Should discontinuity of the osteotomy site 1 year after periacetabular osteotomy be diagnosed as delayed union and not non-union?

Background: Discontinuity at the site of osteotomy is a complication after periacetabular osteotomy. The objectives of this study were to assess whether discontinuity is owed to delayed union or non-union and to clarify the risk factors associated with discontinuity >1 year after periacetabular osteotomy.

Methods: We performed a retrospective review of 104 hips in 95 consecutive patients who underwent periacetabular osteotomy between 2017 and 2021.

The Correlation between the Elastic Modulus of the Achilles Tendon Enthesis and Bone Microstructure in the Calcaneal Crescent.

Background: The calcaneal enthesis, an osseous footprint where the Achilles tendon seamlessly integrates with the bone, represents a complex interface crucial for effective force transmission. Bone adapts to mechanical stress and remodels based on the applied internal and external forces. This study explores the relationship between the elasticity of the Achilles tendon enthesis and the bone microstructure in the calcaneal crescent.

Incidence and clinical outcome of lateral femoral cutaneous nerve injury after periacetabular osteotomy.

Aims: Lateral femoral cutaneous nerve (LFCN) injury is a complication after periacetabular osteo-tomy (PAO) using an anterior approach, which might adversely affect the outcome. However, no prospective study has assessed the incidence and severity of this injury and its effect on the clinical outcomes over a period of time for longer than one year after PAO. The aim of this study was to assess the incidence and severity of the symptoms of LFCN injury for ≥ three years after PAO and report its effect on clinical outcomes.

Life Course Epidemiology of Hip Osteoarthritis in Japan: A Multicenter, Cross-Sectional Study.

Background: The incidence of developmental dysplasia of the hip (DDH) in Japanese newborns has reduced drastically following a primary prevention campaign initiated around 1972 to 1973; this perinatal education campaign promoted maintaining the hips of newborns in the naturally flexed-leg position. The purpose of the present study was to describe the life course epidemiology of hip osteoarthritis (OA) in adolescent and adult patients and to assess its association with exposure to the primary prevention campaign for DDH.

Methods: We included new patients with hip OA diagnosed from January 1, 2022, to December 31, 2022, at 12 core hospitals (8 special-function hospitals and 4 regional medical care support hospitals).

Corticosteroid-associated osteonecrosis of the femoral head in an 87-year-old patient following treatment for COVID-19-associated pneumonia: A case report.

Coronavirus disease 2019 is known to cause severe acute respiratory syndrome, and serious cases need to be treated with corticosteroids. Herein, we report an 87-year-old woman who developed bilateral osteonecrosis of the femoral head after corticosteroid treatment for coronavirus disease 2019-related pneumonia. Sixteen months after treatment, she developed right hip pain without any evidence of trauma.

Assessment of the Hip Flexor Muscles Shortly after Curved Periacetabular Osteotomy using Magnetic Resonance Imaging.

Background: Curved periacetabular osteotomy requires detachment and retraction of the hip flexors. In this study, we evaluated hip flexor muscle status by magnetic resonance imaging (MRI) shortly after curved periacetabular osteotomy.

Methods: We retrospectively evaluated 60 hips of 56 patients by MRI 1 week and 3 months after curved periacetabular osteotomy performed from August 2017 to December 2019.

A case of total hip arthroplasty for nonunion after femoral trochanteric fracture surgery with complete breakage of only the compression screw of the InterTAN nail.

Intramedullary nails are an effective treatment for common femoral trochanteric fractures. However, one of their complications is implant breakage due to poor reduction and nonunion after surgery. We herein report a case of a 54-year-old man who underwent total hip arthroplasty for nonunion after internal fixation of a femoral trochanteric fracture.

Going beyond Binary: Rapid Identification of Protein-Protein Interaction Modulators Using a Multifragment Kinetic Target-Guided Synthesis Approach.

Kinetic target-guided synthesis (KTGS) is a powerful screening approach that enables identification of small molecule modulators for biomolecules. While many KTGS variants have emerged, a majority of the examples suffer from limited throughput and a poor signal/noise ratio, hampering reliable hit detection. Herein, we present our optimized multifragment KTGS screening strategy that tackles these limitations.

Side-to-side variability in the femoral neck anteversion angle: A study of the Japanese population with osteonecrosis of the femoral head.

Background: Side-to-side variability in the femoral neck anteversion angle (FA) reportedly varies from 0.0° to 17.3°.

The role of torsional stress in the development of subchondral insufficiency fracture of the femoral head: A finite element model analysis.

Background: Subchondral insufficiency fracture of the femoral head generally occurs without evidence of trauma or with a history of minor trauma. Insufficient bone quality is considered one cause; however, the detailed mechanism of fracture development at the subchondral area (SA) is not understood. The aim of this study was to clarify the directions of force that cause subchondral fracture using finite element model analysis.

Clinical Outcomes for Total Hip Arthroplasty with and without Previous Curved Periacetabular Osteotomy.

There are currently no reports on the clinical outcomes after total hip arthroplasty (THA) with previous curved periacetabular osteotomy (CPO), although the outcomes after THA with non-CPO types of periacetabular osteotomy have been reported. This study aimed to clarify the differences in clinical outcomes and radiographic features after THA with or without previous CPO. We performed a retrospective case-control with individual matching study.

Mechanical Influence of Pubic Nonunion on the Stress Distribution After Curved Periacetabular Osteotomy: Patient-Specific Three-Dimensional Finite Element Analysis.

Background: Pubic nonunion after curved periacetabular osteotomy (CPO) reportedly occurs in 1%-17% of patients and causes pubic pain in 21%. Furthermore, pubic nonunion is associated with a risk of ischial ramus stress fracture, but the mechanical influence of pubic nonunion has not been fully clarified.

Methods: Patient-specific finite element (FE) analysis was performed using Mechanical Finder software.

Acid ceramidase promotes drug resistance in acute myeloid leukemia through NF-κB-dependent P-glycoprotein upregulation.

Acute myeloid leukemia (AML) is the most common acute leukemia in adults. More than half of older AML patients fail to respond to cytotoxic chemotherapy, and most responders relapse with drug-resistant disease. Failure to achieve complete remission can be partly attributed to the drug resistance advantage of AML blasts that frequently express P-glycoprotein (P-gp), an ATP-binding cassette transporter.

SKI-178: A Multitargeted Inhibitor of Sphingosine Kinase and Microtubule Dynamics Demonstrating Therapeutic Efficacy in Acute Myeloid Leukemia Models.

Aim: To further characterize the selectivity, mechanism-of-action and therapeutic efficacy of the novel small molecule inhibitor, SKI-178.

Methods: Using the state-of-the-art Cellular Thermal Shift Assay (CETSA) technique to detect "direct target engagement" of proteins intact cells, and assays, pharmacological assays and multiple mouse models of acute myeloid leukemia (AML).

Results: Herein, we demonstrate that SKI-178 directly target engages both Sphingosine Kinase 1 and 2.

A carcinogenicity study of diphenylarsinic acid in F344 rats in drinking water for 104 weeks.

Diphenylarsinic acid (DPAA), a neurotoxic organic arsenical used as a chemical warfare agent, is present in the groundwater and soil in some regions of Japan due to illegal dumping after World War II. We previously demonstrated that DPAA promotes diethylnitrosamine-induced liver carcinogenesis in a medium-term rat liver bioassay. The purpose of the present study was to evaluate the potential carcinogenicity of DPAA, including investigation of whether the bile duct hyperplasia in the liver that was observed in a previous 52 week rat chronic study develops into a tumor, when administered to rats in their drinking water for 104 weeks.

Chemopreventive Action by Ethanol-extracted Brazilian Green Propolis on Post-initiation Phase of Inflammation-associated Rat Colon Tumorigenesis.

Background/aim: Propolis has since long been utilized in numerous folk medicines with a variety of medicinal properties. In this study, the effects of ethanol-extracted (EEP) and water-extracted (WEP) Brazilian green propolis on the post-initiation phase of inflammation-associated rat colon tumorigenesis were directly compared.

Materials And Methods: Male F344 rats at 6 weeks of age were subcutaneously injected with 1,2-dimethylhydrazine (DMH) at 40 mg/kg body weight twice during the first week, followed by 1% dextran sodium sulfate (DSS) in drinking water for one week.

A chronic toxicity study of diphenylarsinic acid in F344 rats in drinking water for 52 weeks.

Diphenylarsinic acid (DPAA), a chemical warfare-related neurotoxic organic arsenical, is present in the groundwater and soil in some regions of Japan due to illegal dumping after World War II. The purpose of the present study was to evaluate the potential toxicity of DPAA when administered to rats in their drinking water for 52 weeks. DPAA was administered to groups 1-4 at concentrations of 0, 5, 10, and 20ppm in their drinking water for 52 weeks.

Examination of in vivo mutagenicity of sodium arsenite and dimethylarsinic acid in gpt delta rats.

Arsenic is a well-known human bladder and liver carcinogen, but its exact mechanism of carcinogenicity is not fully understood. Dimethylarsinic acid (DMA) is a major urinary metabolite of sodium arsenite (iAs) and induces urinary bladder cancers in rats. DMA and iAs are negative in in vitro mutagenicity tests.

Acid ceramidase is upregulated in AML and represents a novel therapeutic target.

There is an urgent unmet need for new therapeutics in acute myeloid leukemia (AML) as standard therapy has not changed in the past three decades and outcome remains poor for most patients. Sphingolipid dysregulation through decreased ceramide levels and elevated sphingosine 1-phosphate (S1P) promotes cancer cell growth and survival. Acid ceramidase (AC) catalyzes ceramide breakdown to sphingosine, the precursor for S1P.

Ethanol-Extracted Brazilian Propolis Exerts Protective Effects on Tumorigenesis in Wistar Hannover Rats.

The present study was conducted over a course of 104 weeks to estimate the carcinogenicity of ethanol-extracted Brazilian green propolis (EEP). Groups of 50 male and 50 female Wistar Hannover rats, 6-week-old at commencement were exposed to EEP at doses of 0, 0.5 or 2.

Role of deltaNp63(pos)CD44v(pos) cells in the development of N-nitroso-tris-chloroethylurea-induced peripheral-type mouse lung squamous cell carcinomas.

The role of cells expressing stem cell markers deltaNp63 and CD44v has not yet been elucidated in peripheral-type lung squamous cell carcinoma (pLSCC) carcinogenesis. Female A/J mice were painted topically with N-nitroso-tris-chloroethylurea (NTCU) for induction of pLSCC, and the histopathological and molecular characteristics of NTCU-induced lung lesions were examined. Histopathologically, we found atypical bronchiolar hyperplasia, squamous metaplasia, squamous dysplasia, and pLSCCs in the treated mice.

Ethanol-extracted propolis enhances BBN-initiated urinary bladder carcinogenesis via non-mutagenic mechanisms in rats.

Ethanol-extracted propolis (EEP) is used for medical, dietetic and cosmetic purposes. In this study, the effects of EEP on urinary bladder carcinogenesis, its underlying mechanism and in vivo genotoxicity were investigated. In experiment 1, rats were treated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) for 2 or 4 weeks followed by dietary administration of 0.

Pyoluteorin derivatives induce Mcl-1 degradation and apoptosis in hematological cancer cells.

Mcl-1, a pro-survival member of the Bcl-2 protein family, is an attractive target for cancer therapy. We have recently identified the natural product marinopyrrole A (maritoclax) as a novel small molecule Mcl-1 inhibitor. Here, we describe the structure-activity relationship study of pyoluteorin derivatives based on maritoclax.

Synthesis of cell-permeable stapled BH3 peptide-based Mcl-1 inhibitors containing simple aryl and vinylaryl cross-linkers.

We report the synthesis of a series of distance-matching aryl and vinylaryl cross-linkers for constructing stapled peptides containing cysteines at ,+7 positions. Langevin dynamics simulation studies helped to classify these cross-linkers into two categories: the rigid cross-linkers with narrower S-S distance distribution and the flexible cross-linkers with wider S-S distance distribution. The stapled Noxa BH3 peptides with the flexible distance-matching cross-linkers gave the highest degree of helicity as well as the most potent inhibitory activity against Mcl-1.

Maritoclax induces apoptosis in acute myeloid leukemia cells with elevated Mcl-1 expression.

Acute myeloid leukemia (AML) is one of the deadliest leukemias for which there is an urgent and unmet need for the development of novel treatment strategies. Multiple drug resistance mechanisms mediate poor drug response and relapse in patients, and a selective Mcl-1 inhibitor has been speculated to be a promising agent in the treatment of AML. Here, we describe that maritoclax, a small molecule Mcl-1 inhibitor, induces Mcl-1 proteasomal degradation without transcriptional downregulation.