Effects of mouse utricle stromal tissues on hair cell induction from induced pluripotent stem cells

BACKGROUND: Hair cells are important for maintaining our sense of hearing and balance. However, they are difficult to regenerate in mammals once they are lost. Clarification of the molecular mechanisms underlying inner ear disorders is also impeded by the anatomical limitation of experimental access to the human inner ear. Therefore, the generation of hair cells, possibly from induced pluripotent stem (iPS) cells, is important for regenerative therapy and studies of inner ear diseases. RESULTS: We generated hair cells from mouse iPS cells using an established stepwise induction protocol. First, iPS cells were differentiated into the ectodermal lineage by floating culture. Next, they were treated with basic fibroblast growth factor to induce otic progenitor cells. Finally, the cells were co-cultured with three kinds of mouse utricle tissues: stromal tissue, stromal tissue + sensory epithelium, and the extracellular matrix of stromal tissue. Hair cell-like cells were successfully generated from iPS cells using mouse utricle stromal tissues. However, no hair cell-like cells with hair bundle-like structures were formed using other tissues. CONCLUSIONS: Hair cell-like cells were induced from mouse iPS cells using mouse utricle stromal tissues. Certain soluble factors from mouse utricle stromal cells might be important for induction of hair cells from iPS cells

Fabrication of C₆₀ field-effect transistors with polyimide and Ba_0.4Sr_0.6Ti_0.96O₃ gate insulators

Flexible C60 field-effect transistor (FET) device has been fabricated with polyimide gate insulator on the poly(ethylene terephthalate) substrate, and n-channel normally-off FET properties are observed in this FET device. The field-effect mobility, ?, is estimated to be ~10-2 cm2 V-1 s-1 at 300 K. Furthermore, the C60 FET has been fabricated with high dielectric Ba0.4Sr0.6Ti0.96O3 (BST) gate insulator, showing n-channel properties; the ? value is estimated to be ~10-4 cm2 V-1 s-1 at 300 K. The FET device operates at very low gate voltage, VG, and low drain-source voltage, VDS. Thus these C60 FET devices possess flexibility and low-voltage operation characteristic of polyimide and BST gate insulators, respectively.</p

Output properties of C₆₀ field-effect transistor device with Eu source/drain electrodes

Field-effect transistor (FET) device with thin films of C60 has been fabricated with Eu electrodes exhibiting small work function. The C60 FET device shows n-channel FET properties with high field-effect mobility, 0.50 cm2 V?1 s?1. Furthermore, nonvanishing drain current, i.e., normally on, is observed in this FET device. This originates from small energy barrier for electron from Eu source electrode to lowest unoccupied molecular orbital of C60.</p

Masked CKD in hyperthyroidism and reversible CKD status in hypothyroidism

IntroductionWhile it is well known that thyroid function may affect kidney function, the transition of the chronic kidney disease (CKD) status before and after treatment for thyroid disorders, as well as the factors affecting this change, remains to be explored. In the present study, we focused on the change in kidney function and their affecting factors during the treatment for both hyperthyroidism and hypothyroidism. Methods Eighty-eight patients with hyperthyroidism and fifty-two patients with hypothyroidism were enrolled in a retrospective and longitudinal case series to analyze the changes in kidney function and their affecting factors after treatment for thyroid disorders. Results Along with the improvement of thyroid function after treatment, there was a significant decrease in estimated glomerular filtration rate (eGFR) in hyperthyroidism (an average Delta eGFR of -41.1 mL/min/1.73 m(2)) and an increase in eGFR in hypothyroidism (an average Delta eGFR of 7.1 mL/min/1.73 m(2)). The multiple linear regression analysis revealed that sex, eGFR, free thyroxine (FT4) and free triiodothyronine (FT3) could be considered independent explanatory variables for Delta eGFR in hyperthyroidism, while age, eGFR, and FT3 were detected as independent explanatory variables in hypothyroidism. In addition, the stratification by kidney function at two points, pre- and post-treatment for thyroid disorders, revealed that 4.5% of the participants with hyperthyroidism were pre-defined as non-CKD and post-defined as CKD, indicating the presence of "masked" CKD in hyperthyroidism. On the other hand, 13.5% of the participants with hypothyroidism presented pre-defined CKD and post-defined non-CKD, indicating the presence of "reversible" CKD status in hypothyroidism. Conclusions We uncovered the population of masked CKD in hyperthyroidism and reversible CKD status in hypothyroidism, thereby re-emphasizing the importance of a follow-up to examine kidney function after treatment for hyperthyroidism and the routine evaluation of thyroid function in CKD patients as well as the appropriate hormone therapy if the patient has hypothyroidism

Reappraisal of the Cerebral Blood Flow Measured Using 123I-I-iodoamphetamine Single-photon Emission Computed Tomography in Normal Subjects and Patients with Alzheimer’s Disease and Dementia with Lewy Bodies

Purpose: Our aim was to re-evaluate the usefulness of perfusion single-photon emission computed tomography (SPECT) for the diagnosis of AD and DLB.Methods: A total of 1,232 patients, including 180 cognitively normal subjects (NSs), 148 patients with amnestic mild cognitive impairment (aMCI), 802 patients with AD and 102 patients with dementia with Lewy bodies (DLB) were enrolled. A voxelbasedstereotactic extraction estimation analysis was used to assess hypoperfusion areas using the cut-off value of 20% for the “extent %” and >2 hypoperfused lesions.Results: The top 10 areas with hypoperfusion in AD were the angular gyrus, supramarginal gyrus, precuneus, superior occipital gyrus, inferior parietal lobule, middle temporal gyrus, superior parietal lobule, inferior temporal gyrus, superior temporal gyrus. and posterior cingulate, while DLB had 6 areas in common with AD. The respective sensitivity and specificity for differentiating AD from NSs were 84.2% and 78.9% for 50-59 years old, and 91.8% and 70.0% for 60-69 years old, butthose values decreased from 70 years old. The respective sensitivity and specificity in DLB patients were 100% and 75.6% for 50-69 years old, 84.6% and 70.1% for 70-79 years old and 81.4% and 77.1% for 80-89 years old. In aMCI patients, the 1-year change in the MMSE scores was -2.38±2.02 (n=16) in patients with abnormal SPECT images and -0.67±1.81 (n=18) in those with normal SPECT images (P<0.02).Conclusions: Our study confirms that perfusion SPECT is still a valid alternative for the diagnosis of AD and DLB when fluorodeoxyglucose-PET is unavailable

Time to Bone Union after Hybrid Closed-Wedge High Tibial Osteotomy

Medial open- and lateral closed-wedge high tibial osteotomy (hybrid CWHTO) can overcome the limitations of conventional CWHTO and open-wedge HTO (OWHTO) for medial compartmental osteoarthritis (OA) of the knee. Hybrid CWHTO increases stability by using a rigid locking plate and allows early full weight-bearing. However, the literature contains no information about time to bone union after this new procedure. The aim of this study is to evaluate the time to bone union after hybrid CWHTO. We reviewed 44 knees treated with hybrid CWHTO. Patients were able to stand on both legs on the day after surgery and walked with full weight-bearing within 4 weeks of the procedure. The time to achievement of bone union at the osteotomy site was defined as the number of months until bone union was confirmed on radiographic imaging. The mean time to radiographic confirmation of bone union was 4.5±1.5 months after surgery. Eleven knees (25.0%) required 6 months or more. Radiographic analysis and JOA score improved significantly between before and 1 year after surgery (p<0.01). Hybrid CWHTO is a very useful method for treating medial OA, but radiographic bone union requires 4.5 months on average. We must be aware of bone union after hybrid CWHTO

Combined landscape of single-nucleotide variants and copy number alterations in clonal hematopoiesis

クローン性造血の臨床予後への影響を解明 --遺伝子変異とコピー数異常の統合的な知見--. 京都大学プレスリリース. 2021-07-09.Clonal hematopoiesis (CH) in apparently healthy individuals is implicated in the development of hematological malignancies (HM) and cardiovascular diseases. Previous studies of CH analyzed either single-nucleotide variants and indels (SNVs/indels) or copy number alterations (CNAs), but not both. Here, using a combination of targeted sequencing of 23 CH-related genes and array-based CNA detection of blood-derived DNA, we have delineated the landscape of CH-related SNVs/indels and CNAs in 11, 234 individuals without HM from the BioBank Japan cohort, including 672 individuals with subsequent HM development, and studied the effects of these somatic alterations on mortality from HM and cardiovascular disease, as well as on hematological and cardiovascular phenotypes. The total number of both types of CH-related lesions and their clone size positively correlated with blood count abnormalities and mortality from HM. CH-related SNVs/indels and CNAs exhibited statistically significant co-occurrence in the same individuals. In particular, co-occurrence of SNVs/indels and CNAs affecting DNMT3A, TET2, JAK2 and TP53 resulted in biallelic alterations of these genes and was associated with higher HM mortality. Co-occurrence of SNVs/indels and CNAs also modulated risks for cardiovascular mortality. These findings highlight the importance of detecting both SNVs/indels and CNAs in the evaluation of CH

Spontaneous hyaline cartilage regeneration can be induced in an osteochondral defect created in the femoral condyle using a novel double-network hydrogel

<p>Abstract</p> <p>Background</p> <p>Functional repair of articular osteochondral defects remains a major challenge not only in the field of knee surgery but also in tissue regeneration medicine. The purpose is to clarify whether the spontaneous hyaline cartilage regeneration can be induced in a large osteochondral defect created in the femoral condyle by means of implanting a novel double-network (DN) gel at the bottom of the defect.</p> <p>Methods</p> <p>Twenty-five mature rabbits were used in this study. In the bilateral knees of each animal, we created an osteochondral defect having a diameter of 2.4-mm in the medial condyle. Then, in 21 rabbits, we implanted a DN gel plug into a right knee defect so that a vacant space of 1.5-mm depth (in Group I), 2.5-mm depth (in Group II), or 3.5-mm depth (in Group III) was left. In the left knee, we did not apply any treatment to the defect to obtain the control data. All the rabbits were sacrificed at 4 weeks, and the gross and histological evaluations were performed. The remaining 4 rabbits underwent the same treatment as used in Group II, and real-time PCR analysis was performed at 4 weeks.</p> <p>Results</p> <p>The defect in Group II was filled with a sufficient volume of the hyaline cartilage tissue rich in proteoglycan and type-2 collagen. The Wayne's gross appearance and histology scores showed that Group II was significantly greater than Group I, III, and Control (p < 0.012). The relative expression level of type-2 collagen, aggrecan, and SOX9 mRNAs was significantly greater in Group II than in the control group (p < 0.023).</p> <p>Conclusions</p> <p>This study demonstrated that spontaneous hyaline cartilage regeneration can be induced <it>in vivo </it>in an osteochondral defect created in the femoral condyle by means of implanting the DN gel plug at the bottom of the defect so that an approximately 2-mm deep vacant space was intentionally left in the defect. This fact has prompted us to propose an innovative strategy without cell culture to repair osteochondral lesions in the femoral condyle.</p