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Currently, the number of smartphones with an embedded gyroscope sensor has been increasing due games whose performance relies on 3D augmented reality. In general, teaching papers on the gyroscope sensor address very simple spatial configuration, where the fixed rotation axis coincides to the z-axis of the smartphone. This work presents five experimental setups with different spatial orientations of a smartphone on a turntable. The total angular velocity vector of the turntable is constant, but its projections on the three fixed Cartesian axes of the smartphone varies for the five spatial orientations investigated. For the sake of consistency, the magnitude of the vector sum of the three angular velocities components yielded by the gyroscope sensor was checked by video analysis using the free software, Tracker. The internal consistency between the results provided by this video analysis technique and data from the gyroscope assures us this sensor is reliable for teaching proposals. The main goals of this paper are (i) encourage teachers to effectively incorporate the gyroscope sensor of smartphones in to their classrooms, especially in high schools and undergraduate physics and engineering courses; (ii) spread in the academic syllabus the Tait–Bryan convention, a very intuitive way to perform 3D rotations and; (iii) explain how to interpret data of the three components of angular velocity obtained by the gyroscope sensor in different spatial orientations. [ABSTRACT FROM AUTHOR]

In the present work, we develop a low-cost and simple experiment to visualise Fourier’s synthesis using a short, soft, and light plastic coiled spring oscillating in a horizontal plane, and a basic camera (120 fps). It is shown that the spring obeys a linear wave differential equation, as gravitational influence is neglected. A nonlinear criterion is evaluated to determine if magnitudes of the parameters in the initial conditions satisfy the linear wave equation. Our setup promotes some desirable characteristics that make Fourier’s synthesis experiments feasible, visual, and enlightening: (i) it requires few, common, and cheap resources, and the experiment can be carried out even in a high-school laboratory; (ii) since the spring’s tension is small (∼1 N, on average), the frequencies of normal modes are low (close to 2 Hz), and therefore, it is possible to record the oscillations just with the camera and extract a considerable number of position and time data in just one cycle; (iii) when the video is loaded in the Tracker free software, it can be reproduced in slow motion. Since the frequencies involved are low, an interesting and instructive temporal sequence of images of the spring displaying the typical trapezoidal shape appears clearly; (iv) the tools associated with the Tracker software tools can yield the relevant oscillation parameters, such as the damping constant, amplitudes, frequencies, and phases; and (v) it is possible to carry out superposition of a snapshot of the spring in Tracker at any time, and to draw the related Fourier synthesis graphs. The visual match between the shape of the spring and the theoretical graph is remarkable, and can be enhanced by adding the damping term. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to assess the utility of the combined use of 3D wheel sampling and deep learning-based reconstruction (DLR) for intracranial high-resolution (HR)-time-of-flight (TOF)-magnetic resonance angiography (MRA) at 3 T., Methods: This prospective study enrolled 20 patients who underwent head MRI at 3 T, including TOF-MRA. We used 3D wheel sampling called "fast 3D" and DLR for HR-TOF-MRA (spatial resolution, 0.39 × 0.59 × 0.5 mm 3 ) in addition to conventional MRA (spatial resolution, 0.39 × 0.89 × 1 mm 3 ). We compared contrast and contrast-to-noise ratio between the blood vessels (basilar artery and anterior cerebral artery) and brain parenchyma, full width at half maximum in the P3 segment of the posterior cerebral artery among 3 protocols. Two board-certified radiologists evaluated noise, contrast, sharpness, artifact, and overall image quality of 3 protocols., Results: The contrast and contrast-to-noise ratio of fast 3D-HR-MRA with DLR are comparable or higher than those of conventional MRA and fast 3D-HR-MRA without DLR. The full width at half maximum was significantly lower in fast 3D-MRA with and without DLR than in conventional MRA ( P = 0.006, P < 0.001). In qualitative evaluation, fast 3D-MRA with DLR had significantly higher sharpness and overall image quality than conventional MRA and fast 3D-MRA without DLR (sharpness: P = 0.021, P = 0.001; overall image quality: P = 0.029, P < 0.001)., Conclusions: The combination of 3D wheel sampling and DLR can improve visualization of arteries in intracranial TOF-MRA., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: This study aimed to assess the safety and efficacy of endovascular treatment of unruptured pancreatic arcade aneurysms in a single-center series., Materials and Methods: The electronic medical records of patients who underwent endovascular treatment for unruptured pancreatic arcade aneurysms between 2011 and 2022 at our tertiary center were retrospectively reviewed. The presence of celiac artery stenosis/occlusion; aneurysm number, location, and size; endovascular technique; procedure-related complication incidence; and clinical outcomes were assessed., Results: Twenty-three patients (12 men and 11 women; mean [range] age, 63.8 [45-84] years) with 33 unruptured pancreatic arcade aneurysms were identified. Celiac artery stenosis/occlusion coexisted in 17 (74%) patients. Five (21%) patients had multiple aneurysms. The median aneurysm size was 9.3 mm (range, 4-18 mm). Seven, 6, 6, 5, 4, 3, and 2 aneurysms were located in the gastroduodenal, dorsal pancreatic, anterior superior pancreaticoduodenal, inferior pancreaticoduodenal, posterior inferior pancreaticoduodenal, posterior superior pancreaticoduodenal, and anterior inferior pancreaticoduodenal arteries, respectively. Four (15%) and 22 (85%) aneurysms were treated with endosaccular packing alone and coil embolization with endosaccular packing and parent artery occlusion, respectively, with resulting exclusion from arterial circulation. The remaining 7 aneurysms coexisting with larger aneurysms in other peripancreatic arteries were observed without embolization because they were small and for preserving collateral blood flow to the celiac artery. The treated aneurysms did not rupture or recur during the follow-up period (median, 40 months)., Conclusion: Endovascular treatment is a safe and effective treatment for unruptured pancreatic arcade aneurysms., Level of Evidence: 3, non-controlled retrospective cohort study., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).)

Context: Adrenal crisis (AC) is a life-threatening complication that occurs during follow-up of patients with adrenal insufficiency (AI). No prospective study has thoroughly investigated AC in children with primary and secondary AI., Objective: This work aimed to determine the incidence and risk factors for AC in patients with pediatric-onset AI., Methods: This multicenter, prospective cohort study conducted in Japan enrolled patients diagnosed with AI at age ≤15 years. The incidence of AC was calculated as events per person-year (PY), and risk factors for AC were assessed using Poisson regression multivariable analysis., Results: The study population comprised 349 patients (164 male, 185 female) with a total follow-up of 961 PY. The median age at enrollment was 14.3 years (interquartile range [IQR] 8.5-21.2 years), and the median follow-up was 2.8 years (IQR 2.2-3.3 years). Of these patients, 213 (61%) had primary AI and 136 (39%) had secondary AI. Forty-one AC events occurred in 31 patients during the study period. The calculated incidence of AC was 4.27 per 100 PY (95% CI, 3.15-5.75). Poisson regression analysis identified younger age at enrollment (relative risk [RR] 0.93; 95% CI, 0.89-0.97) and increased number of infections (RR 1.17; 95% CI, 1.07-1.27) as significant risk factors. Female sex (RR 0.99; 95% CI, 0.53-1.86), primary AI (RR 0.65; 95% CI, 0.30-1.41), or equivalent dosage of hydrocortisone per square meter of body area (RR 1.02; 95% CI, 0.96-1.08) was not a significant risk factor., Conclusion: A substantial proportion of patients with pediatric-onset AI experience AC. Younger age and an increased number of infections are independent risk factors for developing AC in these patients., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: To assess the different adjunctive catheter techniques required to achieve complete occlusion of renal arteriovenous malformations (rAVMs) of different angioarchitectural types., Materials and Methods: Overall, data on 18 patients with rAVM (Type 1, n = 7; Type 2, n = 2; Type 3, n = 9; mean age, 53.8 years) who underwent 25 procedures between 2011 and 2022 were reviewed. The clinical presentations, endovascular techniques, arteriovenous malformation (AVM) occlusion rate, adverse events (including the incidence of renal infarction), and clinical symptoms and outcomes (including recurrence/increase of AVM) were analyzed according to the Cho-Do angioarchitectural classification. Posttreatment renal infarction was classified as no infarction, small infarction (<12.5%), medium infarction (12.5%-25%), and large infarction (>25%) using contrast-enhanced computed tomography or magnetic resonance imaging., Results: Hematuria and heart failure were presenting symptoms in 10 and 2 patients, respectively. The embolic materials used were as follows: Type 1 rAVM, coils alone or with n-butyl-2-cyanoacrylate (nBCA); Type 2 rAVM, nBCA alone or with coils; and Type 3 rAVMs, nBCA alone. Fourteen patients underwent adjunctive catheter techniques, including flow control with a balloon catheter and multiple microcatheter placement, alone or in combination. Immediate postprocedural angiography revealed complete occlusion in 15 patients (83%) and marked regression of rAVM in 3 (17%). Small asymptomatic renal infarctions were observed in 6 patients with Type 3 rAVMs without any decrease in renal function. No major adverse events were observed. All symptomatic patients experienced symptom resolution. Recurrence/increase of rAVM was not observed during the mean 32-month follow-up period (range, 2-120 months)., Conclusions: Transarterial embolization using adjunctive catheter techniques according to angioarchitectural types can be an effective treatment for rAVMs., (Copyright © 2024 SIR. Published by Elsevier Inc. All rights reserved.)

Key Message: We proposed models to predict the effects of genomic and environmental factors on daily soybean growth and applied them to soybean growth data obtained with unmanned aerial vehicles. Advances in high-throughput phenotyping technology have made it possible to obtain time-series plant growth data in field trials, enabling genotype-by-environment interaction (G × E) modeling of plant growth. Although the reaction norm is an effective method for quantitatively evaluating G × E and has been implemented in genomic prediction models, no reaction norm models have been applied to plant growth data. Here, we propose a novel reaction norm model for plant growth using spline and random forest models, in which daily growth is explained by environmental factors one day prior. The proposed model was applied to soybean canopy area and height to evaluate the influence of drought stress levels. Changes in the canopy area and height of 198 cultivars were measured by remote sensing using unmanned aerial vehicles. Multiple drought stress levels were set as treatments, and their time-series soil moisture was measured. The models were evaluated using three cross-validation schemes. Although accuracy of the proposed models did not surpass that of single-trait genomic prediction, the results suggest that our model can capture G × E, especially the latter growth period for the random forest model. Also, significant variations in the G × E of the canopy height during the early growth period were visualized using the spline model. This result indicates the effectiveness of the proposed models on plant growth data and the possibility of revealing G × E in various growth stages in plant breeding by applying statistical or machine learning models to time-series phenotype data., (© 2024. The Author(s).)

A 54-year-old man was admitted with obstructive jaundice. Computed tomography showed common bile duct stricture and a tumor around the celiac artery. Repeated endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and endoscopic retrograde cholangiopancreatography (ERCP) as well as a laparotomic biopsy around the celiac artery were diagnostically unsuccessful. Since the bile duct stricture progressed, EUS-FNA and ERCP were performed a third time, finally leading to the diagnosis of diffuse large B-cell lymphoma. The treatment plan and prognosis of obstructive jaundice differ greatly depending on the disease. It is important to conduct careful follow-up and repeated histological examinations with appropriate modifications until a diagnosis is made.

Competing Interests: The authors have nothing to declare.

Objectives: As a novel follow-up method for intracranial aneurysms treated with stent-assisted coil embolization (SACE), we developed four-dimensional magnetic resonance angiography (MRA) with minimized acoustic noise utilizing ultrashort-echo time (4D mUTE-MRA). We aimed to assess whether 4D mUTE-MRA is useful for the evaluation of intracranial aneurysms treated with SACE., Methods: This study included 31 consecutive patients with intracranial aneurysm treated with SACE who underwent 4D mUTE-MRA at 3 T and digital subtraction angiography (DSA). For 4D mUTE-MRA, five dynamic MRA images with a spatial resolution of 0.5 × 0.5 × 0.5 mm 3 were obtained every 200 ms. Two readers independently reviewed the 4D mUTE-MRA images to evaluate the aneurysm occlusion status (total occlusion, residual neck, and residual aneurysm) and the flow in the stent using a 4-point scale (from 1 [not visible] to 4 [excellent]). The interobserver and intermodality agreement was assessed using κ statistics., Results: On DSA images, 10 aneurysms were classified as total occlusion, 14 as residual neck, and 7 as residual aneurysm. In terms of aneurysm occlusion status, the intermodality and interobserver agreement was excellent (κ = 0.92 and κ = 0.96, respectively). For the flow in the stents on 4D mUTE-MRA, the mean score was significantly higher for single stents than multiple stents (p < .001) and for open-cell type stents than closed-cell type (p < .01)., Conclusions: 4D mUTE-MRA is a useful tool with a high spatial and temporal resolution for the evaluation of intracranial aneurysms treated with SACE., Key Points: • In the evaluation of intracranial aneurysms treated with SACE on 4D mUTE-MRA and DSA, the intermodality and interobserver agreement in aneurysm occlusion status was excellent. • 4D mUTE-MRA shows good to excellent visualization of flow in the stents, especially for cases treated with a single or open-cell stent. • 4D mUTE-MRA can provide hemodynamic information related to embolized aneurysms and the distal arteries to stented parent arteries., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Prevention of hypoglycemia is an important strategy for glycemic management in patients with type 1 diabetes mellitus (T1D). Hypoglycemia is difficult to recognize at night while sleeping, particularly when using multiple daily injection (MDI) insulin therapy rather than sensor-augmented insulin-pump therapy. Therefore, it is possible that patients with T1D are at higher risk of nocturnal hypoglycemia when insulin is administered using an MDI regimen. We investigated nocturnal hypoglycemia in 50 pediatric patients with T1D on MDI insulin therapy using data from an intermittently scanned continuous glucose monitoring (isCGM) system. Hypoglycemia was observed on 446 of the 1,270 nights studied. Most of the hypoglycemic episodes were severe (blood glucose <54 mg/dL). On nights when hypoglycemia occurred, the blood glucose concentrations measured using finger-stick blood glucose monitoring (FSGM) before sleep and the next morning were lower than nights when hypoglycemia did not occur. However, few values were below the normal blood glucose range, suggesting that FSGM alone may be insufficient to detect nocturnal hypoglycemia. Approximately 7% of time was spent below the normal glucose range during the 10 hours from 21:00 to 7:00 the next morning. This result suggests that the patients on MDI insulin therapy could end up spending more time in hypoglycemia than is recommended by the American Diabetes Association (time below range <4.0% of time per day). Monitoring glucose levels overnight using an isCGM sensor may improve glycemic management via automatic detection of blood glucose peaks and troughs.

Recently, due to the spread of COVID-19, the implementation of remote learning has been increasing worldwide. This study aims to analyze the difficulties and convenience of using information and communication technology (ICT) for students with disabilities and changes in their perceptions of ICT use after the completion of courses for each form of remote learning. The survey included 122 students with disabilities and 314 students without disabilities via a web-based questionnaire. The questionnaire consisted of four situations, categorized according to the type of remote classes. We conducted an analysis of variance using a two-factor mixed design with disability (non-paired: two levels) × situations (paired: four levels) regarding perceptions of resistance toward ICT and self-rated comprehension as the dependent variables. Results show that students with disabilities were more positive about using ICT than students without disabilities in many items. However, before the courses that required the use of relatively new application software, such as web conferencing systems, students with disabilities showed significantly higher levels of resistance and lower levels of self-assessed comprehension. Further, a comparison of the amount of change in perceptions before and after the course reveals that students with disabilities showed significantly more improvement in negative items before the course. These results suggest the importance of providing opportunities for students with disability to learn how to use ICT and understand its convenience in an environment similar to an actual classroom, given the rapid changes occurring in ICT., Competing Interests: Competing interestOn behalf of all authors, the corresponding author states that there is no conflict of interest., (© The Author(s) 2023.)

With the widespread use of high-throughput phenotyping systems, growth process data are expected to become more easily available. By applying genomic prediction to growth data, it will be possible to predict the growth of untested genotypes. Predicting the growth process will be useful for crop breeding, as variability in the growth process has a significant impact on the management of plant cultivation. However, the integration of growth modeling and genomic prediction has yet to be studied in depth. In this study, we implemented new prediction models to propose a novel growth prediction scheme. Phenotype data of 198 soybean germplasm genotypes were acquired for 3 years in experimental fields in Tottori, Japan. The longitudinal changes in the green fractions were measured using UAV remote sensing. Then, a dynamic model was fitted to the green fraction to extract the dynamic characteristics of the green fraction as five parameters. Using the estimated growth parameters, we developed models for genomic prediction of the growth process and tested whether the inclusion of the dynamic model contributed to better prediction of growth. Our proposed models consist of two steps: first, predicting the parameters of the dynamics model with genomic prediction, and then substituting the predicted values for the parameters of the dynamics model. By evaluating the heritability of the growth parameters, the dynamic model was able to effectively extract genetic diversity in the growth characteristics of the green fraction. In addition, the proposed prediction model showed higher prediction accuracy than conventional genomic prediction models, especially when the future growth of the test population is a prediction target given the observed values in the first half of growth as training data. This indicates that our model was able to successfully combine information from the early growth period with phenotypic data from the training population for prediction. This prediction method could be applied to selection at an early growth stage in crop breeding, and could reduce the cost and time of field trials., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Toda, Sasaki, Ohmori, Yamasaki, Takahashi, Takanashi, Tsuda, Kajiya-Kanegae, Lopez-Lozano, Tsujimoto, Kaga, Nakazono, Fujiwara, Baret and Iwata.)

Case: We report a case of irreducible chronic volar dislocation of the distal radioulnar joint (DRUJ) after surgery for distal radius fracture. The patient underwent volar locking plate fixation for distal radius fracture. Despite the satisfactory alignment of the distal radius, irreducible volar dislocation of the DRUJ was discovered at 5 weeks after the initial surgery. DRUJ reconstruction at 9 weeks after injury using the Adams-Berger procedure resulted in a stable and functional DRUJ and wrist., Conclusion: To prevent postoperative DRUJ instability or dislocation, the DRUJ should be evaluated for stability immediately after fracture fixation., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSCC/B520)., (Copyright © 2021 The Authors. Published by The Journal of Bone and Joint Surgery, Incorporated. All rights reserved.)

Monoclonal antibodies (mAbs) are widely utilized as therapeutic drugs for various diseases, such as cancer, autoimmune diseases, and infectious diseases. Using the avian-derived B cell line DT40, we previously developed an antibody display technology, namely, the ADLib system, which rapidly generates antigen-specific mAbs. Here, we report the development of a human version of the ADLib system and showcase the streamlined generation and optimization of functional human mAbs. Tailored libraries were first constructed by replacing endogenous immunoglobulin genes with designed human counterparts. From these libraries, clones producing full-length human IgGs against distinct antigens can be isolated, as exemplified by the selection of antagonistic mAbs. Taking advantage of avian biology, effective affinity maturation was achieved in a straightforward manner by seamless diversification of the parental clones into secondary libraries followed by single-cell sorting, quickly affording mAbs with improved affinities and functionalities. Collectively, we demonstrate that the human ADLib system could serve as an integrative platform with unique diversity for rapid de novo generation and optimization of therapeutic or diagnostic antibody leads. Furthermore, our results suggest that libraries can be constructed by introducing exogenous genes into DT40 cells, indicating that the ADLib system has the potential to be applied for the rapid and effective directed evolution and optimization of proteins in various fields beyond biomedicine.

Aims: To clarify the effectiveness of the induced membrane technique (IMT) using beta-tricalcium phosphate (β-TCP) for reconstruction of segmental bone defects by evaluating clinical and radiological outcomes, and the effect of defect size and operated site on surgical outcomes., Methods: A review of the medical records was conducted of consecutive 35 lower limbs (30 males and five females; median age 46 years (interquartile range (IQR) 40 to 61)) treated with IMT using β-TCP between 2014 and 2018. Lower Extremity Functional Score (LEFS) was examined preoperatively and at final follow-up to clarify patient-centered outcomes. Bone healing was assessed radiologically, and time from the second stage to bone healing was also evaluated. Patients were divided into ≥ 50 mm and < 50 mm defect groups and into femoral reconstruction, tibial reconstruction, and ankle arthrodesis groups., Results: There were ten and 25 defects in the femur and tibia, respectively. Median LEFS improved significantly from 8 (IQR 1.5 to 19.3) preoperatively to 63.5 (IQR 57 to 73.3) at final follow-up (p < 0.001). Bone healing was achieved in all limbs, and median time from the second stage to bone healing was six months (IQR 5 to 10). Median time to bone healing, preoperative LEFS, or postoperative LEFS did not differ significantly between the defect size groups or among the treatment groups., Conclusion: IMT using β-TCP provided satisfactory clinical and radiological outcomes for segmental bone defects in the lower limbs; surgical outcomes were not influenced by bone defect size or operated part. Cite this article: Bone Joint J  2021;103-B(3):456-461.

Steroid 5α-reductase type 2 deficiency (5αRD2) is a congenital disorder of sex development caused by impairment of conversion from testosterone (T) to 5α-dihydrotestosterone (DHT). DHT deficiency leads to various degrees of undervirilized external genitalia including micropenis, primarily correlated with mutations of the SRD5A2 gene that encodes 5α-reductase type 2. Four Japanese boys with isolated micropenis were diagnosed as 5αRD2 by elevated ratios of serum T/DHT, and decreased ratios of urinary 5α/5β-reduced steroid metabolites. Genetic analyses for SRD5A2 identified that the four patients shared a hypomorphic mutation R227Q that has a residual activity related to the mild-form of 5αRD2. For prepubertal micropenis, DHT was transdermally applied to the four patients at the ages of 4-11 year, increasing a median of stretched penile lengths (SPLs) from 2.6 cm (-2.5 SD) to 4.4 cm (-0.2 SD). Nevertheless, the post-pubertal penile growth was apparently retarded, despite normal levels of T secreted from well-developed testes. The second course of DHT treatment underwent at ages of 12-18 year, but unable to normalize SPLs at a range of 6.0 to 7.0 cm (-3.4 to -2.4 SD). The prostate volumes of two patients were variable at 8.1 and 21 cm 3 , and a sperm cell count of one patient was normal as young adult. DHT treatment contributes to development of the penis and prostate, which are favorable for the potential fertility of 5αRD2 adults. Meanwhile, the retarded penile growth and a risk of prostate overgrowth may complicate the post-pubertal management with DHT for 5αRD2 males.

Background: The stimulatory G-protein α -subunit encoded by GNAS exons 1-13 ( GNAS -Gs α ) mediates signal transduction of multiple G protein-coupled receptors, including arginine vasopressin receptor 2 (AVPR2). Various germline-derived loss-of-function GNAS -Gs α variants of maternal and paternal origin have been found in pseudohypoparathyroidism type Ia and pseudopseudohypoparathyroidism, respectively. Specific somatic gain-of-function GNAS -Gs α variants have been detected in McCune-Albright syndrome and may result in phosphate wasting. However, no germline-derived gain-of-function variant has been identified, implying that such a variant causes embryonic lethality., Methods: We performed whole-exome sequencing in two families with dominantly inherited nephrogenic syndrome of inappropriate antidiuresis (NSIAD) as a salient phenotype after excluding a gain-of-function variant of AVPR2 and functional studies for identified variants., Results: Whole-exome sequencing revealed two GNAS -Gs α candidate variants for NSIAD: GNAS -Gs α p.(F68&#95;G70del) in one family and GNAS -Gs α p.(M255V) in one family. Both variants were absent from public and in-house databases. Of genes with rare variants, GNAS -Gs α alone was involved in AVPR2 signaling and shared by the families. Protein structural analyses revealed a gain-of-function-compatible conformational property for p.M255V-Gs α , although such assessment was not possible for p.F68&#95;G70del-Gs α . Both variants had gain-of-function effects that were significantly milder than those of McCune-Albright syndrome-specific somatic Gs α variants. Model mice for p.F68&#95;G70del-Gs α showed normal survivability and NSIAD-compatible phenotype, whereas those for p.M255V-Gs α exhibited severe failure to thrive., Conclusions: This study shows that germline-derived gain-of-function rare variants of GNAS -Gs α exist and cause NSIAD as a novel Gs α -mediated genetic disease. It is likely that AVPR2 signaling is most sensitive to GNAS -Gs α 's gain-of-function effects., (Copyright © 2019 by the American Society of Nephrology.)

Background Treatment for type 1 diabetes mellitus (T1DM) has greatly changed by the general use of insulin analogs and continuous subcutaneous insulin infusion (CSII). To investigate whether these advances have been translated into continued improvement in glycemic control in Japanese children and adolescents, we analyzed the registration data of the two consecutive recent cohorts of Japanese childhood-onset T1DM patients. Methods The registration data including hemoglobin A1c (HbA1c), hypoglycemia and insulin regimen were compared between the two cohorts (862 patients in the 2008 cohort and 1090 in the 2013 cohort). Results The proportion of subjects with multiple daily insulin injection therapy (MDI) and CSII significantly increased (p<0.0001) from 67.4% and 9.7% to 71.8% and 23.4%, respectively. In the 2013 cohort, almost all patients were treated with basal-bolus treatment using insulin analogs. The use of CSII increased in all age groups, especially in the age group 0-5 years. The rates of overall, moderate and severe hypoglycemia significantly declined from 10.24, 10.18 and 0.056 events/100 persons/period in the 2008 cohort to 0.66, 0.62 and 0.033 in the 2013 cohort (p<0.0001, <0.0001, 0.04), respectively. Contrarily, there were no significant changes in HbA1c values between the two cohorts. Conclusions The popularization of the basal-bolus treatment using insulin analogs hascontributed to a significant decrease in hypoglycemia. In contrast, the intensive insulin treatment may not be enough for the satisfactory improvement of glycemic control in Japanese children and adolescents with T1DM. Considerable points remain, such as diabetic education and support to motivate patients.

The study is designed to determine whether consumption of the soy isoflavones, genistein and daidzein, differentially influence metabolic syndrome, and to further investigate the involvement of Liver X Receptor (LXR) regulation. C57BL/6J mice were fed diets as follows: low fat diet (LF), western-style diet (WD), and WD containing 0.16% (w/w) of genistein (WD + G) or daidzein (WD + D) for 10 weeks. Intake of WD + G and WD + D produced a robust decrease in body weight gain by 40% and 19%, respectively (p < 0.05). Genistein reduced energy intake by 26%, and daidzein decreased energy intake by 8% (p < 0.05). A glucose tolerance test indicated that genistein consumption significantly decreased the incremental areas under the curve (AUC) from 60-120 min, compared to WD-fed mice. Gene array profiling of hepatic mRNA, and cell studies utilizing transiently-transfected HepG2 cells and mouse embryonic fibroblast cells devoid of or expressing LXRα, indicate that genistein and daidzein induce LXR-mediated pathways. In summary, addition of genistein, compared to daidzein, to a western-style diet, more profoundly decreased food intake, body weight gain, while both appear to regulate LXR-mediated pathways.

Purpose: This study aimed to provide preliminary evidence regarding effectiveness of grafting beta-tricalcium phosphate (β-TCP) combined with a cancellous autograft for treating nonunion of long bones in the lower extremity due to infection by evaluating clinical and radiological outcomes., Methods: We retrospectively reviewed the clinical and radiological results in seven patients (six men, one woman; median age 39 years) treated by the induced membrane technique for nonunion of the femur or tibia due to infection. In the second stage of the procedure, the bony defect was filled with a combination of autologous cancellous bone and β-TCP, which were mixed in approximately the same proportions. The time interval between the second stage of the procedure and bone healing was investigated. Radiographic characteristics including maximum bone gap and radiographic apparent bone gap were evaluated., Results: The median follow-up period was 14 months. Bone healing was achieved in a median of six months after the second procedure. The median maximum bone gap and radiographic apparent bone gap were 55 mm and 34 mm, respectively., Discussion: Use of β-TCP, which has osteoconductive ability, with an autograft provided good clinical and radiological outcomes. The findings of this preliminary study suggest the potential of β-TCP as a useful bone substitute for autografts in the induced membrane technique., Conclusions: Our findings suggest that β-TCP may be an effective extender when using the induced membrane technique.

Using an animal model for diet-induced metabolic disease, we have shown previously that the addition of raspberry juice concentrate (RJC) and raspberry puree concentrate (RPC) at a level of 10% of kcal, equivalent to four servings per day, to an obesogenic high-fat, western-style diet (HF) significantly reduced body weight gain, serum resistin levels, and altered the expression of hepatic genes related to lipid metabolism and oxidative stress. This study was designed to examine the effect of a lower level of RJC or RPC consumption, at a level representing a single serving of food per day (2.5% of kcal). For ten weeks, four groups of C57BL/6J mice (n = 8 ea.) were fed: low fat (LF), HF, HF + RJC, or HF + RPC diets. Intake of RJC and RPC decreased final body weight. Hepatic lipid accumulation was significantly decreased in HF + RPC- and HF + RJC-fed mice, compared to HF-fed mice. Further, the relative expression of hepatic genes including Heme oxygenase 1 (Hmox1) and Hormone sensitive lipase (Lipe), were altered by RPC or RJC consumption. In this mouse model of diet-induced metabolic disease, consumption of the equivalent of a single daily serving of either RPC or RJC improved metabolism in mice fed HF diet. We hypothesize that the phytochemicals contained in raspberries, and/or their subsequent metabolites, may be acting to influence gene expression and other regulatory pathways, to produce the metabolic improvements observed in this study.

Purpose: Chipping and lengthening over nailing (CLON) technique was developed to treat femoral shaft nonunion with shortening more than 10 mm. The purpose of the current retrospective case series was to clarify the effectiveness of the CLON technique on the femoral shaft nonunion following intramedullary nailing., Methods: Clinical and radiological outcomes in the patients receiving operative treatment for femoral shaft nonunion between August 2012 and December 2016 were retrospectively reviewed using the Refractory Fracture Data Registry at the authors' institution. The CLON technique was indicated for patients with the femoral shaft nonunion with shortening more than 10 mm., Results: Five patients with median follow-up of 32 months (range, 14 to 50 months) were included in this study. All patients achieved bone union at the median of 8 months after the CLON technique. The median limb length discrepancy was 2.0 mm at the most recent follow-up., Conclusions: The present study demonstrated that the CLON technique for femoral shaft nonunion may be the first choice as operative treatment for femoral shaft nonunion with shortening more than 10 mm.

Context: Most patients with pediatric-onset primary adrenal insufficiency (PAI), such as 21-hydroxylase deficiency, can be diagnosed by measuring the urine or serum levels of steroid metabolites. However, the etiology is often difficult to determine in a subset of patients lacking characteristic biochemical findings., Objective: To assess the frequency of genetic defects in Japanese children with biochemically uncharacterized PAI and characterize the phenotypes of mutation-carrying patients., Methods: We enrolled 63 Japanese children (59 families) with biochemically uncharacterized PAI, and sequenced 12 PAI-associated genes. The pathogenicities of rare variants were assessed based on in silico analyses and structural modeling. We calculated the proportion of mutation-carrying patients according to demographic characteristics., Results: We identified genetic defects in 50 (85%) families: STAR in 19, NR0B1 in 18, SAMD9 in seven, AAAS in two, NNT in two, MC2R in one and CDKN1C in one. NR0B1 defects were identified in 78% of the male patients that received both glucocorticoid and mineralocorticoid replacement therapy and had normal male external genitalia. STAR defects were identified in 67% of female and 9% of male patients. Seven of the 19 patients with STAR defects developed PAI at age two or older, out of whom, five did not have mineralocorticoid deficiency., Conclusions: Molecular testing elucidated the etiologies of most biochemically uncharacterized PAI patients. Genetic defects such as NR0B1 defects are presumed based on phenotypes, while others with broad phenotypic variability, such as STAR defects, are difficult to diagnose. Molecular testing is a rational approach to diagnosis in biochemically uncharacterized PAI patients., (© 2017 European Society of Endocrinology.)