Mild elevation of pulmonary vascular resistance predicts mortality regardless of mean pulmonary artery pressure in mild interstitial lung disease.

BACKGROUND: Pulmonary hypertension (PH) is defined by elevated mean pulmonary arterial pressure (MPAP), and elevated pulmonary vascular resistance (PVR) reflects pulmonary vascular abnormalities. The clinical significance of non-severe PH in patients with various interstitial lung diseases (ILDs) has not been fully elucidated. We aimed to investigate the clinical significance of MPAP and PVR for mortality in patients with newly diagnosed ILD. METHODS: We retrospectively analysed consecutive patients with ILD at initial evaluations that included right heart catheterisation from 2007 to 2018. These patients were classified by MPAP and PVR using the 2022 the European Society of Cardiology (ESC)/the European Respiratory Society (ERS) guidelines for PH. The clinical significance of MPAP and PVR for mortality was analysed. RESULTS: Among 854 patients, 167 (19.6%) had MPAP>20 mm Hg. The proportion of patients with PVR>2 Wood units (WU) among those with MPAP≤20 mm Hg, 202 WU was associated with a higher mortality rate (HR 1.61, 95% CI 1.28 to 2.02, p<0.0001) even in a group with MPAP≤20 mm Hg. CONCLUSIONS: Mild elevation of PVR was associated with a higher mortality rate in patients with newly diagnosed ILD, even in those with MPAP≤20 mm Hg.

Wide-Targeted Semi-Quantitative Analysis of Acidic Glycosphingolipids in Cell Lines and Urine to Develop Potential Screening Biomarkers for Renal Cell Carcinoma.

Glycosphingolipids (GSLs), mainly located in the cell membrane, play various roles in cancer cell function. GSLs have potential as renal cell carcinoma (RCC) biomarkers; however, their analysis in body fluids is challenging because of the complexity of numerous glycans and ceramides. Therefore, we applied wide-targeted lipidomics using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with selected reaction monitoring (SRM) based on theoretical mass to perform a comprehensive measurement of GSLs and evaluate their potency as urinary biomarkers. In semi-quantitative lipidomics, 240 SRM transitions were set based on the reported/speculated structures. We verified the feasibility of measuring GSLs in cells and medium and found that disialosyl globopentaosylceramide (DSGb5 (d18:1/16:0)) increased GSL in the ACHN medium. LC-MS/MS analysis of urine samples from clear cell RCC (ccRCC) patients and healthy controls showed a significant increase in the peak intensity of urinary DSGb5 (d18:1/16:0) in the ccRCC group compared with that in the control group. Receiver operating characteristic analysis indicated that urinary DSGb5 could serve as a sensitive and specific marker for RCC screening, with an AUC of 0.89. This study demonstrated the possibility of urinary screening using DSGb5 (d18:1/16:0). In conclusion, urinary DSGb5 (d18:1/16:0) was a potential biomarker for cancer screening, which could contribute to the treatment of RCC patients.

Predictive model for recurrence of renal cell carcinoma by comparing pre- and postoperative urinary metabolite concentrations.

To improve treatment outcomes in real practice, useful biomarkers are desired when predicting postoperative recurrence for renal cell carcinoma (RCC). We collected data from patients who underwent definitive surgery for RCC and for benign urological tumor at our department between November 2016 and December 2019. We evaluated the differences in pre- and postoperative urinary metabolites with our precise quantitative method and identified predictive factors for RCC recurrence. Additionally, to clarify the significance of metabolites, we measured the intracellular metabolite concentration of three RCC cell lines. Among the 56 patients with RCC, nine had a recurrence (16.0%). When comparing 27 patients with T1a RCC and 10 with benign tumor, a significant difference was observed between pre- and postoperative concentrations among 10 urinary metabolites. In these 10 metabolites, multiple logistic regression analysis identified five metabolites (lactic acid, glycine, 2-hydroxyglutarate, succinic acid, and kynurenic acid) as factors to build our recurrence prediction model. The values of area under the receiver operating characteristic curve, sensitivity, and specificity in this predictive model were 0.894%, 88.9%, and 88.0%, respectively. When stratified into low and high risk groups of recurrence based on this model, we found a significant drop of recurrence-free survival rates among the high risk group. In in vitro studies, intracellular metabolite concentrations of metastatic tumor cell lines were much higher than those of primary tumor cell lines. By using our quantitative evaluation of urinary metabolites, we could predict postoperative recurrence with high sensitivity and specificity. Urinary metabolites could be noninvasive biomarkers to improve patient outcome.

A possible linkage of Eurasian heat wave and East Asian heavy rainfall in Relation to the Rapid Arctic warming.

In June-July 2020 two remarkable weather events occurred in northern Eurasia. One is a severe heat wave that produced a record-breaking temperature of 38 °C at Verkhoyansk, eastern Siberia on 20 June. The other one is heavy rainfall events observed in East Asia (southern China and southwestern Japan) in early July, causing severe floods that brought about considerable damage to infrastructure and the economy, as well as the loss of human lives. Despite the accumulated evidence of stronger and more extreme heat waves and heavy rainfall as a result of global warming, little is known about the linkage between these phenomena. Given that the Arctic is warming twice as fast as the global mean, Arctic warming might be enhancing the increase of heavy rainfall events in East Asia. Here, we investigated the relationship between the Siberian heat wave and the East Asian heavy rainfall that occurred summer in 2020. An empirical orthogonal function (EOF) analysis applied to atmospheric reanalysis data of 1958-2020 period captures dominant summer circulation patterns reflecting atmospheric internal variability and externally forced anomalies. On the basis of these EOF patterns, operational forecasts of summer 2020 using the global model from the Japan Meteorological Agency (JMA) and a global climate model experiment based on 2-K warming future projection are utilized to examine roles of the internal variability and external forcing, respectively. Consistent results between them reveal that development of the blocking high over eastern Siberia has certain impacts on rainfall anomalies over East Asia. By a statistical technique applied to the ensemble forecast data, prediction of the East Asian precipitation is improved by 10-20% of its amplitude. Our research demonstrates possibility that East Asian rainfall is being enhanced by high-latitude atmospheric circulations due to the Arctic warming even in the current climate in which the tropical warming is not yet severe. Suggestions are given that continued Arctic warming and a future increase of tropical warming will lead to increases of the frequency and severity of heavy rainfall events in East Asia.

Effectiveness of monoclonal antibody therapy for COVID-19 patients using a risk scoring system.

INTRODUCTION: Monoclonal antibody therapy has been reported to be highly effective for preventing hospitalisation and severe cases in patients with Coronavirus Disease 2019 (COVID-19). However, since the drug is not readily available, it is important to rapidly and appropriately identify high-risk patients who can benefit most from therapy. Therefore, we designed a risk scoring system to identify at-risk COVID-19 patients in our region during the largest surge of COVID-19, from July to September 2021. METHODS: According to the risk scores, confirmed COVID-19 patients were introduced to receive REGN-CoV-2 to our hospital by regional health centre from 18th August (Term 3). The primary outcome was the comparison of the number of hospitalisation and severe condition with other periods, the 4th wave (Term 1) and the early part of the 5th wave (Term 2) in Japan. RESULTS: During Term 3, 115 patients were stratified with the scoring system and administered REGN-COV-2. The number of hospitalisation vs severe cases were 60 (5.2%) vs 14 (1.2%), 8 (1.5%) vs 3 (0.6%) and 21 (1.2%) vs 2 (0.1%), in term 1, 2 and 3, respectively. Among those aged <60 years, compared with term 1, the relative risk of hospitalisation and severe condition were 0.25 (95% CI: 0.12-0.53) and 0.10 (95% CI: 0.01-0.80), respectively, in term 3. Drug adverse events were fever (3: 2.6%), headache (1: 0.9%) and neck rash (1: 0.9%), all events were resolved within 24 h wth no serious adverse event. CONCLUSIONS: The administration of monoclonal antibody therapy using a risk scoring system significantly reduced the number of hospitalisation and disease severity of COVID-19 without any serious adverse events and avoided regional medical collapse.

Sex-specific Positioning of the Mating Structure in Scale-bearing Gametes of Monostroma angicava and Collinsiella cava (Ulvophyceae, Chlorophyta): A Possible Widespread Difference between Male and Female Gametes.

The gametes of chlorophytes can be divided into two morphological types (types α and ß) based on the position of the mating structure relative to the flagella and eyespot. To elucidate the relationship between the morphological types and the sexes, we studied spatial relationships between the flagellar apparatus-eyespot-mating structures in biflagellate male and female gametes and their fate after fertilization in the anisogamous (Monostroma angicava) and the slightly anisogamous species (Collinsiella cava) using field emission scanning electron microscopy and transmission electron microscopy. The smaller male and larger female gametes of M. angicava had two basal bodies arranged at a 180° angle and the cell surface coated with square-shaped body scales, except for the flagella and mating structures. The mating structure of the female gamete was located on the same side of the flagellar beat plane as the eyespot (type ß), whereas that of the male gamete was located on the opposite side (type α). This mating structure arrangement was also confirmed in C. cava. The initial fusion when male and female gametes were mixed involved the mating structures. In a fusing pair of gametes, each flagellum of one gamete lay alongside one flagellum of the other gamete. As fusion proceeded, the gamete pair transformed into a quadriflagellate planozygote, in which the four basal bodies were arranged in a cruciate pattern. The eyespots were positioned side-by-side on the same side of the cell. These results suggest that the two morphological types of gametes are intimately correlated with the particular sexes.

Basic research on the primary prevention of boxing-related sports injuries with the development of a quantitative motion analysis software.

[Purpose] To develop a quantitative motion analysis software specific to boxing (Fist Tactics Support) and to verify its effectiveness based on the percentage of hits that land on the participants. [Participants and Methods] A total of 24 male professional boxers were divided into two groups: those who used Fist Tactics Support to analyze fight videos and instituted training changes based on the results (Fist Tactics Support group, 12 participants) and those who did not (control group, 12 participants). The overall percentage of hits that landed on the participants in the fights was compared between the two groups and between pre- and post-intervention. [Results] There were no significant differences between the two groups; however, the percentage of hits that landed on the boxers of the Fist Tactics Support group was significantly lower at post-intervention than at pre-intervention. [Conclusion] The use of scientific analysis results in boxing may facilitate the primary prevention of sports injuries.

Accurate quantification of urinary metabolites for predictive models manifest clinicopathology of renal cell carcinoma.

Using surgically resected tissue, we identified characteristic metabolites related to the diagnosis and malignant status of clear cell renal cell carcinoma (ccRCC). Specifically, we quantified these metabolites in urine samples to evaluate their potential as clinically useful noninvasive biomarkers of ccRCC. Between January 2016 and August 2018, we collected urine samples from 87 patients who had pathologically diagnosed ccRCC and from 60 controls who were patients with benign urological conditions. Metabolite concentrations in urine samples were investigated using liquid chromatography-mass spectrometry with an internal standard and adjustment based on urinary creatinine levels. We analyzed the association between metabolite concentration and predictability of diagnosis and of malignant status by multiple logistic regression and receiver operating characteristic (ROC) curves to establish ccRCC predictive models. Of the 47 metabolites identified in our previous study, we quantified 33 metabolites in the urine samples. Multiple logistic regression analysis revealed 5 metabolites (l-glutamic acid, lactate, d-sedoheptulose 7-phosphate, 2-hydroxyglutarate, and myoinositol) for a diagnostic predictive model and 4 metabolites (l-kynurenine, l-glutamine, fructose 6-phosphate, and butyrylcarnitine) for a predictive model for clinical stage III/IV. The sensitivity and specificity of the diagnostic predictive model were 93.1% and 95.0%, respectively, yielding an area under the ROC curve (AUC) of 0.966. The sensitivity and specificity of the predictive model for clinical stage were 88.5% and 75.4%, respectively, with an AUC of 0.837. In conclusion, quantitative analysis of urinary metabolites yielded predictive models for diagnosis and malignant status of ccRCC. Urinary metabolites have the potential to be clinically useful noninvasive biomarkers of ccRCC to improve patient outcomes.

Expression of Ganglioside Disialosyl Globopentaosyl Ceramide in Prostate Biopsy Specimens as a Predictive Marker for Recurrence after Radical Prostatectomy.

Carbohydrate antigens are associated with carcinogenesis, cancer invasion, and metastasis and their expression reflect biological activities of various cancers. We previously reported that expression of disialosyl globopentaosyl ceramide (DSGb5), one of carbohydrate antigens, in radical prostatectomy specimens independently predicted biochemical recurrence (i.e., elevating serum prostate specific antigen without recurrent lesions in the image) after radical prostatectomy. However, it is important to evaluate the prognosis at the diagnosis. In this study we investigated DSGb5 expression in prostate biopsy specimens to develop a novel biomarker for providing appropriate management. Between 2005 and 2011, patients who underwent both prostate biopsy and radical prostatectomy in our institution were included. The median follow-up period was 88 months. DSGb5 expression was assessed by immunohistochemical staining and defined 116 patients as high DSGb5 expression (42 patients) or low DSGb5 expression (74 patients). High DSGb5 expression was significantly associated with lymphovascular invasion in radical prostatectomy specimens on both univariate and multivariable analyses (p = 0.028, 0.027). On multivariable analysis, Gleason Score in prostatectomy specimen, positive resection margin, and DSGb5 expression in the biopsy specimen were independently associated with biochemical recurrence-free survival following radical prostatectomy (p = 0.004, 0.008, 0.024). When targeting only patients with negative resection margin, DSGb5 expression was significantly associated with biochemical recurrence-free survival on both univariate and multivariable analyses (p = 0.006, 0.007). DSGb5 expression in prostate biopsy specimens is predictive of lymphovascular invasion and biochemical recurrence-free survival following radical prostatectomy. DSGb5 is a potential biomarker for preoperatively predicting oncological outcomes of prostate cancer.

Value of global metabolomics in association with diagnosis and clinicopathological factors of renal cell carcinoma.

Renal cell carcinoma (RCC) is a malignant tumor that currently lacks clinically useful biomarkers indicative of early diagnosis or disease status. RCC has commonly been diagnosed based on imaging results. Metabolomics offers a potential technology for discovering biomarkers and therapeutic targets by comprehensive screening of metabolites from patients with various cancers. We aimed to identify metabolites associated with early diagnosis and clinicopathological factors in RCC using global metabolomics (G-Met). Tumor and nontumor tissues were sampled from 20 cases of surgically resected clear cell RCC. G-Met was performed by liquid chromatography mass spectrometry and important metabolites specific to RCC were analyzed by multivariate statistical analysis for cancer diagnostic ability based on area under the curve (AUC) and clinicopathological factors (tumor volume, pathological T stage, Fuhrman grade, presence of coagulation necrosis and distant metastasis). We identified 58 metabolites showing significantly increased levels in tumor tissues, 34 of which showed potential early diagnostic ability (AUC >0.8), but 24 did not discriminate between tumor and nontumor tissues (AUC ≤0.8). We recognized 6 pathways from 9 metabolites with AUC >0.8 and 7 pathways from 10 metabolites with AUC ≤0.8 about malignant status. Clinicopathological factors involving malignant status correlated significantly with metabolites showing AUC ≤0.8 (p = 0.0279). The tricarboxylic acid cycle (TCA) cycle, TCA cycle intermediates, nucleotide sugar pathway and inositol pathway were characteristic pathways for the malignant status of RCC. In conclusion, our study found that metabolites and their pathways allowed discrimination between early diagnosis and malignant status in RCC according to our G-Met protocol.

Penile blood pressure is useful to identify candidates for tadalafil treatment in patients with lower urinary tract symptoms.

OBJECTIVES: To determine whether penile blood pressure (PBP) can be used to identify patients who can benefit from tadalafil treatment, the correlation between PBP at baseline and changes in lower urinary tract symptoms (LUTS) induced by tadalafil treatment was studied prospectively. PATIENTS AND METHODS: Patients with BPH who were poor responders to α1 -blockers and took tadalafil instead of an α1 -blocker were registered between 2014 and 2016. The patients were divided into two groups (low- and high-PBP groups) using the median baseline PBP of 110 mmHg as the threshold. The changes in the International Prostate Symptom Score (IPSS) between before and at 4 and 12 weeks after tadalafil treatment were compared between the low- and high-PBP groups. Multivariate analysis was performed to identify parameters associated with IPSS improvement with tadalafil treatment. RESULTS: In all, 51 patients were investigated. The IPSS in the low-PBP group decreased immediately after the start of treatment, and there was significant improvement in the IPSS from baseline at 4 and 12 weeks after the start of treatment, whilst the IPSS in the high-PBP group did not show significant changes. On multivariate analysis, PBP at baseline, anticholinergic drug use, and IPSS at baseline were significant predictors of a good IPSS response to tadalafil treatment. CONCLUSIONS: This study demonstrated that PBP could reliably identify patients with BPH who could benefit from tadalafil treatment. Patients with low PBP could be better responders to tadalafil.

The effect of the 'One Stretch' exercise on the improvement of low back pain in Japanese nurses: A large-scale, randomized, controlled trial.

Objectives: To evaluate the 'One Stretch' exercise's effect on improvements in low back pain (LBP), psychological factors, and fear avoidance in a large number of nurses. Methods: Between July 2015 and June 2016, we performed a prospective, randomized, parallel-group, multi-center study with central evaluations. Eligible patients were randomly assigned (1:1:1 ratio) to either the control group (Group A) or an intervention group (Group B: 30-min seminar about the 'One Stretch' exercise, Group C: B + physical and psychological approaches to LBP treatment). The primary outcome was subjective improvement from baseline to 6 months (improved/unchanged/worsened) and overall exercise habits (good/poor). Results: There were 4767 participants: 1799, 1430, and 1548 in Groups A, B, and C, respectively. We collected data on 3439 participants (949, 706, and 751 in Groups A, B, and C, respectively) at the 6-month follow-up. The improvement rates in Groups A, B, and C were 13.3%, 23.5%, and 22.6%, respectively. The worsened pain rates were 13.0%, 9.6%, and 8.1%, which decreased as the intervention degree increased (the Cochran-Armitage trend test: p < .0001). In Groups A, B, and C, 15.6%, 64.9%, 48.8% of the patients, respectively, exhibited exercise habits. Conclusion: The 'One Stretch' exercise is useful for improving LBP.

Infliximab-Induced Tubulointerstitial Nephritis with Image Findings of Striated Nephrogram in Crohn's Disease.

Tubulointerstitial nephritis is primary injury to renal tubules and interstititum which could be resulting in decreased renal function. The acute and chronic forms are most often due to allergic drug reactions or to infections. Tubulointerstitial nephritis in Crohn's disease has rarely been reported. Imaging findings of a striated nephrogram on enhanced computed tomography (CT) could represent the clinical state of tubulointerstitial nephritis. This is the first report of tubulointerstitial nephritis caused by infliximab, monoclonal antibody against human tumor necrosis factor-α, showing striated nephrograms in Crohn's disease. The case of a 28-year-old man treated with infliximab for Crohn's disease is described. Infliximab was added to his maintenance therapy, and bowel symptoms were stable. The patient presented with a 2-month history of fever and an elevated C-reactive protein after infliximab administration for 4.5 years. Contrast-enhanced CT showed striated nephrograms in both kidneys. Urinalysis showed no abnormal findings. The pathological diagnosis on CT-guided percutaneous renal needle biopsy was drug-induced tubulointerstitial nephritis because of eosinophilic infiltration with neutrophils mainly in the tubulointerstitial areas. The imaging findings of striated nephrogram are important for the diagnosis of tubulointerstitial nephritis. Tubulointerstitial nephritis could be caused by drug-induced inflammation or direct extension of Crohn's disease as an extra-interstitial manifestation. The treatment strategies for these two diseases are contradictory to each other and inappropriate treatment could worsen the renal function. Needle biopsy is therefore indispensable for differential diagnosis.

L-Lysine suppresses myofibrillar protein degradation and autophagy in skeletal muscles of senescence-accelerated mouse prone 8.

Sarcopenia is a condition of the loss of muscle mass that is associated with aging and that increases the risk for bedridden state, thereby warranting studies of interventions that attenuate sarcopenia. Here the effects of 2-month dietary L-lysine (Lys) supplementation (1.5-3.0 %) on myofibrillar protein degradation and major proteolytic systems were investigated in senescence-accelerated mouse prone 8 (SAMP8). At 36 weeks of age, skeletal muscle and lean body mass was reduced in SAMP8 when compared with control senescence-accelerated mouse resistant 1 (SAMR1). The myofibrillar protein degradation, which was evaluated by the release of 3-methylhistidine, was stimulated in SAMP8, and the autophagy activity, which was evaluated by light chain 3-II, was stimulated in the skeletal muscle of SAMP8. The activation of ubiquitin-proteasome system was not observed in the muscles of SAMP8. However, myofibrillar protein degradation and autophagic activity in skeletal muscles of SAMP8 were suppressed by dietary intake of 3.0 % Lys. The present data indicate that myofibrillar protein degradation by bulk autophagy is stimulated in the skeletal muscles of SAMP8 and that dietary Lys supplementation attenuates sarcopenia in SAMP8 by suppressing autophagic proteolysis.

[CORRESPONDENCE OF POLYMICROBIAL BACTERIURIA IN THE UNCOMPLICATED URINARY TRACT INFECTION OF THE PREMENOPAUSAL WOMAN].

(Objectives) We report the clinical features about polymicrobial bacteria detection cases in the uncomplicated urinary tract infection of the premenopausal woman from the voided midstream urine culture. (Methods) We retrospectively reviewed the premenopausal woman from 18-49 years patients visited Sendai City Hospital from April, 2006 to December, 2014, diagnosed uncomplicated cystitis or uncomplicated pyelonephritis. We analyzed for 375 specimens from the voided midstream urine culture. (Results) Among 375 specimens, the urine culture-positive for uropathogens were 211 specimens. The monomicrobial bacterial were detected in 184 specimens (87.2%) and polymicrobial bacterial specimens were 27 specimens (12.8%). The most combination group was the caused bacteria and periurethral microorganisms in 20 specimens (74.1%). Then 6 periurethral microorganisms specimens (22.2%), the caused bacteria were only 1 specimen was overlapped (3.7%). The case of urinary tract infections recurrence or revealed voiding dysfunction that need periodic treatment were more prevalent in the polymicrobial than the monomicrobial group (22.2% vs 9.8%, p=0.043). (Conclusions) When polymicrobial bacteria were detected in uncomplicated urinary tract infection in premenopausal woman, it was confirmed that there were the most combinations of caused bacteria and periurethral microorganisms. In these cases, treatment intended for only the caused bacteria. A risk of the infection recurrence and voiding dysfunction were statistically significant higher rate in the polymicrobial bacteria detection cases, and it might be necessary to consider that search to complicated urinary tract infection.

Regulatory effects of the L-lysine metabolites, L-2-aminoadipic acid and L-pipecolic acid, on protein turnover in C2C12 myotubes.

We previously showed that L-lysine (Lys) and a metabolite of Lys, L-saccharopine, suppressed autophagic proteolysis in C2C12 myotubes. However, the effects of other metabolites of Lys on protein turnover were unknown. We here investigated the effect of the Lys metabolites, L-2-aminoadipic acid (2-AA) and L-pipecolic acid (Pip), on protein turnover in C2C12 myotubes. 2-AA suppressed myofibrillar protein degradation evaluated by the 3-methylhistidine and autophagy activity evaluated by light chain 3-II at lower concentration (100 µM) than did Lys. On the other hand, Pip stimulated the mammalian target of rapamycin signaling activity. Additionally, 100 µM Pip significantly increased the rates of protein synthesis whereas 100 µM Lys had no effect. These results indicate that in C2C12 myotubes, 2-AA could suppress autophagy and Pip could stimulate the rates of protein synthesis, and these metabolites may contribute to exert effect of Lys on protein turnover.

Attenuation of autophagic-proteolysis in C2C12 cells by saccharopine.

Muscle wasting impairs physical function and leads people to a bedridden state. We previously demonstrated that lysine (Lys) suppresses autophagic-proteolysis through the Akt pathway. However, the effect of metabolites of Lys on proteolysis is unclear. In this study, we investigated the effect of saccharopine (Sac), a metabolite of Lys, on proteolysis in C2C12 cells. When C2C12 myotubes were incubated in serum-free medium containing Sac, the rate of proteolysis, which was evaluated by 3-methylhistidine released from C2C12 myotubes, and autophagy activity, which was assessed by amount of light chain 3-II, were suppressed. Sac stimulated Akt and mammalian target of rapamycin signaling, which was evaluated from eIF4E-binding protein 1 phosphorylation. The suppressive effects of Sac on proteolysis and autophagy were completely abolished by an Akt inhibitor. Therefore, we concluded that Sac suppresses autophagic-proteolysis through Akt as with Lys.

Lysine suppresses protein degradation through autophagic-lysosomal system in C2C12 myotubes.

Muscle mass is determined between protein synthesis and protein degradation. Reduction of muscle mass leads to bedridden condition and attenuation of resistance to diseases. Moreover, bedridden condition leads to additional muscle loss due to disuse muscle atrophy. In our previous study (Sato et al. 2013), we showed that administered lysine (Lys), one of essential amino acid, suppressed protein degradation in skeletal muscle. In this study, we investigated that the mechanism of the suppressive effects of Lys on skeletal muscle proteolysis in C2C12 cell line. C2C12 myotubes were incubated in the serum-free medium containing 10 mM Lys or 20 mM Lys, and myofibrillar protein degradation was determined by the rates of 3-methylhistidine (MeHis) release from the cells. The mammalian target of rapamycin (mTOR) activity from the phosphorylation levels of p70-ribosormal protein S6 kinase 1 and eIF4E-binding protein 1 and the autophagic-lysosomal system activity from the ratio of LC3-II/I in C2C12 myotubes stimulated by 10 mM Lys for 0-3 h were measured. The rates of MeHis release were markedly reduced by addition of Lys. The autophagic-lysosomal system activity was inhibited upon 30 min of Lys supplementation. The activity of mTOR was significantly increased upon 30 min of Lys supplementation. The suppressive effect of Lys on the proteolysis by the autophagic-lysosomal system was maintained partially when mTOR activity was inhibited by 100 nM rapamycin, suggesting that some regulator other than mTOR signaling, for example, Akt, might also suppress the autophagic-lysosomal system. From these results, we suggested that Lys suppressed the activity of the autophagic-lysosomal system in part through activation of mTOR and reduced myofibrillar protein degradation in C2C12 myotubes.

Immediate effects of manual traction on radiographically determined joint space width in the hip joint.

OBJECTIVE: The purpose of this study was to investigate the immediate effects of manual traction of the hip joint on joint space width (JSW) on asymptomatic subjects. METHODS: Asymptomatic, healthy male volunteers (n = 15), aged 25 to 34 years were included in this study. Three radiographs were obtained with the subjects in the supine position, before and after loading with 10% of his body weight, and after manual traction on only the right hip joint. Joint space width was measured by a radiologist at the point described by Jacobson and Sonne-Holm. RESULTS: There were significant changes in JSW on the right hip joint and left hip joint between the baseline (before loading) and immediately after loading. We also observed a significantly increased JSW on only the right hip joint between periods that followed loading and manual traction on the right hip joint. There was no significant change in JSW on the left hip joint between periods that followed loading and manual traction on the right hip joint. CONCLUSIONS: The results of this study suggest that a significant increase in JSW in young, healthy male patients can occur immediately after manual traction of the hip joint.

Rare bird forecast: A combined approach using a long-term dataset of an Arctic seabird and a numerical weather prediction model.

Wildlife observation is a popular activity, and sightings of rare or difficult-to-find animals are often highly desired. However, predicting the sighting probabilities of these animals is a challenge for many observers, and it may only be possible by limited experts with intimate knowledge and skills. To tackle this difficulty, we developed user-friendly forecast systems of the daily observation probabilities of a rare Arctic seabird (Ross's Gull Rhodostethia rosea) in a coastal area in northern Japan. Using a dataset gathered during 16 successive winters, we applied a machine learning technique of self-organizing maps and explored how days with gull sightings were related to the meteorological pressure patterns over the Sea of Okhotsk (Method A). We also built a regression model that explains the relationship between gull sightings and local-scale environmental factors (Method B). We then applied these methods with the operational global numerical weather prediction model (a computer simulation application about the fluid dynamics of Earth's atmosphere) to forecast the daily observation probabilities of our target. Method A demonstrated a strong dependence of gull sightings on the 16 representative weather patterns and forecasted stepwise observation probabilities ranging from 0% to 85.7%. Method B also showed that the strength of the northerly wind and the advancement of the season explained gull sightings and forecasted continuous observation probabilities ranging from 0% to 95.5%. Applying these two methods with the operational global numerical weather prediction model successfully forecasted the varied observation probabilities of Ross's Gull from 1 to 5 days ahead from November to February. A 2-year follow-up observation also validated both forecast systems to be effective for successful observation, especially when both systems forecasted higher observation probabilities. The developed forecast systems would therefore allow cost-effective animal observation and may facilitate a better experience for a variety of wildlife observers.