Mild hyperthermia upregulates PD-L1 in the tumor microenvironment and enhances antitumor efficacy of PD-L1 blockade in murine squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) has a low five-year survival rate because of its high rate of recurrence and metastasis. After surgical resection or radiation, the main treatments for HNSCC, patients sometimes experience functional or aesthetic disorders. Therefore, there is a great demand for the development of non-surgical treatment strategies to improve clinical outcomes and patients' quality of life. One such non-surgical treatment is mild hyperthermia (mHT). Many studies have investigated combination treatments with mHT and immune checkpoint inhibitors in preclinical settings. However, there have been no detailed reports on the effects of mHT on immune checkpoint molecules. Here, we investigated the effects of mHT on the tumor microenvironment (TME), particularly on programmed cell death receptor-1 (PD-1)/programmed cell death ligand-1 (PD-L1), in SCCVII cells and a squamous cell carcinoma mouse model. First, we found that PD-L1 mRNA levels and surface PD-L1 expression significantly increased after mHT. Second, a single tumor model was used to determine the effect of HT on the TME. mHT enhanced the accumulation of CD4+ and CD8+ T cells, elevated PD-L1 expression in the TME, and decreased the PD-1 positive rate of CD4+ T cells. Finally, using a bilateral tumor model, we found that anti-PD-L1 monotherapy and combination therapy resulted in longer survival than the isotype control or mHT monotherapy. Moreover, the combination therapy resulted in a significantly higher survival rate than anti-PD-L1 monotherapy. In conclusion, our findings elucidate changes in PD-L1 expression in the TME and strengthen the rationale for mHT and PD-L1 blockade combination therapy.

Pharmacotherapy for patients with calcium oxalate stones and abnormal urine chemistry: A systematic review and meta-analysis for the Japanese Clinical Practice Guidelines for the Management of Urinary Stones, Third Edition.

We performed a systematic review and meta-analysis to evaluate the benefits and harms of pharmacotherapies for patients with calcium oxalate stones and abnormal urine chemistry. This article is a modified and detailed version of the commentary on Clinical Question 10 described in the Japanese Clinical Practice Guidelines for the Management of Urinary Stones, Third Edition. PubMed and Ichushi Web were searched through August 2020 for articles on pharmacotherapies for calcium oxalate stones (thiazides, citrate preparations, uric acid production inhibitors, and magnesium preparations). Two reviewers independently selected randomized controlled trials reporting reduction of stone recurrence and adverse drug reactions as outcomes and performed data extraction and quality assessment. Meta-analyses with random effects models and rating of the strength of evidence were performed. Pharmacotherapies were shown to significantly reduce stone recurrence (risk ratio 0.47, 95% confidence interval 0.35-0.63). Meanwhile, the pharmacotherapies increased adverse drug reactions leading to study dropout (risk ratio 2.51, 95% confidence interval 1.09-5.75) and adverse drug reactions/adverse events (risk ratio 1.95, 95% confidence interval 1.07-3.56). The reported adverse drug reactions were, however, mainly minor and did not frequently require discontinuation of medication (2%-16%). The strengths of evidence for both outcomes were rated as moderate, because the risk of bias, indirectness, inconsistency, imprecision, and publication bias were all serious except for one item. The overall strength of evidence across outcomes was therefore determined to be moderate. These results support the conditional recommendation to initiate pharmacotherapies for patients with calcium oxalate stones and abnormal urine chemistry.

Anterior talofibular ligament footprint dimension measured using three-dimensional magnetic resonance imaging.

OBJECTIVE: Knowledge of footprint anatomy is essential for ankle anterior talofibular ligament repair and reconstruction. We aimed to determine the intra- and inter-rater measurement reliability of the anterior talofibular ligament footprint dimension using three-dimensional MRI. METHODS: MRI images of 20 ankles with intact ligaments, including 11 with a single bundle and nine with double-bundle ligaments, were analyzed. Imaging was performed using a 3.0-Tesla MRI. Isotropic three-dimensional proton density-weighted images with a voxel size of 0.6 mm were obtained. The fibular and talar footprints were manually segmented using image processing software to create three-dimensional ligament footprints. The lengths, widths, and areas of each sample were measured. A certified orthopedic surgeon and a senior orthopedic fellow performed the measurements twice at 6-week intervals. The intra- and inter-rater differences in the measurements were calculated. RESULTS: The length, width, and area of the single-bundle fibular footprint were 8.7 mm, 5.4 mm, and 37.4 mm2, respectively. Those of the talar footprint were 8.4 mm, 4.3 mm, and 30.1 mm2, respectively. The inferior bundle of the double-bundle ligament was significantly smaller than the single and superior bundles (p < 0.001). No differences were observed between intra-rater measurements by either rater, with maximum differences of 0.7 mm, 0.5, and 1.7 mm2, in length, width, and area, respectively. The maximum inter-rater measurement differences were 1.9 mm, 0.5, and 2.4 mm2, respectively. CONCLUSION: Measurements of the anterior talofibular ligament dimensions using three-dimensional MRI were sufficiently reliable. This measurement method provides in vivo quantitative data on ligament footprint anatomy.

Drumming performance and underlying muscle activities in a professional rock drummer with lower-limb dystonia: a case study.

Task-specific focal dystonia (TSFD), characterized by the loss of fine motor control and coordination, affects drummers' lower-limb movements. This study explores lower-limb dystonia's impact on drumming performance and underlying muscle activity in a professional rock drummer. The drummer executed an eight-beat pattern on a drum kit. The participant reported the occurrence of symptoms when he felt the abnormality such as the loss of control related to involuntary aspects of movement. We measured the peak amplitude of the bass drumhead vibration, synchronization errors as the time elapsed between the metronome onset and the bass drum onset, and amplitude of electromyographic (EMG) recordings centered on metronome beat. Dystonia symptoms primarily manifested in the initial beat, with fewer symptoms on syncopation of the third beat. Analysis revealed decreased bass-drum peak amplitude and earlier synchronization error during the initial beat. EMG measurements of 10 muscles in the affected right lower limb showed significant changes in the Biceps Femoris (BF), Tibialis Anterior (TA), Extensor Digitorum Longus (EDL), and Extensor Digitorum Brevis (EDB) muscles during symptom onset. We observed (1) earlier overactivation of the TA and EDL muscles during the leg lift-up motion or preparatory phase of pedaling, (2) reduced activation of the EDB muscle, and (3) increased activation of the BF muscle during the final pedaling movement when symptoms occurred. These findings suggest that lower-limb dystonia symptoms are characterized by a reduction in amplitude of the bass drumhead vibration and an increase in synchronization error, potentially due to premature overactivation of the ankle dorsiflexor muscles.

Clinical Outcomes of Modified Suture Buttons for Tibial Side Fixation in Anterior Cruciate Ligament Reconstruction: A Retrospective Comparative Study.

Introduction Restoring knee joint stability and resuming sports activities are important objectives of anterior cruciate ligament (ACL) reconstruction. The maintenance of anterior knee stability after ACL reconstruction is contingent on graft tension. Various devices and techniques have been used to achieve robust tibial graft tendon fixation, and their advantages and disadvantages are established. However, a gold standard has not been established. Therefore, we aimed to determine whether anterior knee joint stability and clinical outcomes of graft tendon fixation could be improved using a recently modified suture button (MSB) compared with using an adjustable suspensory fixator (ASF) at 1 year after double-bundle ACL reconstruction. Methods This study retrospectively analyzed postoperative data derived from 79 patients at a single center between January 2016 and December 2021. The patients were assigned to groups that underwent double-bundle ACL reconstruction with tibial fixation using an MSB (n = 30) that maintains tension while tying sutures, or an ASF (n = 49). We then compared complications, clinical outcomes and knee joint stability at 1 year postoperatively. Rates of postoperative infection, graft rupture, implant removal and residual anterior knee laxity (AKL) were compared between the groups using chi-square tests. Patient-reported outcome measures (PROM) based on Forgot Joint Score-12, Knee Injury and Osteoarthritis Outcome, and Lysholm Knee scores were compared using Mann-Whitney U tests. Results One patient in the MSB group developed postoperative infection. Rates of graft rupture and implant removal in the MSB and ASF groups were 3.3% and 4.1%, and 3.6% and 10.2%, respectively. None of the PROMs differed between the groups. The proportions of postoperative AKL were 3.6% and 14.9% in the MSB and ASF groups, respectively. A trend towards lower postoperative AKL in the MSB group did not reach statistical significance (p = 0.25). Conclusions The incidence of AKL at a year after ACL reconstruction using the MSB was 3%. Postoperative AKL and clinical outcomes were comparable between the MSB and ASF groups. A low AKL rate and positive postoperative outcomes indicated that MSB could be an option for tibial-side fixation in ACL reconstruction.

Continuous local antibiotic perfusion for deep infection of the foot and ankle.

BACKGROUND: This study aimed to report the outcome of deep infections of the foot and ankle, which are among the most challenging orthopedic conditions to treat, after continuous local antibiotic perfusion. METHODS: Eleven patients with deep foot and ankle infections were treated with continuous local antibiotic perfusion between January 2019 and March 2024. After surgical debridement, we performed continuous perfusion of high concentrations of gentamicin (60 mg/50 ml) directly into the infected bone and soft tissue for two weeks using bone marrow needles and double-lumen tubes. Patient characteristics, infection relapse, and adverse events were investigated. RESULTS: The mean age of the patients was 53 years (range 12-79 years), with six males and five females. The infections were controlled without additional surgeries in ten patients with a mean follow-up of 40 months (12-62 months). Two patients developed a fungal infection, of which one required an additional debridement surgery, and the other was treated with oral antifungal medication. No adverse events occurred due to high-concentration gentamicin. CONCLUSIONS: Short-term infection control was achieved using continuous local antibiotic perfusion; thus, it can be a treatment option for deep infections of the foot and ankle.

Intra- and interrater measurement reliability of lateral ankle ligament attachment locations using three-dimensional magnetic resonance imaging.

BACKGROUND: We aimed to evaluate the intra- and interrater measurement reliability of the lateral ankle ligament attachment locations using three-dimensional magnetic resonance imaging. METHODS: We analysed 54 participants with a mean age of 43 years who underwent three-dimensional ankle magnetic resonance imaging and had normal lateral ligaments. Bony landmarks of the distal fibula, talus, and calcaneus were identified in the reconstructed images. The centers of the anterior talofibular ligament and calcaneofibular ligament attachments were also identified. The distances between the landmarks and attachments were measured. Two raters performed the measurements twice, and intra- and interrater intraclass correlation coefficients were calculated. RESULTS: The intrarater intraclass correlation coefficient values were between 0.71 and 0.96 for the anterior talofibular ligament attachment measurements and between 0.77 and 0.95 for the calcaneofibular ligament attachments. The interrater intraclass correlation coefficient was higher than 0.7, except for the distance between the anterior talofibular ligament superior bundle and fibular obscure tubercle. The fibular attachment of a single-bundle anterior talofibular ligament was located 13.3 mm from the inferior tip and 43% along the anterior edge of the distal fibula. The superior and inferior bundles of the double-bundle ligament were located at 43% and 23%, respectively. The calcaneofibular ligament fibular attachment was 5.5 mm from the inferior tip, at 16% along the anterior edge of the distal fibula. CONCLUSION: The measurements of anterior talofibular ligament and calcaneofibular ligament attachment locations identified on three-dimensional magnetic resonance imaging were sufficiently reliable. This measurement method provides in vivo anatomical data on the lateral ankle ligament anatomy.

The effects of a teacher-led online mental health literacy program for high school students: a pilot cluster randomized controlled trial.

BACKGROUND: Adolescents are vulnerable to mental health problems, and this vulnerability may be enhanced in situations such as the present COVID-19 pandemic. Online mental health literacy (MHL) education may help adolescents maintain/improve their mental health, especially in situations where face-to-face education is difficult. AIMS: To evaluate the effects of a teacher-led "online Short MHL Program (o-SMHLP)" delivered online to grade 10 students in their classrooms. METHODS: Students (age 15-16) were randomly assigned to an o-SMHLP group (n = 115 (3 classes)) or a control group (n = 155 (4 classes)) at the class level. The program consisted of a 20-minute session which included an animated video. The students completed a self-report questionnaire pre- and post-intervention assessing outcomes including: "Knowledge about mental health/illnesses", "Recognition of necessity to seek help", "Intention to seek help", and "Unwillingness to socialize with people having mental illness". Mixed effects modeling was employed for analyses. RESULTS: All outcomes were significantly improved in the intervention group compared to the control group post-intervention, except for "intention to seek help". CONCLUSIONS: The present study shows the effectiveness of an online MHL intervention while identifying the need for the development of effective online programs targeting adolescents' "intention to seek help".

Estimation of the Radiographic Parameters for Hallux Valgus From Photography of the Feet Using a Deep Convolutional Neural Network.

BACKGROUND: Hallux valgus (HV), also known as bunion deformity, is one of the most common forefoot deformities. Early diagnosis and proper evaluation of HV are important because timely management can improve symptoms and quality of life. Here, we propose a deep learning estimation for the radiographic measurement of HV based on a regression network where the input to the algorithm is digital photographs of the forefoot, and the radiographic measurement of HV is computed as output directly. The purpose of our study was to estimate the radiographic parameters of HV using deep learning, to classify the severity by grade, and to assess the agreement of the predicted measurement with the actual radiographic measurement. METHODS: There were 131 patients enrolled in this study. A total of 248 radiographs and 337 photographs of the feet were acquired. Radiographic parameters, including the HV angle (HVA), M1-M2 angle, and M1-M5 angle, were measured. We constructed a convolutional neural network using Xception and made the classification model into the regression model. Then, we fine-tuned the model using images of the feet and the radiographic parameters. The coefficient of determination (R2) and root mean squared error (RMSE), as well as Cohen's kappa coefficient, were calculated to evaluate the performance of the model. RESULTS: The radiographic parameters, including the HVA, M1-M2 angle, and M1-M5 angle, were predicted with a coefficient of determination (R2)=0.684, root mean squared error (RMSE)=7.91; R2=0.573, RMSE=3.29; R2=0.381, RMSE=5.80, respectively. CONCLUSION: The present study demonstrated that our model could predict the radiographic parameters of HV from photography. Moreover, the agreement between the expected and actual grade of HV was substantial. This study shows a potential application of a convolutional neural network for the screening of HV.

Young-onset type 2 diabetes mellitus enhances proteinuria, but not glomerular filtration rate decline: A Japanese cohort study.

AIMS/INTRODUCTION: The time course of chronic kidney disease in young-onset type 2 diabetes mellitus remains unclear. We compared the trajectories of proteinuria and estimated glomerular filtration rate (eGFR) decline between young-onset (aged ≤40 years) and late-onset (aged >40 years) type 2 diabetes mellitus in a Japanese multicenter cohort. MATERIALS AND METHODS: Participants without diabetic kidney disease were divided into two groups according to age at diagnosis: young- and late-onset. The primary endpoint was eGFR <60 mL/min/1.73 m2, proteinuria or both. Multivariable Cox proportional hazards were calculated to estimate incidence. RESULTS: Among 626 participants with type 2 diabetes mellitus, 78 (12.4%) had young-onset and 548 (87.6%) had late-onset diabetes. The incidence of eGFR <60 mL/min/1.73 m2 was lower (16.7% vs 33.5%, P = 0.003), but that of proteinuria was higher (46.2% vs 28.9%, P = 0.002) in the young-onset type 2 diabetes mellitus group. The Kaplan-Meyer curve showed that young-onset type 2 diabetes mellitus was associated with a decreased hazard ratio (HR) for eGFR <60 mL/min/1.73 m2 and an increased HR for proteinuria compared with late-onset type 2 diabetes mellitus. In the multivariate Cox analysis, young-onset type 2 diabetes mellitus increased the HR (95% confidence interval) of proteinuria (1.53, 95% confidence interval 1.03-2.26), but did not change the eGFR <60 mL/min/1.73 m2 HR. CONCLUSIONS: Young-onset type 2 diabetes mellitus has a lower HR of eGFR <60 mL/min/1.73 m2 and an increased HR of proteinuria compared with late-onset type 2 diabetes mellitus, indicating that young-onset type 2 diabetes mellitus has a different time course for the development of proteinuria and subsequent eGFR decline.

Re-administration of platinum-based chemotherapy for recurrent endometrial cancer: an ancillary analysis of the SGSG-012/GOTIC-004/Intergroup study.

BACKGROUND: We previously demonstrated the applicability of the concept of "platinum sensitivity" in recurrent endometrial cancer. Although immune checkpoint inhibitors have been widely incorporated into endometrial cancer treatment, the debate continues regarding treatment options in patients with recurrent endometrial cancer who have previously received platinum-based chemotherapy. In this study, we assessed the duration of response to secondary platinum-based treatment using pooled data from the SGSG-012/GOTIC-004/Intergroup study. METHODS: Among the 279 participants in the SGSG-012/GOTIC-004/Intergroup study wherein platinum-based chemotherapy was re-administered for managing recurrent endometrial cancer between January 2005 and December 2009, 130 (47%) responded to chemotherapy. We compared the relationship between platinum-free interval and duration of secondary platinum-based treatment using pooled data. RESULTS: In 40 patients (31%), the duration of response to secondary platinum-based treatment exceeded the platinum-free interval. The duration of response to secondary platinum-based treatment exceeded 12 months in 51 patients (39%) [platinum-free interval: < 12 months, 14/48 (29%); 12-23 months, 18/43 (42%); 24-35 months, 8/19 (42%); ≥ 36 months, 11/20 (55%)]. In particular, in eight patients (6%), the duration of response to secondary platinum-based treatment exceeded 36 months [platinum-free interval: < 12 months, 3/48 (6%); 12-23 months, 0/19 (0%); 24-35 months, 2/19 (11%); ≥ 36 months, 3/20 (15%)]. CONCLUSIONS: Re-administration of platinum-based chemotherapy for recurrent endometrial cancer may result in a long-term response exceeding the platinum-free interval in some patients. Even in the current situation, where immune checkpoint inhibitors have been introduced, re-administration of platinum-based chemotherapy is worth considering.

Investigating the Differential Impact of Short- and Long-Term Informal Caregiving on Mental Health Across Adolescence: Data From the Tokyo Teen Cohort.

PURPOSE: Young caregivers experience, on average, poorer mental health outcomes than non-caregiving young people. However, it is unknown to what extent these effects differ with age, or among short-term versus long-term caregivers. Using repeated assessment of young caregiving across multiple waves of a prospective adolescent cohort study, we conducted repeated cross-sectional analyses of caregiver status and contemporaneous depressive symptoms, self-harm, and suicidality in early to middle adolescence. METHODS: Four waves of questionnaire data from a large, longitudinal population-based cohort study (Tokyo Teen Cohort) were analyzed. Caregiver status was collected from participants aged 10, 12, 14, and 16 years. Mental health outcomes assessed were depressive symptoms, self-harm and suicidal feelings. Logistic regression analyses were conducted assessing effects of a) young caregiver status and b) new, long-term, and ex-caregiver 2-year categorizations on mental health outcomes at 12, 14, and 16 years, both unadjusted and adjusted for potential confounders (sex, low income, single-parent household, and parental distress). RESULTS: Depressive symptoms were elevated among long-term caregivers at 14 years (unadjusted odds ratio (uOR): 3.11 [1.33-7.27], adjusted odds ratio (aOR): 2.49 [1.03-5.99]). Borderline associations between long-term caregiving and self-harm (uOR: 3.14 [1.06-9.35], aOR: 2.51 [0.82-7.63]) and suicidal feelings (uOR: 2.49 [0.98-6.34], aOR: 2.06 [0.80-5.33]) were detected at 16 years. No associations were found at age 12 years in primary analyses; sensitivity analyses indicated possible increased depressive symptoms. DISCUSSION: Young caregivers with long-term caregiving roles are at the greatest risk for negative mental health outcomes, with effects concentrated in later adolescence. These findings highlight urgent need for early identification and practical and psychological support for young people shouldering caregiving burdens.

High cost of chemotherapy for gynecologic malignancies.

BACKGROUND: The prognosis of gynecological malignancies has improved with the recent advent of molecularly targeted drugs and immune checkpoint inhibitors. However, these drugs are expensive and contribute to the increasing costs of medical care. METHODS: The Japanese Clinical Oncology Group (JCOG) Health Economics Committee conducted a questionnaire survey of JCOG-affiliated facilities from July 2021 to June 2022 to assess the prevalence of high-cost regimens. RESULTS: A total of 57 affiliated facilities were surveyed regarding standard regimens for advanced ovarian and cervical cancers for gynecological malignancies. Responses were obtained from 39 facilities (68.4%) regarding ovarian cancer and 37 (64.9%) concerning cervical cancer, with respective case counts of 854 and 163. For ovarian cancer, 505 of 854 patients (59.1%) were treated with regimens that included PARP inhibitors, costing >500 000 Japanese yen monthly, while 111 patients (13.0%) received treatments that included bevacizumab, with costs exceeding 200 000 Japanese yen monthly. These costs are ~20 and ~10 times higher than those of the conventional regimens, respectively. For cervical cancer, 79 patients (48.4%) were treated with bevacizumab regimens costing >200 000 Japanese yen per month, ~10 times the cost of conventional treatments. CONCLUSIONS: In this survey, >70% of patients with ovarian cancer were treated with regimens that included poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors or bevacizumab; ~50% of patients with cervical cancer were treated with regimens containing bevacizumab. These treatments were ~10 and ~20 times more expensive than conventional regimens, respectively. These findings can inform future health economics studies, particularly in assessing cost-effectiveness and related matters.

Association between number of confidants and adolescent anxiety/depression: a school-based study.

BACKGROUND: Having no or few confidants is found to be associated with more severe mental health problems and a higher prevalence of depression in adults, but research examining this association in adolescents is scarce. Social relationships may be particularly critical during adolescence, as it is an important developmental period during which vulnerability to mental health problems increases. The present study examined the relationship between having no or few confidants and anxiety/depressive symptoms in adolescents. METHODS: Cross-sectional self-report survey targeting 7-12th grade students (age range: 12-18) was conducted in public junior and senior high schools in Mie and Kochi, Japan. Data from 17,829 students (49.7% boys) were analyzed. Associations between anxiety/depressive symptoms (12-item General Health Questionnaire; score range: 0-12) and the number of confidants (None, 1-3, or ≥ 4) were examined using multilevel regression analyses. The analyses were stratified by gender and school level (junior/senior high), and adjusted for experiences of being physically abused and bullied and the interactions of these experiences with the number of confidants. RESULTS: Having no or 1-3 confidants was associated with more anxiety/depressive symptoms, compared to having ≥ 4 confidants (p < 0.001) in all stratified groups. Having no confidants was associated with more anxiety/depressive symptoms than having 1-3 confidants (p < 0.001); in senior high boys, no difference was observed between having no confidants and having 1-3 confidants. In addition, in senior high boys, victims of bullying who have confidants reported significantly less anxiety/depressive symptoms than the victims who have no confidants (p < 0.01). CONCLUSIONS: Adolescents who had no or few confidants had more anxiety/depressive symptoms. Attention needs to be paid to better identify these adolescents, and avenues to support them need to be established.

Comprehensive Analysis of Wettability in Waterproofed Gas Diffusion Layers for Polymer Electrolyte Fuel Cells.

In polymer electrolyte fuel cells (PEFCs), the gas diffusion layer (GDL) is crucial for managing the flooding tolerance, which is the ability to remove the water produced during power generation from the assembled cell. However, an improved understanding of the properties of GDLs is required to develop effective waterproofing strategies. This study investigated the influence of the polytetrafluoroethylene (PTFE) content on the pore diameter, porosity, wettability, water saturation, and flooding tolerance of waterproofed carbon papers as cathode GDLs in PEFCs. The addition of minimal PTFE (∼6 wt %) to carbon paper provided external waterproofing, whereas internal waterproofing was achieved at a higher PTFE content (∼13 wt %). However, excessive PTFE (∼37 wt %) led to macropore collapse within the carbon paper, reducing fuel cell performance. Although PTFE addition was expected to improve the flooding tolerance, operando synchrotron X-ray radiography revealed that the water saturation level in carbon paper increased with increasing PTFE content. These findings provide a benchmark for assessing whether GDLs meet the flooding tolerance requirements of PEFCs and may be applicable to waterproofed GDLs in electrochemical devices for water and CO2 electrolysis.

A case of Fanconi syndrome that developed following a year of consumption of a red yeast rice supplement.

Although some dietary supplements have been reported to cause renal dysfunction, there have been few reports of supplement-induced Fanconi syndrome. We present the case of a 56-year-old woman with Fanconi syndrome that developed after she consumed a red yeast rice supplement. She was referred to our hospital because of renal dysfunction, and was found to have electrolyte abnormalities, including hypophosphatemia and hypouricemia, renal diabetes, and hyperchloremic metabolic acidosis, and was, therefore, diagnosed with Fanconi syndrome. Renal biopsy revealed proximal tubular injury characterized by severely degenerated tubular epithelial cells as well as mild hypocellular fibrosis. We speculated that the red yeast rice supplement, which the patient had been consuming for approximately 1 year, might be a cause of her syndrome, because reports of renal dysfunction associated with the consumption of red yeast rice supplements have emerged in Japan since 2024. After the supplement was discontinued and oral prednisolone treatment was initiated, the patient's renal function improved and her electrolyte abnormalities were ameliorated. Furthermore, even after tapering off and discontinuing the prednisolone over approximately 12 weeks, her renal function remained. Because Fanconi syndrome may be caused by various exogenous substances, the taking of a thorough medical history is crucial, including with respect to the use not only of prescription medications, but also other substances, including supplements.

Incisura tangent method to determine the transsyndesmotic axis for syndesmotic fixation.

BACKGROUND: Clamping along the transsyndesmotic (TS) axis decreases the risk of malreduction when reducing syndesmotic diastasis. We aimed to measure the difference between the TS axis and the axis determined by the newly proposed fluoroscopic incisura tangent (IT) method. The measurements were compared to those between the TS axis and those based on the center-center (CC) and talar dome lateral (TL) methods. METHODS: We analyzed computed tomographic images of 43 normal ankles. The IT view was simulated using a digitally reconstructed radiograph, in which the anterior and posterior fibular incisura tubercles overlapped on the internally rotated anteroposterior view. The interaxis angle between the TS and the axes determined by the IT method was measured on the axial computed tomographic image corresponding to the radiographic image. The same procedure was repeated using the CC and TL methods. The measured values were compared between the three methods using a one-factor analysis of variance. Furthermore, the measurements of the anteverted and retroverted incisurae were compared for each fluoroscopic method. RESULTS: The mean interaxis angles between the TS were - 0.5 degrees, 6.3 degrees, and - 1.8 degrees for the IT, CC, and TL methods, respectively, with a significantly larger value for the CC method than for the IT and TL methods (P < .001). No significant difference was found in the interaxis angle in the anteverted (-0.1 degrees) and retroverted (-1.0 degrees) incisurae when using the IT method (P = .15). The angles in the retroverted incisurae were larger than those of the anteverted incisurae for the CC and TL methods. CONCLUSION: The fluoroscopic IT method accurately estimated the TS axis. The interaxis angles were consistent, regardless of the incisura anatomy. The fluoroscopic method can be used to clamp and fix the syndesmosis along the TS axis. LEVEL OF EVIDENCE: Ⅳ.

Association of Problematic Internet Use With Psychotic Experiences and Depression in Adolescents: A Cohort Study.

BACKGROUND AND HYPOTHESIS: Problematic internet use (PIU) is prevalent among adolescents. Past research suggested cross-sectional associations between PIU and psychotic experiences, but little information is available on the longitudinal association. We hypothesized that PIU in adolescence may be longitudinally associated with psychotic experiences, adjusting for confounders. STUDY DESIGN: We analyzed a random sample of adolescents in the Tokyo Teen Cohort to examine how PIU at ages 10 (2012-2015), 12 (2014-2017), and 16 (2019-2021) was associated with mental health issues at age 16. PIU was evaluated by the modified Compulsive Internet Use Scale, psychotic experiences by the Adolescent Psychotic-like Symptom Screener, and depression by the Short Mood and Feelings Questionnaire. We also examined the mediating role of social withdrawal. STUDY RESULTS: We analyzed 3171 adolescents; 151 reported psychotic experiences and 327 reported depression at age 16. Compared with the lowest tertile PIU group, the highest tertile PIU group at age 12 showed an increased adjusted risk of psychotic experiences (RD 3.3%, 95% CI 2.9%-3.7%; RR 1.65, 95% CI 1.55-1.73) and depression (RD 5.9%, 95% CI 5.5%-6.3%; RR 1.61, 95% CI 1.55-1.68) at age 16. PIU at age 16 showed analogous results, while PIU at age 10 suggested a smaller impact. Social withdrawal mediated 9.4%-29.0% of the association between PIU and psychotic experiences. CONCLUSIONS: PIU is longitudinally associated with psychotic experiences and depression in adolescents. Further longitudinal and intervention studies are warranted to provide robust public health implications and foster a safer digital future.

Characterization of a hydrothermally aged experimental alumina-toughened zirconia composite.

OBJECTIVES: To assess the effects of different aging protocols on chemical, physical, and mechanical properties of an experimental ATZ composite compared to a zirconia. METHODS: Disc-shaped specimens were obtained through uniaxial pressing of commercial powders (Tosoh), ATZ comprised of 80%ZrO2/20%Al2O3 (TZ-3YS20AB) and 3Y-TZP (3Y-SBE). The specimens of each material were divided into different groups according to the aging protocol: immediate, autoclave aging and hydrothermal reactor aging. The aging protocols were performed at 134 ºC for 20 h at 2.2 bar. Crystalline evaluations were performed using X-Ray Diffraction. The nanoindentation tests measured the elastic modulus (Em) and hardness (H). Biaxial flexural strength was performed, and Weibull statistics were used to determine the characteristic strength and Weibull modulus. The probability of survival was also determined. The Em and H data were analyzed by one-way ANOVA and Tukey test. RESULTS: Diffractograms revealed the presence of monoclinic phase in both materials after aging. The hydrothermal reactor decreased the Em for ATZ compared to its immediate condition; and the H for both ATZ and 3Y-TZP regarding their immediate and autoclave aging conditions, respectively. The aging protocols significantly increased the characteristic strength for ATZ, while decreased for 3Y-TZP. No difference regarding Weibull modulus was observed, except for 3Y-TZP aged in reactor. For missions of up to 500 MPa, both materials presented a high probability of survival (>99 %) irrespective of aging condition. SIGNIFICANCE: The synthesized ATZ composite exhibited greater physical and microstructural stability compared to 3Y-TZP, supporting potential application of the experimental material for long-span reconstructive applications.