Discovery of 2-(6-{[(1R,2R)-2-hydroxycyclohexyl]amino}-4,5-dimethylpyridazin-3-yl)-5-(trifluoromethyl)phenol (ASP0965): A potent, orally active and brain-penetrable NLRP3 inflammasome inhibitor with a novel scaffold for the treatment of α-synucleinopathy.

NLRP3 inflammasome inhibitor is a highly attractive drug target for the treatment of various inflammatory diseases. Here, we report the discovery of pyridazine derivatives as a new class of scaffold for NLRP3 inflammasome inhibitors. We optimized HTS hit 2a to improve both in vitro IL-1β inhibitory activity and the mean photo effect (MPE) value in the in vitro 3T3 neutral red uptake (NRU) phototoxicity test.

Identifying the best reference gene for RT-qPCR analyses of the three-dimensional osteogenic differentiation of human induced pluripotent stem cells.

Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) is an essential tool for gene expression analysis; choosing appropriate reference genes for normalization is crucial to ensure data reliability. However, most studies on osteogenic differentiation have had limited success in identifying optimal reference genes. To the best of our knowledge, no optimal reference genes in three-dimensional (3D) osteogenic differentiation culture experiments using human induced pluripotent stem cells (hiPSCs) have been identified.

Factors Influencing the Postoperative Flexion Angle in Cruciate-Sacrificing Rotating Platform of Total Knee Arthroplasty.

Background: Various factors affect the improvement of range of motion (ROM) after total knee arthroplasty (TKA). However, there are few reports specific to cruciate-sacrificing rotating platform (CSRP) TKA. In this study, factors affecting postoperative ROM improvement of CSRP TKA were investigated.

Ring-closing metathesis of dialkenylcycloalkanes for the synthesis of fused bicycloalkanes and tricycloalkanes.

Ring-closing metathesis of dialkenyldisilacycloalkane using the Grubbs catalyst, followed by hydrogenation, afforded a mixture of two disilabicycloalkanes and tetrasilatricycloalkanes. This method can synthesize a diastereomer mixture of disilabicycloalkanes with one differing alkyl side chain. The observed symmetries of the NMR spectra of -bicycloalkanes depend significantly on the length of the side chain.

Artificial intelligence-assisted ultrasound imaging in hemophilia: research, development, and evaluation of hemarthrosis and synovitis detection.

Background: Joint bleeding can lead to synovitis and arthropathy in people with hemophilia, reducing quality of life. Although early diagnosis is associated with improved therapeutic outcomes, diagnostic ultrasonography requires specialist experience. Artificial intelligence (AI) algorithms may support ultrasonography diagnoses.

Association between postoperative fall history and toe grip strength in patients after total knee arthroplasty: A prospective observational study.

Background: Factors associated with falls after total knee arthroplasty (TKA) have been rarely reported. The aim of this study was to identify factors that influence the incidence of falls after TKA, focusing on toe grip strength (TGS) in particular, which has been associated with falls in older adults.

Methods: 217 patients who underwent TKA were included and followed up for 1 year.

Template Synthesis of Disilacycloalkanes Utilizing the Reactivity of a Siloxane Bond.

The investigation of large and flexible macrocyclic compounds has garnered significant attention due to their functions as host molecules and linkers. Although the synthetic yields of such compounds, achieved by linking two molecular fragments, are often hindered by the flexibility of the molecular skeleton, one of the effective solutions is template synthesis for the macrocycles. In this study, a novel template synthesis for disilacycloalkanes by leveraging the reactivity of a siloxane bond was investigated.

Optimal retractor insertion point for nerve safety during total hip arthroplasty: an anatomical study on the femoral and sciatic nerves in relation to hip motion.

Background: Nerve injury is one of the most serious complications of total hip arthroplasty (THA). It is suspected to be a result from nerve compression or direct injury caused by an acetabular retractor. The anatomical relationship between the acetabular rim and the femoral and sciatic nerves, including hip motion, has not been investigated.

Minimum-incision transsubclavian transcatheter aortic valve replacement with balloon-expandable valve for dialysis patients.

Background: Dialysis patients undergoing transcatheter aortic valve replacement (TAVR) face increased risk and have poorer outcomes than non-dialysis patients. Moreover, TAVR in dialysis patients using an alternative approach is considered extremely risky and little is known about the outcomes. We routinely perform minimum-incision transsubclavian TAVR (MITS-TAVR), which is contraindicated for transfemoral (TF) TAVR.

Single-facility study of the effectiveness of rehabilitation therapy using wearable hybrid assistive limb for patients with bleeding disorders: study protocol for a randomised controlled trial.

Introduction: Haemophilic arthropathy, a serious complication of haemophilia, results from recurrent joint bleeding, causing progressive joint damage and severely impacting patient quality of life. Rehabilitation therapy (RT) effectively addresses declining physical function due to joint degradation, but pain during RT can hinder its success. Therefore, an effective pain-alleviating treatment method is required.

Influences of comorbidities on perioperative rehabilitation in patients with gastrointestinal cancers: a retrospective study.

Background: Older patients are more likely to have comorbidities than younger patients, and multiple comorbidities are associated with mortality in patients with cancer. Therefore, we hypothesized that a functional comorbidity index could predict the therapeutic effects of rehabilitation.

Objectives: In this study, we investigate whether the comorbidities influenced the execution and therapeutic effects of rehabilitation.

Synthesis of Dimethyldisilabicycloalkanes: Cage-Size Effects on the Relative Stabilities between In,Out and Twist-Out,Out Forms.

In large bicycloalkanes, several in/out forms exist, wherein substituents on the bridgehead atoms are oriented either outside or inside the cage. The relative stability between the in,out and twist-out,out forms, which can interconvert through homeomorphic conversion, was found to depend upon the cage size. The in,out form demonstrated thermodynamic stability in the smaller C10 derivative, whereas the twist-out,out form prevailed in the larger derivatives of C14 and C18 plausibly as a result of dispersion forces among the chains.

[Emergent Transcatheter Aortic Valve Implantation for Degenerated Surgical Aortic Valve Under Local Anesthesia:Report of a Case].

An 89-year-old man who had undergone aortic valve replacement with a 21 mm Mosaic bioprosthetic valve at another hospital 14 years ago was admitted to the emergency room for a sudden respiratory distress two days prior and was diagnosed with severe aortic regurgitation( AR) caused by valve insufficiency and acute heart failure secondary to low cardiac function. Upon admission, he was found to have severe hypoxia with PaO2 of 40 mmHg range, and transcatheter aortic valve replacement (TAVI, TAV in SAV) with a 20 mm SAPIEN3 was performed under local anesthesia for fear of hypotension while under general anesthesia. After confirming that AR had completely disappeared, the patient was intubated and discharged from the operating room on a mechanical ventilator.

Synthesis and structure of stannane-based molecular bevel gears having substituents on a tin linker.

Ditriptycylmethanes are known as molecular bevel gears because the two triptycyl groups act as wheels and display correlated rotation in solution. However, introduction of substituents on the methylene junction for chemical modification of the bevel gears has been difficult due to steric hindrance of the triptycyls. In this study, stannane-based molecular bevel gears with organic substituents on the tin linker were achieved by utilizing long Sn-C bonds.

Relationship between fall history and toe grip strength in older adults with knee osteoarthritis in Japan: A cross-sectional study.

Background: Knee osteoarthritis (KOA), one of the most common musculoskeletal diseases in older adults, is associated with a high incidence of falls. Similarly, toe grip strength (TGS) is associated with a history of falls in older adults; however, the relationship between TGS and falls in older adults with KOA who are at risk of falling is not known. Therefore, this study aimed to determine if TGS is associated with a history of falls in older adults with KOA.

Effect of individualized occupational therapy on social functioning in patients with schizophrenia: A five-year follow-up of a randomized controlled trial.

This study aimed to evaluate the long-term effects of adding individualized occupational therapy (IOT) to a three-months group occupational therapy (GOT) on social functioning in inpatients with schizophrenia or schizoaffective disorder at a follow-up investigation five-years after discharge. Initially, patients were randomly assigned to GOT + IOT or GOT alone, with 102 patients, 48 in GOT + IOT and 54 in GOT alone, completing the five years follow-up. The primary outcome was change in social functioning assessed by the Social Functioning Scale (SFS) from baseline to five-year follow-up.

Synthesis and rotational dynamics of diazamacrocycles having bridged 1,4-naphthylene as framed molecular rotors.

The rotation of a part of a molecule has attracted attention because of its possible role in the development of an artificial molecular rotor. In this study, 1,4-naphthylene bridged diazamacrocycles, in which the 1,4-diaminonaphthalene moiety is bridged by two long alkyl chains, were designed as novel framed molecular rotors, and the dependence of the rotation on the frame size were investigated. Framed rotors CnNp ( = 12, 14, 16, 18), where the number in the compound name indicates the length of a side chain, were synthesized by direct cyclization of 1,4-naphthalenediamine with α,ω-dihaloalkane in the presence of NaCO as the base.