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Ryunosuke Fukushi,1 Atsushi Teramoto,1 Mitsunori Yoshimoto,1 Naohisa Miyakoshi,2 Daisuke Kudo,2 Makoto Emori,1 Yoichi Shimada,2 Toshihiko Yamashita1 1Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan; 2Department of Orthopaedic Surgery, Akita University School, Akita, JapanCorrespondence: Ryunosuke Fukushi, Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, S1 W16, Sapporo, Hokkaido, 060-8543, Japan, Tel +81-11-611-2111, Fax +81-11-621-8059, Email ryunosuke_fukushi_521@yahoo.co.jpPurpose: To assess the number of surgeries needed to acquire the necessary skills to perform spine surgery independently.Patients and Methods: A questionnaire on 12 different spinal procedures was sent to orthopedic surgeons affiliated with the spine teams of orthopedic departments at either the Akita University or Sapporo Medical University. Participants were asked to identify whether they (A) could independently perform each procedure, (B) could perform each procedure with the assistance of a senior doctor, or (C) were unable to perform each procedure. Those whose response was (A) were asked how many surgeries were required to acquire the necessary skills. Those who responded to (B) or (C) were asked how many surgeries they believed were required to acquire the skills necessary to operate independently. Participants also responded to 10 questions on surgical training techniques and rated the usefulness of each method.Results: A total of 55 spine surgeons responded to the questionnaire. Group A required significantly fewer surgeries in the following categories to become independent than required Group C: upper cervical spine surgery (7.3/19.3), anterior cervical decompression/fusion (6.7/28.8), posterior cervical decompression/fusion (9.5/27.3), lumbar discectomy (12.6/26.7), endoscopic lumbar discectomy (10.2/24.2), spinal tumor resection (6.5/37.2), and spinal kyphosis surgery (10.3/32.3). Over 80% of participants responded that the following were effective methods: “surgeries where a senior doctor is the main surgeon, and the respondent is the assistant and observer”; “surgeries where the respondent is the main surgeon, and a senior doctor is an assistant”; “self-study using surgery manuals, articles, and textbooks”; and “training through video surgery sessions”.Conclusion: Surgeons who do not perform specific procedures independently require more surgical experience than those who operate independently. Our results may help develop more efficient training methods for spine surgeons.Keywords: surgical experience, surgical training, training system, inexperienced spine surgeons

Shunsuke Jimbo,1 Yoshinori Terashima,1,2 Atsushi Teramoto,1 Tsuneo Takebayashi,3 Izaya Ogon,1 Kota Watanabe,4 Tatsuya Sato,2,5 Nobutoshi Ichise,2 Noritsugu Tohse,2 Toshihiko Yamashita1 1Department of Orthopaedic surgery, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan; 2Department of Cellular Physiology and Signal Transduction, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan; 3Sapporo Maruyama Orthopaedic Hospital, Sapporo 060-0007, Japan; 4Department of Second Division of Physical Therapy, Sapporo Medical University School of Health Sciences, Sapporo 060-8556, Japan; 5Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan Purpose: Ankle osteoarthritis (OA) causes significant pain and debilitation; yet, its underlying mechanisms remain unclear. Clinically, hyaluronic acid (HA) is widely used to treat OA. The present study aimed to investigate the roles of HA in pain-related behavior, joint function, swelling, and pathological changes in cartilage in a rat model of monoiodoacetate (MIA)-induced ankle OA. Materials and methods: Male Sprague Dawley rats were assigned to three experimental groups as follows: 1) MIA rats injected with 1 mg MIA in the right tibiotarsal joint for two consecutive days; 2) sham rats injected with saline instead of MIA; and 3) MIA-HA rats injected with HA in the tibiotarsal joint at 7, 14, and 21 days after MIA injection. Joint swelling, range of motion (ROM), and pain-related behavior were evaluated 1 day before and on the 7th, 14th, 21st, and 28th day after MIA or saline injection. Pathological changes in the ankle joint were assessed 28 days after MIA or saline injection. Results: No significant difference in the degree of ankle swelling or ROM reduction was observed between MIA rats and MIA-HA rats. However, compared with those in MIA rats, mechanical and thermal hypersensitivity was significantly reduced and stride length significantly improved in MIA-HA rats. Histologic analysis revealed that cartilage degeneration was significantly suppressed in MIA-HA rats compared with that in MIA rats, reflecting the chondroprotective effects of HA. Conclusion: HA improved pain-related behavior and stride length and suppressed MIA-induced cartilage degeneration. HA may thus inhibit OA progression and suppress peripheral and/or central sensitization. Keywords: ankle osteoarthritis, monoiodoacetate, osteoarthritis pain, hyaluronic acid

Abstract We report a solution-based approach for the synthesis of oxidation-free MoS2 films, focusing on interface analysis. Through a sulfurization-free solution process and single-step annealing, the oxidation-free MoS2 film is successfully prepared on Si3N4 surfaces, showing improved uniformity with a surface roughness below 0.5 nm and a thickness of 4 nm at a precursor solution concentration of 30 mM, annealed between 700 and 800ºC. The MoS2 films exhibit a hexagonal lattice structure with crystallographic orientations of (1 1 0 0) and (1 2 1 0) with lattice spacings of 0.27 nm and 0.16 nm respectively. Interfacial analysis by X-ray photoelectron spectroscopy (XPS) on SiO2 reveals migration of oxygen species as evidenced by a shift in the Si 2p spectrum at binding energies between 102.6 eV and 102.8 eV. MoS2 films on Si3N4 show a complex Si 2p peak evolution at binding energies between 100.9 and 101.8 eV, providing valuable insights into the synthesis of oxide-free MoS2 films for potential applications in advanced electronic devices.

Abstract Background We previously conducted a retrospective Japanese cohort study of patients who underwent radical prostatectomy (RP) between January 2010 and December 2020 in Ehime Prefecture. This study revealed an increase in the number of RP, but other treatment trends remained unclear. In the current study, we examined prostate cancer treatment in Ehime Prefecture using the hospital-based cancer registry of all designated cancer care hospitals and community cancer care hospitals belonging to the Council of Ehime Cancer Care Hospitals. Methods Trends of prostate cancer were compared by year according to stage and treatment using data from the hospital-based cancer registry between 2011 and 2020. Results The number of patients with stage 1 disease increased over time, but the proportion of patients with stage 1 disease among all patients decreased from 65.2% in 2012 to 56.9% in 2020. The number of patients with stage 2 disease also increased, but the proportion of such patients among all patients remained constant. Meanwhile, the proportions of patients with stage 3 or 4 disease increased significantly over time, while that of patients undergoing RP increased from 29.2% in 2011 to 45.7% in 2020 (P

A 73-year-old man who previously underwent transsphenoidal surgery for a Rathke's cleft cyst presented with headache and fever. Ophthalmological examination revealed the progression of visual impairment. Cerebral magnetic resonance imaging revealed a cystic mass in the sellar and suprasellar regions with rim-like enhancement. An intralesional hyperintense area with temporal enlargement was identified using serial diffusion-weighted imaging. Lumbar cerebrospinal fluid tap findings indicated bacterial meningitis. The patient had undergone a transsphenoidal surgery; an intraoperatively implanted sheet of artificial dura mater from the previous surgery was identified adjacent to the sellar floor. After incising the floor, the pus material was drained and methicillin-sensitive Staphylococcus aureus was identified on culture. Consecutive antibiotic treatment resolved the pituitary abscess (PA). PA may develop as a late complication of transsphenoidal surgery, particularly when an artificial material is implanted during surgery. Clinical signs coupled with temporal findings on diffusion-weighted sequences can facilitate the diagnosis and activity of PA and serve as a guide for proper management.

Abstract Wrist function is a top priority for transradial amputees. However, the combined functional, biomechanical, and cognitive impact of using a powered prosthetic wrist is unclear. Here, we quantify task performance, compensatory movements, and cognitive load while three transradial amputees performed a modified Clothespin Relocation Task using two myoelectric prostheses with and without the wrists. The two myoelectric prostheses include a commercial prosthesis with a built-in powered wrist, and a newly developed inexpensive prosthetic wrist for research purposes, called the “Utah wrist”, that can be adapted to work with various sockets and prostheses. For these three participants, task failure rate decreased significantly from 66% ± 12% without the wrist to 39% ± 9% with the Utah wrist. Compensatory forward leaning movements also decreased significantly, from 24.2° ± 2.5 without the wrist to 12.6° ± 1.0 with the Utah wrist, and from 23.6° ± 7.6 to 15.3° ± 7.2 with the commercial prosthesis with an integrated wrist. Compensatory leftward bending movements also significantly decreased, from 20.8° ± 8.6 to 12.3° ± 5.3, for the commercial with an integrated wrist. Importantly, simultaneous myoelectric control of either prosthetic wrist had no significant impact on cognitive load, as assessed by the NASA Task Load Index survey and a secondary detection response task. This work suggests that functional prosthetic wrists can improve dexterity and reduce compensation without significantly increasing cognitive effort. These results, and the introduction of a new inexpensive prosthetic wrist for research purposes, can aid future research and development and guide the prescription of upper-limb prostheses.

Abstract Emerging evidence indicates that androgen receptor (AR) signaling plays a critical role in the pathogenesis of male-dominant urothelial cancer and its outgrowth. Meanwhile, latrophilins (LPHNs), a group of the G-protein-coupled receptors to which a spider venom latrotoxin (LTX) is known to bind, remain largely uncharacterized in neoplastic diseases. The present study aimed to determine the functional role of LPHN3 (encoded by the ADGRL3 gene), in association with AR signaling, in the progression of bladder cancer. In AR-positive bladder cancer lines, dihydrotestosterone considerably increased the expression levels of ADGRL3 and LPHN3, while chromatin immunoprecipitation assay revealed the binding of AR to the promoter region of ADGRL3. Treatment with LPHN3 ligands (e.g. α-LTX, FLRT3) resulted in the induction of ADGRL3 expression, as well as cell viability, in bladder cancer lines. By contrast, LPHN3 knockdown via shRNA virus infection significantly reduced the viability and migration of these cells. Immunohistochemistry in transurethral resection specimens further showed a strong correlation between LPHN3 and AR expression. Moreover, LPHN3 positivity in muscle-invasive bladder tumors, as an independent prognosticator, was associated with a significantly higher risk of disease progression and disease-specific mortality following radical cystectomy. These findings suggest that LPHN3 functions as a downstream effector of AR and promotes the growth of bladder cancer.

Inflammatory pseudotumors (IPTs) of the spleen are rare and have often been reported to be associated with Epstein-Barr virus (EBV). Radiographically differentiating IPTs of the spleen from other malignant tumors is challenging, and splenectomy is often performed as a definitive treatment. We report a case of an EBV-associated splenic IPT in a male patient in his 70s. Contrast-enhanced computed tomography (CT) revealed a splenic mass that increased from 2.4 cm to 3.9 cm in diameter over one year. Magnetic resonance imaging (MRI) revealed that the mass showed a slightly high intensity on T1-weighted images and heterogeneous low intensity on T2-weighted images. On dynamic contrast-enhanced MRI, the mass showed weak and gradual inhomogeneous enhancement. A 18F-fluorodeoxyglucose (FDG) positron emission tomography/CT demonstrated increased FDG uptake in the mass. Splenectomy was performed and the pathological diagnosis was EBV-associated IPT. EBV-associated splenic IPT can mimic malignant tumors on imaging, making it challenging to differentiate them from other splenic diseases.

Malignant glomus tumors are rare mesenchymal tumors arising from the smooth muscle cells of the glomus body. Primary malignant glomus tumors of the thyroid are atypical. An 80-year-old man presented with a right thyroid tumor on computed tomography (CT) and was suspected of having multiple bilateral pulmonary metastases. The right lobe of the thyroid gland was accompanied by a low-density tumor and calcification inside, and infiltration into the trachea and cervical esophagus was deduced. Core needle biopsy (CNB) confirmed that round to polygonal atypical cells were growing in sheet form around the vascular endothelial cells. Immunohistochemistry results were positive for vimentin and smooth muscle actin (SMA) but negative for pan-cytokeratin and S-100 protein. Chemotherapy with doxorubicin was initiated. However, due to the progression of the disease, doxorubicin was replaced with pazopanib. His condition deteriorated further, and he died 3 months after the treatment. Overall, this disease has a poor prognosis.

Abstract Aims Renal dysfunction in patients with chronic heart failure predicts a poor prognosis. Tolvaptan has a diuretic effect in patients with chronic kidney disease and heart failure without adverse effects on renal function. We aimed to determine the effects of tolvaptan and predictors of worsening renal function in patients with heart failure. Methods and results This post hoc analysis was a sub‐analysis of a single‐centre prospectively randomized trial on the early and short‐term tolvaptan administration. We enrolled 201 participants with decompensated heart failure between January 2014 and March 2019 (early group, n = 104; age: 79.0 ± 12.8 years; late group, n = 97; age: 80.3 ± 10.8 years). Renal ultrasonography was performed before and after the administration of tolvaptan. Urine output and oral water intake significantly increased during tolvaptan administration. The difference between water intake and urine volume increased during tolvaptan administration. Changes in body weight, blood pressure, heart rate, and estimated glomerular filtration rate (eGFR) in both groups were comparable. The changes in peak‐systolic velocity (PSV), acceleration time (AT) of the renal arteries, and resistance index were comparable. The changes in PSV and end‐diastolic velocity (EDV) of the interlobar arteries increased following tolvaptan administration (Δmax PSV: 0.0 ± 14.8 cm/s before tolvaptan vs. 5.6 ± 15.7 cm/s after tolvaptan, P = 0.002; Δmean PSV: 0.4 ± 12.3 vs. 4.9 ± 12.7 cm/s, P = 0.002; Δmax EDV: −0.2 ± 3.5 vs. 1.4 ± 4.0 cm/s, P = 0.001; Δmean EDV: −0.0 ± 3.1 vs. 1.1 ± 3.4 cm/s, P = 0.003). The renal artery AT was negatively correlated with the eGFR (Δmax AT: beta = −0.2354, P = 0.044; Δmean AT: beta = −0.2477, P = 0.035). Conclusions Tolvaptan increased the PSV and EDV of the interlobar artery, which may mean tolvaptan increased renal blood flow. The renal artery AT may be a surrogate for worsening renal function.

The present study examined whether male resveratrol intake affected mitochondrial DNA copy number (mt-cn) and telomere length (TL) in blastocysts fathered by young and aged male mice. C57BL/6N male mice supplied with water or water containing 0.1 mM resveratrol were used for embryo production at 14–23 and 48–58 weeks of age. Two-cell-stage embryos were collected from the oviducts of superovulated female mice (8–15 weeks old) and cultured for 3 days until the blastocyst stage. Mt-cn and TL levels were measured by real-time polymerase chain reaction. Resveratrol intake did not affect body weight or water consumption. Resveratrol intake increased the expression levels of SIRT1 in the liver, the antioxidative ability of serum, and extended TL in the heart, whereas there was no significant difference in mt-cn in the heart or TL in sperm. The rate of blastocyst development was significantly lower in aged male mice than in younger mice, and resveratrol intake increased the total number of blastocysts derived from both young and aged males. Resveratrol intake did not affect mt-cn or TL in blastomeres of blastocyst-stage embryos derived from young mice, but significantly increased both mt-cn and TL in blastomeres of blastocysts derived from aged fathers. In conclusion, resveratrol intake increased mt-cn and TL levels in blastocysts derived from aged male mice.

Abstract We compared the comprehensive clinical outcomes of focal therapy (FT) and robot-assisted radical prostatectomy (RARP) in patients with localized prostate cancer (PC) using a win ratio analysis. After propensity score matching, a win ratio analysis, in which the composite endpoints of failure-free survival (FFS) and the urinary domain of the Expanded Prostate Cancer Index Composite (EPIC) were analyzed, was used for the comparison of the clinical outcomes of FT and RARP for the patients with localized PC. Seventy-two patients were included in each group after propensity score matching. FFS was not significantly different between the groups (p = 0.5044) after 36 months of follow-up. In contrast, the score of the urinary domain of the EPIC in the FT group was significantly better than that in the RARP group (p

Abstract Aims Growth differentiation factor‐15 (GDF15), a cytokine in the transforming growth factor family, is up‐regulated in stress and inflammatory conditions and is elevated in patients with heart failure (HF). However, the age‐specific attributes and prognostic significance of GDF15 across age remain unknown in chronic HF (CHF). Methods and results Serum levels of GDF15 were examined in 942 hypertensive patients (median 68 years) with CHF from the SUPPORT trial across the four age groups [under 50 (n = 73), 51–59 (n = 158), 60–69 (n = 296), and 70–79 years (n = 415)] and in the continuous spectrum. Clinical correlates of GDF15 were explored using the classic stepwise and LASSO (least absolute shrinkage and selection operator) regression approaches. Interaction terms with age were tested in the LASSO regression approach. The associations with the composite outcome of HF hospitalization or all‐cause death were investigated across ages. Median GDF15 levels (pg/mL) increased along with aging, from 691 in under 50 years to 855 in 51–59 years, 1114 in 60–69 years, and 1516 in 70–79 years (trend P

Adrenal leiomyomas are rare and often reported as Epstein-Barr virus (EBV)-associated smooth muscle tumor (SMT) in association with EBV infection in immunocompromised patients. We experienced a case of right adrenal leiomyoma that was incidentally found in a man in his 70s. Computed Tomography (CT) showed a well-circumscribed mass of 3.1 cm in diameter in the right adrenal gland, which increased to 4.9 cm in diameter over 1 year. Preoperative diagnosis was difficult due to the lack of specific imaging findings. He had a history of diffuse large B-cell lymphoma (DLBCL) 8 years ago, and EBV had been detected in his blood. EBV-encoded small RNA(EBER) in situ hybridization (EBER-ISH) of the right adrenal leiomyoma was positive, and the final diagnosis was EBV-associated leiomyoma.

Background Evolocumab is the first monoclonal antibody against proprotein convertase subtilisin/kexin type 9 approved in Japan for familial hypercholesterolemia (FH) and hypercholesterolemia; however, data on its safety and effectiveness in the real‐world setting in Japan are limited. Methods and Results This real‐world, postmarketing, single‐arm study assessed the safety and effectiveness of low‐density lipoprotein cholesterol lowering with evolocumab in patients with homozygous/heterozygous familial hypercholesterolemia and hypercholesterolemia with high risk in Japan (668 sites). The primary safety end point was the incidence (percentage) and number of patients with adverse drug reactions and serious adverse events during the 104‐week follow‐up. Primary effectiveness end points included the percentage change in low‐density lipoprotein cholesterol levels from baseline to week 12, assessed using 2‐sided paired t tests. The safety and effectiveness sets comprised 3724 (homozygous FH, n=108; heterozygous FH, n=2009; hypercholesterolemia with high risk, n=1607) and 2797 (homozygous FH, n=91; heterozygous FH, n=1615; hypercholesterolemia with high risk, n=1091) patients, respectively. Overall, mean age and disease duration were 63.2 and 12.3 years, respectively. Serious adverse drug reactions and serious adverse events were experienced by 0.5% and 10.3% of patients; the incidence rates of myocardial infarction and stroke were 0.7% and 0.3%, respectively. A significant mean±SD percentage change in low‐density lipoprotein cholesterol levels was observed at week 12 among patients with homozygous FH (−45.7%±28.2; P

Considering the number of older adults requiring admission to nursing homes and the stress associated with this transition, nursing home staff should provide care for relocation stress. However, no suitable scale for evaluating relocation stress in Japanese older adults is currently available. This study aimed to translate and cross-culturally adapt the Nursing Home Adjustment Scale (NHAS) from Korean to Japanese and to assess its psychometric properties for nursing home residents in Japan. This observational validation study of a measurement scale involved two steps: (1) NHAS translation to the Japanese version of NHAS (NHAS-J) and cross-cultural adaptation as recommended by the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Task Force for Translation and Cultural Adaptation, and (2) assessment of NHAS-J validity through exploratory factor analysis, confirmatory factor analysis, and convergent validity and its reliability using Cronbach’s alpha for internal consistency. This study included 120 older adults from 12 nursing homes in Japan. The NHAS-J showed satisfactory internal consistency (Cronbach’s alpha = .853). The final NHAS-J structure was categorized into four factors: acceptance of new residence, daily emotions, relationship development, and depressed mood. Confirmatory factor analysis indicated a good fit for the four-factor model. The NHAS-J also demonstrated significant convergent validity with the satisfaction with life ( r = .376, p

Abstract Infections by gastrointestinal parasites are found in a variety of animals worldwide. For the diagnosis of such infections, the flotation method is commonly used to detect parasitic microorganisms, such as oocysts or eggs, in feces. Instead of adding a flotation solution after the final centrifugation step and using a cover slip to collect the parasites, the method using a wire loop for the recovery of the organisms has been reported as one of alternative methods. However, the recovery rates of microorganisms from the flotation method have not been analysed. In the present study, the utility of a flotation method with the use of a wire loop of 8 mm in diameter (the loop method) was evaluated using different numbers of E. tenella oocysts and Heterakis gallinarum eggs, and chicken fecal samples collected at the farms. Consequently, we found that the oocysts and eggs in tubes could be collected at a ratio of 2.00 to 3.08. Thus, our results indicate that the loop method is a simple and time saving method, implicating the application for the estimated OPG/ EPG (Oocysts/Eggs per gram) of the samples.