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Life Science Alliance Aug 2024Dynamic rearrangements of the F-actin cytoskeleton are a hallmark of tumor metastasis. Thus, proteins that govern F-actin rearrangements are of major interest for...
Dynamic rearrangements of the F-actin cytoskeleton are a hallmark of tumor metastasis. Thus, proteins that govern F-actin rearrangements are of major interest for understanding metastasis and potential therapies. We hypothesized that the unique F-actin binding and bundling protein SWAP-70 contributes importantly to metastasis. Orthotopic, ectopic, and short-term tail vein injection mouse breast and lung cancer models revealed a strong positive dependence of lung and bone metastasis on SWAP-70. Breast cancer cell growth, migration, adhesion, and invasion assays revealed SWAP-70's key role in these metastasis-related cell features and the requirement for SWAP-70 to bind F-actin. Biophysical experiments showed that tumor cell stiffness and deformability are negatively modulated by SWAP-70. Together, we present a hitherto undescribed, unique F-actin modulator as an important contributor to tumor metastasis.
Topics: Animals; Actins; Mice; Humans; Female; Cell Line, Tumor; Neoplasm Metastasis; Breast Neoplasms; Lung Neoplasms; Microfilament Proteins; Cell Movement; Actin Cytoskeleton; Cell Proliferation; Cell Adhesion; Protein Binding
PubMed: 38760173
DOI: 10.26508/lsa.202302307 -
BMJ Open May 2024The Bone And MicroBiOme Onset (BAMBOO) study is an ongoing prospective observational cohort study conducted in Tianjin, China, aiming to determine age-appropriate... (Observational Study)
Observational Study
PURPOSE
The Bone And MicroBiOme Onset (BAMBOO) study is an ongoing prospective observational cohort study conducted in Tianjin, China, aiming to determine age-appropriate trajectories for microbiome maturation and bone development and to identify the influence of dietary factors in the process.
PARTICIPANTS
The recruitment started in September 2021 and was completed in February 2023. A total of 1380 subjects were recruited, 690 at birth (group 1) and 690 at 6 months of age (group 2). Groups 1 and 2 will be followed up for 12 months and 36 months, respectively.
FINDINGS TO DATE
The age of the mothers was 31.1±3.7 (mean±SD), and the birth weight of infants was 3.3±0.5 kg with an incidence of caesarean section 50.4%. Food diary information of the first 100 subjects showed that 64 food items were introduced by 6 months. A pilot microbiome analysis revealed that at the species level, bacterial communities were composed of mostly and , which were consistent with that of previous reports. Feasibility assessments of breast milk vitamin D and human milk oligosaccharides were validated through certified reference measurements. The early data assessment showed a high reliability of the data generated from this study.
FUTURE PLANS
Data collection will be completed in August 2025. Four stage-statistical analyses will be performed as the cohort reaches certain age thresholds before the final report. Analysis of BAMBOO data will be used to develop age-appropriate trajectories for microbiome maturation and bone development for children aged 0-3 years and investigate the contribution of dietary factors in the process.
TRIAL REGISTRATION NUMBER
ChiCTR2100049972.
Topics: Humans; China; Infant; Female; Prospective Studies; Infant, Newborn; Male; Bone Development; Milk, Human; Gastrointestinal Microbiome; Adult; Child, Preschool; Vitamin D; Diet; Cohort Studies
PubMed: 38760054
DOI: 10.1136/bmjopen-2023-075417 -
European Journal of Dentistry May 2024Osteoporosis is a disease characterized by disruption of the bone microarchitecture. It is observed in both sexes, but to a greater extent in women. It affects the whole...
Osteoporosis is a disease characterized by disruption of the bone microarchitecture. It is observed in both sexes, but to a greater extent in women. It affects the whole body, including the jaws. The main indicator of the presence of osteoporosis accepted by the World Health Organization is bone mineral density. The aim of this article is to find data on the influence of osteoporosis on apical periodontitis, to investigate how the intake of osteoporosis drugs affects apical periodontitis, and to establish various data that may be of benefit to the dental practitioner when treating patients with osteoporosis and apical periodontitis. Open-access publications are included. The presence of osteoporosis is important to the dentist. Apical periodontitis in these patients has a faster progression. They are characterized by inflammation and destruction of the tissues located around the tooth root. Osteoporosis has a destructive effect on bone tissue through different mechanisms: nuclear factor-κβ ligand and NLRP3/Caspase-1/IL-1β cascade. It is also associated with low estrogen levels. Various medications such as corticosteroids, bisphosphonates (alendronate, zoledronate (Zoledronic acid), calcitonin, raloxifene, and strontium used to treat osteoporosis can affect the course of apical periodontitis. When treating patients with periapical lesions, the dentist must take a proper medical history and general medical history. In cases of osteoporosis or taking bisphosphonates and other medications, consideration should be given to whether consultation with a specialist is necessary, what treatment approach would be most appropriate, and what the prognosis will be. Chronic diseases affect both the general state of the body and dental health. It has been found that in patients with osteoporosis, inflammation of the apical periodontium develops with faster bone resorption. Before starting dental treatment, it is important to specify the etiology of osteoporosis, the bone density of each patient, as well as the medications they are taking.
PubMed: 38759999
DOI: 10.1055/s-0044-1785533 -
European Journal of Dentistry May 2024This article reappraises the accuracy and factors associated with the detection of the cementoenamel junction (CEJ) using the tactile method.
OBJECTIVES
This article reappraises the accuracy and factors associated with the detection of the cementoenamel junction (CEJ) using the tactile method.
MATERIALS AND METHODS
A total of 111 tooth sites of 7 patients scheduled for flap surgery were selected for the study. The CEJ was detected in a blind manner using the conventional tactile method with a standard periodontal probe by a single, trained examiner. A custom-made stent was prepared to standardize the measurements and the distance from a fixed reference point on the stent to the CEJ was measured before (apparent CEJ) and after (real CEJ) opening a gingival flap. To evaluate the effect of local anesthesia (LA) on the measurement error, assessment with and without LA given prior to the measurement was also evaluated. The bone crest-CEJ distance at each site was also recorded in all sites.
STATISTICAL ANALYSIS
The measurement error of apparent versus real distance, if any, was compared using Cohen's weighted kappa coefficient (WKC) (± 1 mm).
RESULTS
A weak WKC (WKC = 0.539) was found between the apparent and real CEJ distance. Higher WKCs were noted at posterior and proximal sites than the anterior and buccal/lingual sites, respectively (0.840 and 0.545 vs. 0.475 and 0.488). A higher confluence of the agreements was noted when CEJ distance was measured in anesthetized sites (WKC = 0.703). Sites without bone loss showed more coronal deviation of CEJ detection, as opposed to apical deviation seen at sites with bone loss.
CONCLUSION
The conventional CEJ detection using the tactile method was relatively imprecise depending on the anatomical location of the tooth and the bone loss at the site of measurement. However, the detection accuracy improved when the sites were anesthetized. In clinical terms, our data, reported here for the first time imply that, in the absence of visual cues, posterior tooth site measurements of periodontal attachment loss were more reliable in comparison to the other sites. The bone crest level also impacted the measurement deviation to some extent, implying that, possible overestimate of clinical attachment loss may occur at sites without bone loss.
PubMed: 38759998
DOI: 10.1055/s-0044-1786865 -
PloS One 2024The global number of people with diabetes is estimated to reach 643 million by 2030 of whom 19-34% will present with diabetic foot ulceration. Insoles which offload...
The effect of calcaneus and metatarsal head offloading insoles on healthy subjects' gait kinematics, kinetics, asymmetry, and the implications for plantar pressure management: A pilot study.
BACKGROUND
The global number of people with diabetes is estimated to reach 643 million by 2030 of whom 19-34% will present with diabetic foot ulceration. Insoles which offload high-risk ulcerative regions on the foot, by removing insole material, are the main contemporary conservative treatment to maintain mobility and reduce the likelihood of ulceration. However, their effect on the rest of the foot and relationship with key gait propulsive and balance kinematics and kinetics has not been well researched.
PURPOSE
The aim of this study is to investigate the effect of offloading insoles on gait kinematics, kinetics, and plantar pressure throughout the gait cycle.
METHODS
10 healthy subjects were recruited for this experiment to walk in 6 different insole conditions. Subjects walked at three speeds on a treadmill for 10 minutes while both plantar pressure and gait kinematics, kinetics were measured using an in-shoe pressure measurement insole and motion capture system/force plates. Average peak plantar pressure, pressure time integrals, gait kinematics and centre of force were analysed.
RESULTS
The average peak plantar pressure and pressure time integrals changed by -30% (-68% to 3%) and -36% (-75% to -1%) at the region of interest when applying offloading insoles, whereas the heel strike and toe-off velocity changed by 15% (-6% to 32%) and 12% (-2% to 19%) whilst walking at three speeds.
CONCLUSION
The study found that offloading insoles reduced plantar pressure in the region of interest with loading transferred to surrounding regions increasing the risk of higher pressure time integrals in these locations. Heel strike and toe-off velocities were increased under certain configurations of offloading insoles which may explain the higher plantar pressures and supporting the potential of integrating kinematic gait variables within a more optimal therapeutic approach. However, there was inter-individual variability in responses for all variables measured supporting individualised prescription.
Topics: Humans; Gait; Biomechanical Phenomena; Pilot Projects; Male; Pressure; Female; Adult; Foot Orthoses; Calcaneus; Healthy Volunteers; Shoes; Kinetics; Walking; Metatarsus; Foot
PubMed: 38758937
DOI: 10.1371/journal.pone.0303826 -
PloS One 2024The implantation of uncemented prostheses requires the application of sufficient forces to achieve a press-fit of the implant in the bone. Excessive forces have to be...
The implantation of uncemented prostheses requires the application of sufficient forces to achieve a press-fit of the implant in the bone. Excessive forces have to be omitted to limit bone damage. Force measurements along the force transmission path between mallet and implant are frequently used to investigate this trade-off. Placing a load cell at a position of interest (PoI), which might be the implant bone interface or the head taper junction, is technically challenging or even impossible so that nearby positions are chosen. Thus, a certain inertia and stiffness remain between the PoI and the sensor, and consequently the measured dynamic forces differ from those at the PoI. This experimental and numerical study aimed to investigate the amount of force reduction along the transmission path while joining femoral heads to stem tapers. Forces were measured in vitro at the tip of the mallet, directly above the polymer tip of the impactor and below the stem taper. Springs and masses were used to represent the responding tissue of a patient. A semi-empirical numerical model of the force transmission path was developed and validated in order to simulate a larger range of responding tissue properties than experimentally possible and to investigate the influence of different surgical instruments. A distinct attenuation was observed since the peak forces at the impactor reached 35% of the applied peak forces and 21% at the stem taper, respectively. The force curves were replicated with a median root mean square error of 3.8% of the corresponding mallet blow for the impactor and 3.6% for the stem. The force measurement position and the used surgical instruments have a strong influence on the measured forces. Consequently, the exact measurement conditions with regard to sensor positioning and used surgical instruments have to be specified and hence only studies with similar setups should be compared to avoid misestimation of the forces at the PoI. The proposed dynamic numerical model is a useful tool to calculate the impact of the chosen or changed mechanical parameters prior to executing experiments and also to extrapolate the effect of changing the applied forces to the resulting forces at the PoI.
Topics: Humans; Hip Prosthesis; Stress, Mechanical; Biomechanical Phenomena; Femur Head; Models, Theoretical
PubMed: 38758920
DOI: 10.1371/journal.pone.0303682 -
Medicine May 2024Soft tissue sarcoma (STS) incidence, progression, and metastasis are tightly linked to the tumor microenvironment (TME). The modification patterns mediated by...
Soft tissue sarcoma (STS) incidence, progression, and metastasis are tightly linked to the tumor microenvironment (TME). The modification patterns mediated by pyroptosis-related genes (PRGs) in STS are unknown regarding the immune cell infiltration landscape of TME, immunotherapy effect, and prognostic value. First, we downloaded STS samples from the Cancer Genome Atlas (TCGA) and gene-expression omnibus (GEO) databases. Based on 52 PRGs, 2 pyroptosis modification patterns were analyzed, and the associations of pyroptosis modification patterns with immune cell infiltration in the TME were elucidated systematically. To quantify PRG modification patterns in STS patients, we generated a pyroptosis scoring system using principal component analysis (PCA). We identified 2 distinct pyroptosis modification patterns in STS. Compared to PRG cluster A, the prognosis of cluster B was better. These 2 pyroptosis modification patterns corresponded to different characteristics of immune cell infiltration in the TME and biological behaviors. In the pyroptosis scoring system, a high pyroptosis score was connected to higher immune cell infiltration, stronger immune surveillance, immune-killing effects on tumor cells, and better clinical benefits. The results from 3 anti-PD1/PD-L1-treated immune cohorts demonstrated that higher pyroptosis scores are also closely connected to better immunotherapy results. We demonstrated that pyroptosis modification is essential to the STS microenvironment. Moreover, the pyroptosis score is a reliable and independent prognostic factor in STS patients, enabling a richer understanding of the STS microenvironment and the screening of immunotherapy candidates, predicting the immunotherapeutic effects for individual STS patients, and guiding the use of chemotherapy drugs.
Topics: Humans; Tumor Microenvironment; Pyroptosis; Sarcoma; Immunotherapy; Prognosis; Gene Expression Regulation, Neoplastic
PubMed: 38758862
DOI: 10.1097/MD.0000000000038173 -
Medicine May 2024The management of comminuted quadrilateral fractures remains challenging, and treatment options are constantly evolving. The purpose of the present study was to examine... (Observational Study)
Observational Study Comparative Study
Comparison of 2 different fixation techniques of comminuted acetabular quadrilateral surface fractures using square bracket-shaped tubular plate or interfragmentary screws in addition to supra/infrapectineal plate fixation: An observational study.
The management of comminuted quadrilateral fractures remains challenging, and treatment options are constantly evolving. The purpose of the present study was to examine the outcomes of 2 different fixation techniques in the management of comminuted quadrilateral fractures. Twenty-two patients with comminuted quadrilateral acetabular fractures were surgically treated with interfragmentary lag screw (group 1) and square bracket-shaped tubular (SBST) plate technique (group 2), in addition to suprapectineal and infrapectineal pelvic reconstruction plate fixation between January 2016 and July 2019 at our clinic. 2 years follow-up control data of each group were compared in terms of radiological and functional results, and complications. According to the functional score comparison, the mean Merle d'Aubigne Postel scoring system (MAP) score was 15.2/15.6 (P = .632), and the mean Harris hip scoring (HHS) system score was 74.65/77.3 (P = .664) in groups 1 and 2, respectively. Radiological comparison was performed according to matta radiological criteria (MRC), and 2 excellent, 6 good, 2 poor, 4 excellent, 4 good, and 4 poor radiological results were observed in groups 1 and 2, respectively. intraarticular screw penetration was detected in 3 patients in group 1, while there was no articular implant penetration in group 2 (P = .001). We believe that satisfactory results can be obtained with the SBST plate technique, offering functional and clinical outcomes that are similar to those of the interfragmentary screw technique. The SBST plate technique is superior in terms of avoiding intraarticular screw penetration and related revision surgery.
Topics: Humans; Acetabulum; Bone Plates; Female; Male; Fracture Fixation, Internal; Bone Screws; Middle Aged; Adult; Fractures, Comminuted; Treatment Outcome; Retrospective Studies; Fractures, Bone
PubMed: 38758854
DOI: 10.1097/MD.0000000000038252 -
Medicine May 2024Gout is a chronic disease characterized by deposition of monosodium urate crystals. Tophi develop in some individuals with untreated or uncontrolled gout, which leads to...
INTRODUCTION
Gout is a chronic disease characterized by deposition of monosodium urate crystals. Tophi develop in some individuals with untreated or uncontrolled gout, which leads to ulcerations, cosmetic problems, mechanical obstruction of joint movement, joint damage and musculoskeletal disability. Currently, the treatment of gouty tophi is controversial and challenging. Both surgical and internal medical treatments have limitations and require further exploration in clinical practice.
PATIENT CONCERNS
In Case 1, we treated a patient with severe infection of diabetic foot ulcers with concomitant multiple gouty tophi in the same limb. A systematic management strategy was formulated to close the wound and save the limb. The ulcers healed successfully after half a year. In Case 2, a giant gouty tophi located in the first metatarsophalangeal joint of the left foot was removed by surgical treatment and vancomycin-loaded bone cement implantation. In Case 3, we present a case of gouty tophi that was resolved by standardized systemic medical management.
DIAGNOSIS
Three patients were all diagnosed with gout accompanied by gouty deposition, although there were other different comorbidities.
INTERVENTIONS
In case 1, we used debridement to gradually remove gouty tophi. In case 2, the giant gouty tophi was removed by surgical operation. In case 3, the gouty tophi disappeared after standardized treatment with medicine, diet and lifestyle management.
OUTCOMES
Three patients underwent different treatment therapies to remove gouty tophi based on their specific conditions.
LESSONS
We explored effective interventions for tophi in gout by surgical or other interventions in combination with pharmacotherapy.
Topics: Humans; Male; Gout; Aged; Limb Salvage; Middle Aged; Debridement; Metatarsophalangeal Joint; Anti-Bacterial Agents; Female; Vancomycin; Diabetic Foot
PubMed: 38758848
DOI: 10.1097/MD.0000000000038137 -
Medicine May 2024The aim of this study was to compare the biomechanical performance of pedicle screw construction and locking compression plate fixation in posterior pelvic ring injuries...
BACKGROUND
The aim of this study was to compare the biomechanical performance of pedicle screw construction and locking compression plate fixation in posterior pelvic ring injuries analyzed by finite element method.
METHODS
A 3-dimensional finite element model of the spine-pelvis-femur complex with ligaments was reconstructed from computed tomography images. An unstable posterior pelvic ring injury was created, which was fixed with a pedicle screw construction or locking compression plate. A follower load of 400 N was applied to the upper surface of the vertebrae to simulate the upper body weight, while the ends of the proximal femurs were fixed. The construct stiffness, the maximum vertical displacement, the maximum posterior displacement, the maximum right displacement, and the overall maximum displacement of the sacrum, and stress distributions of the implants and pelvises were assessed.
RESULTS
The construct stiffness of the pedicle screw model (435.14 N/mm) was 2 times that of the plate model (217.01 N/mm). The maximum vertical displacement, the maximum posterior displacement, the maximum right displacement, and the overall maximum displacement of the sacrum in the pedicle screw model were smaller than those in the plate model (0.919, 1.299, 0.259, and 1.413 mm in the pedicle screw model, and 1.843, 2.300, 1.053, and 2.895 mm in the plate model, respectively). The peak stresses of the implant and pelvis in the pedicle screw model decreased by 80.4% and 25% when compared with the plate model (44.57 and 34.48 MPa in the pedicle screw model, and 227.47 and 45.97 MPa in the plate model, respectively).
CONCLUSION
The study suggested that the pedicle screw construction could provide better fixation stability than the locking compression plate and serves as the recommended fixation method for the treatment of posterior pelvic ring injuries.
Topics: Bone Plates; Humans; Finite Element Analysis; Pelvic Bones; Pedicle Screws; Biomechanical Phenomena; Fracture Fixation, Internal; Tomography, X-Ray Computed; Fractures, Bone
PubMed: 38758846
DOI: 10.1097/MD.0000000000038258