Restricted kinematically aligned total knee arthroplasty with an anatomically designed implant can restore constitutional coronal lower limb alignment.

PURPOSE: Restricted kinematically aligned total knee arthroplasty (rKA-TKA) may not restore the constitutional varus alignment in most patients with knee osteoarthritis. This study aimed to investigate (1) the extent to which constitutional lower limb alignment can be restored by rKA-TKA using an anatomically designed implant and (2) which lower limb alignment parameters are associated with patient-reported outcome measures (PROMs). METHODS: This study included 60 patients who underwent rKA-TKA using an anatomically designed implant. Radiographic alignment parameters, including mechanical lateral distal femoral angle (mLDFA), medial proximal tibial angle (MPTA), coronal hip-knee-ankle angle (HKA), coronal joint line obliquity (JLO), posterior tibial slope (PTS), single-leg standing knee flexion angle (KFA), sagittal JLO, and arithmetic HKA (aHKA), were evaluated preoperatively and postoperatively. The Western Ontario and McMaster Universities Arthritis Index (WOMAC) was used for clinical evaluation. RESULTS: The mLDFA, MPTA, and aHKA showed no significant differences before and after surgery. Coronal HKA and PTS have significantly changed from 8.1 ± 8.7° and 9.9 ± 8.6° preoperatively to 3.5 ± 3.1° and 2.5 ± 2.0° postoperatively, respectively (p < 0.001 for each comparison). The postoperative WOMAC total score was significantly correlated with the KFA (r = 0.4063, p = 0.0034) and sagittal JLO (r = -0.3435, p = 0.0157). Postoperative KFA is a causal factor for the increased postoperative WOMAC total score (r = 1.416, 95% confidence interval: 0.491-2.342, p = 0.003). CONCLUSION: rKA-TKA using an anatomically designed implant can restore constitutional coronal lower limb alignment, while postoperative KFA and sagittal JLO were associated with poor PROMs. Care should be taken for the postoperative KFA because it is a risk factor for poor PROMs. LEVEL OF EVIDENCE: Level III, case-control study.

Nutrition Assessment and Education of Patients with Heart Failure by Cardiologists.

Although nutritional assessment and education are important for hospitalized patients with heart failure, the extent of their implementation in real-world clinical practice is unknown. Therefore, this study aimed to investigate the evaluation and management of nutrition during hospitalization for heart failure using a questionnaire survey for cardiologists.In this cross-sectional multicenter survey, 147 cardiologists from 32 institutions completed a web-based questionnaire (response rate, 95%).The survey showed that 78.2% of the respondents performed a nutritional assessment for hospitalized patients, whereas 38.3% used objective tools. In contrast, only 9.5% of the respondents evaluated the presence or absence of cardiac cachexia. Most respondents (89.8%) reported providing nutritional education to their patients before hospital discharge. However, compared with the number of respondents who provided information on sodium (97.0%) and water (63.6%) restrictions, a limited number of respondents provided guidance on optimal protein (20.5%) and micronutrient (9.1%) intake as part of the nutritional education. Less than 50% of the respondents provided guidance on optimal calorie intake (43.2%) and ideal body weight (34.8%) as a part of the nutritional education for patients identified as malnourished.Although nutritional assessment is widely performed for hospitalized patients with heart failure, most assessments are subjective rather than objective. Nutritional education, frequently provided before hospital discharge, is limited to information on water or salt intake restrictions. Therefore, more comprehensive and individualized nutritional assessments and counselling with a scientific basis are required.

Prognostic value of estimating appendicular muscle mass in heart failure using creatinine/cystatin C.

BACKGROUND AND AIMS: Heart failure with concomitant sarcopenia has a poor prognosis; therefore, simple methods for evaluating the appendicular skeletal muscle mass index (ASMI) are required. Recently, a model incorporating anthropometric data and the sarcopenia index (i.e., serum creatinine-to-cystatin C ratio [Cre/CysC]), was developed to estimate the ASMI. We hypothesized that this model was superior to the traditional model, which uses only anthropometric data to predict prognosis. This retrospective cohort study compared the prognostic value of low ASMI as defined by the biomarker and anthropometric models in patients with heart failure. METHODS AND RESULTS: Among 847 patients, we estimated ASMI using an anthropometric model (incorporating age, body weight, and height) in 791 patients and a biomarker model (incorporating age, body weight, hemoglobin, and Cre/CysC) in 562 patients. The primary outcome was all-cause mortality. Overall, 53.4% and 39.1% of patients were diagnosed with low ASMI (using the Asian Working Group for Sarcopenia cut-off) by the anthropometric and biomarker models, respectively. The two models showed a poor agreement in the diagnosis of low ASMI (kappa: 0.57, 95% confidence interval: 0.50-0.63). Kaplan-Meier curves showed that a low ASMI was significantly associated with all-cause death in both models. However, this association was retained after adjustment for other covariates in the biomarker model (hazard ratio: 2.32, p = 0.001) but not in the anthropometric model (hazard ratio: 0.79, p = 0.360). CONCLUSION: Among patients hospitalized with heart failure, a low ASMI estimated using the biomarker model, and not the anthropometric model, was significantly associated with all-cause mortality.

Clinical and prognostic implications of hyaluronic acid in hospitalized patients with heart failure.

We investigated the clinical and prognostic implications of hyaluronic acid, a liver fibrosis marker, in patients with heart failure. We measured hyaluronic acid levels on admission in 655 hospitalized patients with heart failure between January 2015 and December 2019. Patients were stratified into three groups according to hyaluronic acid level: low (< 84.3 ng/mL, n = 219), middle (84.3-188.2 ng/mL, n = 218), and high (≥ 188.2 ng/mL, n = 218). The primary endpoint was all-cause death. The high hyaluronic acid group had higher N-terminal pro-brain-type natriuretic peptide levels, larger inferior vena cava, and shorter tricuspid annular plane systolic excursion than the other two groups. During the follow-up period (median 485 days), 132 all-cause deaths were observed: 27 (12.3%) in the low, 37 (17.0%) in the middle, and 68 (31.2%) in the high hyaluronic acid (P < 0.001) groups. Cox proportional hazards analysis revealed that higher log-transformed hyaluronic acid levels were significantly associated with all-cause death (hazard ratio, 1.38; 95% confidence interval, 1.15-1.66; P < 0.001). No significant interaction was observed between hyaluronic acid level and reduced/preserved left ventricular ejection fraction on all-cause death (P = 0.409). Hyaluronic acid provided additional prognostic predictability to pre-existing prognostic factors, including the fibrosis-4 index (continuous net reclassification improvement, 0.232; 95% confidence interval, 0.022-0.441; P = 0.030). In hospitalized patients with heart failure, hyaluronic acid was associated with right ventricular dysfunction and congestion and was independently associated with prognosis regardless of left ventricular ejection fraction.

Sagittal alignment cut-off values for predicting future fall-related fractures in community-dwelling osteoporotic women.

PURPOSE: Determining the optimal cut-off value of sagittal alignment for detecting osteoporotic patients at high risk for fall-related fractures is essential for understanding fracture risk and informing clinicians and physical therapists. We determined the optimal cut-off value of sagittal alignment for detecting osteoporotic patients at high risk for fall-related fractures in this study. METHODS: In the retrospective cohort study, we enrolled a total of 255 women aged ≥ 65 years who visited an outpatient osteoporosis clinic. We measured participants' bone mineral density and sagittal alignment, including sagittal vertical axis (SVA), pelvic tilt, thoracic kyphosis, pelvic incidence, lumbar lordosis, global tilt, and gap score at the initial visit. The cut-off value for sagittal alignment that was significantly associated with fall-related fractures was calculated after using multivariate Cox proportional hazards regression analysis. RESULTS: Ultimately, 192 patients were included in the analysis. After a mean follow-up of 3.0 years, 12.0% (n = 23) had fractures due to falls. Multivariate Cox regression analysis confirmed that SVA (hazard ratio [HR] = 1.022, 95% confidence interval [CI] = 1.005-1.039) was the only independent predictor of fall-related fracture occurrence. The predictive ability of SVA for the occurrence of fall-related fractures was moderate (area under the curve [AUC] = 0.728, 95% CI = 0.623-0.834), with a cut-off value of 100 mm for SVA. SVA classified by cut-off value was also associated with an increased risk of developing fall-related fractures (HR = 17.002, 95% CI = 4.102-70.475). CONCLUSION: We found that assessing the cut-off value of sagittal alignment would be useful information in understanding fracture risk in postmenopausal older women.

Joint gap produced by manual stress is dependent on the surgeon's experience and is smaller in flexion in robotic-assisted total knee arthroplasty.

PURPOSE: This study aimed to retrospectively investigate (1) the reproducibility of gap measurements by manual stress using the Z-shaped retractor depending on the surgeon's experience with this maneuver and (2) the consistency of the gap distraction force produced by manual stress throughout the range of motion (ROM) in the robotic-assisted total knee arthroplasty (TKA). It was hypothesized that the joint gap produced by manual stress is not reproducible depending on the surgeon's experience, and the distraction force applied by manual stress throughout the ROM is not constant. METHODS: Medial and lateral joint gaps were obtained throughout the ROM by manual stress or a tensioner by two surgeons with different levels of experience in robotic-assisted TKA. The association between the differences in gap measurement by the two surgeons and the preoperative radiographic parameters, including the hip-knee-ankle (HKA) angle and absolute and relative varus/valgus laxities were analyzed. RESULTS: The experienced surgeon produced significantly greater gaps than the inexperienced surgeon from 0° to 100° flexion, with a mean difference of 0.35 ± 0.12 mm in the medial gap (p < 0.0001), and from 10° to 120° flexion with a mean difference of 0.57 ± 0.13 mm in the lateral gap (p < 0.0001). The tensioner produced a significantly greater medial gap from 70° to 110° flexion with a mean difference of 0.32 ± 0.01 mm in the medial gap (p < 0.0001) and from 0° to 110° flexion with a mean difference of 1.12 ± 0.26 mm in the lateral gap (p < 0.0001). The differences in gap distance by manual stress between experienced and inexperienced surgeons were moderately correlated with the HKA angle in the lateral gap (r = 0.40, p = 0.01). The gap differences due to manual stress and a tensioner showed moderate negative correlation with the HKA angle in the medial gap (r = - 0.50, p = 0.001) and weak negative correlation with the absolute valgus laxity in the lateral gap (r = - 0.35, p = 0.03). CONCLUSIONS: The joint distraction force by manual stress may differ depending on the surgeon's experience and tended to be smaller in deep flexion; therefore, the flexion gap may be underestimated. Surgeons should determine implant positioning considering gap balance by manual stress, taking into account these characteristics of the manual stress maneuver. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Pyrrole-2-carboxaldehydes: Origins and Physiological Activities.

Pyrrole-2-carboxaldehyde (Py-2-C) derivatives have been isolated from many natural sources, including fungi, plants (roots, leaves, and seeds), and microorganisms. The well-known diabetes molecular marker, pyrraline, which is produced after sequential reactions in vivo, has a Py-2-C skeleton. Py-2-Cs can be chemically produced by the strong acid-catalyzed condensation of glucose and amino acid derivatives in vitro. These observations indicate the importance of the Py-2-C skeleton in vivo and suggest that molecules containing this skeleton have various biological functions. In this review, we have summarized Py-2-C derivatives based on their origins. We also discuss the structural characteristics, natural sources, and physiological activities of isolated compounds containing the Py-2-C group.

Does locomotive syndrome severity predict future fragility fractures in community-dwelling women with osteoporosis?

OBJECTIVES: We investigated whether the locomotive syndrome (LS) severity affects future fragility fractures in osteoporosis patients. METHODS: In this retrospective cohort study, 315 women with osteoporosis (mean follow-up period, 2.8 years) were reviewed, of whom 244 were included in the analysis. At baseline, we obtained medical information, bone mineral density of the lumbar spine and femoral neck, and sagittal vertical axis. Additionally, LS risk was assessed using the two-step test, stand-up test, and 25-question geriatric locomotive function scale scores. The LS risk test results were used to classify LS severity, which was rated on a 4-point scale from stage 0 (robust) to 3 (worsening). Cox proportional hazards regression analysis was used to determine the association of the severity with future fragility fracture. RESULTS: Fragility fractures occurred in 37 of 315 participants (11.8%). This study showed that sagittal vertical axis (hazard ratio = 1.014; 95% confidence interval, 1.005-1.023; p value = 0.003) and LS severity (hazard ratio =1.748; 95% confidence interval, 1.133-2.699; p = 0.012) were independent risk factors for incidence of fragility fracture. CONCLUSIONS: This study revealed the LS severity to predicted fragility fractures. We suggested that the progression of LS associated with osteoporosis increases the fracture risk.

Prevalence and Prognostic Relevance of Isolated Tubular Dysfunction in Patients With Acute Heart Failure.

BACKGROUND: Renal dysfunction includes glomerular dysfunction (GD) and tubular dysfunction (TD); however, there is limited information regarding the prevalence, coexistence, and prognostic relevance of TD and GD among patients with acute heart failure (AHF).Methods and Results:This study reviewed 489 patients with AHF who had undergone testing at the time of their admission to identify GD (estimated glomerular filtration rate <60 mL/min/1.73 m2) and TD (urinary ß-2-microglobulin ≥300 µg/gCr). Patients were grouped according to the presence/absence of GD and TD as having neither condition (n=116), isolated TD (n=101), isolated GD (n=83), or coexisting GD plus TD (n=189). During a median follow up of 466 days (interquartile range: 170-871 days), 107 deaths were observed. Kaplan-Meier curve analysis revealed that, relative to the absence of a GD and TD group, higher mortality rates were observed in the groups with isolated TD, isolated GD, and coexisting GD plus TD (log-rank P<0.001). Similarly, the adjusted Cox regression analyses revealed that significantly higher risks of mortality were associated with isolated TD, isolated GD, and coexisting GD plus TD. Moreover, isolated GD and isolated TD were both independently associated with increased risks of all-cause mortality. CONCLUSIONS: As a significant proportion of patients with AHF had isolated TD and an increased risk of mortality, patients with AHF should be screened for TD even if they do not have GD.

Medial proximal tibial angle at the posterior tibial plateau represents the pre-arthritic constitutional medial proximal tibial angle in anterior cruciate ligament-intact, advanced osteoarthritis of the knee.

PURPOSE: In kinematically aligned total knee arthroplasty (TKA), it is necessary to infer the pre-arthritic constitutional medial proximal tibial angle (MPTA) in advanced osteoarthritis (OA) of the knee with bone loss. The aim of this study was to investigate whether MPTA at the posterior tibial plateau represents the pre-arthritic constitutional MPTA in anterior cruciate ligament (ACL)-intact, advanced OA knees. It was hypothesized that MPTA at the posterior tibial plateau represents the pre-arthritic constitutional MPTA of ACL-intact, advanced knee OA. METHODS: One hundred varus, anterior cruciate ligament (ACL)-intact, advanced OA knees were analysed. The hip-knee-ankle (HKA) angle and MPTA were assessed on computed radiography (CR) and MPTAs at the anterior, middle, and posterior part of the tibial plateau were assessed on computed tomography (CT) images. The association between these parameters was also analysed. RESULTS: CR images showed an HKA angle of 172.4 ± 4.1° and MPTA of 84.3 ± 2.5°. CT images showed different MPTAs in the three regions, ranging from 83.9 ± 2.4° to 85.9 ± 2.8°. The middle MPTA was the lowest at 83.9 ± 2.4°. HKA angle correlated with the middle MPTA (r = 0.3355, 95% confidence interval [CI] 0.1489-0.4991, p = 0.0006) and ΔMPTA (Middle-Posterior) (r = 0.5128, 95% CI 0.3518-0.6443, p < 0.0001). CONCLUSION: The MPTA at the posterior tibial plateau represents the pre-arthritic constitutional MPTA in ACL-intact, advanced OA knees. LEVEL OF EVIDENCE: III, retrospective cohort study.

The A118G single-nucleotide polymorphism in OPRM1 is a risk factor for asthma severity.

BACKGROUND: Although population studies have implicated emotional burden in asthma severity, the underlying genetic risk factors are not completely understood. We aimed to evaluate the genetic influence of a functional single-nucleotide polymorphism (SNP) in the stress-related µ-opioid receptor gene (OPRM1; A118G SNP, rs1799971) on asthma severity. METHODS: We initially assessed disease severity in asthmatic outpatients carrying A118G. Using an ovalbumin-induced experimental asthma rodent model harboring the functionally equivalent SNP, we investigated the mechanism by which this SNP influences the allergic immune response. RESULTS: Among 292 outpatients, 168 underwent airway hyperresponsiveness (AHR) to methacholine testing. Compared with patients carrying the AA and AG genotypes, those carrying the GG genotype exhibited enhanced AHR. The stress levels were presumed to be moderate among patients and were comparable among genotypes. Compared with Oprm1 AA mice, GG mice demonstrated aggravated asthma-related features and increased pulmonary interleukin-4+CD4+ effector and effector memory T cells under everyday life stress conditions. Intraperitoneal naloxone methiodide injection reduced effector CD4+ T cell elevation associated with increased eosinophil numbers in bronchoalveolar lavage fluid of GG mice to the levels in AA mice, suggesting that elevated Th2 cell generation in the bronchial lymph node (BLN) of GG mice induces enhanced eosinophilic inflammation. CONCLUSIONS: Without forced stress exposure, patients with asthma carrying the OPRM1 GG genotype exhibit enhanced AHR, attributable to enhanced Th2 cell differentiation in the regional lymph node. Further research is necessary to elucidate the role of the OPRM1 A118G genotype in the Th2 cell differentiation pathway in the BLN.

Early introduction of very small amounts of multiple foods to infants: A randomized trial.

BACKGROUND: We investigated whether multiple food allergies could be safely prevented by simultaneously administering very small amounts of multiple foods. METHODS: Infants 3-4 months old with atopic dermatitis from 14 primary care pediatric clinics in Japan were enrolled in this randomized, placebo-controlled trial. The infants were administered either mixed allergenic food powder (MP) containing egg, milk, wheat, soybean, buckwheat, and peanuts, or placebo powder (PP). The amount of powder was increased in a stepwise manner on weeks 2 and 4, and continued until week 12. The occurrence of food allergy episodes after powder intervention was assessed at 18 months old. This trial was registered with the University Hospital Medical Information Network Clinical Trials Registry (number UMIN000027837). RESULTS: A total of 163 participants were randomly allocated to either the MP group (n = 83) or the PP group (n = 80). The incidence of food allergy episodes by 18 months was significantly different between the MP and PP groups (7/83 vs. 19/80, respectively; risk ratio 0.301 [95% CI 0.116-0.784]; P = 0.0066). Egg allergies were reduced in the MP group. In addition, food allergy episodes from any of the other five foods were significantly reduced, although the reductions in those due to individual foods were not significant. CONCLUSIONS: Gradually increasing the intake of very small amounts of multiple foods in early infancy can safely reduce the incidence of egg allergies. Other foods may also suppress food allergies, but no definitive conclusions could be reached.

Commensal-bacteria-derived butyrate promotes the T-cell-independent IgA response in the colon.

Secretory immunoglobulin A (SIgA), the most abundant antibody isotype in the body, maintains a mutual relationship with commensal bacteria and acts as a primary barrier at the mucosal surface. Colonization by commensal bacteria induces an IgA response, at least partly through a T-cell-independent process. However, the mechanism underlying the commensal-bacteria-induced T-cell-independent IgA response has yet to be fully clarified. Here, we show that commensal-bacteria-derived butyrate promotes T-cell-independent IgA class switching recombination (CSR) in the mouse colon. Notably, the butyrate concentration in human stools correlated positively with the amount of IgA. Butyrate up-regulated the production of transforming growth factor ß1 and all-trans retinoic acid by CD103+CD11b+ dendritic cells, both of which are critical for T-cell-independent IgA CSR. This effect was mediated by G-protein-coupled receptor 41 (GPR41/FFA3) and GPR109a/HCA2, and the inhibition of histone deacetylase. The butyrate-induced IgA response reinforced the colonic barrier function, preventing systemic bacterial dissemination under inflammatory conditions. These observations demonstrate that commensal-bacteria-derived butyrate contributes to the maintenance of the gut immune homeostasis by facilitating the T-cell-independent IgA response in the colon.

Altered Immune Regulation of Dendritic Cells and Enhanced Cytokine Production of T Cells in the Pathogenesis of Eosinophilic Chronic Rhinosinusitis.

INTRODUCTION: Eosinophilic chronic rhinosinusitis (ECRS) is a refractory chronic disease defined by recurrent nasal polyps with severe eosinophilic infiltration. This is mainly due to enhanced type 2-dominant immune responses, but the underlying mechanism is still not fully understood. OBJECTIVE AND METHODS: In the present study, we aimed to determine the characteristics of dendritic cells (DCs) and cytokine profiles of T cells in the peripheral blood of individuals with ECRS and age- and sex-matched healthy controls (HC). RESULTS AND CONCLUSION: The ratios of myeloid (m)DC1s to DCs and PD-L1+ mDC1s to mDC1s were higher in ECRS patients than in HC. The proportions of plasmacytoid (p)DCs in DCs, and human leukocyte antigen-DR+ pDCs and ILT3+ pDCs in pDCs were lower in ECRS patients than in HC. In a characterization of T cells, IL-4+CD4+, IFN-γ+CD4+, IL-4+IFN-γ+CD4+, IL-4+Foxp3+CD4+, IFN-γ+Foxp3+CD4+, IFN-γ+IL-4-Foxp3-CD4+, IL-4+CD8+, IL-4+IFN-γ+CD8+, and IL-4+Foxp3+CD8+ T-cell populations were significantly higher in ECRS patients than in HC. These results suggest that the enhanced immune regulation of mDC1, diminished capacity of pDCs, and increased proportion of the T-cell phenotypes in peripheral blood might be factors in ECRS pathogenesis.

Stand-up test predicts occurrence of non-traumatic vertebral fracture in outpatient women with osteoporosis.

INTRODUCTION: The purpose of this retrospective study was to clarify the incidence of non-traumatic vertebral fracture among outpatient women with osteoporosis and to determine whether the stand-up test predicted the occurrence of non-traumatic vertebral fracture. MATERIALS AND METHODS: A total of 242 postmenopausal women over 60 years of age who received outpatient osteoporosis treatment at our hospital between November 2013 and July 2020 were longitudinally evaluated in this study. We obtained medical information and radiographic parameters, including sagittal vertical axis, thoracic kyphosis, pelvic incidence, lumbar lordosis, pelvic tilt, and sacral slope at baseline. Additionally, we measured physical parameters, including height, weight, body mass index, lumbar bone mineral density, visual analog scale score for pain, and the stand-up test. RESULTS: Vertebral fractures occurred in 20 of 242 participants (8.3%), and accounted for 48.8% the 41 total fractures in the study group. Among vertebral fractures, eight (40.0%) were traumatic, resulting from falls, and 12 (60.0%) were non-traumatic. Cox multivariate logistic regression analysis adjusted for age, body mass index, lumbar bone mineral density, and the time to non-traumatic vertebral fracture showed that the sagittal vertical axis (HR = 1.013, 95% CI 1.001-1.026), stand-up test score (HR = 3.977, 95% CI 1.156-13.683), and presence of difficulty with standing from a 20-cm-high seat using both legs (HR = 3.329, 95% CI 1.625-6.82) were independent risk factors for the occurrence of non-traumatic vertebral fracture. CONCLUSION: The stand-up test may be useful as a simple screening tool for non-traumatic vertebral fracture in patients with osteoporosis.

Polyamines polarized Th2/Th9 cell-fate decision by regulating GATA3 expression.

Polyamines produced by both prokaryotes and eukaryotes are bioactive substances with pleiotropic effects. Accumulating evidence has demonstrated that polyamines contribute to anti-inflammatory responses by suppressing the expression of proinflammatory cytokines in mononuclear cells and macrophages. However, the effects of polyamines on CD4+ T cell responses remain to be elucidated. Here, we investigated the effect of polyamines on cell fate decisions of naïve CD4+ T cells in vitro. We found that endogenously generated polyamines are essential for the development of T helper 2 (Th2) cells. Treatment with DL-2-difluoromethylornithine (DFMO), an inhibitor of polyamine biosynthesis, diminished GATA3 expression in CD4+ T cells under Th2-skewed conditions. Supplementation of exogenous polyamines rescued GATA3 downregulation caused by DFMO treatment in CD4+ T cells. Transcriptome analysis revealed that deprivation of endogenous polyamines resulted in upregulated Th9-related genes, such as Il9, Irf4, and Batf3, even under the Th2-skewing conditions. Depletion of intracellular polyamines reduced GATA3 expression but increased IL-9-producing CD4+ T cells under both Th2 and Th9-skewing conditions. Furthermore, oral administration of DFMO increased IL-9-producing CD4+ T cells in small intestine in mice. Thus, our data indicate that polyamines play a critical role in the regulation of the Th2/Th9 balance.

Reference values for the locomotive syndrome risk test quantifying mobility of 8681 adults aged 20-89 years: A cross-sectional nationwide study in Japan.

BACKGROUND: The locomotive syndrome risk test was developed to quantify the decrease in mobility among adults, which could eventually lead to disability. The purpose of this study was to establish reference values for the locomotive syndrome risk test for adults and investigate the influence of age and sex. METHODS: We analyzed 8681 independent community dwellers (3607 men, 5074 women). Data pertaining to locomotive syndrome risk test (the two-step test, the stand-up test, and the 25-question geriatric locomotive function scale [GLFS-25]) scores were collected from seven administrative areas of Japan. RESULTS: The reference values of the three test scores were generated and all three test scores gradually decreased among young-to-middle-aged individuals and rapidly decreased in individuals aged over 60 years. The stand-up test score began decreasing significantly from the age of 30 years. The trajectories of decrease in the two-step test score with age was slightly different between men and women especially among the middle-aged individuals. The two physical test scores were more sensitive to aging than the self-reported test score. CONCLUSION: The reference values generated in this study could be employed to determine whether an individual has mobility comparable to independent community dwellers of the same age and sex.

Identification of a Novel Pyrrole Alkaloid from the Edible Mushroom Basidiomycetes-X (Echigoshirayukidake).

Three pyrrole alkaloid derivatives were isolated from the edible mushroom Basidiomycetes-X (Echigoshirayukidake) by water extraction followed by ethyl acetate fractionation. The chemical structures determined by MS and NMR were 4-[2-formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl] butanoic acid (compound I), 4-[2-formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl] butanamide (compound II), and 5-(hydroxymethyl)-1H-pyrrole-2-carboxaldehyde (compound III). Compound I was found to be the major component, followed by compound II, and compound III was the minor component. The dry powder of Basidiomycetes-X contained approximately 825 µg g-1 compound I and 484 µg g-1 compound II. Compound II was found to be a novel pyrrole aldehyde homologue not previously reported and thus is a specific component of this mushroom.

Elevated Periostin Concentrations in the Bronchoalveolar Lavage Fluid of Patients with Eosinophilic Pneumonia.

BACKGROUND: Eosinophilic pneumonia (EP) is characterized by massive pulmonary infiltration by eosinophils. Although serum periostin is a novel marker for eosinophil-dominant asthma, the upregulation of periostin in the airway of asthmatics is controversial. In this study, we examined whether periostin concentrations are elevated in the bronchoalveolar lavage fluid (BALF) of patients with EP. METHODS: BAL was performed in healthy volunteers and in patients with acute eosinophilic pneumonia (AEP), chronic eosinophilic pneumonia (CEP), and sarcoidosis. The periostin concentrations in the BALF were measured. RESULTS: The periostin concentration in the BALF increased significantly with pulmonary eosinophil ia and was higher in AEP and CEP patients than in healthy volunteers and sarcoidosis patients, even after adjusting the albumin concentration. In pulmonary eosinophilia, the periostin concentration correlated with the eosinophil and lymphocyte counts, the concentration of albumin, and the concentration of cytokines such as IL-5, IL-13, and transforming growth factor ß1. CONCLUSIONS: Although some blood leakage may be involved in the elevation of periostin in the BALF of EP, periostin can be induced locally, at least in part. Therefore, periostin may play a role in the development of EP.

3,4-dihydroxybenzalacetone and caffeic acid phenethyl ester induce preconditioning ER stress and autophagy in SH-SY5Y cells.

3,4-dihydroxybenzalacetone (DBL) and Caffeic acid phenethyl ester (CAPE) are both catechol-containing phenylpropanoid derivatives with diverse bioactivities. In the present study, we analyzed the ability of these compounds to activate the unfolded protein response (UPR) and the oxidative stress response. When human SH-SY5Y neuroblastoma cells were treated with DBL or CAPE, the expression of endoplasmic reticulum (ER) stress-related genes such as HSPA5, HYOU1, DDIT3, and SEC61b increased to a larger extent in response to CAPE treatment, while that of antioxidant genes such as HMOX1, GCLM, and NQO1 increased to a larger extent in response to DBL treatment. DNA microarray analysis confirmed the strong link of these compounds to ER stress. Regarding the mechanism, activation of the UPR by these compounds was associated with enhanced levels of oxidized proteins in the ER, and N-acetyl cysteine (NAC), which provides anti-oxidative effects, suppressed the induction of the UPR-target genes. Furthermore, both compounds enhanced the expression of LC3-II, a marker of autophagy, and 4-Phenylbutyric acid (4-PBA), a chemical chaperone that reduces ER stress, suppressed it. Finally, pretreatment of cells with DBL, CAPE or low doses of ER stressors protected cells against a neurotoxin 6-hydroxydopamine (6-OHDA) in an autophagy-dependent manner. These results suggest that DBL and CAPE induce oxidized protein-mediated ER stress and autophagy that may have a preconditioning effect in SH-SY5Y cells.