculoskeletal injuries.

There is lacking information about the physiological response when conducting training of older men in a real-life setting. Seventy-six sedentary men aged 72.3 ± 0.6 (means ± SE; range: 63–92) years with a height, body mass and body mass index of 178.9 ± 0.8 cm; 92.1 ± 2.2 kg: 28.7 ± 0.6 kg/m2, respectively, were recruited to floorball (FG, n = 29), strength (SG, n = 38) or bowls (BG, n = 9) training 1 h twice a week in municipal activity centers and senior sport clubs. Subjects were tested at baseline, after 12 and 24 weeks. Twelve weeks of floorball and strength training lead to reduced blood Hb1Ac, body mass, fat mass, visceral and android fat. Further, SG had a decrease in gynoid fat and blood total and LDL cholesterol. Both groups decreased heart rate at rest. In SG, systolic and diastolic blood pressure were also reduced. FG increased markers for bone growth. FG and SG improved functional capacity. The improvements in FG and SG were maintained after 24 weeks. BG did not have any changes. In conclusion, older men conducting floorball or strength training twice a week in a real-life setting can improve functional capacity and a high number of health factors, whereas playing bowls does not lead to physiological changes.

Can the type of implant rehabilitation influence peri-implant bone loss in case of full-arch mandibular prosthesis? The purpose of the study was to assess, by orthopantomograms (OPG), bone loss around implants in different types of implant-supported prosthetic rehabilitations and evaluate potential risk factors associated with the number and location of implants that may have an association with bone defect. A radiographic study was conducted on 22317 OPGs in the time range from 2010 to 2024. All OPGs with implant-supported prosthetic mandibular rehabilitations were included in the study. A total of 155 OPGs were evaluated, with peri-implant bone loss identified in 64 (41.3%). Distal implants (furthest from the center) across various positioning patterns were most susceptible to bone loss, with positions 3.6 and 4.6 demonstrating the most frequent occurrences (25 and 26 cases, respectively). χ² test revealed significant associations between both implant positioning pattern (p &lt; 0.001) and number of implants (p &lt; 0.001) with peri-implant bone loss. Also by updating the sample of OPGs, increased susceptibility to bone resorption was found for implants placed distal to the mental foramen compared to mesial ones in full-arch implant-supported fixed prostheses. Prospective clinical studies will then be useful to investigate this finding further.

Background: The receptor activator of the nuclear factor-kB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) pathway is a determining pathway in the balance between bone formation and resorption; disruptions in this complex can affect bone metabolism. Methods: This study analyzed the changes in RANKL, OPG and 25(OH)D levels, the RANKL/OPG ratio, and other bone turnover markers (BTM) from diagnosis to complete remission in children with acute lym-phoblastic leukemia (ALL). This is a prospective observational cohort study. This study was carried out in the Instituto Mexicano del Seguro Social in Mexico City. Thirty-three patients (4-17 years) with newly diagnosed B-cell ALL were included. The patients were treated with the HP09 chemotherapy protocol. Children who had previously been treated with corticosteroids were excluded. A pe-ripheral blood sample at diagnosis and remission was collected to determine the 25(OH)D and BTM concentrations. Results: Increased RANKL (p=0.001) and osteocalcin (p

Background: Since there is no cure for amyotrophic lateral sclerosis (ALS) currently, it is very important for searching diagnostic biomarkers and novel treatments to reduce the severity of this disease; one of these treatment approaches is stem cell transplantation. This study aims to evaluate the safety and efficacy of repeated transplantation of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) in patients with ALS by analyzing molecular data. Methods: In this single-centre, open-label, phase II clinical trial, retrospective study, fifteen confirmed ALS patients entered the study based on defined inclusion and exclusion criteria and underwent repeated stem cell transplantation (3 times BM-MSCs transplantation (1×10^6) , MSC/Kg BW per injection) concurrently intrathecally (IT) and intravenously (IV), with one-month interval). Clinical assessment of molecular investigation by evaluating specific microRNAs expression (Mir206, 133a-3p, 338-3p) in the patient's serum and Cerebra spinal fluid (CSF) samples were done three times during the 3-month follow-up. Statistical analysis includes paired T-test or Wilcoxon signed ranks. Results: No serious adverse effects were reported following stem cell transplantation. Besides, the mentioned microRNA expression slightly increased but still non-significant (P&gt;0.05). Conclusions: Although Our study demonstrated non-signifying results. However, the still increasing of these MircRNAs in serum and CSF overall, can indicate that repeated transplantation of BM-MSCs was a safe procedure in ALS patients, leading to delay in disease progression and improvement in clinical symptoms. Future studies are needed to confirm these results.

This study aimed to demonstrate the potential role of Dual Energy CT in assessing Bone Mineral Density (BMD) in postmenopausal women. A retrospective study was conducted on 51 postmenopausal female patients who underwent DXA and DECT examinations for other clinical reasons. DECT images were acquired with spectral imaging using a 256-slice system. These images were processed and visualized using an HAP(fat) map. Statistical analysis was performed using the Bland-Altman method to assess agreement between DXA and DECT HAP(fat) measurements. Mean BMD, vertebral and femoral T-scores were obtained. For vertebral analysis, the Bland-Altman plot showed an inverse correlation (R2: -0.042; RMSE: 0.690) between T-scores and DECT HAP(fat) values for measurements from L1 to L4, while a good linear correlation (R2: 0.341; RMSE: 0.589) it was found for measurements at the femoral neck. In conclusion, we demonstrated the enhanced accuracy of BMD calculation through DECT, finding a statistically significant correlation only at the femoral neck where BMD results do not seem to be influenced by the overlap of the measurements on cortical and trabecular bone. This outcome could be beneficial in the future by reducing radiation exposure for patients already undergoing follow-up for chronic conditions.

Oral bone defects occur as a result of trauma, cancer, infections, periodontal diseases, and caries. Autogenic and allogenic grafts are the gold standard used to treat and regenerate damaged or defective bone segments. However, these materials do not possess the antimicrobial properties necessary to inhibit the invasion of the numerous deleterious pathogens present in the oral microbiota. In the present study poly(ε-caprolactone) (PCL), nano-hydroxyapatite (nHAp), and a commercial extract of Humulus lupulus L. (hops) were electrospun into polymeric matrices to assess their po-tential for drug delivery and bone regeneration. The fabricated matrices were analyzed by scanning electron microscopy (SEM), tensile analysis, thermogravimetric analysis (TGA), FT-IR assay, and in vitro hydrolytic degradation. The antimi-crobial properties were evaluated against the oral pathogens Streptococcus mutans, Porphyromonas gingivalis, and Aggregatibacter actinomycetemcomitans. The cytocompatibility was proved by the MTT assay. SEM analysis proved the nanostructured matrices have suitable fiber size. The present research provides new information about the interaction of natural compounds with ceramic and polymeric biomaterials. The hop extract and other natural or synthetic medicinal agents can be effectively loaded into PCL fibers and has the potential to be used in biomedical applications.

Background: One challenge in implant dentistry is to reduce marginal bone resorption to avoid long-term esthetic and biological complications. Sub-gingival implant placement has been suggested as a suitable strategy. Methods: 38 healthy patients were enrolled to receive bone level (BL – Control group) or 2 mm sub-crestal (SC - Test group) conical connection, platform-switched implants. An immediate tissue level abutment was used in the Test group by following a One Time Abutment (OTA) restorative procedure. Marginal Bone Modification (MBM) was calcu-latied on standardized radiographs at surgery (T0), loading (T1), and 6 months (T2) and 12 months after loading (T3), and cathegorised in Bone Loss (BL) if the resorption occurred below the implant neck and Bone Remodeling (BR) if above. Pocket probing depth (PPD), Bleeding on probing (BoP) and Plaque Index (PI) were also collected. Results: The mean MBM in the test group after 12 months was 0.61mm, compared to 0.52mm in the control group. However, no BL was observed in the test group, as the MBM completely occurred above the implant neck as BR, whilst in the control group MBM corresponded in total to BL. The average PPD was 2.38mm in the test group and 3.04mm in the control group after 12 months, BoP 50% and 43%, PI 33% and 19.44% respectively. Conclusions: Sub-crestal conical connection, platform-switched implants could be a suitable clinical choice to avoid BL with exposure of the treated implants surfaces.

People are increasingly encouraged to reduce animal food consumption and shift towards plant-based diets, however the implications for children’s health are unclear. In this narrative review of research in high-income settings, we summarize evidence on the increasing consump-tion of plant-based diets in children, and update an earlier systematic review regarding their associations with children’s health outcomes. The evidence indicates that vegan but not vege-tarian diets can restrict growth relative to omnivorous children, and increase the risk of being stunted and underweight although the percentage affected is relatively small. Bone mineral content is reduced in vegetarian and especially vegan children, compared to omnivores. Both vegetarian and vegan children who do not use vitamin B12 supplements manifest with B12 defi-ciency, however supplementation rectifies this problem. Both vegetarians and vegans have lower concentrations of 25 (OH)D if unsupplemented, and lower body iron stores, but usually have normal iron metabolism markers. Both groups are at risk of iodine deficiency and this might affect thyroid health. Children consuming a vegan diet have more favorable lipid profile than omniv-orous children, however the results for vegetarian diet are inconsistent and vary by outcome. Based on the same scientific evidence, national and international dietary recommendations are heterogeneous, with some countries supporting plant-based diets among infants, children and adolescents, and others discouraging them. We offer a research roadmap, highlighting what is needed to provide adequate evidence to harmonize dietary recommendations for plant-based diets in children. A number of measures should urgently be introduced at international and na-tional levels to improve the safety of their use in children.

Percutaneous kyphoplasty (PKP) is a highly successful treatment option for Kümmell's disease (KD). Due to the obstruction of the fibrocartilaginous membrane at the periphery of the intervertebral vacuum cleft (IVC) and inadequate osteointegration of conventional bone cement, there is insufficient locking strength between trabecular bone and bone cement in Kümmell's disease (KD), leading to postoperative displacement of the bone cement and sub-sequent early surgical failure. However, there is no standard strategy managing this complica-tion at present. We reported a rare case of premature bone cement displacement resulting in adjacent vertebra fracture. An 80-year-old male with Kümmell's disease at T10 received per-cutaneous kyphoplasty (PKP) with bone cement leaking into the upper disc. Only 3 days after the surgery, the patient complained of severe back pain again. X-ray and MRI showed bone cement displacement at T10, adjacent vertebra fracture at T9. In consideration of poor toler-ance of open surgery for the old patient, we successfully revised by using percutaneous ky-phoplasty with multi-point anchoring technique (A-PKP). During a 10-month postoperative follow-up, the patient reported pain relief. X-ray and three-dimensional CT scan revealed no obvious progress of bone cement displacement. Although the exact mechanism underlying this rare complication remains unclear, we observed that the premature bone cement dis-placement can result in adjacent vertebra fracture especially when the pattern of bone cement is blocky. Percutaneous kyphoplasty with multi-point anchoring technique (A-PKP) appears effective in managing this complication.

: For a long time, atherosclerosis has been regarded as a mere lipid deposit in the blood vessels. However, in the recent years a growing body of experimental and clinical evidence have highlighted the role of inflammation and immunity as a central mechanism of disease. Moreover, in the last decade the coming of next-generation sequencing and its application to large human population has broken the barrier between inflammation and cancer. Indeed, acquired mutation in key genes related to the control of hematopoiesis and myeloproliferation have paved the way to establish the new concept of clonal hematopoiesis of indeterminate potential. This phenomenon is being considered not such “indeterminate”, but as an emerging cardiovascular risk factor. Thus, this may explain the mechanisms of myeloproliferation and inflammation in atherosclerosis. And in a bidirectional journey, it has helped to explain the extremely high cardiovascular risk in cancer survivors, in particular in myeloprolfierative neoplasm patients. A deeper understanding of these mechanisms may pave the way for the future early diagnosis and potential preemptive treatments of the leading worldwide cause of death.

Fibrodysplasia Ossificans Progressiva (FOP) is an enigmatic, ultra-rare genetic disorder characterized by progressive heterotopic ossification, wherein soft connective tissues undergo pathological transformation into bone structures. This incapacitating process severely limits patient mobility and poses formidable challenges for therapeutic intervention. Predominantly caused by missense mutations in the ACVR1 gene, the disorder has hitherto defied comprehensive mechanistic understanding and effective treatment paradigms. This write-up offers a comprehensive overview of the contemporary understanding of FOP's complex pathobiology, underscored by advances in molecular genetics and proteomic studies. We shed light on targeted therapy, spanning genetic therapeutics, enzymatic and transcriptional modulation, stem cell therapies, and innovative immunotherapies. We also focused on the intricate complexities surrounding clinical trial design for ultra-rare disorders like FOP, addressing fundamental statistical limitations, ethical conundrums, and methodological advancements essential for the success of interventional studies. We advocate for the adoption of a multi-disciplinary approach that converges bench-to-bedside research, clinical expertise, and ethical considerations to tackle the challenges of ultra-rare diseases like FOP and comparable ultra-rare diseases. Overall, this article serves a dual role: as a definitive scientific resource for ongoing and future FOP research and as a call to action for innovative solutions to address methodological and ethical challenges that impede progress in the broader field of medical research for ultra-rare conditions.

Different bone bruise patterns observed on magnetic resonance imaging (MRI) after non-contact anterior cruciate ligament (ACL) rupture and lateral patellar dislocation may indicate different injury mechanism of knee. In order to investigate the typical bone bruising patterns after ACL rupture and patellar dislocation. In this study, 77 ACL rupture and 77 patellar dislocation patients’ knee MR images with bone bruises between August 2020 and March 2022at our institution were selected and analyzed, respectively. Sagittal and transverse planes images were used to determine the bone bruise location in the lateral-medial and superior-inferior directions of the MR images. The presence, location, and intensity of the bone bruises within specific compartments of the femur and tibial after ACL rupture and patellar dislocation were recorded. Relative bone bruise patterns of the ACL rupture and patellar dislocation were classified and analyzed. Results showed that there were 4 kinds of bone bruise (1-,2-,3-,4- bone bruises) patterns after ACL rupture. The most common two patterns after ACL rupture were 3- bone bruises (including lateral side of femur and both lateral and medial side of tibia, LF+BT; both lateral and medial side of femur and lateral side of tibia, BF+LT, medial side of femur and both lateral and medial side of tibia, MF+BT) followed by 4- bone bruises (both lateral and medial side of femur and tibia, BF+BT), 2- bone bruises (LF+LT, lateral side of femur and tibia; MF+LT, medial side of femur and lateral side of tibia; LF+MT, lateral side of femur and medial side of tibia; MF+MT, medial side of femur and tibia; 0+BT, both lateral and medial side of tibia;), and 1- bone bruise (0+LT, only lateral side of tibia). There was only 1 pattern bone bruise (latera femur and medial patella bone bruise) of patellar dislocation, the most common pattern of patellar dislocation was in the inferior medial patella and lateral anterior inferior femur. The results suggest that the pattern of bone bruise after ACL rupture and patellar dislocation is completely different. There were 4 kinds of bone bruise patterns after non-contact ACL rupture while there was only 1 kind of bone bruise pattern after patellar dislocation bone bruise patients which was in the inferior medial patella and lateral anterior inferior femur.

Introduction: Osteosarcomas of the jaw (OSJ) are rare tumors with a different behavior from osteosarcomas of other bones. This study aims to analyze the clinical, pathological, and therapeutic characteristics of this type of sarcoma. Methods: a retrospective observational study of cases diagnosed with OSJ registered at the “La Paz” University Hospital (Madrid). Results: Eight cases with a diagnosis of OSJ were obtained in a study period of 22 years (2000-2022). The mean age was 41 years. The distribution was 1:1 between the maxilla and mandible. Painful inflammation was the most frequent clinical manifestation. Conventional osteoblastic osteosarcoma was the most common. Survival at 5 years was 50%, while at 10 years, it decreased to 25%. Conclusions: OSJ differs from conventional osteosarcomas of long tubular bones. Surgery continues to be the mainstay of treatment; more studies are needed in which more standardized protocols can be proposed for adjuvant therapeutic management.

In recent years, bone tissue engineering (BTE) has made significant progress in promoting the direct and functional connection between bone and graft, including osseointegration and osteoconduction, to facilitate the healing of damaged bone tissues. Herein, we introduce a new, environmentally friendly, and cost-effective method for synthesizing reduced graphene oxide (rGO) and hydroxyapatite (HAp). The method uses epigallocatechin-3-O-gallate (EGCG) as a reducing agent to synthesize rGO (E-rGO), and HAp powder is obtained from Atlantic bluefin tuna (Thunnus thynnus). The physicochemical analysis indicated that the E-rGO/HAp composites had exceptional properties for use as BTE scaffolds, as well as high purity. Moreover, we discovered that E-rGO/HAp composites facilitated not only proliferation, but also early and late osteogenic differentiation of human mesenchymal stem cells (hMSCs). Our work suggests that E-rGO/HAp composites may play a significant role in promoting the spontaneous osteogenic differentiation of hMSCs, and we envision that the E-rGO/HAp composites could serve as promising candidates for BTE scaffolds, stem cell differentiation stimulators, and implantable device components due to their biocompatible and bioactive properties. Overall, we suggest a new approach for developing cost-effective and environmentally friendly E-rGO/HAp composite materials for BTE application.

Bone tissue engineering has been developed in the past decades, with the engineering of bone substitutes on the vanguard of this regenerative approach. PCL based scaffolds are fairly applied for bone regeneration, and several composites have been incorporated, as to improve the devices’ mechanical properties and tissue ingrowth. In this study, HA was incorporated on PCL based scaffolds with two different proportions, 80:20 and 60:40. Devices were produced with two different techniques, SC and MB, and further investigated with regards to their mechanical characteristics and in vitro cytocompatibility. Results show the MB devices to present more promising mechanical properties, along with the incorporation of HA. The latter is also related to an increase in osteogenic activity and promotion. Overall, this study suggest PCL:HA scaffolds to be promising candidates for bone tissue engineering, particularly when produced by the MB method.

Patients often need the use of their arms to assist with functional activities, but after bone disruption, pushing is frequently limited to less than 4.5 kg. No method exists to measure arm weight bearing objectively in clinical settings. This project aimed to design, construct, and test a walker for patients who need to limit arm force to prevent excessive bone stress during post-fracture (iatrogenic or traumatic) ossification. First, a qualitative study was conducted to obtain critiques of a Clinical Force Measuring (CFM) walker prototype from rehabilitation professionals. Key statements and phrases were coded that allowed “themes” to emerge from transcribed interviews, which guided device revisions. Next, a second CFM Walker prototype was designed based on the qualitative data and device criteria/constraints and finally tested. The result was fabrication of a new lightweight, streamlined, and cost-effective prototype walker with a simple visual display and auditory cue with upper limit alarms. Key features included attachments for medical equipment and thin film force-sensing resistors integrated into the walker handles that progressively activated 3 LEDs and a buzzer when arm force exceeded programmed thresholds. The innovative CFM Walker will help patients with restricted arm weight bearing, especially elderly adults, recover safer and faster in the future.

Materials based on Mg2+-containing phosphates are gaining great relevance in the field of bone tissue repair via regenerative medicine methods. Magnesium ions, together with condensed phosphate ions, play a significant role in the process of bone remodeling, affecting the early stage of bone regeneration through active participation in the process of osteosynthesis. Here we pro-vide a comprehensive overview of the usage of biomaterials based on magnesium phosphate and magnesium calcium phosphate in bone reconstruction. The role of magnesium ions in angiogene-sis, an important process associated with osteogenesis, is considered. Finally, the biological properties of magnesium phosphates for bone regeneration are summarized. They show promis-ing results in terms of use as bone replacement material.

The combination of calcium phosphates (CaP) with bioactive glasses (BG) has received an increased interest in the field of bone tissue engineering. In the present work, biphasic calcium phosphates (BCP) obtained by hydrothermal transformation (HT) of cuttlefish bone (CB) were coated with a Sr-, Mg- and Zn-doped sol-gel derived BG. The scaffolds were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The initial CB structure was maintained after HT and the scaffold functionalization did not jeopardize the internal structure. The results of in vitro bio-mineralization after immersing the BG coated scaffolds in simulated body fluid (SBF) showed extensive formation of bone-like apatite onto the surface of the scaffolds. Overall, the functionalized CB derived BCP scaffolds revealed promising properties for their use in bone tissue engineering field.

The present study is the second step (concerning the normal-diet restoration) of the our previous one (concerning the calcium-free diet) to determine whether the normal-diet restoration, with/without concomitant PTH(1-34) administration, can influence amounts and deposition sites of the total bone mass. Histomorphometric evaluations and immunohistochemical analysis for Sclerostin expression were conducted on the vertebral bodies and femurs in rat model. The final goals are: i) to define timing and manners of bone mass changes when calcium is restored in the diet; ii) to analyze the different involvement of the two bony architectures having different metabolism (i.e. trabecular versus cortical bone); iii) to verify the eventual role of PTH(1-34) administration. Results evidenced the greater involvement of the trabecular bone with respect to the cortical one, in answering to different calcium diet content, and the effect of PTH mostly in the recovery of trabecular bony architecture. The main findings emerged from the present study are: i) the importance of the interplay between mineral homeostasis and skeletal homeostasis in modulating and guiding bone answers to dietary/metabolic alterations and ii) the evidence that the more involved bony architecture is the trabecular one, the most susceptible to the dynamical balance of the two homeostases.

Butyric acid as a histone deacetylase (HDAC) inhibitor was produced by a number of periodontal and root canal microorganisms (such as Porphyromonas, Fusobacterium etc.). Butyric acid may affect the biological activities of periodontal/periapical cells such as osteoblasts, periodontal ligament cells etc., and thus affect periodontal/periapical tissue destruction and healing. The purposes of this study were to study the toxic effects of butyrate on matrix and mineralization markers’ expression of MG-63 osteoblasts. Cell viability and proliferation were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Cellular apoptosis and necrosis were analyzed by propidium iodide/Annexin V flow cytometry. Protein and mRNA expression of OPG, and RANKL were analyzed by western blotting and RT-PCR. OPG, soluble RANKL (sRANKL), 8-isoprostane, pro-collagen I, MMP-2, osteonectin (SPARC), osteocalcin and osteopontin secretion into culture medium were measured by enzyme-linked immunosorbant assay. Histone H3 acetylation levels were evaluated by immunofluorescent staining (IF) and western blot. We found that butyrate induced morphologic changes of growing MG-63 cells, with bigger and flattened in appearance. Butyrate activated histone H3 acetylation of MG-63 cells. Exposure of MG-63 cells to butyrate partly decreased cell number with no marked increase in apoptosis and necrosis. Butyrate stimulated RANKL protein expression, whereas it inhibited OPG protein expression. Butyrate also inhibited the secretion of OPG in MG-63 cells, whereas sRANKL level was below detection limit. Butyrate stimulated 8-isoprostane, MMP-2 and osteopontin secretion, but not procollagen I, osteonectin, osteocalcin in MG-63 cells. In conclusion, butyric acid generated by periodontal and root canal microorganisms may potentially induce bony destruction and impair bone repair by alteration of OPG/RANKL expression/secretion, 8-isoprostane, MMP-2, and osteopontin secretion, and affect cell proliferation. These effects are possibly related to increased histone acetylation. These events are important in the pathogenesis of periodontal and periapical destruction.

In this study, four kinds of animal bone marrow powders were extracted with n-hexane using the Soxhlet extraction method. Polyunsaturated fatty acids were enriched by urea inclusion and low temperature crystallization method, then were further evaluated antioxidant and antibacterial activities. These results showed that the oil composition of the n-hexane extracts of four kinds of animal bone marrow primarily consisted of palmitic acid (18.57–31.01%), stearic acid (3.6–20.95%), and oleic acid (40.22–58.69%). The ratios of saturated fatty acids (SFA)/unsaturated fatty acids (UFA) were 1/1.417, 1/1.327, 1/2.140, and 1.285/1 for sheep, bovine, horse, and camel bone marrow oil, respectively. The SFA/UFA ratios determined by the urea inclusion method were 1/1.518, 1/1.390, 1/2.037, and 1.216/1, respectively. The SFA/UFA ratios according to the low temperature crystallization method with acetone were 1/1.920, 1/2.141, 1/2.360, and 1/1.157 for sheep, bovine, horse, and camel bone marrow oil, respectively. These enrichment methods effected the concentrations of UFAs from the camel bone marrow oil. Among the methods, the low temperature crystallization method effectively enriched the UFAs. All four bone marrow oils exhibited strong antioxidant and antimicrobial activities. The horse bone marrow oil showed the strongest antioxidant activity. Both antioxidant and antimicrobial activity improved after enrichment of the UFAs. These results lay a theoretical basis for application bone marrow oil resources in food and medicine.

The human degenerative cartilage has low regenerative potential. Chondrocyte transplantation offers a promising strategy for cartilage treatment and regeneration. Currently chondrogenesis using human pluripotent stem cells are accomplished using human recombinant growth factors. Here, we differentiated human induced pluripotent stem cells (hiPSCs) into chondrocytes and cartilage pellet using minicircle vectors. Minicircles are used as a non-viral gene delivery system for gene therapy in various diseases. Non-viral gene delivery can produce growth factors without integrating into the host genome. Minicircle vectors containing bone morphogenetic protein 2 (BMP2) and transforming growth factor, beta 3 (TGFβ3) were successfully generated and delivered to hiPSC-derived outgrowth (OG) cells. Cell pellets generated using minicircle-transfected OG cells successfully differentiated into chondrogenic lineage. Chondrogenic pellets transfected with growth factor-encoding minicircles effectively recovered osteochondral defect in rat models. Taken together, this work shows the potential application of minicircles in cartilage regeneration using hiPSCs.

The hypothesis that consumption of Aronia melanocarpa berries (chokeberries) extract, recently reported by us to improve bone metabolism in female rats at low-level and moderate chronic exposure to cadmium (1 and 5 mg Cd/kg diet for up to 24 months), may increase the bone resistance to fracture was investigated. Biomechanical properties of the neck (bending test with vertical head loading) and diaphysis (three-point bending test) of the femur of rats administered 0.1% aqueous chokeberry extract (65.74% of polyphenols) or/and Cd in the diet (1 and 5 mg Cd/kg) for 3, 10, 17, and 24 months were evaluated. Moreover, procollagen I was assayed in the bone tissue. The low-level and moderate exposure to Cd decreased procollagen I concentration in the bone tissue and weakened biomechanical properties of the femoral neck and diaphysis. Chokeberry extract administration under the exposure to Cd improved the bone collagen biosynthesis and femur biomechanical properties. The results allow for the conclusion that consumption of chokeberry products under exposure to Cd may improve the bone biomechanical properties and protect from fracture. This study provides support for Aronia melanocarpa berries being a promising natural agent for the skeleton protection under low-level and moderate chronic exposure to Cd.

Some studies have demonstrated that in vivo degradation processes are influenced by the material’s physico-chemical properties. The present study compares two hydroxyapatites manufactured on an industrial scale, deproteinized at low and high temperatures, and how physico-chemical properties can influence the mineral degradation process of material performance in bone biopsies retrieved 6 months after maxillary sinus augmentation. Residual biomaterial particles were examined by field scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX) to determine the composition and degree of degradation of the bone graft substitute material. According to the EDX analysis, the Ca/P ratio significantly lowered in the residual biomaterial (1.08±0.32) compared to the initial composition (2.22±0.08) for the low-temperature sintered group, which also presented high porosity, low crystallinity, low density, a large surface area, and poor stability and a high resorption rate compared to the high-temperature sintered material. This demonstrates that variations in the physico-chemical properties of bone substitute material clearly influence the degradation process. Further studies are needed to determine whether the resorption of deproteinized bone particles proceeds slowly enough to allow sufficient time for bone maturation to occur.

Following traumatic brain injury (TBI), secondary brain damage due to chronic inflammation is the most predominant cause of the delayed onset of mood and memory disorders. Currently no therapeutic approach is available to effectively mitigate secondary brain injury after TBI. One reason is the blood-brain barrier (BBB), which prevents passage of most therapeutic agents into the brain. Peptides have been among the leading candidates for CNS therapy due to their low immunogenicity and toxicity, bioavailability, and ease of modification. In this study, we demonstrated that non-invasive intranasal administration of KAFAK, a cell penetrating anti-inflammatory peptide, traversed the BBB in a murine model of diffuse, moderate TBI. Notably, KAFAK treatment reduced the production of pro-inflammatory cytokines that contribute to secondary injury. Furthermore, behavioral tests showed improved or restored neurological, memory, and locomotor performance in KAFAK-treated mice. This study demonstrates KAFAK's ability to cross the blood-brain barrier, to lower pro-inflammatory cytokine levels in vivo, and to restore function after a moderate TBI.

Despite innovative advances in anti-infective therapies and vaccine development technologies, community-acquired pneumonia (CAP) remains the most persistent cause of infection-related mortality globally. Confronting the ongoing threat posed by Streptococcus pneumoniae (the pneumococcus), the most common bacterial cause of CAP, particularly to the non-immune elderly, remains challenging due to the propensity of the elderly to develop invasive pneumococcal disease (IPD), together with the predilection of the pathogen for the heart. The resultant development of often fatal cardiovascular events (CVEs), particularly during the first seven days of acute infection, is now recognized as a relatively common complication of IPD. The current review represents an update on the prevalence and types of CVEs associated with acute bacterial CAP, particularly IPD. In addition, it is focused on recent insights into the involvement of the pneumococcal pore-forming toxin, pneumolysin (Ply), in subverting host immune defenses, particularly the protective functions of the alveolar macrophage during early-stage disease. This, in turn, enables extra-pulmonary dissemination of the pathogen, leading to cardiac invasion, cardiotoxicity and myocardial dysfunction. The review concludes with an overview of the current status of macrolide antibiotics in the treatment of bacterial CAP in general, as well as severe pneumococcal CAP, including a consideration of the mechanisms by which these agents inhibit the production of Ply by macrolide-resistant strains of the pathogen.

Cement manufacturing is one of the most energy-intensive industries in the world. Most of the cost of producing cement is accounted by fuel consumption and power expenditures. Thermal power plants are the major source of electricity in Pakistan. But they are not efficient and environmentally friendly. This study simulates four different models for five cement plants of Pakistan on Homer Pro software and compares the optimal solutions based on the net present cost (NPC), levelized cost of electricity (LCOE) and greenhouse gas (GHG) emissions. Model-1 consists of solar panels, electrolyzer, hydrogen tank, hydrogen generator and converter. Model-2 has only a diesel generator and acts as a base case in this study. Model-3 has solar panels and a battery-converter system. In Model-4, diesel generators, solar panels and converters are considered. Based on NPC, the most optimal model is Model-4, having a 0.249 $/KWh LCOE in islanded systems. The NPC and operating costs are US$540 million and US$ 32.5 million per year, respectively, with a 29.80% reduction in CO2 emissions when compared to the base case. Based on GHG emissions, Model-1 and Model-3 are the best models with 0% GHG emissions. Sensitivity analyses is also performed using the parameters of load, inflation rate and discounted rate. The results prove that the proposed hybrid micropower systems (HMS) can sustainably provide electricity for 24 hours a day to the sites under consideration with minimum objectives.

Knowledge about one’s innate health is central to a variety of positive mental health markers. However, men living in prison rarely receive education about how to access these internal resources. As such, this study seeks to replicate and extend emerging data on an innate health intervention. Volunteers from HMP Nottingham, England (n=126) participated in normal prison programming and the intervention group (n=65) received an additional 3-day intensive. The primary question: Does innate health function as a mediator in the same way self-control does within an incarcerated population? We conducted a mediation analysis, tested social desirability bias, and examined the impact of the intervention on crucial variables. This study found higher levels of innate health, self-control, wellbeing, and prosocial behavior and lower levels of aggression in the intervention group as compared to the control group. Importantly, innate health did play a mediating role equivalent to and/or partnering with self-control.

Addressing non-unions involves stabilizing the affected area through osteosynthesis and improving bone biology using bone grafts. However, there is no consensus on the optimal treatment method. This study aims to compare outcomes of non-union revision using conventional treatment methods (metal hardware ± graft) versus osteosynthesis with the human, allogeneic cortical bone screw (Shark Screw®). Thirty-four patients underwent conventional treatment, while 28 cases received Shark Screws®. Patient demographics, bone healing, time to bone healing, and complications were assessed. Results revealed a healing rate of 96.4% for the Shark Screw® group, compared to 82.3% for the conventionally treated group. The Shark Screw® group exhibited a tendency for faster bone healing (9.4±3.2 vs. 12.9±8.5 weeks, p=0.05061). Hardware irritations led to six metal removals in the conventional group versus two in the Shark Screw® group. The Shark Screw® emerges as a promising option for personalized non-union treatment in the foot, ankle, and select lower leg cases, facilitating effective osteosynthesis and grafting within a single construct, promoting high union rates, low complications, and a rapid healing process.

Ecological footprint calculators are digital tools that help individuals calculate their environmental or climate impact, with the aim of stimulating pro-environmental behaviour change. These footprint calculators typically take an information-provision approach, but this strategy assumes that increased levels of knowledge result in increased levels of pro-environmental behaviour (i.e., a reduced footprint). This is not a given – existing literature on the relationship between environmental knowledge and pro-environmental behaviour is inconclusive, and this relationship may be different from that of environmental knowledge and ecological footprint. As such, we investigated the relationship between environmental knowledge and ecological footprint as estimated by a footprint calculator. 448 Dutch participants completed an online survey, including an ecological footprint calculator. We found no evidence for a relationship between environmental knowledge and ecological footprint calculator outcome. Rather, an exploratory analysis of our data showed that environmental values were more important predictors of ecological footprint. The finding that increased levels of knowledge are not related to a reduced ecological footprint suggests that calculators would do well to move beyond information provision, and employ additional behaviour change strategies. Based on our exploratory analysis, we provide several concrete examples of potential strategies.

Objective: Scaphoid fractures, particularly occult and non-displaced fractures, are difficult to detect using traditional X-ray methods due to their subtle appearance and variability in bone density. The study proposes a two-stage CNN approach to detect and classify scaphoid fractures using anterior-posterior (AP) and lateral (LA) X-ray views for more accurate diagnosis. Methods: The study emphasizes the use of multi-view X-ray images (AP and LA views) to improve fracture detection and classification. The multi-view fusion module helps integrate information from both views to enhance detection accuracy, particularly for occult fractures that may not be visible in a single view. The proposed method includes two stages that are stage 1: Detect the scaphoid bone using Faster R-CNN and Feature Pyramid Network (FPN) for region proposal and small object detection. The detection accuracy for scaphoid localization is 100% with Intersection over Union (IoU) scores of 0.8662 for AP views and 0.8478 for LA views. And stage 2: Perform fracture classification using a ResNet backbone and FPN combined with a multi-view fusion module to combine features from both AP and LA views. This stage achieves a classification accuracy of 89.94%, recall of 87.33%, and precision of 90.36%. Results: The proposed model performs well in both scaphoid bone detection and fracture classification. The multi-view fusion approach significantly improves recall and accuracy in detecting fractures compared to single-view approaches. In scaphoid detection, both AP and LA views achieved 100% detection accuracy. In fracture detection, using multi-view fusion, the accuracy for AP views reached 87.16%, and for LA views, it reached 83.83%. Conclusion: The multi-view fusion model effectively improves the detection of scaphoid fractures, particularly in cases of occult and non-displaced fractures. The model provides a reliable, automated approach to assist clinicians in detecting and diagnosing scaphoid fractures more efficiently.

Primary bone lymphoma of the spine (PBL) is a rare entity and the most shared type of non-Hodgkin lymphoma (LNH) appearing in bone lesions deprived of nodal or extra-nodal in-volvement and accounting for approximately 2% of all lymphomas. Most PBL are diffuse large B-cell lymphomas (DLBCL) and commonly involve the appendicular skeleton. Due to its atypical location and non-specific clinical imaging features mimicking certain neoplastic or infectious processes, this pathology may be misdiagnosed, thus complicating and delaying diagnosis. Our case reports a patient in her sixties who had been suffering from chronic low back pain for a year, and had gradually started to develop cruralgia and fever. She underwent a blood sample, magnetic resonance imaging (MRI), and positron emission tomography (18F-FDG-PET/CT) which revealed significant inflammatory syndrome, a pattern of spondylodiscitis at the L3-L4 level associated with morphological and metabolic invasion extending posteriorly, raising suspicion of epiduritis. No other lesions were found on the rest of the body. Neurosurgical management was performed and a biopsy was made. Histological results showed aggressive and diffuse large B-cell lymphoma, suggesting a diagnosis of PBL. This case highlights the first case of spondylodiscitis mimicking PBL in the lumbar spine, the intricacies of the diagnostic work-up, and the complexity of discriminating with an infectious process in the spine, as both have a similar, non-specific clinical presentation with different prognosis and therapeutic management.

Background: The main objective of this study is to develop a customized metatarsophalangeal implant for the treatment of various conditions affecting this specific joint. This approach involves replacing the joint with a custom implant designed specifically to fit each patient's unique anatomical structure. The need for custom implants stems from the obvious lack of size variety available, which presents a major challenge when, the search for the ideal size implant can be a hard task, also when considering the possibility of extensive modification of the bone to adapt it to the available implant. This adaptation, often synonymous with bone reduction, can cause significant post-operative pain for the patient and impact healing time. Methods: A comparative study of modeling software was carried out to select the perfect software, by defining and comparing the relevant criteria. Similarly, the different biomaterial options were examined and compared to select the one best suited to this project, mentioning the imaging modality used to determine the types of images used for our approach. Finally, the 3D printers used in this work were represented, highlighting their technical characteristics. Findings: A resin metatarsophalangeal implant prototype was created using 3D modeling and reconstruction software and tools. Interpretation: Reconstruction and 3D modeling techniques are revolutionizing implant creation, offering customized solutions for patients suffering from metatarsophalangeal joint disorders caused by a wide range of diseases. These results have significant implications for disability management and rehabilitation, encouraging further exploration and progress.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disorder but kidneys are not the only organs involved in this systemic disorder. Individuals with the condition may display additional manifestations beyond the renal system, involving liver, pancreas and brain in the con-text of cystic manifestations, while vascular system, gastrointestinal tract, bones, and cardiac valves in the context of non-cystic manifestations. Despite kidney involvement remain the main feature of the disease, thanks to new generation therapies, early diagnosis and better management of kidney related problems, a new wave of complications must be faced from clinicians who treated polycystic patients. Involvement of the liver represents the most prevalent extrarenal manifestation and grows importance in symptom burden and quality of life. Vascular abnormalities are a key factor for patients’ life expectancy and there’s still de-bate whether to screen or not to screen all patients. Arterial hypertension is often the earliest onset among polycystic patients leading to frequent cardiovascular complications. Although cardiac valvular abnormali-ties is a frequent complication, it rarely leads to relevant problems in the clinical history of polycystic pa-tients. One of the new relevant aspects concern bone disorders, that can exert a considerable influence on the clinical course of these patients. This review aims to provide the “state of art” among extrarenal mani-festation of ADPKD.

The Sarcoma Assessment Measure (SAM) was developed as a sarcoma-specific patient-reported outcome measure to be used in clinical practice. We have reported in detail how SAM has been developed in collaboration with patients and healthcare professionals. The aim of this paper is to report the preliminary validation of SAM. The 22-item SAM was administered alongside a validated quality of life questionnaire and measure of activities of daily living. Linear modelling was used to build a measure, which had predictive validity in comparison to more established outcome measures. Of the 762 patients who participated in the study, 44.1% identified as male, and participant age ranged from 13-82 years. Clinically, participants presented with a range of soft tissue (82.2%) and bone (21.8%) sarcomas. Our preliminary analysis indicates that SAM accounts for 35% of the Global quality of life scale and 18% of the TESS so psychometrically it overlaps with quality of life and activities of daily living, but also measures distinct concerns. This demonstrates that this measure picks up issues that are important to patients with sarcoma that are not reflected in other measures. We have established the preliminary validity of SAM and believe it has utility as a patient-reported outcome measure both as a research tool and for assessing the impact of symptoms and dysfunction related to sarcoma as part of clinical care. Further validation using a larger and more clinically diverse sample is now needed.

Chronological frameworks based on artefact typologies are essential for interpreting the archaeological record, but they inadvertently treat transitions between phases as abrupt events and disregard the temporality of transformation processes within and between individual phases. This study presents an absolute chronological investigation of a dynamic material culture from Early Iron Age urnfields in Denmark. The chronological framework of Early Iron Age in Southern Scandinavia is largely unconstrained by absolute dating, primarily due to it coinciding with the so-called ‘Hallstatt calibration plateau’ (c.750 to 400 cal BC), and it is difficult to correlate it with Central European chronologies due to a lack of imported artefacts. This study applies recent methodological advances in radiocarbon dating and Bayesian chronological modelling, specifically a statistical model for wood-age offsets in cremated bone and presents the first large-scale radiocarbon investigation of regional material culture from Early Iron Age in Southern Jutland, Denmark. Dated material is primarily cremated bone from 111 cremation burials from three urnfields. The study presents absolute date ranges for 16 types of pottery and 15 types of metalwork, which include most of the recognised metalwork types from the period. This provides new insights into gradual change in material culture, when certain artefact types were in production and primary use, how quickly types were taken up and later abandoned, and distinguishing periods of faster and slower change. The study also provides the first absolute chronology for the period, enabling correlation with chronologies from other regions. Urnfields were introduced at the Bronze-Iron Age transformation, which is often assumed to have occurred c.530-500 BC. We demonstrate that this transformation took place in the 7^th century BC, however, which revives the discussion of whether the final Bronze Age period VI should be interpreted as a transitional phase to the Iron Age.

The advent of zirconia ceramics with excellent mechanical, biomechanical and optical properties has made it an attractive metal-free substitute for titanium implants. Both animal and human studies have documented shortcomings with titanium implants. A review of the current literature on 3 iterations of zirconia implant designs has been challenging due to heterogeneous success data and limited follow-up. Zirconia implants hold promise for a new generation of dental implants, but technical developments are needed for design and material enhancements that will need to be validated by long-term rigorous studies.

Bone metastasis detection and quantification on bone scintigraphy is challenging and clinical important for treatment and patient’s life quality. To develop a CNN based diagnostic system for automated segmentation on bone metastasis regions is non-trivial, especially for a small dataset. A dataset in house comprising 100 breast cancer patients and 100 prostate cancer patients is utilized for this research. The Double U-Net model is adapted through the integration of background removal, adding negative samples, and transfer learning methods for bone metastasis detection. The performance is investigated via 10-fold cross-validation and computed in pixel-wise scale. The best model we achieved has precision of 63.08%, sensitivity of 70.82%, and F1-score of 66.72%. The developed system has the potential to provide pre-diagnostic reports for physicians in final decisions and the calculation of the bone scan index (BSI) with the combination with bone skeleton segmentation.

Parathyroid-hormone-related protein (PTHrP) is encoded by PTHLH gene which, by alternative promoter usage and splicing mechanisms, can give rise to at least three isoforms of 139, 141 and 173 amino acids with distinct C-terminals. PTHrP is subjected to different post-translational processing that generates smaller bioactive forms, comprising amino terminus, midregion (containing a nuclear/nucleolar targeting signal) and carboxy terminus peptides. Both the full-length protein and the discrete peptides are key controllers of viability, proliferation, differentiation and apoptosis in diverse normal and pathological biological systems via the reprogramming of gene expression and remodulation of PKA or PKC-mediated signalization mechanisms. The aim of this review is to pick up selected studies on PTHrP-associated signatures as revealed by molecular profiling assays, focusing on the available data about exemplary differentiating, differentiated or non-tumoral cell and tissue models. In particular, the data presented relate to adipose, bone, dental, cartilaginous and skin tissues, and also intestinal, renal, hepatic, pulmonary and pancreatic epithelia, with a focus on hepatic fibrosis-, pancreatitis- and diabetes-related changes as diseased states. Whether reported, the biochemical and/or physiological aspects associated with the specific molecular modulation of gene expression and signal transduction pathways in the target model systems under examination will be also briefly commented.

Calcium/calmodulin (CaM)-dependent protein kinase kinase 2 (CaMKK2) regulates bone remodeling through its effects on osteoblasts and osteoclasts. However, its role in osteocytes, the most abundant bone cell type, and the master regulator of bone remodeling, remains unknown. Here we report that the conditional deletion of CaMKK2 from osteocytes using Dentine matrix protein 1 (Dmp1)-8kb-Cre mice led to enhanced bone mass only in female mice owing to a suppression of osteoclasts. Conditioned media isolated from female CaMKK2-deficient osteocytes inhibited osteoclast formation and function in in vitro assays, indicating a role for osteocyte-secreted factors. Proteomics analysis revealed significantly higher levels of extracellular calpastatin, a specific inhibitor of calcium-dependent cysteine proteases calpains, in female CaMKK2 null osteocyte conditioned media, compared to media from female control osteocytes. Further, exogenously added non-cell permeable recombinant calpastatin domain I elicited a marked, dose-dependent inhibition of female wild-type osteoclasts and depletion of calpastatin from female CaMKK2-deficient osteocyte conditioned media reversed the inhibition of matrix resorption by osteoclasts. Our findings reveal a novel role for extracellular calpastatin in regulating female osteoclast function and unravel a novel CaMKK2-mediated paracrine mechanism of osteoclast regulation by female osteocytes.

Methacrylated silk (Sil-MA) is a chemically modified silk fibroin specifically designed to be crosslinkable under UV light. This allows the structuring of this material throught additive manufacturing techniques and then to easily prototype patient specific construct. In this study we used Sil-MA to produce single layer crosslinked structures that can be withdrawal and ejected recovering their shape after rehydration. A complete chemical and physical characterization of the material has been conducted. Additionally, we tested the material biocompatibility according to the International Standard Organization protocols (ISO 10993) ensuring the possibility to use it in future trials. The material was also tested to verify its ability to support the osteogenesis. Two different additive manufacturing techniques have been tested (a Digital Light Processing (DLP) UV projector and a pneumatic extrusion technique) to develop Sil-MA grid. Finally, we provide a proof-of-concept that the printed Sil-MA structures are injectable.

Interferon gamma (IFNg) is a pleiotropic cytokine that can potentially reprogramme the tumour microenvironment. However, the antitumour immunomodulatory properties of IFNg still need to be validated due to variable therapeutic outcomes in preclinical and clinical studies. We developed a replication-deficient Semliki Forest virus vector expressing IFNg (SFV/IFNg) and evaluated its immunomodulatory antitumour potential in vitro in a model of 3D spheroids and in vivo in immunocompetent 4T1 mouse breast cancer model. We demonstrated that SFV-derived IFN-g stimulated bone marrow macrophages to acquire the tumoricidal M1 phenotype in 3D nonattached conditions. Coculturing SFV/IFNg-infected 4T1 spheroids with BMDMs inhibited spheroid growth. In the orthotopic 4T1 mouse model, intratumoural administration of SFV/IFNg virus particles alone or in combination with the Pam3CSK4 TLR2/1 ligand led to significant inhibition of tumour growth compared to the administration of the control SFV/Luc virus particles. Analysis of the composition of intra-tumoural lymphoid cells isolated from tumours after SFV/IFNg treatment revealed an increase in CD4+ and CD8+ and a decrease in T-reg (CD4+/CD25+/FoxP3+) cell populations. Furthermore, a significant decrease in the populations of cells bearing myeloid cell markers CD11b, CD38 and CD206 was observed. In conclusion, the SFV/IFNg vector induces a therapeutic antitumour T-cell response and inhibits myeloid cell infiltration in treated tumours.

Cough peak flow (CPF) is a measurement to evaluate the risk of cough dysfunction and can be measured using various devices, such as spirometers. However, complex device setup and the face mask required to be firmly attached to the mouth impose burdens on both patients and their caregivers. Therefore, this study develops a novel cough strength evaluation method using cough sounds. This paper presents an exponential model to estimate CPF from the cough peak sound pressure level (CPSL). We investigated the relationship between cough sounds and cough flows and the effects of a measurement condition of cough sound, microphone type, and participant’s height and gender on CPF estimation accuracy. The results confirmed that the proposed model estimated CPF with a high accuracy. The absolute error between CPFs and estimated CPFs were significantly lower when the microphone distance from the participant’s mouth was within 30 cm than when the distance exceeded 30 cm. Analysis of the model parameters showed that the estimation accuracy was not affected by participant’s height or gender. These results indicate that the proposed model has the potential to improve the feasibility of measuring and assessing CPF.

Disrupted nutrient recycling is a significant problem for Europe, while phosphorus and nitrogen are wasted instead of being used for plant nutrition. Mineral phosphate is critical raw material, which contains environmentally hazardous elements such as cadmium and uranium. Therefore, phosphorus recovery from agricultural by-product streams is critically important key priority. Phosphorus recovery from food grade animal bone by-products have been applied researched since 2002 with objective driven evolution progress towards specialized pyrolysis processing technology and animal bone char product (ABC) developments in economical industrial scale. Different animal bone by-products tested under different conditions at 400 kg/h throughput capacity in the continuously operated 3R zero emission autothermal carbonization system. The different material core treatment temperatures (between >300°C and <850°C) were combined with different residence times under industrial productive processing conditions. It has been industrial demonstrated that material core treatment temperature <850°C with 20 minutes residence time is necessary to achieve high quality ABC with useful agronomic value. The output ABC product having concentrated >30% phosphorus pentoxide (P2O5) and specific quality innovative fertilizer for agronomical efficient organic and low input farming applications as functional organic fertilizer, soil improver, growing medium and/or fertilizing product blend with high mineral phosphate fertiliser replacement value.

Alzheimer’s disease (AD) causes dementia and memory loss in the elderly. Deposits of beta-amyloid peptide and hyperphosphorylated tau protein are present in AD’s brain. A filtrate of Helicobacter pylori’s culture was previously found to induce hyperphosphorylation of tau in vivo, suggesting that bacterial exotoxins could permeate the blood brain barrier and directly induce tau’s phosphorylation. H. pylori, which infects ~60% of the world population and causes gastritis and gastric cancer, produces a pro-inflammatory urease (HPU). Here the neurotoxic potential of HPU was investigated in cultured cells and in rats. SH-SY5Y neuroblastoma cells exposed HPU (50-300 nM) produced reactive oxygen species (ROS) and had an increased [Ca2+]i. HPU-treated BV-2 microglial cells produced ROS, cytokines IL-1β and TNF-α, expressed Iba1 and showed reduced viability, consistent with a neurotoxic effect of HPU. Rats received daily i.p. HPU (5 µg) for 7 days. Hyperphosphorylation of tau at Thr205, Ser199 and Ser396 sites was seen in hippocampal homogenates of treated rats, with no alterations in total tau or GSK-3b levels. HPU was not detected in the brain homogenates. Behavioral tests were performed to assess cognitive impairments. Our findings support previous data suggesting an association between infection by H. pylori and tauopathies such as AD, possibly mediated by its urease.

Background: Wideband tympanometry (WBT) has the potential to distinguish various mechanical middle ear and inner ear pathologies noninvasively. This study investigated the diagnostic value of WBT in the diagnosis of enlarged vestibular aqueduct (EVA). Methods: The absorbance and resonance frequency (RF) of patients with EVA (40 ears, 25 patients) and matched population controls (39 ears, 28 subjects) were compared, alongside receiver operating characteristic (ROC) analysis. Correlations between VA width and RF were also examined. Results: Patients with EVA had higher absorbance at low frequencies (226–917 Hz) and lower absorbance at high frequencies (2,520–4,896 Hz) compared to controls. The RF of the EVA group was significantly lower versus controls (751 [391–1,165] vs. 933 [628–1,346] Hz). ROC analysis revealed area under the curve values of 0.771 and 0.801 respectively, for absorbance and RF. RF had a sensitivity, specificity, positive predictive value, and negative predictive value of 74.4%, 82.5%, 76.7%, and 80.6%, respectively, for diagnosing EVA. In the EVA group, the VA midpoint width (r = −0.334) and VA petrous width (r = −0.402) both significantly correlated with RF. Conclusion: Our findings support the utility of WBT for diagnosing EVA, with RF as the optimal index used.

Pluripotent stem cells (PSCs) hold many potential research and clinical benefits due to their ability to differentiate into nearly every cell type in the body. They are often used as model systems for early stages of ontogenesis to better understand key developmental pathways, and for drug screening. However, in order to fully realise the potential of PSCs and their translational applications, a deeper understanding of developmental pathways, especially in humans, is required. Several signalling molecules play important roles during development and are required for proper differentiation of PSCs. The concentration and timing of signal activation is important, with perturbations resulting in improper development and/or pathology. Bone morphogenetic protein (BMP) is one such key signalling molecule involved in the specification and differentiation of various cell types and tissues in the human body including tooth and otic development. In this review, we describe the role of BMP signalling and its regulation, the consequences of BMP dysregulation in disease and differentiation, and how PSCs can be used to investigate the effects of BMP modulation during development, mainly focusing on otic development. Finally, we emphasise the unique role of BMP4 in otic specification and how refined knowledge in controlling its regulation could lead to the generation of more robust and reproducible human PSC-derived otic organoids for research and translational applications.

Using polymethylmethacrylate (PMMA) bone cement is widespread in orthopedic surgeries for implant fixation and as a carrier for antibiotic delivery to prevent and treat infections. This review comprehensively evaluates in vitro studies investigating the antibiotic elution profiles and mechanical properties of PMMA bone cement. We explore the kinetics of antibiotic release, factors influencing elution efficiency, and the impact of various antibiotics on the mechanical properties of PMMA composites. At the same time, we examine how the inclusion of antibiotics affects the mechanical integrity of PMMA, including parameters such as compressive strength, tensile strength, and fatigue resistance. Through a detailed analysis of these studies, this review aims to provide insights into optimizing PMMA bone cement formulations for enhanced therapeutic efficacy and structural performance.

Precise classification of sarcomas is crucial to drive optimal clinical management. In this prospective, multicenter, observational study within the Hellenic Group of Sarcoma and Rare Cancers (HGSRC) we assessed the effect of expert pathology review, coupled with the application of molecular diagnostics, on diagnosis and management of sarcoma patients. Newly diagnosed sarcoma patients were addressed by their physicians to one of the two sarcoma pathologists of HGSRC for histopathological diagnostic assessment. RNA next-generation sequencing was per-formed to all samples, using a platform targeting 86 sarcoma gene fusions. Additional molecular methods were performed on the opinion of the expert pathologist. Therefore, the expert pathologist provided a final diagnosis based on the histopathological findings and, when necessary on molecular tests. In total, 128 specimens from 122 patients were assessed. Among the 119 cases in which there was a preliminary diagnosis by a non-sarcoma pathologist, there were 37 modifications in diagnosis (31.1%) by the sarcoma pathologist, resulting in 17 (14.2%) modifications in management. Among the 110 cases in which molecular tests were performed, there were 29 modifications in diagnosis (26.4%) through the genomic results, resulting in 12 (10.9%) modifications in management. Our study confirms that expert pathology review is of utmost importance for the optimal sarcoma diagnosis and management and should be assisted by molecular methods in selected cases.

Chronic kidney disease (CKD) and cardiovascular disease (CVD) are highly prevalent conditions, each significantly contributing to the global burden of morbidity and mortality. CVD and CKD share a great number of common risk factor, such as hypertension, diabetes, obesity, and smoking among others. Their relationship extends beyond these factors, encompassing intricate interplay between the two systems. Within this complex network of pathophysiological processes, vitamin D has emerged as a potential linchpin, exerting influence over diverse physiological pathways implicated in both CKD and CVD. In recent years, scientific exploration has unveiled a close connection between these two prevalent conditions and vitamin D, a crucial hormone traditionally recognized for its role in bone health. This article aims to provide an extensive review of vitamin D's multifaceted and expanding actions concerning its involvement in CKD and CVD.

Aging, a natural process occurring in both normal and degenerative conditions, is closely associated with collagen degradation, impacting various bodily systems such as the skin. The continuous aging of the skin, influenced by both intrinsic and extrinsic factors, underscores the importance of collagen in dermatological and cosmetic contexts. Notably, collagen supplements enriched with essential amino acids like proline and glycine along with marine fish collagen have become popular for their safety and effectiveness in mitigating the aging process. To compile relevant literature on the anti-aging applications of marine collagen, a systematic search and analysis of peer-reviewed papers was conducted using reputable databases including PubMed, Cochrane Library, Web of Science, and Embase, covering publications from 1956 to 2023. From in vitro to in vivo experiments, the reviewed studies elucidate the anti-aging benefits of marine collagen, emphasizing its role in combating skin aging and promoting overall skin health. Many bioactive marine peptides exhibit diverse anti-aging properties, including free radical scavenging, apoptosis inhibition, lifespan extension in various organisms, and protective effects in aging humans. Furthermore, the peptide production of hyaluronic acid is discussed as a mechanism to fortify collagen and enhance skin moisture, contributing to the anti-aging effects of collagen supplementation. The integration of bio-tissue engineering in marine collagen applications is also explored, highlighting its proven utility in addressing skin and bone damage. Insights from this review illuminate the diverse biomedical applications of marine collagen alongside keystone molecular editing tools such as CRISPR, positioning it as a versatile resource in anti-aging interventions. However, limitations to the scope of its application exist. Thus, by delving into these nuanced considerations, this review contributes to a comprehensive understanding of the potential and challenges associated with marine collagen in the realm of anti-aging applications.

Enzalutamide is a second-generation androgen-receptor inhibitor that increases overall survival (OS) rates in patients with metastatic castration-resistant prostate cancer (mCRPC). This study evaluates the efficacy of circulating tumor cell (CTC) status as a prognostic biomarker after enzalutamide administration. A retrospective subgroup analysis and prognostic survey of 43 patients with mCRPC and bone metastases, treated in Juntendo University-affiliated hospitals from 2015–2022, were conducted. Patients were treated with 160 mg enzalutamide daily. CTC analyses on blood samples were performed regularly before and every three months post-treatment. Relationship between the patients' clinical factors and the OS rate was analyzed using the log-rank test; the median OS was 37 months. Patients with no detected CTCs at baseline showed significantly longer OS than those with CTCs at baseline. Furthermore, patients showing negative reversion of CTCs during enzalutamide treatment had significantly longer OS than patients with CTC-positive continuation. Two biomarkers–higher hemoglobin at baseline and achieving negative-reversion of CTCs–were significantly associated with prolonged OS. This study suggests that patients achieving CTC-negative reversion during treatment for mCRPC with bone metastases exhibit improved long-term OS. Chronological measurement of CTC status might be clinically useful in treatment of mCRPC.

Recently, nanotechnologies have become increasingly prominent in the field of bone tissue engineering (BTE), offering substantial potential to advance the field forward. These advancements manifest in two primary ways: the localized application of nanoengineered materials to enhance bone regeneration and their use as nano-vehicles for delivering bioactive compounds. Despite significant progress in the development of bone substitutes over the past few decades, it is worth noting that the quest to identify the optimal biomaterial for bone regeneration remains a subject of intense debate. Ever since its initial discovery, poly(lactic-co-glycolic acid) (PLGA) has found widespread use in BTE due to its favorable biocompatibility and customizable biodegradability. This review provides an overview of contemporary advancements in the development of bone regeneration materials using PLGA polymer. The review covers some of PLGA properties with a special focus on modifications of these properties towards bone regeneration. Furthermore, we delve into the techniques for synthesizing PLGA nanoparticles (NPs), the diverse forms in which these NPs can be fabricated, and the bioactive molecules that exhibit therapeutic potential for promoting bone regeneration. Additionally, we addressed some of the current concerns regarding the safety of PLGA NPs, and PLGA-based products available in the market. Finally, we briefly discussed some of the current challenges and proposed some strategies to functionally enhance the fabrication of PLGA NPs towards BTE. We envisage that the utilization of PLGA NP holds significant potential as a potent tool in advancing therapies for intractable bone diseases.

Chlorhexidine digluconate (CHX) has shown the ability to significantly reduce inflammation and marginal bone loss (MBL) at 1-year follow-up but limited data exists regarding its long-term efficacy in peri implant stability. The objective was to compare the long-term effects of a placebo gel (16 patients in Group A) or a 0.20% CHX gel (15 patients in Group B) used at each previous surgical and prosthetic stage. Follow-ups were conducted in 2022, investigating by biological, radiological, clinical, mechanical evaluation the long-term effects. Data were statistically analyzed. The research achieved a 96.7% implant success rate over five years, but 41.9% of patients didn't attend annual oral hygiene check-ups. The average MBL was 1.04 ± 0.39 mm, with no significant differences between the two groups. Notably, patients who attended regular periodontal check-ups experienced significantly less MBL than those who didn't (p &lt;0.05). At five years, the effects of CHX were reduced, with both groups showing moderate bone loss. The results suggest early disinfection could enhance both short and long-term outcomes. In fact, patient with initial minor MBL preserve this advantage also at 5 years of follow-up. Additionally, the data underscore the importance of annual check-ups in early detection and management of biological and mechanical complications.

The objective of this study is to clarify the effect of restoring the lowered masticatory muscle functional pressure and correcting the imbalance of bilateral masticatory muscle functional pressure on jawbone growth during growth and development with quantitative evaluation of the changes in micro/nanostructural characteristics of entheses. Male Wistar rats aged 4 weeks were divided into an experimental group injected with a botulinum toxin serotype A (BoNT/A) formulation to reduce muscle function (BTX group) and a control group (CTRL group). They were euthanized after 6, 8, 10, 12, and 16 weeks after measuring the difference between the midline of the upper and lower incisors. The mandibles were harvested for histological examination, second harmonic generation imaging, and quantitative evaluation of biological apatite (BAp) crystal alignment. The midline difference decreased with age in weeks. In rats from 6 weeks after BoNT/A administration to 12 weeks after administration, collagen fibre bundle diameter was significantly smaller in the BTX group; the difference between the two groups decreased with increasing age. BAp crystal alignment was significantly different on the X-axis and the Y-axis on the BTX group from 6 weeks after BoNT/A administration to 10 weeks after administration. Asymmetry of mandibular bone formation caused by load imbalance during growth could be corrected by adjustment of the function of the masseter muscle on either side.

Quantification of bone loss for follow-up comparisons has not been routinely performed in patients with parietal thinning so far. This study compares different methodological approaches including both 2- and 3-dimensional methods in computerized tomographies of a single patient. The 2-dimensional method provides accurate measurements of bone thickness, while the 3-dimensional method allows for a more comprehensive view of the bone's structure, including parameters like shape, size, and thickness. The techniques provided valuable data for the treating physician and suggest a possible effect of corticosteroids in this individual patient. The study concludes that 3-dimensional reconstruction of computerized tomographies with subsequent 2-dimensional analyses appears justified for routine radiological practice to increase clinical awareness of the size of the parietal bone defects and allow for quantification of bone loss during long-term follow-ups. Further validation of the proposed analytical approaches is warranted in larger studies to investigate patterns of bone thinning across the skull and changes in bone volumes over time, with specialized software to be approved for such analyses.

Malnutrition is one of major factors of bone and cartilage disorders. Pacific cod (Gadus macrocephalus) processing waste is a cheap and highly promising source of bioactive substances, including collagen-derived peptides and amino acids, for bone and cartilage structure stabilization. Addition of these substances to a functional drink is one of the ways to achieve their fast intestinal absorption. Collagen hydrolysate was obtained via enzymatic hydrolysis, ultrafiltration, freeze-drying, and grinding to powder. The lyophilized hydrolysate was a light gray powder with high protein content (>90%), including collagen (about 85% of total protein) and a complete set of essential and non-essential amino acids. The hydrolysate was applicable as a protein food supply or a structure-forming food component due to presence of collagen fiber fragments. An isotonic fitness drink (osmolality 298.1 ± 2.1 mOsm/L) containing the hydrolysate and vitamin C as a cofactor in collagen biosynthesis was prepared. Addition of the hydrolysate did not adversely affect its organoleptic parameters. Production of such functional foods and drinks is one of the beneficial ways of fish processing waste utilization.

The musculoskeletal system consisting of bones and muscles have been recognized as endocrine organs secreting hormones that are involved in regulating metabolic and inflammatory pathways. Obesity and type 2 diabetes (T2D) are associated with several musculoskeletal system complications. We hypothesized that an interaction exists between adipomyokines namely, irisin and METRNL, and various bone markers in individuals with obesity and T2D. A total of 228 individuals were enrolled in this study, including 124 non-diabetic and 104 T2D. A Multiplex assay was used to assess the level of various bone markers namely Osteoactivin, Syndecan, osteoprotegerin (OPG) and osteonectin/SPARC. Our data shows elevated levels of Osteoactivin, Syndecan, OPG and SPARC in T2D as compared to non-T2D individuals (p ≤ 0.05). Using Spearman’s correlation, irisin was positively correlated only with Osteoactivin and OPG (p &lt; 0.05). Similarly, a positive association was observed between METRNL and Osteoactivin (p &lt; 0.05). The strong positive association shown in our study between irisin, METRNL and various bone markers emphasises the strong interaction between these organs. This suggests that a dysregulation in the functional interaction between these molecules could play a possible role in the development of bone and muscle related complications that are associated with obesity and T2D.

Achievement of solid fusion of the lumbosacral junction (L5-S1 level) is an important factor in adult spinal deformity (ASD) surgery. The purpose of this study is to explore the effectiveness and feasibility of injectable rhBMP-2 (a combination of Eschericia coli-derived rhBMP-2 and hydrogel type β-TCP carrier; NOVOSIS Inject) as a bone substitute for the fusion of lumbosacral junction. 20 patients (average age 69.1 years) diagnosed with ASD with sagittal imbalance who underwent surgical treatment including anterior lumbar interbody fusion (ALIF) in the L5-S1 level were evaluated. Injectable rhBMP-2 was applied in L5-S1 ALIF and followed-up for 1-year. Solid fusion rates and changes of clinical outcomes (Oswestry Disability Index [ODI], Visual Analog Scale [VAS] of back and leg) were measured and analyzed at 6 and 12 months after surgery. All postoperative adverse events were evaluated about the association with injectable rhBMP-2. Fusion rates were 68.4% and 100% at 6 and 12 months after surgery. Compared to baseline, ODI were improved to 45.8% and 63.7%, VAS(back) were improved to 69.2% and 72.8%, and VAS(leg) were improved to 49.2% and 64.8% at 6 and 12 months after surgery (p&lt;0.001, respectively). There were no adverse events associated with injectable rhBMP-2. Thus, injectable rhBMP-2 may be a suitable choice of a bone graft substitute when achieving solid interbody fusion in the lumbosacral junction.