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Fracture Risk of Sodium-Glucose Cotransporter-2 Inhibitors in Chronic Kidney Disease.

Clin J Am Soc Nephrol 2022 May 26. Epub 2022 May 26.

Institute for Clinical and Evaluative Sciences (ICES), London, Ontario, Canada.

Background And Objectives: Sodium-glucose cotransporter-2 (SGLT2) inhibitors have been associated with a higher risk of skeletal fractures in some randomized, placebo-controlled trials. Secondary hyperparathyroidism and increased bone turnover (also common in CKD) may contribute to the observed fracture risk. We aimed to determine if SGLT2 inhibitor use associates with a higher risk of fractures compared with dipeptidyl peptidase-4 (DPP-4) inhibitors, which have no known association with fracture risk. Read More

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Non-tuberculous mycobacterial thoracic osteomyelitis in an immunocompetent host: a rare presentation of .

BMJ Case Rep 2022 May 26;15(5). Epub 2022 May 26.

Department of Infectious Diseases, The University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA.

An immunocompetent man in his 40s presented with 3 months of mid-thoracic back pain which progressed to include progressive paraesthesias and lower extremity weakness. Investigations revealed thoracic spine osteomyelitis with signs of cord compression. He underwent neurosurgical intervention, including laminectomy, spinal cord decompression and partial resection of an epidural mass. Read More

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The Effects of a Physical Education Intervention Program on the Bone Properties of Second- and Third-Grade Pupils: A Cluster Randomized Controlled Trial.

J Phys Act Health 2022 May 26:1-11. Epub 2022 May 26.

School of Education, The Academic College at Wingate, Netanya,Israel.

Background: Many young children do not participate in sufficient physical activity for promoting optimal bone growth. The objective of this study was to investigate the effect of young children who participated in a school-based intervention program on bone properties. The program included structured physical activity, with a focus on the application of mechanical loads on the upper and lower limbs. Read More

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MicroRNA-26b regulates BMSC osteogenic differentiation of TMJ subchondral bone through β-catenin in osteoarthritis.

Bone 2022 May 23:116448. Epub 2022 May 23.

Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research & Clinical Research Center of Shaanxi Province for Dental and Maxillofacial Diseases, Department of Orthodontics, Stomatological Hospital, Xi'an Jiaotong University, Xi'an, PR China. Electronic address:

Temporomandibular joint osteoarthritis (TMJ-OA) is a degenerative disease of the joint. The early manifestations of TMJ-OA are abnormal remodeling of condylar subchondral bone. In bone tissue, bone marrow mesenchymal stem cells (BMSCs) and osteoblasts play important roles in the differentiation and maturation of most hematopoietic cells. Read More

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Hormone sensitive lipase ablation promotes bone regeneration.

Biochim Biophys Acta Mol Basis Dis 2022 May 23:166449. Epub 2022 May 23.

Division of Endocrinology, Gerontology, and Metabolism, Stanford University, Stanford, CA, USA; Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA; Stanford Diabetes Research Center, Stanford, CA, USA. Electronic address:

There is an inverse relationship between the differentiation of mesenchymal stem cells (MSCs) along either an adipocyte or osteoblast lineage, with lineage differentiation known to be mediated by transcription factors PPARγ and Runx2, respectively. Endogenous ligands for PPARγ are generated during the hydrolysis of triacylglycerols to fatty acids through the actions of lipases such as hormone sensitive lipase (HSL). To examine whether reduced production of endogenous PPARγ ligands would influence bone regeneration, we examined the effects of HSL knockout on fracture repair in mice using a tibial mono-cortical defect as a model. Read More

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Loss of CD226 protects apolipoprotein E-deficient mice from diet-induced atherosclerosis.

Biochim Biophys Acta Mol Basis Dis 2022 May 23:166452. Epub 2022 May 23.

Institute of Medical Research, Northwestern Polytechnical University, 127 West Youyi Road, Xi'an, Shaanxi 710072, China; Department of Immunology, Fourth Military Medical University, 169 West Changle Road, Xi'an, Shaanxi 710032, China. Electronic address:

CD226 is a costimulatory molecule that regulates immune cell functions in T cells, natural killer cells, and macrophages. Because macrophage-derived foam cell formation is a crucial factor contributing to the development of atherosclerosis, we aimed to evaluate the potential roles of CD226 in the pathogenesis of atherosclerosis. The effects of CD226 on atherosclerosis were investigated in CD226 and apolipoprotein E double-knockout (CD226 ApoE) mice fed with a high-cholesterol atherogenic diet. Read More

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Mobilization-based chemotherapy-free engraftment of gene-edited human hematopoietic stem cells.

Cell 2022 May 18. Epub 2022 May 18.

San Raffaele Telethon Institute for Gene Therapy, IRCCS San Raffaele Scientific Institute, Milan 20132, Italy; Vita-Salute San Raffaele University, Milan 20132, Italy. Electronic address:

Hematopoietic stem/progenitor cell gene therapy (HSPC-GT) is proving successful to treat several genetic diseases. HSPCs are mobilized, harvested, genetically corrected ex vivo, and infused, after the administration of toxic myeloablative conditioning to deplete the bone marrow (BM) for the modified cells. We show that mobilizers create an opportunity for seamless engraftment of exogenous cells, which effectively outcompete those mobilized, to repopulate the depleted BM. Read More

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Long-term mechanical loading is required for the formation of 3D bioprinted functional osteocyte bone organoids.

Biofabrication 2022 May 26. Epub 2022 May 26.

ETH Zurich Department of Health Sciences and Technology, Leopold-Ruzicka-Weg 4, Zurich, Zürich, 8093, SWITZERLAND.

Mechanical loading has been shown to influence various osteogenic responses of bone-derived cells and bone formation in vivo. However, the influence of mechanical stimulation on the formation of bone organoid in vitro is not clearly understood. Here, 3D bioprinted human mesenchymal stem cells (hMSCs)-laden graphene oxide composite scaffolds were cultured in a novel cyclic-loading bioreactors for up to 56 days. Read More

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Engineering of cardiac microtissues by microfluidic cell encapsulation in thermoshrinking non-crosslinked PNIPAAm gels.

Biofabrication 2022 May 26. Epub 2022 May 26.

University Hospital Cologne, Robert Koch Str. 39, Koln, Nordrhein-Westfalen, 50931, GERMANY.

Multicellular agglomerates in form of irregularly shaped or spherical clusters can recapitulate cell-cell interactions and are referred to as microtissues. Microtissues gain increasing attention in several fields including cardiovascular research. Cardiac microtissues are evolving as excellent model systems for drug testing in vitro (organ-on-a-chip), are used as tissue bricks in 3D printing processes and pave the way for improved cell replacement therapies in vivo. Read More

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A biodegradable 3D woven magnesium-based scaffold for orthopedic implants.

Biofabrication 2022 May 26. Epub 2022 May 26.

Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD 21218, USA, Baltimore, Maryland, 21218-2625, UNITED STATES.

Porous Magnesium (Mg) is a promising biodegradable scaffold for treating critical-size bone defects, and as an essential element for human metabolism, Mg has shown sufficient biocompatibility. Its elastic moduli and yield strengths are closer to those of cortical bone than common, inert metallic implants, effectively reducing stress concentrations around host tissue as well as stress shielding. More importantly, Mg can degrade and be absorbed in the human body in a safe and controlled manner, thereby reducing the need for second surgeries to remove implants. Read More

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Fluoride exposure induces lysosomal dysfunction unveiled by an integrated transcriptomic and metabolomic study in bone marrow mesenchymal stem cells.

Ecotoxicol Environ Saf 2022 May 23;239:113672. Epub 2022 May 23.

Department of Occupational Health (Key Laboratory of Electromagnetic Radiation Protection, Ministry of Education), Third Military Medical University, Chongqing, China. Electronic address:

Fluoride has received much attention for its predominant bone toxicity in the human body. However, the toxic mechanism of bone injury caused by fluoride exposure remains largely unclear. Bone marrow mesenchymal stem cells (BMSCs) are widely used as model cells for evaluating bone toxicity after environmental toxicant exposure. Read More

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Polydopamine and hyaluronic acid immobilisation on vancomycin-loaded titanium nanotube for prophylaxis of implant infections.

Colloids Surf B Biointerfaces 2022 May 18;216:112582. Epub 2022 May 18.

Department of Orthopedics, Changhai hospital Affiliated to the Navy Military Medical University, Shanghai, China. Electronic address:

Titanium nanotube (Ti-NT) is an attractive substrate for local drug delivery, however, it is difficult to control the burst drug release and achieve sustained release from these nanotubes. In the present study, we investigated the feasibility of controlling drug release from Ti-NT within polydopamine and hyaluronic acid films, to achieve antibacterial activity and osteogenic promotion. Vancomycin was loaded into the Ti-NT by lyophilisation. Read More

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Impact of oxygen-calcium-generating and bone morphogenetic protein-2 nanoparticles on survival and differentiation of bone marrow-derived mesenchymal stem cells in the 3D bio-printed scaffold.

Colloids Surf B Biointerfaces 2022 May 19;216:112581. Epub 2022 May 19.

Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Leicester School of Pharmacy, De Montfort University, Leicester, UK. Electronic address:

Although stem cell therapy is a major area of interest in tissue engineering, providing proper oxygen tension, good viability, and cell differentiation remain challenges in tissue-engineered scaffolds. In this study, an osteogenic scaffold was fabricated using the 3D bio-printing technique. The bio-ink contained alginate hydrogel, encapsulated human bone marrow-derived mesenchymal stem cells (hBM-MSCs), calcium peroxide nanoparticles (CPO NPs) as an oxygen generating biomaterial, and bone morphogenic protein-2 nanoparticles (BMP2 NPs) as an osteoinductive growth factor. Read More

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Whole body magnetic resonance imaging in healthy children and adolescents: Bone marrow appearances of the appendicular skeleton.

Eur J Radiol 2022 May 20;153:110365. Epub 2022 May 20.

Department of Radiology, University Hospital of North-Norway, Tromsø, Norway; Department of Clinical Medicine, UiT, The Arctic University of Norway, Tromsø, Norway. Electronic address:

Objective: To describe the appearances of bone marrow in the appendicular skeleton on fat-suppressed T2-weighted sequences as assessed by whole-body MRI in healthy and asymptomatic children and adolescents.

Material And Methods: Following ethical approval, we assessed the bone marrow of the extremities on water-only Dixon T2-weighted images as part of a whole-body MRI in 196 healthy and asymptomatic children aged 5-19 years. Based on a newly devised and validated scoring system, we graded intensity (0-2 scale) and extension (1-4 scale) of focal high signal bone marrow areas, and divided them into minor or major findings, based on intensity and extension, reflecting their potential conspicuousness in a clinical setting. Read More

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Voluntary physical activity mitigates alveolar bone loss in mice with ligature-induced experimental periodontitis.

Arch Oral Biol 2022 May 11;140:105451. Epub 2022 May 11.

Health Sciences Department, Federal University of Lavras (UFLA), Lavras, Minas Gerais, Brazil. Electronic address:

Objective: To investigate the effect of voluntary physical activity (VPA) on inflammatory profile and the progression of experimental periodontal disease (PD) in mice.

Methods: Male C57BL/6 mice were randomly distributed into Control; VPA; PD and PD/VPA groups. We registered VPA (total volume of revolutions) and average speed (revolutions/minute) in a free running wheel for 30 days. Read More

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A 2-bp deletion mutation in gene leading to lysosomal acid sphingomyelinase deficiency in a Chinese consanguineous pedigree.

J Pediatr Endocrinol Metab 2022 May 27. Epub 2022 May 27.

Prenatal Diagnosis Department, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.

Background: Niemann-Pick disease type A (NPDA, MIM: 257200) is an autosomal recessive sphingolipidosis caused by lysosomal acid sphingomyelinase (ASM) deficiency. A cluster of genes located at chromosome 11p15 have been reported to be imprinted genes, such as TSSC5, TSSC3, and ZNF215 that flanking SMPD1 gene. It was reported by a few recent studies that SMPD1 gene was paternally imprinted and maternally preferentially expressed. Read More

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Formulation and Characterization of Raloxifene Nanostructured Lipid Carriers for Permeability and Uptake Enhancement Applications.

Assay Drug Dev Technol 2022 May 26. Epub 2022 May 26.

Department of Pharmaceutical Sciences, Taneja College of Pharmacy, University of South Florida, Tampa, Florida, USA.

Raloxifene (RLX), a biopharmaceutical classification system (BCS) class II drug, is a selective estrogen receptor modulator (SERM) having an estrogenic effect on the bone and an antiestrogenic effect on the endometrium and breast. Low solubility, high permeability, high metabolism, and low bioavailability are the characteristics of raloxifene. Although 60% is absorbed orally, raloxifene shows extremely poor bioavailability (2%) owing to its low solubility and extensive (>90%) intestinal/hepatic first-pass metabolism. Read More

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Quantitative parameters of digital occlusal analysis in dental implant supported restorative reconstruction recent 5 years: a systematic review.

Acta Odontol Scand 2022 May 26:1-17. Epub 2022 May 26.

Department of Periodontics and Implant Dentistry, Faculty of Dentistry, Thammasat University, Phatum Thani, Thailand.

Objective: The aims of this systematic review were to evaluate the clinical masticatory performance of implant-supported restorations, observe the occlusal force changes in the distribution of the implant restoration and reveal the positive and negative contributing factors of implant design and components based on the outcomes of digital occlusal measurement.

Material And Methods: An extensive search was conducted through PubMed and CENTRAL to identify clinical trials on implant-retained restorations using digital occlusal analysis methods. Two researchers assessed the identified studies and data extraction independently, and the data synthesis strategies without meta-analysis that summarizes the effect estimates were adopted. Read More

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Krüppel-like factor 4 promotes the proliferation and osteogenic differentiation of BMSCs through SOX2/IGF2 pathway.

Acta Biochim Pol 2022 May 26. Epub 2022 May 26.

Department of Orthopaedics, Funing People's Hospital, Yancheng City, Jiangsu Province, China.

Objectives: Human bone marrow mesenchymal stem cells (BMSCs) have multi-lineage differentiation potential and have been widely researched in regenerative medicine. The purpose of this research was to explore whether Krüppel-like factor 4 (KLF4) can regulate the osteogenic differentiation of BMSCs.

Methods: We transfected human BMSCs with KLF4 overexpression plasmid and si-KLF4 to study the effects of KLF4. Read More

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A preliminary, observational study using whole-blood RNA sequencing reveals differential expression of inflammatory and bone markers post-implantation of percutaneous osseointegrated prostheses.

PLoS One 2022 26;17(5):e0268977. Epub 2022 May 26.

Research, George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, Utah, United States of America.

Aims: While the benefits of direct skeletal attachment of artificial limbs are well recognized, device failure due to infection and insufficient osseointegration remain obstacles to obtaining consistently successful outcomes. Currently, the potential for device failure is assessed by subjective pain, clinical function scores, radiographic evidence of bone atrophy, and the presence of radiolucent lines at the bone-implant interface, and subjective pain and function scores. Our hypothesis is that measurable biological indices might add another objective means to assess trends toward bone and stomal healing. Read More

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Lncrna ANGPTL1-3 and its target microRNA-30a exhibit potency as biomarkers for bortezomib response and prognosis in multiple myeloma patients.

Hematology 2022 Dec;27(1):596-602

Department of Hematology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.

Objective: Long non-coding RNA ANGPTL1-3 (lnc-ANGPTL1-3) is previously observed to induce bortezomib resistance via targeting microRNA-30a (miR-30a) in multiple myeloma (MM). Hence, this study aimed to further explore the relationship between lnc-ANGPTL1-3 and miR-30a and their linkage with disease properties and prognosis in bortezomib-treated MM patients.

Methods: Fifty-nine MM patients underwent treatment with the bortezomib-based regimen, and 30 healthy donors were consecutively enrolled. Read More

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December 2022

Treosulfan Compared with Reduced-Intensity Busulfan Improves Allogeneic Hematopoietic Cell Transplantation Outcomes of Older Acute Myeloid Leukemia and Myelodysplastic Syndrome Patients: Final Analysis of a Prospective Randomized Trial.

Am J Hematol 2022 May 26. Epub 2022 May 26.

Policlinic G.B. Rossi Borgo Rome, Verona, Italy.

The phase III study was designed to compare event-free survival (EFS) after treosulfan-based conditioning with a widely applied reduced-intensity conditioning (RIC) busulfan regimen in older or comorbid patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) undergoing allogeneic hematopoietic cell transplantation (HCT). A previously reported confirmatory interim analysis of the randomized clinical study including 476 patients demonstrated statistically significant non-inferiority for treosulfan with clinically meaningful improvement in EFS. Here, the final study results and pre-specified subgroup analyses of all 570 randomized patients with completed longer term follow-up are presented. Read More

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Rational Design of Bisphosphonate Lipid-like Materials for mRNA Delivery to the Bone Microenvironment.

J Am Chem Soc 2022 May 26. Epub 2022 May 26.

Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.

The development of lipid nanoparticle (LNP) formulations for targeting the bone microenvironment holds significant potential for nucleic acid therapeutic applications including bone regeneration, cancer, and hematopoietic stem cell therapies. However, therapeutic delivery to bone remains a significant challenge due to several biological barriers, such as low blood flow in bone, blood-bone marrow barriers, and low affinity between drugs and bone minerals, which leads to unfavorable therapeutic dosages in the bone microenvironment. Here, we construct a series of bisphosphonate (BP) lipid-like materials possessing a high affinity for bone minerals, as a means to overcome biological barriers to deliver mRNA therapeutics efficiently to the bone microenvironment . Read More

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Assessment and comparison of image quality between two real-time sequences for dynamic MRI of distal joints at 3.0 Tesla.

Acta Radiol 2022 May 26:2841851221101889. Epub 2022 May 26.

Laboratory of Medical Information Processing (LATIM), INSERM-UMR 1101, Brest, France.

Background: Real-time sequences allow functional evaluation of various joint structures during a continuous motion and help understand the pathomechanics of underlying musculoskeletal diseases.

Purpose: To assess and compare the image quality of the two most frequently used real-time sequences for joint dynamic magnetic resonance imaging (MRI), acquired during finger and ankle joint motion.

Material And Methods: A real-time dynamic acquisition protocol, including radiofrequency (RF)-spoiled and balanced steady-state free precession (bSSFP) sequences, optimized for temporal resolution with similar spatial resolution, was performed using a 3. Read More

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Are medical students interested in research? - students' attitudes towards research.

Ann Med 2022 Dec;54(1):1538-1547

Laboratory of Centre for Preclinical Research, Department of Experimental and Clinical Physiology, Medical University of Warsaw, Warsaw, Poland.

Background: Throughout the years significant progress has been observed in all medical fields. It was possible to achieve thanks to a wide range of scientists, including physician-scientists. However, in recent years their number is significantly declining. Read More

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December 2022

Changes in the Number of Mesenchymal Stem Cells in Bone Marrow at Different Periods after In Vivo Exposure of the Bone Marrow to Local Infrared Laser Radiation.

Bull Exp Biol Med 2022 May 26. Epub 2022 May 26.

Institute of Photonic Technologies, Russian Academy of Sciences, Federal Research Center of Crystallography and Photonics, Russian Academy of Sciences, Moscow, Russia.

We determined optimal parameters of bone marrow (BM) irradiation in vivo for rapid increase in the number of mesenchymal stem cells (MSC) at the initial stages of the culturing without changing the karyotype, polyploidy, which are observed at higher passages. Such an increase is necessary to achieve the required number of cells at the initial passages for subsequent transplantation into the body. It was shown that after irradiation with λ=0. Read More

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MRD in ALL: Optimization and Innovations.

Curr Hematol Malig Rep 2022 May 26. Epub 2022 May 26.

Department of Medicine, Division of Hematology and Oncology, University of Virginia Comprehensive Cancer Center, 1300 Jefferson Park Ave, PO Box 800716, Charlottesville, VA, 22908, USA.

Purpose Of Review: Measurable residual disease (MRD) is an important monitoring parameter that can help predict survival outcomes in acute lymphoblastic leukemia (ALL). Identifying patients with MRD has the potential to decrease the risk of relapse with the initiation of early salvage therapy and to help guide decision making regarding allogeneic hematopoietic cell transplantation. In this review, we discuss MRD in ALL, focusing on advantages and limitations between MRD testing techniques and how to monitor MRD in specific patient populations. Read More

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ASO Author Reflections: Are Older Patients with Proximal Femoral Bone Metastases Fit for Endoprosthetic Replacement?

Ann Surg Oncol 2022 May 26. Epub 2022 May 26.

Department of Orthopedic Surgery, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, Sichuan, China.

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