A Review: Methodologies to Promote the Differentiation of Mesenchymal Stem Cells for the Regeneration of Intervertebral Disc Cells Following Intervertebral Disc Degeneration.

Intervertebral disc (IVD) degeneration (IDD), a highly prevalent pathological condition worldwide, is widely associated with back pain. Treatments available compensate for the impaired function of the degenerated IVD but typically have incomplete resolutions because of their adverse complications. Therefore, fundamental regenerative treatments need exploration. Mesenchymal stem cell (MSC) therapy has been recognized as a mainstream research objective by the World Health Organization and was consequently studied by various research groups. Implanted MSCs exert anti-inflammatory, anti-apoptotic, and anti-pyroptotic effects and promote extracellular component production, as well as differentiation into IVD cells themselves. Hence, the ultimate goal of MSC therapy is to recover IVD cells and consequently regenerate the extracellular matrix of degenerated IVDs. Notably, in addition to MSC implantation, healthy nucleus pulposus (NP) cells (NPCs) have been implanted to regenerate NP, which is currently undergoing clinical trials. NPC-derived exosomes have been investigated for their ability to differentiate MSCs from NPC-like phenotypes. A stable and economical source of IVD cells may include allogeneic MSCs from the cell bank for differentiation into IVD cells. Therefore, multiple alternative therapeutic options should be considered if a refined protocol for the differentiation of MSCs into IVD cells is established. In this study, we comprehensively reviewed the molecules, scaffolds, and environmental factors that facilitate the differentiation of MSCs into IVD cells for regenerative therapies for IDD.

Three-stage total knee arthroplasty combined with deformity correction and leg lengthening using Taylor spatial frames and conversion to internal fixation for severe intra- and extra-articular deformities and hypoplasia in a patient with hemophilic knee arthropathy: A case report.

BACKGROUND: Hemophilic arthropathy is a cause of severe knee deformity, because chronic synovitis due to repeated hemarthrosis affects the area of the epiphyseal plates in juvenile cases. Total knee arthroplasty (TKA) is the standard treatment for end-stage knee arthropathy. However, it is difficult to perform one-stage TKA in patients with severe intra- and extra-articular deformities. CASE PRESENTATION: We reported a case of hemophilic arthropathy in a 55-year-old male with leg length discrepancy of 4 cm, limited range of knee motion (-40° extension and 85° flexion), intra-articular deformity (medial proximal tibial angle: 69°; mechanical lateral distal femoral angle: 79°), extra-articular deformity at the distal femoral metaphyseal (30° valgus and 45° flexion deformity), and varus malalignment (% mechanical axis: 33%). We planned a three-stage TKA. Firstly, we performed gradual correction and lengthening of the distal femur using Taylor spatial flame. Six months after surgery, we performed conversion surgery from external fixation to internal fixation. Finally, we performed TKA with rotating hinged type implant. Two years after surgery, physical examination showed a normal gait, leg length discrepancy of 2 cm (the right leg was shorter), improvement in the range of knee motion (0° extension and 100° flexion). CONCLUSION: To the best of our knowledge, this presents the first combination of three-stage TKA with correction of femoral deformity and leg lengthening using a Taylor spatial frame and conversion to internal fixation in a patient with hemophilic knee arthropathy and severe intra- and extra-articular deformities.

Characteristics of treatment-naïve quiescent choroidal neovascularization detected by optical coherence tomography angiography in patients with age-related macular degeneration.

PURPOSE: To determine the characteristics of eyes with treatment-naïve quiescent choroidal neovascularization (CNV) detected by optical coherence tomography angiography (OCTA). METHODS: Thirty-eight eyes of 37 treatment-naïve consecutive patients (30 men, 7 women, average 69.8 years) were studied. Quiescent CNVs were detected by OCTA (RTVue XR Avanti, Optovue, Fremont, CA) in all eyes. Swept-source OCT (SS-OCT; DRI-OCT, Topcon, Japan) confirmed the absence of exudation. The symptoms, visual acuity, CNV size, and status of the fellow eye were evaluated. Patients were followed longitudinally and the length of follow-up period and development of exudation were recorded for each patient. We also investigated patients' medical records from their referral hospitals in search of prior exudation. RESULTS: All eyes with quiescent CNV were diagnosed at the initial visit with sub-retinal pigment epithelium CNVs, i.e., type 1 CNV, from the OCT and OCTA images. Prior exudation was confirmed in 15 eyes (39.5%) from their medical records of the referral hospitals. Symptoms were present in 18 eyes (47.3%). An exudative CNV was present in 12 of the fellow eyes. Exudation developed in 12 eyes (31.6%) during an average follow-up period of 25.1 months. One-half of the eyes had a prior exudation. The CNV at the baseline in eyes that developed exudation during the follow-up period was larger than eyes without exudation; however, the difference was not significant (0.59±0.47 vs 0.48±0.32 mm2, P = 0.50). CONCLUSION: Quiescent CNVs will develop exudation in approximately 30% of the eyes during a mean 2-year follow-up period. These findings must be remembered when investigating quiescent CNVs that could not be distinguished from eyes with former active CNV and naturally deactivate CNV.

Efficacy of endobronchial ultrasound-guided transbronchial biopsy without guide sheath for small peripheral pulmonary lesions (≤15 mm): A retrospective cohort study.

INTRODUCTION: Endobronchial ultrasonography-guided transbronchial biopsy (EBUS-TBB) with guide sheath (GS) is an effective procedure for diagnosing small peripheral pulmonary lesions (PPLs) (≤20 mm in the largest diameter). However, samples obtained using EBUS-TBB with GS are small, and the diagnostic yield of small PPLs biopsied using EBUS-TBB with GS is unsatisfactory. OBJECTIVES: The aim of this study was to evaluate the diagnostic yield of small PPLs using EBUS-TBB without GS compared to that with GS. MATERIALS AND METHODS: Between 1 April 2013 and 31 March 2015, 276 consecutive lesions were biopsied using EBUS-TBB with GS or without GS. We retrospectively compared EBUS-TBB with and without GS in terms of the diagnostic yield and complications related to small PPLs (≤20 mm). RESULTS: Of the 276 lesions who underwent EBUS-TBB with or without GS, we identified 80 lesions with small PPLs (≤20 mm). Sixty-two lesions were successfully diagnosed by EBUS-TBB (77.5%, diagnostic yield). The diagnostic yield of PPLs using EBUS-TBB without GS was not significantly higher than that using EBUS-TBB with GS (34/41 = 82.9% and 28/39 = 71.7%, respectively; p = 0.233). However, according to size (≤15 mm or > 15 mm), location (upper, middle/lingular, or lower area), and structure (solid nodule or ground-glass opacity), the diagnostic yield of small PPLs (≤15 mm) using EBUS-TBB without GS was significantly higher than with GS (21/26 = 80.7% vs. 8/16 = 50.0%, p = 0.036). There were no complications among the two groups. CONCLUSIONS: EBUS-TBB without GS is an effective and safe procedure for diagnosing small PPLs (≤15 mm) compared to that with GS.

Coronal Hamate Fractures with Carpometacarpal Dislocation Treated Effectively Using Headless Compression Screws with Percutaneous Pinning Fixation by Using the 2-Directional Approach: A Report of 2 Cases.

CASE: Coronal shear fractures of the hamate are relatively rare injuries. Surgical intervention is recommended for displaced fractures. However, there is no established surgical procedure for the displaced coronal shear fractures of the hamate. Therefore, we present 2 cases of the displaced coronal hamate fracture with metacarpal dislocations, which were successfully managed with open reduction and internal fixation, using the headless compression screw by the 2-directional approach. CONCLUSION: Our procedure ensured that the screw's distal end captured the hamate hook, and the displaced bone fragments were reduced considerably in both cases.

Long-term changes in pollutant load outflows and purification function in a paddy field watershed using a circular irrigation system.

A long-term investigation on the water quality and hydrology was carried out for 8 years and 7 months (from October 1991 to April 2000) in a paddy field watershed using a circular irrigation system. The annual amount of rainfall ranged from 1270 to 2226 mm and it was found that the amount of irrigation water tended to decrease as rainfall increased. Phosphorus and chemical oxygen demand (COD) concentrations tended to decrease with the river flowing down, whereas nitrogen concentrations showed no significant difference. The annual outflow loads (sum of the net-outflow load during irrigation periods and the outflow load during non-irrigation periods) of total nitrogen (T-N), total phosphorus (T-P), and COD ranged from 13.6 to 75.3 kg ha(-1)yr(-1), -3.55 to 2.21 kg ha(-1)yr(-1), and -24.7 to 48.5 kg ha(-1)yr(-1), respectively. The negative values for T-P and COD loads indicated that the study watershed performed a purification function. The change in annual pollutant loads was primarily attributed to the amount of hydrological water volumes (the annual amount of rainfall or that of rainfall plus irrigation water) for T-N and COD loads and partially for T-P load. In addition, the purification function was related to the hydraulic retention time, and the study watershed allows sufficient retention for pollutant purification for phosphorus and COD contents and partially for nitrogen content.

Overlap coefficient for assessing the similarity of pharmacokinetic data between ethnically different populations.

We developed a method to assess the similarity of pharmacokinetic data between ethnically different populations. An evaluation of confidence intervals for the mean difference in pharmacokinetic parameters, such as area under the concentration-versus-time curve (AUC), between populations is often used. We propose the use of the overlap coefficient (OC), which represents the proportion of overlap between two probability distributions, as a measure of the similarity between distributions. We considered five OC estimators--two parametric ones and three nonparametric ones. Simulation studies were conducted to compare the performance of the five OC estimators and their bootstrap confidence intervals. Results showed that nonparametric estimators with fixed-bandwidth kernel density estimation had a smaller mean squared error in almost all situations, and their coverage probabilities were close to the nominal level. The proposed method was applied to pharmacokinetic data from a bridging study of a combination therapy for metastatic colorectal cancer patients in the USA and Japan. From the analyses of this study, it was suggested that the distributions of the logarithmically transformed AUC for leucovorin and 5-fluorouracil were similar between the two populations.

Further evaluation of the skin micronucleus test: results obtained using 10 polycyclic aromatic hydrocarbons.

The standard in vivo micronucleus (MN) test detects clastogenicity in hematopoietic cells and is not suitable for detecting chemicals that target the skin. Previously, we have developed an in vivo rodent skin MN test that is simple to perform and can be applied to several laboratory animals, including the hairless mouse-a species whose use simplifies the procedure of skin testing. In this paper, we report new data that confirms the predictive ability of the test. Following the application of 10 polycyclic aromatic hydrocarbons (7,12-dimethylbenz[a]anthracene; 3-methylcholanthrene; benzo[a]pyrene; dibenz[a,h]anthracene; benz[a]anthracene; dibenz[a,c]anthracene; chrysene; benzo[e]pyrene; pyrene; anthracene) with various degrees of genotoxicity to the dorsal skin of hairless mice, we found that these compounds caused MN production that in general correlated with their reported carcinogenicity. We believe that this test will be useful in detecting skin clastogens that test negative when analyzed using the standard micronucleus test.

Phosphorus purification in a paddy field watershed using a circular irrigation system and the role of iron compounds.

In a paddy field watershed using a circular irrigation system, it was clear that the watershed tended to purify phosphorus by an analysis on the mass balance of pollutants. A reasonable hypothesis was that the phosphorus precipitation with iron compounds in a river may affect the purification. To verify this, an investigation on phosphorus and iron in the river water and sediments were conducted. Total iron (T-Fe) concentration in the river ranged from 3 to 10 mg/L, and the concentration increased with the river flowing down, whereas dissolved iron (D-Fe) concentrations tended to decrease. The concentrations of total phosphorus (T-P) and phosphate phosphorus (PO4-P) also tended to decrease as the river flowing down. From the analysis of mass balance, the study watershed was considered to be a substantial iron source, having 307 and 206 kg/ha of annual outflow loads. In the sediment of the river, T-P ranged from 834 to 2440 microg/g, and most of the inorganic compound was Fe-P. In addition, The Bray No.2 phosphorus (441-1030 microg/g) was much higher than in paddy soils. Therefore, the sediment contained a large amount of phosphorus and was fertile. From the results of laboratory-based experiments, it can be said that iron compounds in the river were sufficient for the precipitation of phosphorus. Since the accumulated sediment in the river was conventionally dredged up and transported to adjacent paddy fields, it was considered to be that this operation played a significant role in phosphorus resource recycling.

Further evaluation of an in vivo micronucleus test on rat and mouse skin: results with five skin carcinogens.

In a previous paper, we presented a practical in vivo micronucleus (MN) test that used rat skin as the target organ. To evaluate the test, as well as to determine the reproducibility and applicability of the method to mice, we used it to test the effect of five skin carcinogens (N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), 4-nitroquinoline 1-oxide (4NQO), 7,12-dimethylbenz[a]anthracene (DMBA), and benzo[a]pyrene (B[a]P)) on rat and mouse skin. All five compounds significantly and dose-dependently increased the MN frequencies in the basal cells of the chemical-treated skin. These results indicated the reproducibility of the test results and also the applicability of the test to mice as well as rats.