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Objective: Spleen volume increases in patients with advanced heart failure (HF) after left ventricular assist device (LVAD) implantation. However, the relationship between spleen volume and exercise tolerance (peak oxygen consumption [VO 2 ]) in these patients remains unknown. In this exploratory study, we enrolled 27 patients with HF using a LVAD (median age: 46 years). Patients underwent blood testing, echocardiography, right heart catheterization, computed tomography (CT), and cardiopulmonary exercise testing. Spleen size was measured using CT volumetry, and the correlations/causal relationships of factors affecting peak VO 2 were identified using structural equation modeling., Results: The median spleen volume was 190.0 mL, and peak VO 2 was 13.2 mL/kg/min. The factors affecting peak VO 2 were peak heart rate (HR; β = 0.402, P = .015), pulmonary capillary wedge pressure (PCWP; β =  - 0.698, P = .014), right ventricular stroke work index (β = 0.533, P = .001), blood hemoglobin concentration (β = 0.359, P = .007), and spleen volume (β = 0.215, P = .041). Spleen volume correlated with peak HR, PCWP, and hemoglobin concentration, reflecting sympathetic activity, cardiac preload, and oxygen-carrying capacity, respectively, and was thus related to peak VO 2 . These results suggest an association between spleen volume and exercise tolerance in advanced HF., (© 2022. The Author(s).)

Background: The anterior cruciate ligament (ACL) has a key role as a dynamic stabilizer of the knee joints, and ACL dysfunction caused by traumatic or degenerative rupture accelerates osteoarthritis progression. Thus, it is important to prevent the degenerative rupture of the ACL. 4-Methylumbelliferone (4-MU), a pre-approved drug, exerts anti-inflammatory effects in osteoarthritis chondrocytes. It was originally used as an inhibitor of hyaluronan synthesis in chondrocytes., Methods: In this study, we investigated whether 4-MU affects the expression of catabolic factors, such as matrix metalloproteinase (MMP)-1, MMP-3, and interleukin (IL)-6, in ACL-derived cells and ACL explant cultures using immunohistochemistry, real-time RT-qPCR, and capillary western immunoassay. Furthermore, the hyaluronan concentration was evaluated using a colorimetric assay. Statistical analyses were conducted using analysis of variance for multi-group comparisons, followed by Tukey or Tukey-Kramer post hoc test., Results: Our results revealed, for the first time, that 4-MU suppressed the IL-β-induced upregulation of pro-catabolic factors, such as MMP-1, MMP-3, and IL-6, in ACL-derived cells. This suppressive effect was also observed in the cultured ligament tissues in ex vivo experiments. 4-MU also reversed an enhanced dependence on glycolysis in IL-1β-activated ACL-derived cells. Furthermore, we found that the suppressive effects of 4-MU were exerted directly and not through the inhibition of hyaluronan synthesis., Conclusions: We conclude that 4-MU could be an effective and useful treatment for knee osteoarthritis, owing to its anti-inflammatory effect on, not only chondrocytes but also on ligament cells., (© 2021. The Author(s).)

Background: The emergence of immune checkpoint inhibitors (ICIs) has brought about a paradigm shift in cancer treatment as the use of these drugs has become more frequent and for a longer duration. As a result of T-cell-mediated inflammation at the programmed cell death-1, programmed death-ligand-1, and cytotoxic T-lymphocyte antigen-4 pathways, immune-related adverse events (irAEs) occur in various organs and can cause a rare but potentially induced cardiotoxicity. Although irAEs are associated with the efficacy of ICI therapy and better prognosis, there is limited information about the correlation between irAEs and cardiotoxicity and whether the benefits of irAEs apply to patients with underlying cardiovascular disease. This study aimed to investigate the association of irAEs and treatment efficacy in patients undergoing ICI therapy with and without a cardiovascular history., Methods: We performed a retrospective review of the medical records of 409 consecutive patients who received ICI therapy from September 2014 to October 2019., Results: Median patient age was 69 years (29.6% were female). The median follow-up period was 278 days. In total, 69 (16.9%) patients had a history of any cardiovascular disease and 14 (3.4%) patients experienced cardiovascular irAEs after ICI administration. The rate of cardiovascular irAEs was higher in patients with prior non-cardiovascular irAEs than without. The prognosis of patients with irAEs ( +) was significantly better than that of the patients without irAEs (P < 0.001); additionally, this tendency did not depend on the presence or absence of a cardiovascular history. Furthermore, the Cox proportional hazards analysis revealed that irAEs were an independent predictor of mortality., Conclusions: Although cardiovascular irAEs may be related to prior non-cardiovascular irAEs under ICI therapy, the occurrence of irAEs had a better prognostic impact and this tendency was not affected by cardiovascular history.

Background: Whether vitamin D supplementation has any effect on body fat percentage, especially among elite athletes, remains unclear. The aim of this study was to evaluate the effect of vitamin D supplementation on serum vitamin D level in elite male collegiate athletes and to analyze its effect on body fat percentage., Methods: We enrolled a total of 42 elite male collegiate athletes in this prospective cohort study. In March 2020, body composition monitoring and blood test were performed. All athletes were provided with vitamin D3 supplement tablets of 25 μg/day. The use of the supplement was dependent on athletes' preference. During the study period, their club activities were stopped for 2 months due to the coronavirus disease 2019 outbreak. A second examination, similar to the first one, was performed after approximately 3 months. Supplement usage by each athlete was also confirmed. The participants were divided into a non-supplement group (without supplementation, n = 15) and a supplement group (with supplementation, n = 27)., Results: Regarding baseline data at initial examination, the non-supplement and supplement groups showed significant differences in the mean body fat percentage (9.0% and 12.1%, respectively; P = 0.03) and serum 25(OH)D level (22.7 and 18.5 ng/mL, respectively, P = 0.02). At the time of the second examination, there were no significant differences in the results of both the groups. In terms of mean change value from the first to the second examination, there were significant differences in body fat percentage (1.9 and 0.2%, respectively, P = 0.02) and serum 25(OH)D level (1.7 and 7.2 ng/mL, respectively, P < 0.001) between the two groups. A significant negative correlation was observed between the change ratio of body fat percentage and change value of serum 25(OH)D level (r =  - 0.37, P = 0.02)., Conclusions: Vitamin D supplementation of 25 μg/day significantly increased the serum 25(OH)D level in elite male collegiate athletes. Vitamin D supplementation may play a role in maintaining athletes' body fat percentage under circumstances where sports activity has decreased.

Background: For the diagnosis of Sarcopenia, European Working Group on Sarcopenia in Older People (EWGSOP) revised the algorisms in 2019, where they added computed tomography (CT) as an assessment tool not only for quantity but also for quality in research purpose. However, the evidence for clinical appreciation of CT has been lacking. Therefore, we investigated the correlation between CT and various motor function tests to assess the utility of CT as a potential diagnostic tool for sarcopenia., Methods: In total, 214 patients who were examined at our center during the study period (2016-2017) were included in the study. Single-slice CT scan of the mid-thigh region was performed, from which cross-sectional area (CSA) and CT attenuation value (CTV) of quadriceps femoris were evaluated for each subject. Other assessments included skeletal muscle mass index by DXA and BIA, muscle strength and physical performance. Furthermore, subjects were classified into four groups as per the Asia Working Group of Sarcopenia (AWGS) 2019 criteria as those with: normal, poor muscle function/strength (poor function), sarcopenia and severe sarcopenia., Results: Knee muscle strength correlated with CSA (r = 0.60) and the correlation was significantly greater than that with DXA and BIA. For physical performance, standing-up test correlated with CSA (r = - 0.20) and CTV (r = - 0.40) and walking speed with CTV (r = 0.43), which was significantly greater than that with DXA and BIA. The CSA was significantly lower in women with sarcopenia group and in both men and women with severe sarcopenia (all p < 0.01). Furthermore, CTV was significantly lower in women with poor-function and in both men and women with severe sarcopenia group (all p < 0.01)., Conclusions: CSA mostly correlated with muscle strength, whereas CTV mostly correlated with physical performance. CT with measurements of CSA and CTV enables the evaluation of muscle mass and quality simultaneously. CT is believed to be useful in inferring evaluation of motor function and assessment of sarcopenia.

Nephrogenic adenoma, also referred to nephrogenic metaplasia, is a benign proliferative lesion of urothelium, usually associated with chronic physical stimuli or inflammation. Familial Mediterranean fever is an inherited autosomal recessive disease characterized by recurrent short episodes of fever. The site of mutation is found in MEFV gene which controls inflammatory responses. We have experienced a case of nephrogenic adenoma in a 16-year-old girl with Familial Mediterranean Fever, showing proliferative lesions diffusely in the urinary bladder and multifocally in the other parts of urinary tract. These lesions disappeared after colchicine treatment. We searched for MEFV gene mutation using the specimen from the resected urinary bladder and detected heterozygous mutation of E148Q. There is a possibility that control of inflammation caused by the surgery for vesicoureteral reflux in the local site didn't work well on the background of heterozygous mutation of MEFV gene, and as a result, nephrogenic adenoma appeared. This is the first report of a combination of two rare diseases. We have to be aware that nephrogenic adenoma can occur in association with Familial Mediterranean Fever, and the former condition should be taken into consideration when rendering a correct pathological diagnosis.

Introduction: Increased expression of aggrecanase-1 (ADAMTS-4) has emerged as an important factor in osteoarthritis (OA) and other joint diseases. This study aimed to determine whether the expression of ADAMTS-4 in human chondrocytes is regulated by miRNA., Methods: MiRNA targets were identified using bioinformatics. Chondrocytes were isolated from knee cartilage and treated with interleukin-1 beta (IL-1β). Gene expression was quantified using TaqMan assays and protein production was determined by immunoblotting. Luciferase reporter assay was used to verify interaction between miRNA and target messenger RNA (mRNA)., Results: In silico analysis predicted putative target sequence of miR-125b on ADAMTS-4. MiR-125b was expressed in both normal and OA chondrocytes, with significantly lower expression in OA chondrocytes than in normal chondrocytes. Furthermore, IL-1β-induced upregulation of ADAMTS-4 was suppressed by overexpression of miR-125b in human OA chondrocytes. In the luciferase reporter assay, mutation of the putative miR-125b binding site in the ADAMTS-4 3'UTR abrogated the suppressive effect of miR125., Conclusions: Our results indicate that miR-125b plays an important role in regulating the expression of ADAMTS-4 in human chondrocytes and this identifies miR-125b as a novel therapeutic target in OA.

Background: Whole genome radiation hybrid (WG-RH) maps serve as "scaffolds" to significantly improve the orientation of small bacterial artificial chromosome (BAC) contigs, order genes within the contigs and assist assembly of a sequence-ready map for virtually any species. Here, we report the construction of a porcine: human comparative map for pig (Sus scrofa) chromosome 10 (SSC10) using the IMNpRH2(12,000-rad) porcine WG-RH panel, integrated with the IMpRH(7000-rad) WG-RH, genetic and BAC fingerprinted contig (FPC) maps., Results: Map vectors from the IMNpRH2(12,000-rad) and IMpRH(7,000-rad) panels were merged to construct parallel framework (FW) maps, within which FW markers common to both panels have an identical order. This strategy reduced map discrepancies between the two panels and significantly improved map accuracy. A total of 216 markers, including 50 microsatellites (MSs), 97 genes and ESTs, and 69 BAC end sequences (BESs), were ordered within two linkage groups at two point (2 pt) LOD score of 8. One linkage group covers SSC10p with accumulated map distances of 738.2 cR(7,000) and 1814.5 cR(12,000), respectively. The second group covers SSC10q at map distances of 1336.9 cR(7,000) and 3353.6 cR(12,000), yielding an overall average map resolution of 16.4 kb/cR(12,000) or 393.5 kb per marker on SSC10. This represents an approximately 2.5-fold increase in map resolution over the IMpRH(7,000-rad) panel. Based on 127 porcine markers that have homologous sequences in the human genome, a detailed comparative map between SSC10 and human (Homo sapiens) chromosome (HSA) 1, 9 and 10 was built., Conclusion: This initial comparative RH map of SSC10 refines the syntenic regions between SSC10 and HSA1, 9 and 10. It integrates the IMNpRH2(12,000-rad) and IMpRH(7,000-rad), genetic and BAC FPC maps and provides a scaffold to close potential gaps between contigs prior to genome sequencing and assembly. This map is also useful in fine mapping of QTLs on SSC10.