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Abstract In rice (Oryza sativa L.) production, dry direct seeding is one of the most essential technologies to reduce labor input and to increase net income. Field experiments were conducted in southwestern Japan in 2019 and 2020 to determine the effects of nitrogen (N) application rate and timing on grain yield, lodging, grain appearance, and protein content in dry direct broadcast seeded rice under different weather conditions. In 2019, plants had larger source ability using the normal solar radiation at the tillering stage, regardless of N application timings. Plants with applied N at the reproductive stage produced the highest grain yield and the highest percentage of undamaged grains under high air temperature condition during the early ripening stage. In 2020, plants did not have larger source ability due to the lower solar radiation at the tillering stage. Plants with applied N at the reproductive stage produced the highest grain yield but produced the highest percentage of green immature grains. These results mean that solar radiation at the tillering stage may be important for increasing grain yield and quality in dry direct broadcast seeded rice. Therefore, since plants grown under normal solar radiation condition at the tillering stage may have large source ability, more N application at the reproductive stage may be recommended to increase grain yield. In contrast, since plants grown under low solar radiation condition at the tillering stage may have small source ability, less N application at the reproductive stage may be recommended to decrease the occurrence of green immature grains.

This study is focused on hardware-based anonymization of location data for addressing privacy concerns while maintaining data utility in applications such as traffic-congestion prediction. The anonymization process involves approximating user location data to map intersections, identifying trajectories, and applying k-anonymization. However, the processing time in software implementation should be minimized. For real-time services, the process must be completed within 30 s to 1 min, which corresponds to the information update interval. Service requirements cannot be met when the volume of data and the scale of maps increase. To address this issue, we implemented a hardware accelerator on an field programmable gate array to perform the process with the aim of reducing the processing time. As a result, the maximum throughput of the proposed mechanism was approximately 150,000 data/s, which surpasses the target value of 130,000 data/s. The data retention rate, which represents information loss, was approximately 90% for the commonly used range of $10\le k\le 20$ . The difference in the data retention rate compared with the software implementation was approximately 1%. These results confirmed the effectiveness of the anonymization results obtained using the proposed mechanism.

A comprehensive analysis of cross-country skiing races is a pivotal step in establishing effective training objectives and tactical strategies. This study aimed to develop a method of classifying sub-techniques and analyzing skiing characteristics during cross-country skiing skating style timed races on snow using high-precision kinematic GNSS devices. The study involved attaching GNSS devices to the heads of two athletes during skating style timed races on cross-country ski courses. These devices provided precise positional data and recorded vertical and horizontal head movements and velocity over ground (VOG). Based on these data, sub-techniques were classified by defining waveform patterns for G2, G3, G4, and G6P (G6 with poling action). The validity of the classification was verified by comparing the GNSS data with video analysis, a process that yielded classification accuracies ranging from 95.0% to 98.8% for G2, G3, G4, and G6P. Notably, G4 emerged as the fastest technique, with sub-technique selection varying among skiers and being influenced by skiing velocity and course inclination. The study’s findings have practical implications for athletes and coaches as they demonstrate that high-precision kinematic GNSS devices can accurately classify sub-techniques and detect skiing characteristics during skating style cross-country skiing races, thereby providing valuable insights for training and strategy development.

A precise, simple, and rapid growth diagnosis method using normalized difference vegetation index (NDVI) obtained by unmanned aerial vehicle (UAV), which will help determine nitrogen (N) application rate to increase grain yield in numerous farmers' fields, is necessary for the development of a robust production system for rice (Oryza sativa L.). In the present study, we examined the relationship between UAV-NDVI and NDVI measured with the GreenSeeker handheld crop sensor (GS-NDVI), and between grain yield and UAV-NDVI or GS-NDVI at the reproductive stage in the plant communities at 4–1 ​week (wk) before heading in 2018 and 2019 and in 2020 and 2021, respectively. In the data of each measurement day in 2018 and 2019, the relationship between UAV-NDVI and GS-NDVI was strongly positive. However, in the pooled data of different measurement days, the relationship between UAV-NDVI and GS-NDVI was weakly positive. This was because GS-NDVI was more constant under various climatic conditions and across various time of day than UAV-NDVI at the reproductive stage. Furthermore, in the pooled data of different years in 2020 and 2021, GS-NDVI correlated more strongly with grain yield than UAV-NDVI between 3 and 1 ​wk before heading. To increase the efficiency of growth diagnosis and yield prediction in the numerous farmers’ fields, UAV-NDVI could be used with correction by a few measurements of GS-NDVI determined on the same day.

Itching due to atopic dermatitis causes sleep disorders in children, but its pathology is unknown. The aim of this study is to investigate nocturnal scratching as an indirect index of itching during sleep and its relationship with depth of sleep in children with atopic dermatitis. Nocturnal scratching was measured in a total of 20 children with atopic dermatitis, using a smartwatch installed with the application Itch Tracker. Depth of sleep was analysed using polysomnography. The severity of atopic dermatitis was scored using Eczema Area and Severity Index (EASI) and Patient-Oriented Eczema Measure (POEM). The number and time of nocturnal scratching measured by Itch Tracker had a significantly positive correlation with EASI scores, whereas POEM scores were not correlated with EASI scores. Mean sleep efficiency was 90.0% and scratching episodes (n = 67) started mainly during the awake stage or light sleep stages. In the scratching episodes that started during sleep stages (n = 34), the sleep stage changed to a lighter one or to the awake stage in 35.5% of episodes. Itch Tracker is applicable to measure nocturnal scratching in children. Nocturnal scratching can deteriorate quality of sleep by changing the sleep stage to a lighter one or to the awake stage.

Median arcuate ligament syndrome is a clinical condition in which the median arcuate ligament causes compression and narrowing of the celiac artery. It has been reported that collateral pathways, which is developed by the decrease of blood flow from the celiac artery, facilitates the formation of aneurysms. Aneurysms around the pancreas in particular require aggressive therapeutic intervention, because a rupture can be fatal. We herein report two cases of pancreaticoduodenal aneurysms associated with median arcuate ligament syndrome treated by coil embolization and median arcuate ligament incision. Case 1 required a hybrid procedure in which median arcuate ligament incision and coil embolization were performed simultaneously. In Case 2, the median arcuate ligament incision was performed about 3 months after emergency endovascular hemostasis for hemorrhagic duodenal ulcer. In both cases, there were no major postoperative complications and no recurrence of aneurysm. Median arcuate ligament incision may be effective to prevent organ ischemia and aneurysm recurrence after coil embolization of intra-abdominal aneurysms associated with median arcuate ligament syndrome.

Abstract Hyperhomocysteinemia was reported to enhance endoplasmic reticulum (ER) stress and subsequent apoptosis in several cells. However, the precise mechanisms of smoking susceptibility associated with hyperhomocysteinemia has not been fully elucidated. This study included 7- to 9-week-old C57BL6 male mice induced with hyperhomocysteinemia and were exposed to cigarette smoke (CS). A549 cells (human alveolar epithelial cell line) were cultured with homocysteine and were exposed to cigarette smoke extract (CSE) to observe cell viability and expression of proteins related to the ER stress. After 6 months of CS exposure, pulmonary emphysema was more severely induced in the group under the condition of hyperhomocysteinemia compared to that in the control group. The apoptotic A549 cells increased as homocysteine concentration increased and that was enhanced by CSE. Protein expression levels of ER stress markers were significantly increased after simultaneous stimulation. Notably, vitamin B12 and folate supplementation improved ER stress after simultaneous stimulation of A549 cells. In this study, we showed that hyperhomocysteinemia exacerbates CS exposure-induced emphysema in mice, suggesting that hyperhomocysteinemia and CS stimulation enhance ER stress and subsequent induced apoptosis in alveolar epithelial cells. It was suggested that there is a synergistic effect between homocysteine and CS.

Abstract Background Upper extremity deep vein thrombosis (UEDVT) is relatively rare but cannot be negligible because it can cause fatal complications. Although it is reported that the occurrence rate of UEDVT has increased due to central venous catheter (CVC), cancer, and surgical invasion, there is still limited information for esophagectomy. The aim of this study was to evaluate the clinical factors, including CVC placement and thromboprophylaxis approach, as well as retrosternal space’s width as a predictive factor for UEDVT in patients receiving esophagectomy. Methods This study included 66 patients who underwent esophagectomy with retrosternal reconstruction using a gastric tube. All patients routinely underwent contrast-enhanced computed tomography (CT) on the 4th postoperative day. Low-molecular-weight-heparin (LMWH) was routinely administered by the 2nd postoperative day. To evaluate retrosternal space’s width, (a) The distance from sternum to brachiocephalic artery and (b) the distance from sternum to vertebra were measured by preoperative CT, and the ratio of (a) to (b) was defined as the width of retrosternal space. Results Among all patients, 11 (16.7%) suffered from UEDVT, and none was preoperatively received CVC placement, while 7 were inserted in non-UEDVT cases. Retrosternal space’s width in patients with UEDVT was significantly smaller than that in patients without UEDVT (0.17 vs. 0.26; P

Abstract Background Proximal gastrectomy is a widely performed procedure that has become more common with an increasing number of proximal gastric cancer cases. Several types of reconstructive procedures after proximal gastrectomy have been developed, and it remains controversial which procedure is the most advantageous with regard to the preservation of postoperative gastric stump function and nutritional status. In the present study, we retrospectively analyzed reconstructive procedures in a consecutive case series for proximal gastrectomy, primarily focusing on postoperative body weight maintenance, nutritional status, and gastric remnant functional preservation. Methods We enrolled 69 patients who had undergone proximal gastrectomy for gastric cancer in our institute between 2005 and 2020. Short-term complications, preservation of gastric remnant functions, nutritional status, and post-operative weight changes were compared. Results After proximal gastrectomy, the numbers of patients who underwent direct esophago-gastrostomy, jejunal interposition, double tract reconstruction, and the double flap technique were 9, 10, 14, and 36, respectively. The patients in whom the double flap technique was performed suffered no reflux esophagitis after surgery. Prevalence of gastric residual at 12 months after surgery was lowest in the double flap technique group. Moreover, the double flap technique group had a better tendency regarding post-operative changes of serum albumin ratios. Furthermore, the post-operative body weight change ratio of the double flap technique group was smallest among all groups and was significantly better than that of the double tract group. Conclusions The double flap technique after proximal gastrectomy was considered the most effective technique for reconstruction which leads to better bodyweight maintenance, and results in less reflux esophagitis.

Abstract Trastuzumab deruxtecan (T-DXd), a HER2-targeting antibody–drug conjugate with a topoisomerase I inhibitor deruxtecan (DXd), exhibits an excellent anti-tumor effect in previously treated HER2-positive tumors. A recent study demonstrated that T-DXd not only suppressed tumor growth but also enhanced anti-tumor immunity through increasing the number of tumor-infiltrating CD8+ T cells and enhancement of major-histocompatibility-complex class I expression on tumor cells in a mouse model. However, the effect of T-DXd on anti-tumor immune responses in human cancers is largely unknown. We investigated the effect of T-DXd on the expression of HLA class I and CXCL9/10/11, T-cell chemoattractants, in HER2-positive human gastric cancer (GC) cells. We found that T-DXd significantly inhibited GC cell proliferation in a HER2-dependent manner, while it slightly increased the expression of HLA class I in HER2-positive GC cells. Moreover, we revealed that T-DXd significantly induced mRNA expression of CXCL9/10/11 in HER2-positive GC cells. T-DXd-triggered up-regulation of these chemokines was mediated through the activation of DNA damage signaling pathways. These results suggest that T-DXd triggers anti-tumor immune responses at least in part through induction of the expression of HLA class I and CXCL9/10/11 on HER2-positive GC cells, resulting in the enhancement of anti-tumor immunity in human GC.

Abstract High night temperature (HNT) often reduces yield in field crops. In rice, HNT during the ripening stage diminishes endosperm cell size, resulting in a considerable reduction in final kernel weight; however, little is known about the underlying mechanisms at cell level. In this study, we performed picolitre pressure-probe-electrospray-ionization mass spectrometry to directly determine metabolites in growing inner endosperm cells of intact seeds produced under HNT conditions, combining with 13C feeding and water status measurements including in situ turgor assay. Microscopic observation in the inner zone suggested that approximately 24.2% of decrease in cell expansion rate occurred under HNT at early ripening stage, leading to a reduction in cell volume. It has been shown that HNT-treated plants were subjected to mild shoot water deficit at night and endosperm cell turgor was sustained by a decline in osmotic potential. Cell metabolomics also suggests that active solute accumulation was caused by a partial inhibition of wall and starch biosynthesis under HNT conditions. Because metabolites were detected in the single cells, it is concluded that a partial arrest of cell expansion observed in the inner endosperms was caused by osmotic adjustment at mild water deficit during HNT conditions.

Background: The deterioration of pulmonary function, such as FEV1-decline, is strongly associated with poor prognosis in patients with chronic obstructive pulmonary disease (COPD). However, few investigations shed light on useful biomarkers for predicting the decline of pulmonary function. We evaluated whether thymus and activation-regulated chemokine (TARC), a Th2 inflammation marker, could predict rapid FEV1-decline in COPD patients. Methods: We recruited 161 patients with stable COPD and performed pulmonary function test once every six months. At the time of registration, blood tests, including serum levels of TARC were performed. We assessed the correlation between changes in parameters of pulmonary function tests and serum levels of TARC. The rapid-decline in pulmonary function was determined using 25th percentile of change in FEV1 or FEV1 percent predicted (%FEV1) per year. Results: In the FEV1-rapid-decline group, the frequency of exacerbations, the degree of emphysema, and serum levels of TARC was higher than in the non-rapid-decline group. When using %FEV1 as a classifier instead of FEV1, age, the frequency of exacerbations, the degree of emphysema and serum levels of TARC in the rapid-decline group was significantly greater than those in the non-rapid-decline group. In univariate logistic regression analysis, TARC was the significant predictive factor for rapid-decline group. In multivariate analysis adjusted for emphysema, serum levels of TARC are independently significant predicting factors for the rapid-decline group. Conclusions: TARC is an independent predictive biomarker for the rapid-decline in FEV1. Measuring serum TARC levels may help the management of COPD patients by predicting the risk of FEV1 decline.

Abstract Epstein-Barr virus-positive gastric cancer [EBV (+) GC] is a distinct GC subtype with unique genetic and epigenetic aberrations. Here, we examined resected GC samples and publicly available microarray data and The Cancer Genome Atlas (TCGA) database to identify the mechanism underlying overexpression of PD-L1 in EBV (+) GC. We found that high levels of PD-L1 overexpression in EBV (+) GC were caused by focal amplification of CD274. By contrast, relatively high expression of PD-L1 in tumor tissue and infiltrating immune cells correlated with CD8 lymphocyte infiltration and IFN-γ expression via IRF3 activation. Since we reported previously that PD-L1 expression is associated both with the presence of CD8 T cells in the tumor microenvironment and with IFN-γ expression in GC, we examined a database to see whether IFN-γ-associated overexpression of PD-L1 plays a significant role in EBV (+) GC. Immunohistochemical staining showed that expression of the IRF3 signature in clinical GC samples was higher in EBV (+) than in EBV (−) cases. The data presented herein reveal a unique dual mechanism underlying PD-L1 overexpression in EBV (+) GC: high focal amplification of CD274 or IFN-γ-mediated signaling via activation of IRF3.

Enhancing crop traits that increase grain yield under elevated CO2 concentrations is an important option for increasing the future productivity of rice. Here, we compared the growth and yield of five varieties with different genetic background under Free-Air CO2 Enrichment (FACE) conditions to identify traits responsible for varietal differences in yield increase under elevated CO2. Three high-yielding and two standard rice varieties grown under FACE conditions commonly had (1) shorter growth periods, (2) higher dry matter production, (3) higher numbers of spikelets (sink capacity) and panicles; and (4) higher yield than those grown under ambient CO2. Yield enhancement by elevated CO2 (FACE/Ambient), however, differed significantly among varieties, ranging from 1.10 to 1.25. The greater response of the sink capacity, defined as the product of spikelet number and single grain mass, was the main factor involved in yield increase. Three high-yielding varieties (Momiroman, Takanari, and Hokuriku 193) had greater sink capacity than two standard varieties and the sink capacity of these varieties significantly increased under FACE condition. However, yield enhancement in elevated CO2 was lower in Hokuriku 193 than in Momiroman and Takanari. In Hokuriku 193, sink production was relatively low while dry matter production was similar to the others. Therefore, larger increase in sink production efficiency per unit of dry matter production under FACE was found to be a particularly important varietal trait, suggesting that efforts to develop varieties suited to the predicted elevated CO2 condition should focus on this and the related traits.

To enhance the yield potential of rice by breeding, it is important to reveal the genetic factors affecting yield components in high-yielding cultivars. Quantitative trait loci (QTL) analysis for panicle structure and spikelet weight as an index of grain filling was conducted using recombinant inbred lines (RILs) derived from a cross between an indica-dominant high-yielding cultivar, Takanari, and a japonica-dominant high-yielding cultivar, Momiroman in 2012 and 2013 in eastern Japan. The grain-filling ability of Takanari is reported to be better than that of Momiroman. Since grain filling is generally better near the tip of the panicle and decreases as the number of branches from the rachis increases, we classified whole panicles into upper and lower side panicles and spikelets into primary, secondary, and tertiary spikelets according to the number of branches from the rachis. On chromosomes 1, 4, and 6, QTLs regulating the number of spikelets per panicle and panicle structure were detected and were most likely identical to GN1a, SPIKE, and APO1, respectively, which has been previously reported as QTLs regulating the number of spikelets per panicle. Takanari produced much heavier secondary and tertiary spikelets than Momiroman on the lower side panicle. On chromosome 5, novel QTLs regulating spikelet weight were detected. The Takanari allele enhanced secondary and tertiary spikelet weight on the lower side panicle. These results indicate that it may be possible to enhance sink capacity and translocation of source with a combination of novel QTLs detected on chromosome 5 and GN1, APO1, and SPIKE.

Phosphoribosylaminoimidazole carboxylase, phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS) encodes an enzyme that catalyzes de novo purine biosynthesis. Although PAICS has been implicated as a potential therapeutic target in several cancers, its clinical and prognostic significance in colorectal cancer (CRC) is not fully understood. To elucidate the roles of PAICS in CRC, we investigated PAICS expression in four cohorts consisting of a total of 1659 samples based on quantitative RT-PCR, microarray and RNA-seq analysis. Despite upregulated PAICS levels in tumor compared to those of normal mucosa, we found a decreasing trend of PAICS expression during tumor progression and metastasis. We conducted immunohistochemistry on 252 specimens, showing that PAICS protein was strongly expressed in the majority of CRCs, but not in adjacent mucosa. Notably, 29.0% of tumors lacked PAICS staining, and PAICS-negative expression in tumor had significant prognostic impact on poor cancer-specific survival in stage III CRC. Correspondingly, decreased levels of PAICS transcript were also correlated with poor relapse-free survival particularly in stage III patients, and this finding was robustly confirmed in three microarray datasets of a total of 802 stage II-III patients. Bioinformatics analysis of CRC tissues and cell lines consistently indicated a correlation between decreased PAICS expression and copy number loss of chromosome arm 4q. In conclusion, our results suggest that PAICS expression is downregulated during tumor progression due to genetic deletion of chromosome 4q in microsatellite stable but chromosomally unstable tumors. Furthermore, decreased expression of PAICS transcript or loss of PAICS protein may provide prognostic stratification for postoperative patients with stage III CRC.

Background: We previously reported the results of lung sound analysis in patients with bronchial asthma and demonstrated that the exhalation-to-inhalation sound pressure ratio in the low frequency range between 100 and 200 Hz (E/I LF) was correlated with the presence of airway inflammation and airway obstruction. We classified asthma patients by airway inflammation phenotype using the induced sputum eosinophil and neutrophil ratio and determined whether this phenotype could be predicted using E/I LF and fractional exhaled nitric oxide values. Methods: Steroid-naive bronchial asthma patients were classified into four phenotypes, including “Low inflammation” (35 patients), “Eosinophilic type” (58 patients), “Neutrophilic type” (15 patients), and “Mixed type” (15 patients) based on the results of induced sputum examinations. The E/I LF data and FeNO levels were then evaluated for the four phenotype groups; the prediction powers of these two indices were then analyzed for each phenotype. Results: The median E/I LF value was highest in the “Mixed type” and lowest in the “Low inflammation” group. FeNO differentiated between the “Low inflammation” and “Eosinophilic type” groups, “Low inflammation” and “Neutrophilic type” groups, and “Neutrophilic type” and “Mixed type” (p

Abstract The global atmospheric CO2 concentration has been increasing annually. To determine the trait that effectively increases rice (Oryza sativa L.) grain yield under increased atmospheric CO2 concentrations, as predicted in the near future, we grew a chromosome segment substitution line (CSSL) and a near-isogenic line (NIL) producing high spikelet numbers per panicle (CSSL-GN1 and NIL-APO1, respectively) under free-air CO2 enrichment (FACE) conditions and examined the effects of a large sink capacity on grain yield, its components, and growth-related traits under increased atmospheric CO2 concentrations. Under ambient conditions, CSSL-GN1 and NIL-APO1 exhibited a similar grain yield to Koshihikari, as a result of the trade-off between increased spikelet number and reduced grain filling. However, under FACE conditions, CSSL-GN1 and NIL-APO1 had an equal or a higher grain yield than Koshihikari because of the higher number of spikelets and lower reduction in grain filling. Thus, the improvement of source activity by increased atmospheric CO2 concentrations can lead to enhanced grain yield in rice lines that have a large sink capacity. Therefore, introducing alleles that increase sink capacity into conventional varieties represents a strategy that can be used to develop high-yielding varieties under increased atmospheric CO2 concentrations, such as those predicted in the near future.

Background: We assessed whether lung sound analysis (LSA) is a valid measure of airway obstruction and inflammation in patients with bronchial asthma during treatment with inhaled corticosteroids (ICSs). Methods: 63 good adherence patients with bronchial asthma and 18 poor adherence patients were examined by LSA, spirometry, fractional exhaled nitric oxide (FeNO), and induced sputum. The expiration-to-inspiration lung sound power ratio at low frequencies between 100 and 200 Hz (E/I LF) obtained by LSA was compared between healthy volunteers and bronchial asthma patients. Next, post-ICS treatment changes were compared in bronchial asthma patients between the good adherence patients and the poor adherence patients. Results: E/I LF was significantly higher in bronchial asthma patients (0.62 ± 0.21) than in healthy volunteers (0.44 ± 0.12, p

Enhancing crop yield response to elevated CO2 concentrations (E-[CO2]) is an important adaptation measure to climate change. A high-yielding indica rice cultivar “Takanari” has recently been identified as a potential candidate for high productivity in E-[CO2] resulting from its large sink and source capacities. To fully utilize these traits, nitrogen should play a major role, but it is unknown how N levels influence the yield response of Takanari to E-[CO2]. We therefore compared grain yield and quality of Takanari with those of Koshihikari, a standard japonica cultivar, in response to Free-Air CO2 enrichment (FACE, +200 μmol mol−1) under three N levels (0, 8, and 12 g m−2) over three seasons. The biomass of both cultivars increased under E-[CO2] at all N levels; however, the harvest index decreased under E-[CO2] in the N-limited treatment for Koshihikari but not for Takanari. The decreased harvest index of Koshihikari resulted from limited enhancement of spikelet number under N-limitation. In contrast, spikelet number increased in E-[CO2] in Takanari even without N application, resulting in significant yield enhancement, averaging 18% over 3 years, whereas Koshihikari exhibited virtually no increase in yield in E-[CO2] under the N-limited condition. Grain appearance quality of Koshihikari was severely reduced by E-[CO2], most notably in N-limited and hot conditions, by a substantial increase in chalky grain, but chalky grain % did not increase in E-[CO2] even without N fertilizer. These results indicated that Takanari could retain its high yield advantage over Koshihikari with limited increase in chalkiness even under limited N conditions and that it could be a useful genetic resource for improving N use efficiency under E-[CO2].

Increased concentrations of atmospheric CO2 are predicted to reduce the content of essential elements such as protein, zinc, and iron in C3 grains and legumes, threatening the nutrition of billions of people in the next 50 years. However, this prediction has mostly been limited to grain crops, and moreover, we have little information about either the underlying mechanism or an effective intervention to mitigate these reductions. Here, we present a broader picture of the reductions in elemental content among crops grown under elevated CO2 concentration. By using a new approach, flow analysis of elements, we show that lower absorption and/or translocation to grains is a key factor underlying such elemental changes. On the basis of these findings, we propose two effective interventions-namely, growing C4 instead of C3 crops, and genetic improvements-to minimize the elemental changes in crops, and thereby avoid an impairment of human nutrition under conditions of elevated CO2.

In vertebrates, the initial step in heme biosynthesis is the production of 5-aminolevulinic acid (ALA) by ALA synthase (ALAS). ALA formation is believed to be the rate-limiting step for cellular heme production. Recently, several cohort studies have demonstrated the potential of ALA as a treatment for individuals with prediabetes and type-2 diabetes mellitus. These studies imply that a mechanism exists by which ALA or heme can control glucose metabolism. The ALAS1 gene encodes a ubiquitously expressed isozyme. Mice heterozygous null for ALAS1 (A1+/-s) experience impaired glucose tolerance (IGT) and insulin resistance (IR) beyond 20-weeks of age (aged A1+/-s). IGT and IR were remedied in aged A1+/-s by the oral administration of ALA for 1 week. However, the positive effect of ALA proved to be reversible and was lost upon termination of ALA administration. In the skeletal muscle of aged A1+/-s an attenuation of mitochondrial function is observed, coinciding with IGT and IR. Oral administration of ALA for 1-week brought about only a partial improvement in mitochondrial activity however, a 6-week period of ALA treatment was sufficient to remedy mitochondrial function. Studies on differentiated C2C12 myocytes indicate that the impairment of glucose metabolism is a cell autonomous effect and that ALA deficiency ultimately leads to heme depletion. This sequela is evidenced by a reduction of glucose uptake in C2C12 cells following the knockdown of ALAS1 or the inhibition of heme biosynthesis by succinylacetone. Our data provide in vivo proof that ALA deficiency attenuates mitochondrial function, and causes IGT and IR in an age-dependent manner. The data reveals an unexpected metabolic link between heme and glucose that is relevant to the pathogenesis of IGT/IR.

Background:. The optimum number of microvascular anastomoses for safe free tissue transfer is controversial. Although the case for 2 venous anastomoses versus 1 anastomosis has been argued, the use of an additional arterial anastomosis has not been examined in detail. Methods:. Twelve patients who underwent 2 arterial anastomoses for a free flap transfer were identified retrospectively from the medical records of patients undergoing reconstruction for head and neck cancer. The free flaps were limited to anterolateral thigh (ALT) flaps. Results:. All flaps survived. Complications included venous thrombosis (n = 1), reexploration (n = 1), and leakage (n = 3). The vascular patterns of dual-arterialized ALT flaps were classified into 3 groups. Types 1 and 2 were ALT flaps that had 2 vascular sources from the descending and lateral branches of the lateral circumflex femoral artery. The number of accompanying veins differed between type 1 (3 veins) and type 2 (2 veins). Type 3 differed from a conventional ALT flap nourished by the descending branch of the lateral circumflex femoral artery (1 vein) by the addition of anastomosis of an artery branching from the descending branch to the vastus medialis muscle. The total operation times for these 3 types of ALT were similar. Conclusions:. An additional arterial anastomosis to the free cutaneous flap did not cause any congestion or disturb the balance between inflow and outflow. If the surgeon considers that the first arterial anastomosis is unreliable, an additional anastomosis might be an option in ALT transfer.

The aim of this study was to use small unmanned aerial vehicles (UAVs) for determining high-resolution normalized difference vegetation index (NDVI) values. Subsequently, these results were used to assess their correlations with fertilizer application levels and the yields of rice and wheat crops. For multispectral sensing, we flew two types of small UAVs (DJI Phantom 4 and DJI Phantom 4 Pro)—each equipped with a compact multispectral sensor (Parrot Sequoia). The information collected was composed of numerous RGB orthomosaic images as well as reflectance maps with spatial resolution greater than a ground sampling distance of 10.5 cm. From 223 UAV flight campaigns over 120 fields with a total area coverage of 77.48 ha, we determined that the highest efficiency for the UAV-based remote sensing measurement was approximately 19.8 ha per 10 min while flying 100 m above ground level. During image processing, we developed and used a batch image alignment algorithm—a program written in Python language–to calculate the NDVI values in experimental plots or fields in a batch of NDVI index maps. The color NDVI distribution maps of wide rice fields identified differences in stages of ripening and lodging-injury areas, which accorded with practical crop growth status from aboveground observation. For direct-seeded rice, variation in the grain yield was most closely related to that in the NDVI at the early reproductive and late ripening stages. For wheat, the NDVI values were highly correlated with the yield ( R 2 = 0.601–0.809) from the middle reproductive to the early ripening stages. Furthermore, using the NDVI values, it was possible to differentiate the levels of fertilizer application for both rice and wheat. These results indicate that the small UAV-derived NDVI values are effective for predicting yield and detecting fertilizer application levels during rice and wheat production.

The contribution of cell wall components and nonstructural carbohydrate (NSC) to grain filling in rice (Oryza sativa L.) was clarified by investigating the differences in the dynamics of hemicellulose, sugar composition of hemicellulose, β-(1→3),(1→4)-glucan, and NSC among cultivars with different grain filling capacities. This investigation was performed using the stems of standard, high yield and low harvest index (HI) cultivars. Hemicellulose concentration in stems tended to decrease slightly during the grain filling stage. This decrease was attributed to a decrease in β-(1→3),(1→4)-glucan concentration, which was detected as a decrease in glucose composition of hemicellulose in the stems during the grain filling stage. The rate of decrease and decrease in the amount of β-(1→3),(1→4)-glucan in the stems differed among the cultivars. These were higher in high yield and high HI cultivars than in relatively low yield and low HI cultivars. Moreover, a positive correlation was observed between the rate of decrease in β-(1→3),(1→4)-glucan and NSC, indicating similarities in the dynamics of β-(1→3),(1→4)-glucan and NSC among the cultivars. When the top half of panicle was removed, β-(1→3),(1→4)-glucan and NSC concentrations in the culm and leaf sheath did not decrease during the grain filling stage. Therefore, the β-(1→3),(1→4)-glucan in stems might be one of the sources that supply substrate to panicle as well as NSC.

One of the limiting factors of soybean yield in southwestern Japan is soil moisture fluctuation from flooding to drought. The Farm-Oriented Enhancing Aquatic System (FOEAS), which consists of underdrain and sub-irrigation systems and can keep groundwater levels stable, was developed in 2005 to solve this problem. To obtain basic information on soybean cultivation using the FOEAS in southwestern Japan, we examined the growth response to groundwater level by using two cultivars (cv. Fukuyutaka and Sachiyutaka) in 2008 and 2010. Plant growth, yield, yield components and seed components (protein and oil contents) were analyzed. We also studied the effect of sowing time (normal or late). The groundwater level was controlled at depths of 20 and 35 cm or not treated (NT) as a control. The groundwater level could be kept at the target depths (20 and 35 cm) by FOEAS throughout the experimental period, but that in the NT plot fluctuated greatly. The growth and yield of Sachiyutaka might be increased by FOEAS, especially in late sowing, but the yield of normal sown Sachiyutaka was decreased in the 20-cm plot in 2010. Yield of late-sown Fukuyutaka tended to be decreased in the 20-cm plot. These results suggest that (1) the optimum groundwater level for yield of Sachiyutaka is between 20 and 35 cm, regardless of sowing time and (2) the groundwater level should not be kept at 20 cm for late-sown Fukuyutaka. Further studies are needed to determine the optimum groundwater level for each cultivar.

Chest auscultation is commonly performed during respiratory physical therapy (RPT). However, the changes in breath sounds in children with atelectasis have not been previously reported. The aim of this study was to clarify the characteristics of breath sounds in children with atelectasis using acoustic measurements.The subjects of this study were 13 children with right middle lobe atelectasis (3-7 years) and 14 healthy children (3-7 years). Lung sounds at the bilateral fifth intercostal spaces on the midclavicular line were recorded. The right-to-left ratio (R/L ratio) and the expiration to inspiration ratio (E/I ratio) of the breath sound sound pressure were calculated separately for three octave bands (100-200 Hz, 200-400 Hz, and 400-800 Hz). These data were then compared between the atelectasis and control groups. In addition, the same measurements were repeated after treatment, including RPT, in the atelectasis group.Before treatment, the inspiratory R/L ratios for all the frequency bands were significantly lower in the atelectasis group than in the control group, and the E/I ratios for all the frequency bands were significantly higher in the atelectasis group than in the control group. After treatment, the inspiratory R/L ratios of the atelectasis group did not increase significantly, but the E/I ratios decreased for all the frequency bands and became similar to those of the control group.Breath sound attenuation in the atelectatic area remained unchanged even after radiographical resolution, suggesting a continued decrease in local ventilation. On the other hand, the elevated E/I ratio for the atelectatic area was normalized after treatment. Therefore, the differences between inspiratory and expiration sound intensities may be an important marker of atelectatic improvement in children.

The effects of planting time (early or normal), nitrogen (N) application rate (150 or 225 kg N ha-1), and N application method (early, even, and late application of extra N) on total digestible nutrient (TDN) concentration and yield of forage rice (Oryza sativa L.) in southwestern Japan were examined. For optimal forage rice production, it is important to maximize nutritional level in leaves and stems rather than panicles because the hull restricts cattle’s ability to digest rice grain. In particular, it is important to maximize the TDN in leaf sheath plus stems (stems) which are the major part of the crop rather than leaf blades (leaves). Stem TDN yield was higher with early planting (340 g m-2) than with normal planting (217 g m-2) irrespective of N application rate or method. The high stem TDN yield with early planting resulted from both the high DM yield and the high TDN and organic cellular content (OCC) concentration. Stem TDN yield was not affected by the N application rate. With both early and normal plantings, stem TDN yield was higher with early N application (374 and 226 g m-2, respectively) than with late N application (305 and 208 g m-2, respectively). With early planting, the high stem TDN yield with method 1 resulted from both the high DM yield and the high TDN and OCC concentration. Thus, to obtain high stem TDN concentration and yield of forage rice, early planting and early N application are recommended.

The aim of this study was to determine suitable culture conditions for maintaining the activity of cytochrome p450 (CYP) 3A4 and drug transporters in primary cultured human hepatocytes. Human hepatocytes were isolated using the two-step collagenase perfusion technique and were cultured with four different media, serum-free William’s E medium (serum-free WEM), WEM containing fetal calf serum (FCS-WEM), WEM with human serum (HS-WEM), and Lanford’s medium. The albumin levels were maintained for 7 days in hepatocytes. Although CYP3A4 mRNA levels gradually decreased from 3 days, CYP3A4 and hepatocyte nuclear factor-4α alpha protein levels and activities were maintained for 7 days in hepatocytes cultured with serum-free WEM and Lanford’s but not in those with FCS-WEM and HS-WEM. Furthermore, CYP3A4 protein levels were significantly increased by the addition of rifampicin and dexamethasone to the culture media, indicating that the induction potential was maintained. The protein levels of P-glycoprotein, multi-drug-resistance-2, and breast cancer-resistance protein were maintained for 7 days in all media. Serum-free WEM and Lanford’s also maintained protein levels of CYP2C19, CYP2D6, and organic anion transporter polypeptide in the hepatocytes. Serum-free WEM and Lanford’s may be appropriate culture media for maintaining CYP3A4 and drug transporter protein levels in primary cultured hepatocytes. Keywords:: CYP3A4, HNF-4α, primary hepatocyte, ATP-binding cassette transporter, Lanford’s medium

We analyzed the relationship between growth-related traits at anthesis and protein content of grain at maturity to develop a method of estimating the nitrogen (N) application rates at anthesis required to obtain the target protein content of grain in the bread wheat (Triticum aestivum L.) cultivar Minaminokaori in three crop seasons in southwestern Japan. The protein content of grain had a higher positive correlation with leaf blade dry weight (DW) and the leaf area index (LAI)×SPAD value than with the SPAD value. Moreover, the relationships between leaf blade DW and protein content of grain and between LAI×SPAD value and protein content of grain could be approximated well using quadratic functions for each N application rate at anthesis. Thus, N application rate at anthesis required to obtain the target protein content of grain can be estimated by using these quadratic functions.

We examined the effects of cutting height and trampling over stubbles of the first crop on dry matter yield in twice harvesting of forage rice Oryza sativa L., Tachiaoba and Taporuri. Dry matter yield of the second crop, after the first harvest at the full-heading stage, increased with increasing cutting height. However, the dry matter yield of the first crop decreased with increasing cutting height. Overall, total dry matter yield did not vary with the cutting height. Dry matter yield and its components of the second crop were not greatly affected by the trampling treatment. At cutting heights of 15 and 5 cm from the base, the number of tillers developed from unelongated nodes was increased by the trampling treatment. Thus, although the number of tillers developed from the elongated nodes was decreased after the trampling treatment, the decrease is compensated for by the increased number of tillers from unelongated nodes.

We examined the effects of planting time on the dry matter (DM) yield of the forage rice cultivar Tachiaoba in southwestern Japan. DM yield was much higher with early planting than with normal planting. Dry weight (DW) per tiller was much higher with early planting than with normal planting. Thus, early planting is effective to obtain high DM yield. DM yield was closely related to the DW increase from transplanting to the full-heading stage (DW increase before heading) and DW per tiller. These results suggest that early planting leads to an increase in DW at the full-heading stage through an increase in DW per tiller and gives a high DM yield at the yellow-ripe stage. We also examined the effects of nitrogen (N) application rate and method on DM yield at the yellow-ripe stage. DM yield was higher with application of 22.5 g N m-2 than with 15.0 g N m-2. Although DW per tiller was slightly lower with application of 22.5 g N m-2 than with 15.0 g N m-2, the number of tillers per square meter was much higher with application of 22.5 g N m-2 than with 15.0 g N m-2. DM yield was the highest with N application method 1 that was applied more N early, followed by methods 2 that was applied more N evenly over time and 3 that was applied more N later. The number of tillers per square meter was much higher with method 1 than with method 2 or 3. Thus, application of 22.5 g N m-2 by method 1 is effective to obtain high DM yield. With both early and normal plantings, DM yield was closely related to the DW increase before heading and the number of tillers per square meter. These results suggest that application of 22.5 g N m-2 by method 1 lead to an increase in DW at the full-heading stage through an increase in the number of tillers per square meter resulting in a high DM yield at the yellow-ripe stage.

We examined the effects of seeding rate, 50 or 150 seeds m-2, nitrogen (N) application rate at active tillering and jointing, 4 and 2 g N m-2, respectively, or none, and N application rate at anthesis, 0, 2, 4, or 6 g N m-2, on grain yield and protein content of a bread wheat cultivar, ‘Minaminokaori’, during the 2004–2005 crop season in southwestern Japan. Grain yield was similar at a seeding rate of 50 and 150 seeds m-2. It was higher when 4 and 2 g N m-2 were applied at active tillering and jointing, respectively (4–2N), than when no N was applied at these stages (0–0N). However, it was not influenced by N application rate at anthesis. Grain protein content was similar at 50 and 150 seeds m-2. It was higher in 4–2N than in 0–0N. It was the highest when 6 g N m-2 was applied at anthesis, followed by 4, 2, and 0 g N m-2. The SPAD value at anthesis was higher at 50 than 150 seeds m-2, but leaf area index (LAI) at anthesis was similar at 50 and 150 seeds m-2 and protein content of grain was nearly the same at 50 and 150 seeds m-2 irrespective of N application rate at anthesis. LAI and the SPAD value were higher in 4–2N than in 0–0N and the protein content of grain was also higher in 4–2N than in 0–0N irrespective of N application rate at anthesis. Therefore, both LAI and the SPAD value may be important traits related to the N application rate at anthesis suitable for yielding wheat grain with a high protein content.

The effect of nitrogen (N) application rates at active tillering and anthesis on grain yield and protein content of a bread wheat cultivar, ‘Minaminokaori’, was examined in the field study conducted in Fukuoka, Japan. Number of spikes, leaf area index (LAI), and SPAD value at anthesis increased significantly (P < 0.05) with increasing N application rate at active tillering. Grain yield also increased significantly (P < 0.05) because of the increased number of spikes. However, grain yield did not increase significantly (P > 0.05) with increasing N application rate at anthesis. The slope of the relationship between N application rate at active tillering and grain yield was about 3 times that of the relationship between N application rate at anthesis and grain yield. These results indicate that N application at active tillering is more effective than N application at anthesis for increasing grain yield. Increasing N application rate at active tillering and anthesis generally increased grain protein content. However, the slope of the relationship between N application rate at anthesis and grain protein content was about 2 times that of the relationship between N application rate at active tillering and grain protein content. These results indicate that N application at anthesis is more effective than N application at active tillering for increasing grain protein content. The interaction between N application rates at active tillering and anthesis was significant (P < 0.05) for grain protein content. With the application of 4 g N m–2 at active tillering, grain protein content increased linearly at a rate of about 0.5% per 1 g N m–2 (from 10.9% to 14.0%) with increasing N application rate (from 0 to 6 g N m–2) at anthesis. However, the rate of increase in grain protein content with increasing N application rate at anthesis was greater with 0 g N m–2 at active tillering than that with 4 g N m–2 at active tillering, whereas that with 8 g N m–2 at active tillering was smaller than that with 4 g N m–2 at active tillering. Application of 8 g N m–2 at tillering resulted in the highest SPAD value at anthesis; this was followed by the results for 4 and 0 g N m–2. Therefore, the SPAD value may be an important trait to decide N application rate at anthesis.

OBJECTIVE: To evaluate the neuroprotective effect of mild hypothermia during temporary focal ischemia in cats. METHOD: 20 cats underwent middle cerebral artery 60 minutes occlusion and 24 hours reperfusion: 10 under normothermia and 10 under mild hypothermia (32º C). Brain coronal sections 2mm thick were stained with 2,3,5-triphenyltetrazolium hydrochloride, photographed and evaluated with software for volume calculation. RESULTS:Cortical ischemia was found in 7 and basal ganglia ischemia in 8 animals of group 1 and in both regions in 5 animals of group 2 (no difference: p=0.6499 for cortical; p=0.3498 for basal ganglia). No ischemia was found in 5 animals of group 2 and in none of group 1 (significant difference, p=0.0325). The infarct volume was greater in group 1 than 2 (p=0.0433). CONCLUSION: Mild hypothermia did not interfere with location of ischemia, but it was effective for reducing the infarct volume.OBJETIVO: Avaliar o efeito neuroprotetor da hipotermia leve na isquemia cerebral focal temporária em gatos. MÉTODO: Oclusão da artéria cerebral média durante 60 minutos e 24 horas de reperfusão em 10 gatos sob normotermia e 10 sob hipotermia leve (32º C). Secções cerebrais coronais de 2 mm coradas com 2,3,5-cloreto de trifeniltetrazolio, fotografadas e cálculos volumétricos (hemisférios/áreas isquêmicas) com programa específico. RESULTADOS: Isquemia cortical em 7 e nos gânglios da base em 8 animais do grupo 1 e em ambas as regiões em 5 animais do grupo 2 (sem diferença: p=0,6499 cortical; p=0,3498 gânglios da base). Cinco animais do grupo 2 e nenhum do grupo 1 não apresentaram isquemia (diferença significante, p=0,0325). O volume do infarto foi maior no grupo 1 (p=0,0433). CONCLUSÃO: Hipotermia leve não interferiu com a localização da isquemia mas foi eficaz para reduzir o volume do infarto.

The phenological development of winter wheat Iwainodaichi seeded early was compared with that of spring wheat Chikugoizumi based on the temperature. In this paper, the developmental phase from the sowing to double ridge is referred to phase 1, that from double ridge to anthesis phase 2 and that from the anthesis to maturity phase 3. The duration of phase 1 in Iwainodaichi was almost constant independent of the mean temperature in this phase, but that in Chikugoizumi decreased as the mean temperature in this phase increased. When seeded early, the duration of phase 1 was obviously longer in Iwainodaichi than in Chikugoizumi since the mean temperature in this phase was higher when seeded early. The duration of phase 2 decreased in both varieties as the mean temperature and photoperiod in this phase increased. When seeded early, phase 2 was shorter in Iwainodaichi than in Chikugoizumi, since the mean temperature was higher and photoperiod longer in this phase in Iwainodaichi than in Chikugoizumi. The duration of phase 3 decreased as the mean temperature in this phase increased in both varieties and was shorter in Iwainodaichi than in Chikugoizumi at the same mean temperature. Consequently, Iwainodaichi reached the double ridge stage later but reached maturity at about the same time as Chikugoizumi when seeded early.

To evaluate the feasibility of conservation tillage in combination with reduced biocide and fertilization regimes, we conducted a field experiment using conventional and reduced tillage, with or without reduced biocide, and fertilization regimes for growing soybean, sugar beet, and spring wheat in this order for three years. Root biomass and sugar yield of sugar beet did not differ with any combinations of conservation practice. Although leaf biomass was significantly reduced under reduced chemical fertilization (replaced partially with manure compost), it was compensated by a greater specific leaf area. Early crop growth of soybean, and spring wheat was increased to some extent under reduced tillage, which indicated a better nutrient utilization, as well when combined with reduced biocide application. However, reduced fertilization could not supply as much nitrogen as conventional chemical fertilization especially in the combination with reduced tillage. Larger amount or long-term application of organic fertilization may be necessary under reduced tillage compared to the requirement under conventional tillage to compensate for lower rate of nitrogen release from organic matter.

INTRODUÇÃO: A isquemia cerebral é uma doença freqüente e de difícil tratamento médico. De particular interesse neurocirúrgico são as situações de vasoespasmo após hemorragia subaracnóidea, de oclusão temporária de vasos nas neurocirurgias e de tromboses de artérias intracranianas. A lesão cerebral resultante da isquemia depende da sua duração e pode ser agravada pela reperfusão do território isquêmico. Vários estudos clínicos e experimentais têm sido realizados para melhor entender esses fenômenos. OBJETIVO: Este trabalho visou a avaliação precoce dos efeitos da isquemia focal seguida da reperfusão no cérebro de gatos. MÉTODOS: A isquemia cerebral foi provocada por clipagem temporária da artéria cerebral média por tempos determinados com reperfusão durante 10 minutos, e avaliação foi efetuada através da análise da respiração mitocondrial no tecido isquemiado. Resultados - Houve redução significativa no consumo de O2 nas amostras de tecido cerebral isquemiado por 60 minutos, seguidos de 10 minutos de reperfusão, quando comparadas ao tecido cerebral contralateral (não isquemiado). CONCLUSÕES: Com base nos resultados obtidos, pode-se concluir que o tempo de duração da isquemia foi um fator determinante na alteração da respiração mitocondrial de gatos submetidos à isquemia e reperfusão de curta duração (alterações significativas apenas após 60 minutos de isquemia seguidos de 10 de reperfusão).

The response of microarthropod populations to different combinations of conservations! agricultural practices was investigated in two field experiments. In the first experiment, cropping systems with combinations of tillage (conventional or reduced), biocide application (conventional or reduced), and fertilization (chemical or cattle manure compost) were compared. In the second experiment, five treatments including four fallow managements that received different levels of tillage, biocide, and organic matter input from vegetation were compared. The springtail (Collembola) population was higher with less tillage, less biocide application, and more organic matter input in both experiments, and these effects were additive; there was no specific combination of practices that has an interacting effect. The mite (Acari) population was also higher under most conservations! treatments, and a significant interaction effect between tillage and organic matter application was found. A large increase in the Acari population under the combination of reduced tillage and higher organic matter input suggested that beneficial effects of these practices on the Acari community could be increased by integrating these practices. There was no significant correlation between the microarthropod populations and plant cover or soil chemical/physical properties measured. Slight changes in soil environments caused by agricultural practices may affect microarthropod communities substantially even before the changes in soil properties become detectable.

Os hematomas epidurais espontâneos são raramente descritos na literatura. Estão associados a doenças infecciosas do crânio, distúrbios da coagulação, malformações vasculares da dura-máter e metástases na calota craniana. Os autores relatam dois casos de hematomas epidurais espontâneos de diferentes etiologias e discutem aspectos relacionados à hemostasia.

Os autores relatam o caso de um paciente de 7 anos de idade, com quadro de dor cervical e tetraparesia progressiva há 2 meses, que apresentava lesão cística intrarraquiana de C4 a C6. Foi submetido a exerese da lesão por via anterior, através de corporectomia de C5-C6 e reconstrução com enxerto de crista ilíaca e placa metálica. O diagnóstico anátomo-patológico da lesão foi de cisto enterógeno. Aspectos relacionados a apresentação clínica, embriologiae tratamento dessa lesão são discutidos.The authors report the case of a 7 years old boy with cervical pain and tetraparesis progressing by two months. He presented an intraspinal cystic lesion from C4 to C6. Exeresis of the lesion was undergone by anterior way through a corpectomy of C5-C6 followed by reconstruction with bone graft of the iliac crest and metallic plaque. Anatomic diagnosis of the lesion was enterogenous cyst. Aspects of clinical presentation, embryology and treatment of these cysts are discussed.

Chronic obstructive pulmonary disease is a common disability among elderly subjects with a heavy cigarette smoking habit. In contrast to the population that is susceptible to smoking, in whom pulmonary function worsens with the length of exposure to cigarette smoke, there are elderly individuals whose pulmonary function is not impaired. However, to date, the characteristics of this resistant smoking population have not been investigated. We aimed to identify a biomarker in individuals in whom lung health is maintained despite smoking. Blood sampling and spirometry were performed on 3,257 subjects who participated in a community-based annual health check in Takahata, Japan, from 2004 to 2006. We selected 117 elderly smokers (age ≥70, Brinkman index ≥600, smoking years ≥30). The 'smoking resistant' group met the following criteria: FEV1/FVC ≥0.7, and FEV1%predicted ≥80. Spirometry was re-evaluated in 147 male, current smokers in 2009. Baseline serum iron (sFe) levels were higher in the smoke resistant group compared with the non-resistant group. In those with low sFe levels, FEV1/FVC was reduced in male subjects. These spirometric measures were positively associated with sFe levels in men. Multiple linear regression analysis revealed that sFe levels were predictive for spirometric values, independent of other clinical factors. In addition, sFe levels were predictive for a decline in FEV1.Serum iron levels may be a biomarker for the spirometric susceptibility of individuals to cigarette smoke.

Chronic obstructive pulmonary disease is a known risk factor for cardiovascular death in Western countries. Because Japan has a low cardiovascular death rate, the association between a lower level of forced expiratory volume in 1 s (FEV1) and mortality in Japan's general population is unknown. To clarify this, we conducted a community-based longitudinal study. This study included 3253 subjects, who received spirometry from 2004 to 2006 in Takahata, with a 7-year follow-up. The causes of death were assessed on the basis of the death certificate. In 338 subjects, airflow obstruction was observed by spirometry. A total of 127 subjects died. Cardiovascular death was the second highest cause of death in this population. The pulmonary functions of the deceased subjects were significantly lower than those of the subjects who were alive at the end of follow-up. The relative risk of death by all causes, respiratory failure, lung cancer, and cardiovascular disease was significantly increased with airflow obstruction. The Kaplan-Meier analysis showed that all-cause and cardiovascular mortality significantly increased with a worsening severity of airflow obstruction. After adjusting for possible factors that could influence prognosis, a Cox proportional hazard model analysis revealed that a lower level of FEV1 was an independent risk factor for all-cause and cardiovascular mortality (per 10% increase; hazard ratio [HR], 0.89; 95% confidence interval [CI], 0.82-0.98; and HR, 0.72; 95% CI, 0.61-0.86, respectively). In conclusion, airflow obstruction is an independent risk factor for all-cause and cardiovascular death in the Japanese general population. Spirometry might be a useful test to evaluate the risk of cardiovascular death and detect the risk of respiratory death by lung cancer or respiratory failure in healthy Japanese individuals.

BACKGROUND: Accumulating evidence suggests the involvement of an autoimmune mechanism in the pathogenesis of respiratory dysfunction. The aim of this study was to investigate the relationship between pulmonary function and serum antibodies to several connective tissue disease autoantigens (ACTDA) levels, which has not been investigated in a general population. METHODS: Blood sampling and spirometry were performed for subjects (n = 3,257) aged ≥40 years who participated in a community-based annual health check in Takahata, Japan, from 2004 to 2006. ACTDA was measured by enzyme immunoassay, and subjects with ACTDA values ≥20 were defined as positive. RESULTS: In males, there were significant inverse relationships between logarithmically transformed ACTDA values and spirometric parameters, including % predicted values for forced expiratory volume in 1 s (FEV1) and maximal midexpiratory flow (MMF) as well as FEV1/forced vital capacity (FVC). Multiple linear regression analysis revealed that except for the relationship between ACTDA and FEV1/FVC, these relationships were still significant after adjustment for Brinkman index (a measure of inhaled cigarette consumption). The prevalence of positive ACTDA was greater in male never-smokers with mixed ventilation disorders and relatively severe airflow obstruction (% predicted FEV1 below the median value). CONCLUSIONS: Autoimmunity may be involved in the mechanism of impaired pulmonary function in the general population.

MyD88, a Toll/interleukin-1 receptor homology (TIR) domain-containing adaptor protein, mediates signals from the Toll-like receptors (TLR) or IL-1/IL-18 receptors to downstream kinases. In MyD88-dependent TLR4 signaling, the function of MyD88 is enhanced by another TIR domain-containing adaptor, Mal/TIRAP, which brings MyD88 to the plasma membrane and promotes its interaction with the cytosolic region of TLR4. Hence, Mal is recognized as the "sorting adaptor" for MyD88. In this study, a direct interaction between MyD88-TIR and another membrane-sorting adaptor, TRAM/TICAM-2, was demonstrated in vitro. Cell-based assays including RNA interference experiments and TRAM deficient mice revealed that the interplay between MyD88 and TRAM in cells is important in mediating IL-18 signal transduction. Live cell imaging further demonstrated the co-localized accumulation of MyD88 and TRAM in the membrane regions in HEK293 cells. These findings suggest that TRAM serves as the sorting adaptor for MyD88 in IL-18 signaling, which then facilitates the signal transduction. The binding sites for TRAM are located in the TIR domain of MyD88 and actually overlap with the binding sites for Mal. MyD88, the multifunctional signaling adaptor that works together with most of the TLR members and with the IL-1/IL-18 receptors, can interact with two distinct sorting adaptors, TRAM and Mal, in a conserved manner in a distinct context.

Relatamos o caso de uma mulher de 55 anos, hipertensa leve, em uso de beta bloqueador, que apresentou quadro súbito de síndrome de compressão medular, caracterizado por dor cervical intensa, evoluindo para tetraplegia com nível de sensibilidade em C4. Foi diagnosticado, por ressonância magnética, hematoma intrarraquidiano extradural cervical , que foi aspirado cirurgicamente através de laminectomia. A paciente encontra-se em acompanhamento fisioterápico e evolui com melhora da motricidade e sensibilidade.