Radiological Findings of the Lumbar Spine in High School and Collegiate Sumo Wrestlers.

Background: Sumo wrestling is a traditional sport in Japan and becoming popular worldwide. Risk factors for lower back injuries in sumo wrestlers are heavier weight and larger body mass index (BMI). The mawashi (loincloth belt) worn by sumo wrestlers has been shown to restrict motion of the lumbar spine. Purpose: To study the effects of sumo wrestling on the lumbar spine of high school and freshmen collegiate wrestlers, investigating the relationship between radiological findings, wearing of the mawashi during training, and lower back symptoms. Study Design: Case series; Level of evidence, 4. Methods: From 2001 to 2017, a total of 197 members of the Japanese Sumo Federation (55 high school and 142 college freshman students) underwent routine radiographic examination of their lumbar spines and answered a questionnaire regarding lumbar symptoms. Wrestlers were classified as symptomatic and asymptomatic based on responses to a custom questionnaire. We used the unpaired t test to evaluate patient demographics and the chi square test to analyze radiographic lumbar spine abnormalities between symptomatic and asymptomatic wrestlers. Results: The wrestlers' mean height, weight, BMI, and duration in the sport were 174.0 ± 6.7 cm, 107.1 ± 22.4 kg, 35.2 ± 6.4, and 8.0 ± 3.2 years, respectively. There were 91 participants in the symptomatic group (46.2%) and 106 (53.8%) in the asymptomatic group. Ten wrestlers (5.1%) had osteophyte formations in the lumbar body; 8 of the 11 osteophytes (72.7%) appeared in the upper lumbar spine. Of the total, 48 wrestlers (24.4%) had deformities (Schmorl nodules) in the lumbar body, and 23 of 50 (46.0%) and 10 of 16 (62.5%) deformities were found in the upper lumbar spine of collegiate and high school wrestlers, respectively. Five wrestlers of the total 197 athletes (2.5%) had disc space narrowing in the lumbar body, with 3 of the 5 cases of disc space narrowing (60.0%) found in the upper lumbar spine. Spondylolysis in the lumbar body was found in 25 wrestlers (12.7%); 19 of the 91 symptomatic wrestlers (20.9%) had spondylolysis, compared with 6 of the 106 (5.7%) asymptomatic wrestlers (P = .0028). Conclusion: Almost one-third of sumo wrestlers had ≥1 abnormal radiological finding in the lumbar spine. There was a significant relationship between symptomatic wrestlers and spondylolysis.

Autologous Osteochondral Grafts for Knee Osteochondral Diseases Result in Good Patient-Reported Outcomes in Patients Older Than 60 Years.

Purpose: This study aims to examine the clinical autologous osteochondral grafts (AOG) outcomes for knee osteochondral diseases at operative ages >60 years, and to determine whether patients are able to sit straight in Japanese style after AOG. Methods: All patients who underwent AOG for knee osteochondral diseases between November 2001 and April 2018 were retrospectively identified. The inclusion criteria were AOG only without osteotomy, operative ages between 60 and 79 years, >2 years of follow-up, and involved femorotibial angle between 169° and 179° (normal alignment). Patients who underwent osteotomy to improve knee alignment and patients with inflammatory diseases such as rheumatoid arthritis were excluded. The patients' knee symptoms and their clinical outcome were evaluated according to the criteria of the knee scoring system of the Japanese Orthopedic Association (JOA), International Knee Documentation Committee (IKDC) subjective score, and the ability of straight sitting in Japanese style. Results: This study enrolled 57 cases and 60 knee joints during the study period. The follow-up ratio was 85.1%. Moreover, 14 men and 43 women and 29 right and 31 left knee joints were included in this study. The mean operative age and mean follow-up period were 67.8 years (range 60-76 years) and 81.1 months (range 24-167 months), respectively. In addition, the study involved 30 cases and 32 knee joints (60s group), and 27 cases and 28 knee joints (70s group). Moreover, 34 cases and 36 knee joints had osteonecrosis (ON group), and 23 cases and 24 knee joints had cartilage injury (CI group). The IKDC subjective and JOA scores in both the 60s and 70s groups showed significant differences: 2 years after AOG ＞at the follow-up period, ＞at the preoperative period. The scores in both the CI and ON groups showed similar significant differences. Furthermore, 8.3% and 53.5% of the patients could sit straight in Japanese style at the preoperative period and 2 years after AOG, respectively. Conclusion: Even if the patient's operative age was >60 years, the AOG only for their knee osteochondral diseases had good clinical outcomes, including the ability to sit straight in Japanese style. Level of Evidence: IV, Therapeutic case series Key words: autologous osteochondral grafts, aged patients, clinical outcome, knee joint, straight sitting in Japanese style.

Preoperative diagnosis of knee cartilage, meniscal, and ligament injuries by magnetic resonance imaging.

PURPOSE: The purpose of the study was to report on the current accuracy measures specific to 1.5-Tesla MRI of the knee in the patient population prone to injuries of the anterior cruciate ligament (ACL), the menisci, and the articular cartilage. METHODS: We accrued patients between January 2018 through August 2021 who underwent a preoperative MRI and were diagnosed with an articular cartilage injury either due to unevenness of articular cartilage in T2-weighted sequences or due to the irregularity of subchondral bone in T1-weighted sequences. All patients were treated arthroscopically. Sensitivity, specificity, and accuracy were calculated for the detection of ACL, meniscus, and cartilage injuries. A P-value of < 0.05 represented statistical significance. RESULTS: One-hundred and forty-seven cases which included 150 knee joints were enrolled in this study. The mean age at the time of surgery was 42.9 years-old. The sensitivity in the diagnosis of ACL injuries was significantly greater than that in the diagnosis of cartilage injuries (P = 0.0083). The ratios of the equality of operative indication in 6 recipient sites were found to be between 90.0% and 96.0%. The diagnostic critical point was within a 1 cm in diameter. CONCLUSION: The diagnostic sensitivity in cartilage injuries was significantly lower than ones of ACL and meniscal injuries. The ratios of the equality of operative indication was determined to be between 90.0% and 96.0%, if we consider the unevenness of articular cartilage or the irregularity of subchondral bone. LEVEL OF EVIDENCE: Level III, Prospective diagnostic cohort study.

Intraoperative Acoustic Evaluation of Living Human Knee Cartilage-Comparison with Respect to Cartilage Degeneration and Aging.

OBJECTIVE: The objective of the study was to evaluate the mechanical properties of living human knee cartilage using our ultrasonic device, and to compare the measurements with respect to cartilage degeneration and aging. DESIGN: A total of 95 knees which had undergone arthroscopic knee surgery, from 88 patients, were included in the study, with informed consent. All procedures were reviewed and approved by the ethical committee of our hospital. In the study group, there were 41 men, 47 women, 39 right knees, and 56 left knees. The conditions primarily included knee osteoarthritis and anterior cruciate ligament rupture. The mean operative age was 44.1 years old (range = 10-83). We compared mechanical properties of the knee cartilage with respect to aging and gender, in comparison with normal cartilage. A P value of <0.05 represented statistical significance. RESULTS: In the context of the International Cartilage Repair Society (ICRS) classification of cartilage degeneration (grade 0-3), the signal intensity in grade 0 was significantly larger than that in grade 1, 2, or 3. The thickness in grade 0 was significantly higher than that in grade 1, 2, or 3. Normal cartilage in older women had the lowest signal intensity and the least cartilage thickness among all the groups. CONCLUSION: The ultrasonic system we developed was able to detect early degenerative changes in living cartilage in knees. The lowest signal intensity and least cartilage thickness in normal cartilage among older women were correlated to a large prevalence of knee osteoarthritis in women. LEVEL OF EVIDENCE: Level IV, case series.

Mosaicplasty With High Tibial Osteotomy for Knee Subchondral Insufficiency Fracture Had Better Magnetic Resonance Observation of Cartilage Repair Tissue Scores With Less Bone Marrow Edema and Better Plug Union and Less Plug Necrosis Compared With Mosaicplasty Alone.

PURPOSE: To determine the magnetic resonance imaging (MRI) findings after mosaicplasty (MOS) for knee subchondral insufficiency fracture (SIFK), and to analyze the relationship between MRI findings and clinical outcomes. METHODS: We retrospectively reviewed the cases of consecutive patients who underwent MOS for SIFK with/without high tibial osteotomy (HTO) between January 1998 and December 2015. The MRI findings at 12 months after the surgery were assessed by the modified magnetic resonance observation of cartilage repair tissue (MOCART) score to determine the degree of bone marrow edema (BME), plug union, and plug necrosis. The clinical outcomes were assessed by Lysholm score to clarify the minimal clinically important difference (MCID) and patient acceptable symptom state analysis. RESULTS: In total, 58 patients (17 men and 41 women) were enrolled in this study. Among them, 30 knees were treated by MOS alone and 28 knees were treated by MOS with HTO. The MOCART scores of patients who received MOS alone were significantly lower in BME score (P = .0060), plug union score (P = .0216), and in plug necrosis score (P = .0326) than patients who received MOS with HTO. BME lesion was less likely to persist among elderly (odds ratio 1.20, P = .0248) and female (OR 41.8, P = .0118) patients. The MCID of Lysholm score was 6.6 in MOS alone and 8.4 in MOS with HTO cases, but there were no significant association between MRI findings and the postoperative Lysholm score. CONCLUSIONS: The MOS with HTO cases had better MOCART scores with less BME, better plug union, and less plug necrosis compared with MOS alone cases. Female and older patients had better resolution of BME, but there was no significant correlation between MRI findings and the postoperative Lysholm score. All cases in both groups showed improvement of Lysholm score exceeding MCID; thus, MOS may be effective as a joint preserving surgery for SIFK. LEVEL OF EVIDENCE: Level IV, clinical case series.

Myocardial TRPC6-mediated Zn2+ influx induces beneficial positive inotropy through ß-adrenoceptors.

Baroreflex control of cardiac contraction (positive inotropy) through sympathetic nerve activation is important for cardiocirculatory homeostasis. Transient receptor potential canonical subfamily (TRPC) channels are responsible for α1-adrenoceptor (α1AR)-stimulated cation entry and their upregulation is associated with pathological cardiac remodeling. Whether TRPC channels participate in physiological pump functions remains unclear. We demonstrate that TRPC6-specific Zn2+ influx potentiates ß-adrenoceptor (ßAR)-stimulated positive inotropy in rodent cardiomyocytes. Deletion of trpc6 impairs sympathetic nerve-activated positive inotropy but not chronotropy in mice. TRPC6-mediated Zn2+ influx boosts α1AR-stimulated ßAR/Gs-dependent signaling in rat cardiomyocytes by inhibiting ß-arrestin-mediated ßAR internalization. Replacing two TRPC6-specific amino acids in the pore region with TRPC3 residues diminishes the α1AR-stimulated Zn2+ influx and positive inotropic response. Pharmacological enhancement of TRPC6-mediated Zn2+ influx prevents chronic heart failure progression in mice. Our data demonstrate that TRPC6-mediated Zn2+ influx with α1AR stimulation enhances baroreflex-induced positive inotropy, which may be a new therapeutic strategy for chronic heart failure.

CNP, the Third Natriuretic Peptide: Its Biology and Significance to the Cardiovascular System.

The natriuretic peptide family consists of three biologically active peptides: ANP, BNP, and CNP. CNP is more widely expressed than the other two peptides, with significant levels in the central nervous system, osteochondral system, and vascular system. The receptor that is mainly targeted by CNP is GC-B, which differs from GC-A, the receptor targeted by ANP and BNP. Consequently, the actions of CNP differ somewhat from those of ANP and BNP. CNP knockout leads to severe dwarfism, and there has been important research into the role of CNP in the osteochondral system. As a result, a CNP analog is now available for clinical use in patients with achondroplasia. In the cardiovascular system, CNP and its downstream signaling are involved in the regulatory mechanisms underlying myocardial remodeling, cardiac function, vascular tone, angiogenesis, and fibrosis, among others. This review focuses on the roles of CNP in the cardiovascular system and considers its potential for clinical application in the treatment of cardiovascular diseases.

B-Type Natriuretic Peptide (BNP) Revisited-Is BNP Still a Biomarker for Heart Failure in the Angiotensin Receptor/Neprilysin Inhibitor Era?

Myocardial wall stress, cytokines, hormones, and ischemia all stimulate B-type (or brain) natriuretic peptide (BNP) gene expression. Within the myocardium, ProBNP-108, a BNP precursor, undergoes glycosylation, after which a portion is cleaved by furin into mature BNP-32 and N-terminal proBNP-76, depending on the glycosylation status. As a result, active BNP, less active proBNP, and inactive N-terminal proBNP all circulate in the blood. There are three major pathways for BNP clearance: (1) cellular internalization via natriuretic peptide receptor (NPR)-A and NPR-C; (2) degradation by proteases in the blood, including neprilysin, dipeptidyl-peptidase-IV, insulin degrading enzyme, etc.; and (3) excretion in the urine. Because neprilysin has lower substrate specificity for BNP than atrial natriuretic peptide (ANP), the increase in plasma BNP after angiotensin receptor neprilysin inhibitor (ARNI) administration is much smaller than the increase in plasma ANP. Currently available BNP immunoassays react with both mature BNP and proBNP. Therefore, BNP measured with an immunoassay is mature BNP + proBNP. ARNI administration increases mature BNP but not proBNP, as the latter is not degraded by neprilysin. Consequently, measured plasma BNP initially increases with ARNI administration by the amount of the increase in mature BNP. Later, ARNI reduces myocardial wall stress, and the resultant reduction in BNP production more than offsets the increase in mature BNP mediated by inhibiting degradation by neprilysin, which lowers plasma BNP levels. These results suggest that even in the ARNI era, BNP can be used for diagnosis and assessment of the pathophysiology and prognosis of heart failure, though the mild increases early during ARNI administration should be taken into consideration.

Radiological osteoarthritic knee joint changes in high school and collegiate sumo wrestlers: The observational study.

We examined the effects of sumo on their knee joints, and investigated the relationship between radiological changes and knee joints symptoms, and the relationship between knee radiological changes and the physical characteristics of the wrestlers. Fifty-six high-school and 128 college freshman sumo wrestlers who belonged to the Japanese Sumo Federation. To evaluate radiological changes in the knee joints of high-school and college freshmen sumo wrestlers. They underwent routine radiographic examination of their knee joints and were instructed to answer a questionnaire regarding their knee symptoms as a medical check. The mean height, weight, body mass index (BMI), and sumo career/experience of the participants were 174.1 cm, 106.9 kg, 35.1 kg/m2, and 7.9 years, respectively. Twenty-five high-school (44.6%) and 54 collegiate (42.2%) sumo wrestlers had some knee symptoms, which was significantly associated with sumo career as a risk factor. Five high-school (8.9 %) and 18 collegiate (14.1 %) sumo wrestlers had joint space narrowing. Considering the relationship between knee symptoms and radiological changes, significant correlations between osteophyte formation and bony sclerosis and knee symptoms were observed. According to the Kellgren-Laurence (KL) classification, 7 high-school (12.5%) and 26 collegiate (20.3%) sumo wrestlers were grade 2, 3, or 4. The risk factors of degenerative radiographic changes in the knee joints of the participants were heavyweight, large BMI, and older age. The knee osteoarthritic changes had already appeared in 12.5% high-school sumo wrestlers at the admission.

Autologous Osteochondral Grafts Result in Improved Clinical Outcomes in Patients With Early Knee Osteoarthritis.

Purpose: To determine whether autologous osteochondral grafts improve clinical outcomes in early knee osteoarthritis (EKOA) and whether the grafts prevent progression of radiographic joint degeneration. Methods: In this study, we identified patients older than 40 years with EKOA having no traumatic events, with grade 0, 1, or 2 on the Kellgren-Lawrence (KL) classification and more than grade 3 of cartilage degeneration according to the International Cartilage Repair Society scale. Recipient sites were as follows: 14 patellofemoral (PF3) joint, 18 medial femoral condyle (M1), and 6 lateral femoral condyle (L2). Japanese Orthopedic Association (JOA) score and International Knee Documentation (IKDC) subjective score (SUB) were examined as clinical outcomes. Results: The study included 31 knees in 31 patients who underwent autologous osteochondral grafts for EKOA and more than two years follow-up. The sample included 15 men and 16 women. The mean operative age was 56.0 years, and the mean follow-up period was 76 months (range, 24-170 months). In the preoperative period, JOA and SUB were 73.9 and 49.5, respectively. At follow-up, the JOA and SUB scores were 93.7 and 84.5, respectively. The differences were statistically significant. Progression of KL classification occurred in 0% of the PF3 group, 17% of the L2 group, and 33% of the M1 group. The outcomes of the M1 group significantly became worse (P = .0381) than those of the L2 and the PF3 groups, and the PF3 group significantly maintained good clinical outcomes (P = .0334). Conclusion: Autologous osteochondral grafts for degenerated cartilage improved clinical outcomes of EKOA even if the recipient had cartilage degeneration, and not trauma. The PF3 group maintained significantly good clinical outcomes, and the M1 group became significantly worse.

The Oral Administration of Highly-Bioavailable Curcumin for One Year Has Clinical and Chondro-Protective Effects: A Randomized, Double-Blinded, Placebo-Controlled Prospective Study.

Purpose: The purpose of this study was to determine the clinical and chondroprotective efficacy and safety of orally administered Theracurmin in patients who underwent mosaicplasty for knee chondral or osteochondral diseases over 12 months of treatment. Methods: We enrolled 50 patients, older than 20 years of age, who underwent mosaicplasty for their knee joint diseases. Theracurmin at 180 mg of curcumin per day or placebo was administered orally every day for 12 months. Because 7 patients dropped out of the study, 43 patients were examined; they included 14 men and 29 women and 24 right and 19 left knees. The mean operative age was 59.5 years (range, 24-84 years). We evaluated the Japanese Orthopaedic Association knee osteoarthritis score (JOA), visual analog scale (VAS), and Japanese Knee Osteoarthritis Measure (JKOM) as clinical symptoms; T2 mapping values using magnetic resonance imaging as an indication of the chondroprotective effect; and blood concentration of curcumin at 0, 3, 6, and 12 months after the operations. We performed intraoperative acoustic evaluation of articular cartilage as a measure of chondroprotective effect during the operations and second-look arthroscopy. Results: The JOA, VAS and JKOM at 3, 6, and 12 months were significantly better than those during the preoperative period. However, the values of JOA, VAS and JKOM and T2 mapping were not significantly different between the Theracurmin and placebo groups. The blood concentration of curcumin in the Theracurmin group was significantly higher than that in the placebo group at 3, 6, and 12 months after the operations. Cartilage stiffness and surface roughness were significantly better in the Theracurmin group than in the placebo group at second-look arthroscopy. Conclusions: The oral administration of Theracurmin for 1 year demonstrated significantly better chondroprotective effects and no worse clinical effects and adverse events than the placebo. Level of Evidence: Level I, double-blinded, placebo-controlled, prospective study.

The Contribution of Deleterious Rare Alleles in ENPP1 and Osteomalacia Causative Genes to Atypical Femoral Fracture.

CONTEXT: Atypical femoral fractures (AFFs) are very rare atraumatic or mild trauma fractures in the subtrochanteric region or femoral shaft. Some unique genetic variants in Asian populations might confer susceptibility to AFF, since the incidence of AFFs is higher in Asian populations. OBJECTIVE: Because rare variants have been found to be causative in some diseases and the roles of osteomalacia causative genes have not been reported, we investigated rare variants in genes causing abnormal mineralization. METHODS: Exome sequencing was performed to detect variants in gene coding and boundary regions, and the frequencies of deleterious rare alleles were compared between Japanese patients with AFF (n = 42) and controls of the 4.7KJPN panel of Tohoku Medical Megabank by whole genome sequencing (n = 4773). RESULTS: The frequency of the deleterious rare allele of ENPP1 was significantly increased in AFF (P = .0012, corrected P [Pc] = .0155, OR 4.73, 95% CI 2.15-10.40). In multigene panel analysis, the frequencies of deleterious rare alleles of candidate genes were increased in AFF (P = .0025, OR 2.72, 95% CI 1.49-4.93). Principal component analysis of bone metabolism markers identified a subgroup of patients with AFF with higher frequencies of deleterious rare alleles in ENPP1 (P = 4.69 × 10-5, Pc = .0006, OR 8.47, 95% CI 3.76-19.09) and the candidate genes (P = 1.08 × 10-5, OR 5.21, 95% CI 2.76-9.86). CONCLUSION: AFF is associated with genes including ENPP1 that cause abnormal mineralization, suggesting that osteomalacia is an underlying condition predisposing to AFF and that higher incident rates of AFFs in Asian populations might be explained by the genetic risk factors including ENPP1.

Changes in BNP levels from discharge to 6-month visit predict subsequent outcomes in patients with acute heart failure.

BACKGROUND: This study aimed to investigate the association between changes in brain natriuretic peptide (BNP) from discharge to 6-month visit and subsequent clinical outcomes in patients with acute heart failure (AHF). METHODS: Among 1246 patients enrolled in the prospective longitudinal follow-up study nested from the Kyoto Congestive Heart Failure registry, this study population included 446 patients with available paired BNP data at discharge and 6-month index visit. This study population was classified into 3 groups by percent change in BNP from discharge to 6-month visit; the low tertile (≤-44%, N = 149), the middle tertile (>-44% and ≤22%, N = 149) and the high tertile (>22%, N = 148). FINDINGS: The cumulative 180-day incidence after the index visit of the primary outcome measure (a composite endpoint of all-cause death or hospitalization for HF) was significantly higher in the high and middle tertiles than in the low tertile (26.8% and 14.4% versus 6.9%, log-rank P<0.0001). The adjusted excess risk of the high tertile relative to the low tertile remained significant for the primary outcome measure (hazard ratio: 3.43, 95% confidence interval: 1.51-8.46, P = 0.003). CONCLUSIONS: Percent change in BNP was associated with a subsequent risk for a composite of all-cause death and hospitalization for HF after adjustment of the absolute BNP values, suggesting that observing the change in BNP levels, in addition to absolute BNP levels themselves, helps us to manage patient with HF.

The effects of alendronate on the suppression of bone resorption and the promotion of cartilage formation in the human mosaicplasty donor site: A randomized, double-blind, placebo-controlled prospective study.

BACKGROUND: We previously reported that early alendronate administration accelerated bone formation and improved the quality of repaired cartilage in the donor site in rabbits. To investigate whether alendronate administration has effects in humans similar to those observed in rabbits. METHODS: The study cohort included 35 patients over the age of 12-years old who underwent mosaicplasty without osteoporotic therapy from March 2011 to October 2012. The donor sites were medial or lateral in the patellofemoral joint. Placebo (P) or Bonalon containing 35 mg of alendronate (A) was administered orally every week for 8 weeks. The cohort comprised 15 male and 20 female, including 14 right and 21 left knees. The mean age at the time of surgery was 57.1 years. Bone formation was examined using computer tomography and lateral knee radiography, and cartilage formation was examined using magnetic resonance imaging (MRI), second-look assessment, and intraoperative acoustic evaluation. The clinical outcomes were assessed using the Japanese Orthopaedic Association knee score and visual analog scale (VAS). Bone and cartilage formation in the donor site and clinical outcomes were assessed at 3, 6, and 12 months after mosaicplasty. RESULTS: The ratio of TRAP-5b in group A was significantly smaller than that in group P at 2 and 8 weeks after mosaicplasty. The extent of bone formation in the donor sites in group A was significantly greater than that in group P at 3 and 6 months after mosaicplasty. Cartilage formation did not differ significantly between the two groups as determined by MRI, macroscopic assessment, and intraoperative acoustic evaluation. Clinical outcomes did not differ significantly between the two groups, and no negative clinical outcomes were observed. CONCLUSION: Early alendronate administration accelerated bone formation but not cartilage formation in the mosaicplasty donor site in humans.

NRSF-GNAO1 Pathway Contributes to the Regulation of Cardiac Ca2+ Homeostasis.

BACKGROUND: During the development of heart failure, a fetal cardiac gene program is reactivated and accelerates pathological cardiac remodeling. We previously reported that a transcriptional repressor, NRSF (neuron restrictive silencer factor), suppresses the fetal cardiac gene program, thereby maintaining cardiac integrity. The underlying molecular mechanisms remain to be determined, however. METHODS: We aim to elucidate molecular mechanisms by which NRSF maintains normal cardiac function. We generated cardiac-specific NRSF knockout mice and analyzed cardiac gene expression profiles in those mice and mice cardiac-specifically expressing a dominant-negative NRSF mutant. RESULTS: We found that cardiac expression of Gαo, an inhibitory G protein encoded in humans by GNAO1, is transcriptionally regulated by NRSF and is increased in the ventricles of several mouse models of heart failure. Genetic knockdown of Gnao1 ameliorated the cardiac dysfunction and prolonged survival rates in these mouse heart failure models. Conversely, cardiac-specific overexpression of GNAO1 in mice was sufficient to induce cardiac dysfunction. Mechanistically, we observed that increasing Gαo expression increased surface sarcolemmal L-type Ca2+ channel activity, activated CaMKII (calcium/calmodulin-dependent kinase-II) signaling, and impaired Ca2+ handling in ventricular myocytes, which led to cardiac dysfunction. CONCLUSIONS: These findings shed light on a novel function of Gαo in the regulation of cardiac Ca2+ homeostasis and systolic function and suggest Gαo may be an effective therapeutic target for the treatment of heart failure.

Molecular ratio of mature B-type natriuretic peptide in acute heart failure: an indicator for ventricular contractile recovery.

AIMS: The methodology to distinguish between the heart failure (HF) with recovered ejection fraction (HFrecEF) and those with continuously reduced ejection fraction (EF) (HFcrEF) on admission has not been established. We recently demonstrated that the ratio of plasma levels of pro-B-type natriuretic peptide (proBNP) to total BNP (proBNP plus mature BNP) is decreased on admission in patients with mild acute HF, but not in severe acute HF as a compensatory mechanism for activating cyclic GMP via increases of bioactive mature BNP. We aimed to test the hypothesis that the ratio of bioactive mature BNP to total BNP is associated with reverse remodelling capacity in patients with HF with reduced EF. METHODS AND RESULTS: Plasma proBNP and total BNP were measured in patients with acute decompensated HF by using specific and sensitive enzyme immunochemiluminescent assay. Estimated percent mature BNP (%emBNP) was calculated as ([total BNP - proBNP]/total BNP) × 100. We retrospectively identified the patients with reduced EF (≤40%, on admission) who had echocardiographic data after discharge (n = 93). We defined patients with increased EF by >10% during the follow-up term (median, 545 days) after the admission as HFrecEF group. We compared patient characteristics, %emBNP, and other biomarkers between HFrecEF and HFcrEF. Of the enrolled patients with HFrecEF (n = 32) and HFcrEF (n = 61), on admission, %emBNP was significantly higher in HFrecEF than in HFcrEF (44.1% vs. 36.9%; P < 0.05). There were no significant differences in left ventricular EF on admission between the two groups. The univariate analysis revealed that %emBNP on admission was associated with HFrecEF occurrence rate (P < 0.05), in contrast both total BNP and high-sensitive cardiac troponin-T levels were not associated with HFrecEF occurrence rate. CONCLUSIONS: The ratio of mature BNP to total BNP in plasma at the time of hospital admission may be predictive of left ventricular contractile recovery. Preservation of the capacity to convert proBNP to mature BNP, but not myocardial injury itself, is associated with future ventricular contractile recovery.

Intra-Articular Injections of Curcumin Monoglucuronide TBP1901 Suppresses Articular Cartilage Damage and Regulates Subchondral Bone Alteration in an Osteoarthritis Rat Model.

OBJECTIVE: Curcumin monoglucuronide (TBP1901) is highly water soluble and can convert to free form curcumin, which has pharmacological effects, on intravenous administration. This study aimed to investigate the effectiveness of TBP1901 intra-articular injections in an osteoarthritis (OA) rat model. METHODS: Sixty-four male Wistar rats (12 weeks old) who underwent destabilized medial meniscus (DMM) surgery were randomly separated into the TBP1901 injection or saline solution (control) injection group. They were sacrificed at 1, 2, 6, or 10 weeks postoperatively (weeks 1, 2, 6, and 10; n = 8 for each group). TBP1901 (30 mg/mL) or saline solution of 50 µL was injected into the knee joints twice a week during weeks 1 and 2 to investigate the effects in the acute phase of posttraumatic (PT) OA or once a week during weeks 6 and 10 to investigate it in the chronic phase of PTOA. Histology, immunohistochemistry, and micro-computed tomography were performed to evaluate the changes in OA. RESULTS: TBP1901 injections significantly reduced synovial inflammation at weeks 1 and 2, and tumor necrosis factor-α expression in the articular cartilage at week 6. The TBP1901 injections also significantly suppressed articular cartilage damage, subchondral bone (SB) plate thickening, SB plate perforation, and osteophyte formation at week 10. CONCLUSIONS: TBP1901 intra-articular injections suppressed synovial inflammation in the acute phase of PTOA in DMM rats. In the chronic phase, TBP1901 suppresses articular cartilage damage and regulates SB plate changes.

Potential pitfalls when interpreting plasma BNP levels in heart failure practice.

B-type (or brain) natriuretic peptide (BNP) is synthesized in cardiac myocytes and released constitutively into the circulation. Pressure/volume overload, neurohumoral factors, cytokines, and ischemia enhance BNP gene expression, and then precursor proBNP is produced. It has been thought that proBNP is cleaved into active BNP molecule and inactive marker molecule NT-proBNP intracellularly by processing enzyme furin, and they are released into the circulation. However, recent studies have shown that considerable amount of uncleaved proBNP circulates in the blood. The commercially available BNP assay kits consist of two antibodies that sandwich the BNP molecule. Therefore, if proBNP is present, BNP assay kit cross-reacts to proBNP and measures it as BNP. Therefore, it should be noted that the current BNP value is proBNP plus BNP. BNP and NT-proBNP have been established as a biomarker for heart failure patients presenting dyspnea. But many pitfalls are present for interpreting the BNP value. For example, the presence of renal dysfunction, age, female sex, atrial fibrillation, inflammation, hyperthyroidism, use of sacubitril/valsartan, and macro-proBNPemia overestimate BNP value, whereas the presence of obesity, immediately after acute coronary syndrome onset, and pericardial effusion underestimate BNP value. In the management for heart failure patients, BNP plays an important role. Therefore, clinicians should note the pitfall of interpretation of BNP and we describe the mechanism involved.

Overview of the 84th Annual Scientific Meeting of the Japanese Circulation Society　- Change Practice!

Due to the COVID-19 pandemic, the 84thAnnual Meeting of the Japanese Circulation Society (JCS) was held in a web-based format for the first time in its history as "The Week for JCS 2020" from Monday, July 27 to Sunday, August 2, 2020. All sessions, including general abstracts, were streamed live or on-demand. The main theme of the meeting was "Change Practice!" and the aim was to organize the latest findings in the field of cardiovascular medicine and discuss how to change practice. The total number of registered attendees was over 16,800, far exceeding our expectations, and many of the sessions were viewed by far more people than at conventional face-to-face scientific meetings. At this conference, the power of online information dissemination was fully demonstrated, and the evolution of online academic meetings will be a direction that cannot be reversed in the future. The meeting was completed with great success, and we express our heartfelt gratitude to all affiliates for their enormous amount of work, cooperation, and support.