Does successful rotator cuff repair improve muscle atrophy and fatty infiltration of the rotator cuff? A retrospective magnetic resonance imaging study performed shortly after surgery as a reference.

学位記番号：医博甲173

Genetic Characterization of Conserved Charged Residues in the Bacterial Flagellar Type III Export Protein FlhA

For assembly of the bacterial flagellum, most of flagellar proteins are transported to the distal end of the flagellum by the flagellar type III protein export apparatus powered by proton motive force (PMF) across the cytoplasmic membrane. FlhA is an integral membrane protein of the export apparatus and is involved in an early stage of the export process along with three soluble proteins, FliH, FliI, and FliJ, but the energy coupling mechanism remains unknown. Here, we carried out site-directed mutagenesis of eight, highly conserved charged residues in putative juxta- and trans-membrane helices of FlhA. Only Asp-208 was an essential acidic residue. Most of the FlhA substitutions were tolerated, but resulted in loss-of-function in the ΔfliH-fliI mutant background, even with the second-site flhB(P28T) mutation that increases the probability of flagellar protein export in the absence of FliH and FliI. The addition of FliH and FliI allowed the D45A, R85A, R94K and R270A mutant proteins to work even in the presence of the flhB(P28T) mutation. Suppressor analysis of a flhA(K203W) mutation showed an interaction between FlhA and FliR. Taken all together, we suggest that Asp-208 is directly involved in PMF-driven protein export and that the cooperative interactions of FlhA with FlhB, FliH, FliI, and FliR drive the translocation of export substrate

A comparison between the adverse event profiles of patients receiving palbociclib and abemaciclib: analysis of two real-world databases

Background Palbociclib and abemaciclib are cyclin-dependent kinase (CDK) 4/6 inhibitors currently used to treat breast cancer. Although their therapeutic efficacies are considered comparable, differences in adverse event (AE) profiles of the two drugs remain unclear. Aim We analysed two real-world databases, the World Health Organization’s VigiBase and the Food and Drug Administration Adverse Event Reporting System (FAERS), to identify differences in AE profiles of palbociclib and abemaciclib. Method Data of patients with breast cancer receiving palbociclib or abemaciclib recorded until December 2022 were extracted from the VigiBase and FAERS databases. In total, 200 types of AEs were analysed. The reporting odds ratios were calculated using a disproportionality analysis. Results Cytopenia was frequently reported in patients receiving palbociclib, whereas interstitial lung disease and diarrhoea were frequently reported in those receiving abemaciclib. Moreover, psychiatric and nervous system disorders were more common in the palbociclib group, whereas renal and urinary disorders were more common in the abemaciclib group. Conclusion This study is the first to show comprehensively the disparities in the AE profiles of palbociclib and abemaciclib. The findings highlight the importance of considering these differences when selecting a suitable CDK4/6 inhibitor to ensure safe and favourable outcomes for patients with breast cancer

PIXE ANALYSIS OF PLATINUM-CONTAINING DDS DRUGS

Background/Aim: X-ray Drug Delivery System (DDS) is a combination of pinpoint X-ray andDDS, which can reduce side effects of radiation and chemicals. Polymericmicelle is one of the most promising DDS carriers having long circulationand high accumulation in solid tumor. Cisplatin micelle is a newlydeveloped DDS drug which contains cisplatin (1 nm) in a polymeric micelle(30 nm). The micelle collapses in the presence of chlorine ion, and thedrug is gradually released. To optimize the therapeutic effect, the uptakecharacteristics of DDS drugs should be fully understood. The aim of thisstudy is to directly measure cellular uptake of cisplatin micelle by usingParticle Induced X-ray Emission (PIXE).Methods: Chinese Hamster Ovary cells were treated with cisplatin or cisplatinmicelle for 0.5-24 hours. The PIXE analysis was conducted at NationalInstitute of Radiological Sciences, Chiba, Japan. By counting the number ofcharacteristic X-rays emitted during proton beam irradiation, the elementaldistribution was obtained. The signals of Pt-L alpha (9.441 keV) werecorresponding to the amount of platinum contained in the cells.Results: After 24-hours incubation, the Pt signal from the cells treated withcisplatin micelle was about 1/9 of that of cisplatin alone. This resultsuggests that cisplatin contained in a micelle is not well released in 24hours. Next, the cisplatin micelle was exposed to the media, which containschlorine ion, before the 24-hours incubation. The exposure improved theuptake. Amount of Pt in the cells agreed with collapsed amount of themicelle.Conclusion: Uptake of cisplatin micelle was directly observed by PIXE. Themicelles (30nm) did not pass through the cellular membrane, and theircollapsing rate (releasing rate of cisplatin) played an important role incytotoxicity. The obtained information is useful for application of DDSdrugs to radiation therapy.8th ASIA OCEANIA CONGRESS OF MEDICAL PHYSIC

PIXE ANALYSIS OF PLATINUM-CONTAINING DDS DRUGS

Background/Aim: X-ray Drug Delivery System (DDS) is a combination of pinpoint X-ray andDDS, which can reduce side effects of radiation and chemicals. Polymericmicelle is one of the most promising DDS carriers having long circulationand high accumulation in solid tumor. Cisplatin micelle is a newlydeveloped DDS drug which contains cisplatin (1 nm) in a polymeric micelle(30 nm). The micelle collapses in the presence of chlorine ion, and thedrug is gradually released. To optimize the therapeutic effect, the uptakecharacteristics of DDS drugs should be fully understood. The aim of thisstudy is to directly measure cellular uptake of cisplatin micelle by usingParticle Induced X-ray Emission (PIXE).Methods: Chinese Hamster Ovary cells were treated with cisplatin or cisplatinmicelle for 0.5-24 hours. The PIXE analysis was conducted at NationalInstitute of Radiological Sciences, Chiba, Japan. By counting the number ofcharacteristic X-rays emitted during proton beam irradiation, the elementaldistribution was obtained. The signals of Pt-L alpha (9.441 keV) werecorresponding to the amount of platinum contained in the cells.Results: After 24-hours incubation, the Pt signal from the cells treated withcisplatin micelle was about 1/9 of that of cisplatin alone. This resultsuggests that cisplatin contained in a micelle is not well released in 24hours. Next, the cisplatin micelle was exposed to the media, which containschlorine ion, before the 24-hours incubation. The exposure improved theuptake. Amount of Pt in the cells agreed with collapsed amount of themicelle.Conclusion: Uptake of cisplatin micelle was directly observed by PIXE. Themicelles (30nm) did not pass through the cellular membrane, and theircollapsing rate (releasing rate of cisplatin) played an important role incytotoxicity. The obtained information is useful for application of DDSdrugs to radiation therapy.8th ASIA OCEANIA CONGRESS OF MEDICAL PHYSIC

Triamcinolone acetonide with arthroscopic capsular release for frozen shoulder promotes early recovery of shoulder abduction

Background: Current treatment options for frozen shoulder are not established as the standard-of-care. The condition may resolve without intervention, but symptoms may persist despite treatment. Frozen shoulder is associated with inflammatory reactions that can reduce quality of life. Our aim was to determine whether triamcinolone acetonide, an immunosuppressive steroid, improved functional recovery when administered after arthroscopic capsular release (ACR) for frozen shoulder. Methods: We selected participants using inclusion and exclusion criteria designed to reduce the impact of potential confounding factors. Under general anesthesia, we performed ACR followed by manipulation to ensure adequate range of motion (ROM) and wound closure. In the steroid treatment group, we injected triamcinolone acetonide into the glenohumeral joint immediately prior to wound closure. The follow-up period was six months. To determine the efficacy of steroids in improving overall post procedure functional recovery we statistically analyzed data from various qualitative and quantitative variables. Results: Our study consisted of 22 patients with frozen shoulder, 11 in each of the surgery-only and surgery with steroid injection groups. There were no significant differences between groups in the demographic data of the study participants. We observed significantly greater improvements in abduction ROM in the steroid treatment group than in the surgery-only group, at three and six months post treatment. Improvements in other movement parameters were similar in both groups. The steroid-treated group had a significantly higher numerical rating scale score for night pain at three months post treatment than the surgery-only group. Conclusions: Postoperative steroid treatment led to early recovery of the abduction ROM in patients with frozen shoulder. Hence, the current standard-of-care protocol for frozen shoulder and other similar conditions requiring surgical intervention should include this type of treatment. Therapeutic reduction in the inflammatory response following ACR can significantly improve prognosis and quality of life