Three-dimensional image analysis specifies the root distribution for drought avoidance in the early growth stage of rice.

BACKGROUND AND AIMS: Root system architecture (RSA) plays a key role in plant adaptation to drought because deep rooting enables better water uptake than shallow rooting under terminal drought. Understanding RSA during early plant development is essential for improving crop yields, as early drought can affect subsequent shoot growth. Herein, we demonstrate that root distribution in the topsoil significantly impacts shoot growth during the early stages of rice (Oryza sativa) development under drought, as assessed through three-dimensional (3D) image analysis. METHODS: We used 109 F12 recombinant inbred lines (RILs) obtained from a cross between shallow-rooting lowland rice and deep-rooting upland rice, representing a population with diverse RSA. We applied a moderate drought during the early development of rice grown in a plant pot (25 cm height) by stopping irrigation 14 days after sowing (DAS). Time-series RSA at 14, 21, and 28 DAS was visualized by X-ray computed tomography, and subsequently compared between drought and well-watered conditions. Following this analysis, we further investigated drought-avoidant RSA by testing 20 randomly selected RILs under drought conditions. KEY RESULTS: We inferred the root location that most influences shoot growth using a hierarchical Bayes approach: the root segment depth, which positively impacted shoot growth, ranged between 1.7-3.4 cm under drought conditions and between 0.0-1.7 cm under well-watered conditions. Drought-avoidant RILs had a higher root density in the lower layers of the topsoil compared to the others. CONCLUSIONS: Fine classification of soil layers using 3D image analysis revealed that increasing root density in the lower layers of the topsoil, rather than in the subsoil, is advantageous for drought avoidance during the early growth stage of rice.

Cardioembolic Stroke: Past Advancements, Current Challenges, and Future Directions.

Cardioembolic stroke accounts for over 20% of ischemic strokes and is associated with worse outcomes than other types of strokes. Atrial fibrillation (AF) is the most common risk factor for cardioembolic stroke. In this narrative review, we present an update about cardioembolic stroke mainly related to AF and atrial cardiopathy. Direct oral anticoagulants (DOACs) have revolutionized stroke prevention in patients with AF; however, their efficacy in preventing recurrent embolic stroke of unknown source remains uncertain. Various cardiac monitoring methods are used to detect AF, which is crucial for preventing stroke recurrence. DOACs are preferred over warfarin for AF-related stroke prevention; however, the timing of initiation after acute ischemic stroke is debated. Resuming anticoagulation after intracerebral hemorrhage in AF patients requires careful assessment of the risks. While catheter ablation may reduce the incidence of cardiovascular events, its effect on stroke prevention is unclear, especially in heart failure patients. Atrial cardiopathy is the emerging cause of embolic stroke of unknown source, which indicates atrial structural and functional disorders that can precede AF. Future research should focus on refining stroke risk prediction models, optimizing AF detection, understanding the roles of ablation and anticoagulation in stroke prevention, and establishing atrial cardiopathy as a therapeutic target, which could significantly reduce the burden of stroke.

iPOTs: Internet of Things-based pot system controlling optional treatment of soil water condition for plant phenotyping under drought stress.

A cultivation facility that can assist users in controlling the soil water condition is needed for accurately phenotyping plants under drought stress in an artificial environment. Here we report the Internet of Things-based pot system controlling optional treatment of soil water condition (iPOTs), an automatic irrigation system that mimics the drought condition in a growth chamber. The Wi-Fi-enabled iPOTs system allows water supply from the bottom of the pot, based on the soil water level set by the user, and automatically controls the soil water level at a desired depth. The iPOTs also allows users to monitor environmental parameters, such as soil temperature, air temperature, humidity, and light intensity, in each pot. To verify whether the iPOTs mimics the drought condition, we conducted a drought stress test on rice (Oryza sativa L.) varieties and near-isogenic lines, with diverse root system architecture, using the iPOTs system installed in a growth chamber. Similar to the results of a previous drought stress field trial, the growth of shallow-rooted rice accessions was severely affected by drought stress compared with that of deep-rooted accessions. The microclimate data obtained using the iPOTs system increased the accuracy of plant growth evaluation. Transcriptome analysis revealed that pot positions in the growth chamber had little impact on plant growth. Together, these results suggest that the iPOTs system is a reliable platform for phenotyping plants under drought stress.

Predicting of molecules mediating an interaction between bovine embryos and uterine epithelial cells.

Embryo-maternal reproductive tract interactions are pivotal for successful pregnancy. The present study predicted the molecules modulating embryo-uterine communication by comparing two sets of differentially expressed genes (DEGs): DEGs in uterine epithelial cells (UECs) collected from the uterus with and without blastocysts and DEGs between blastocysts developed in vivo and in vitro. Cows were subjected to super ovulation (SOV), followed by insemination or non-insemination at estrus (SOV + AI and SOV cows). Seven days after estrus, the uterus was flushed to collect UECs, and the presence of blastocysts in the uterus was confirmed. UECs were subjected to RNA-Sequencing (RNA-Seq) to identify DEGs. Publicly available RNA-Seq data of in vivo and in vitro developed bovine blastocysts were used to determine DEGs. Then, using ingenuity pathway analysis, activated- and inhibited-upstream regulators (USRs) for UECs in blastocysts were compared with those for blastocysts developed in vivo. RNA-Seq of UECs revealed that the DEGs were associated with immune response and cell adhesion pathways. The activated and inhibited USRs of UECs derived from SOV+ AI cows overlapped with the activated and inhibited USRs of blastocysts developed in vivo. Overlapping activated USRs include leukemia inhibitory factor, interleukin 6, fibroblast growth factor-2, transforming growth factor beta-1, and epidermal growth factor. In conclusion, the present study predicted the molecules that potentially mediate communication between the developing embryo and the uterus in vivo and prepare the uterus for pregnancy.

Genome-wide association study of individual sugar content in fruit of Japanese pear (Pyrus spp.).

BACKGROUND: Understanding mechanisms of sugar accumulation and composition is essential to determining fruit quality and maintaining a desirable balance of sugars in plant storage organs. The major sugars in mature Rosaceae fruits are sucrose, fructose, glucose, and sorbitol. Among these, sucrose and fructose have high sweetness, whereas glucose and sorbitol have low sweetness. Japanese pear has extensive variation in individual sugar contents in mature fruit. Increasing total sugar content and that of individual high-sweetness sugars is a major target of breeding programs. The objective of this study was to identify quantitative trait loci (QTLs) associated with fruit traits including individual sugar accumulation, to infer the candidate genes underlying the QTLs, and to assess the potential of genomic selection for breeding pear fruit traits. RESULTS: We evaluated 10 fruit traits and conducted genome-wide association studies (GWAS) for 106 cultivars and 17 breeding populations (1112 F1 individuals) using 3484 tag single-nucleotide polymorphisms (SNPs). By implementing a mixed linear model and a Bayesian multiple-QTL model in GWAS, 56 SNPs associated with fruit traits were identified. In particular, a SNP located close to acid invertase gene PPAIV3 on chromosome 7 and a newly identified SNP on chromosome 11 had quite large effects on accumulation of sucrose and glucose, respectively. We used 'Golden Delicious' doubled haploid 13 (GDDH13), an apple reference genome, to infer the candidate genes for the identified SNPs. In the region flanking the SNP on chromosome 11, there is a tandem repeat of early responsive to dehydration (ERD6)-like sugar transporter genes that might play a role in the phenotypes observed. CONCLUSIONS: SNPs associated with individual sugar accumulation were newly identified at several loci, and candidate genes underlying QTLs were inferred using advanced apple genome information. The candidate genes for the QTLs are conserved across Pyrinae genomes, which will be useful for further fruit quality studies in Rosaceae. The accuracies of genomic selection for sucrose, fructose, and glucose with genomic best linear unbiased prediction (GBLUP) were relatively high (0.67-0.75), suggesting that it would be possible to select individuals having high-sweetness fruit with high sucrose and fructose contents and low glucose content.

Status of Acute Stroke Practice in Patients with a Cardiac Implantable Electronic Device.

Although diagnostic and therapeutic strategies for acute stroke patients in Japan depend largely on magnetic resonance imaging (MRI), patients with cardiac implantable electronic devices (CIED) must still rely on com-puted tomography (CT). We retrospectively analyzed clinical and neuroimaging data of ischemic stroke patients with CIED treated at our hospital. Forty-five patients were enrolled in the study. Patients were divided into two groups according to whether corresponding lesions were detected (group A, n = 21) or not detected (group B, n = 24) by the first brain CT. We also evaluated in detail the clinical courses of patients who arrived at hospital within therapeutic time windows for recanalization therapy. Negative fresh infarct in the first CT was associated, though not significantly, with early onset-to-arrival time and subcortical white matter infarction. Five patients did not undergo recanalization therapy because their families did not agree to the procedure. The reasons for their lack of consent included inadequate information about the safety and efficacy of recanalization therapy because MRI could not be performed. Our study confirmed delayed detection of the corresponding lesion and undertreatment for acute stroke in patients with CIED.

Structure-dependent receptor subtype selectivity and G protein subtype preference of heterocyclic agonists in heterologously expressed silkworm octopamine receptors.

(R)-Octopamine (OA), a major invertebrate biogenic amine, plays an important role in a wide variety of physiological processes as a neurohormone, neuromodulator, and neurotransmitter in insects. OA receptors (OARs) are class A G protein-coupled receptors that specifically bind OA to activate downstream signaling cascades by coupling to G proteins and presumably other regulatory proteins. These receptors are broadly classified as α- and ß-adrenergic-like OARs (α- and ß-ALOARs). OARs are considered important targets of insecticides and acaricides. In the present study, we examined the actions of an array of 13 heterocyclic OAR agonists with the moieties that correspond to the phenyl group and the basic nitrogen atom of OA on α- and ß-ALOARs from the silkworm (Bombyx mori) and the signaling pathways activated through these actions. The results indicated that these compounds display structure-dependent receptor subtype selectivity and G protein subtype preference, underscoring the need to determine which subtype and signaling pathway mediates toxicologically relevant effects for the efficient discovery of novel pest control chemicals. The results of insecticidal assays using B. mori larvae suggested that the activation of signal transduction pathways via α-ALOARs might be mainly responsible for the toxicological effects of the heterocycles.

A cross-sectional study of relationships between periodontal disease and general health: The Hitachi Oral Healthcare Survey.

BACKGROUND: This cross-sectional study performed to clarify the relationship between periodontal disease and non-communicable diseases (NCDs), such as obesity, diabetes mellitus, impaired glucose tolerance (IGT), chronic obstructive pulmonary disease (COPD), and atherosclerotic cardiovascular disease (ASCVD) by introducing dental examinations into the annual health examinations conducted by Japanese companies, and to highlights the importance of a medical system that connects dental and medical professionals. METHODS: A total of 1.022 Hitachi Ltd. employees were enrolled in this cross-sectional study. We examined correlations and odds ratios (ORs) between the dental and overall health of employees using stratification and multiple logistic regression analyses based on the periodontal health indicators, general health indicators, and occlusal force. RESULTS: The adjusted OR of PPD for obesity (OR, 1.42; 95% confidence interval [CI], 1.09-1.84; p = 0.009), IGT (OR, 1.48; 95% CI, 1.00-2.20; p = 0.049), and COPD (OR, 1.38; 95% CI, 1.02-1.88; p = 0.038) significantly differed. The adjusted OR of body mass index (OR, 1.28; 95% CI 1.15-1.42; p < 0.001), haemoglobin A1C (HbA1c) (OR, 4.34; 95% CI, 1.89-9.98; p < 0.001), fasting blood glucose (FBG) levels (OR, 1.08; 95% CI 1.04-1.11; p < 0.001), postbronchodilator forced expiratory volume in one second/forced vital capacity ratio (%FEV1) (OR, 0.95; 95% CI 0.91-1.00; p = 0.031) and smoking (OR, 2.32; 95% CI 1.62-3.33; p < 0.001) for severe periodontal disease also significantly differed. Occlusal force was significantly reduced in employees aged 50-59 years compared to those aged 40-49 years. Both PPD, HbA1c, FBG levels were significantly associated with occlusal force among employees with moderate/severe periodontitis. PPD was significantly associated with occlusal force among employees with and moderate COPD, and ASCVD. %FEV1 was significantly associated with occlusal force among employees with IGT. CONCLUSIONS: This cross-sectional study revealed mutual relationships among periodontal disease, NCDs, and occlusal force on Japanese corporate workers. We demonstrated that a comprehensive, regional healthcare system centred on annual integrated dental and physical health examinations in the workplace will benefit employees and positively impact corporate health insurance.

Association of changes in commute mode with body mass index and visceral adiposity: a longitudinal study.

BACKGROUND: Prospective data are sparse for active commuting to work and body weight in Asia. We assessed the association of 5-year changes in commuting mode with body mass index (BMI) and the indicators of abdominal obesity in Japanese working adults. METHODS: In this longitudinal study, we studied 29,758 participants (25,808 men and 3950 women) in Japan aged 30 to 64 years at baseline who underwent further health examination 5 years after the baseline examination. Changes in BMI were calculated from objectively measured body height and weight at baseline and follow-up examination. Visceral and subcutaneous fat areas and waist circumference measured by computed tomography scans were used as indicators for abdominal adiposity. Linear regression was applied to estimate the association of changes in commuting mode with the obesity outcomes. RESULTS: Within the 5-year study period, adults who maintained inactive commuting gained weight, and compared with this group, adults who switched to inactive commuting had higher weight gain; conversely, adults who switched to active or public transportation commuting and especially those who maintained active or public transportation commuting experienced less weight gain. Subgroup analysis showed similar tendency across the different transitions of leisure-time exercise or occupational physical activity. For example, among adults who maintained no exercise (n = 16,087), the adjusted mean (95% confidence intervals) of the BMI change over 5 years in kg/m2 were 0.27 (0.24 to 0.30) for maintained inactive commuting group (reference), 0.34 (0.30 to 0.38) for switching to inactive commuting group (P = 0.046), 0.20 (0.18 to 0.22) for switching to active commuting or public transportation group (P = 0.001), and 0.09 (0.06 to 0.13) for maintained active commuting or public transportation group (P < 0.001). Maintained inactive commuting tended to be associated with larger gain in abdominal adiposity indicators. CONCLUSION: Switching from inactive commuting mode to more physically active commuting mode and maintaining active commuting can promote body weight control among working adults across different levels of occupational or leisure-time physical activity.

QTL analysis of resistance to bacterial wilt caused by Ralstonia solanacearum in potato.

Ralstonia solanacearum causes bacterial wilt, a soil-borne disease and one of the most important maladies of potato and other Solanaceae crops. We analyzed the resistance of a potato clone to bacterial wilt by quantitative trait locus (QTL) analysis. A resistant diploid potato clone 10-03-30 was crossed with a susceptible diploid clone F1-1 to generate a diploid, two-way pseudo-testcross F1 population comprised of 94 genotypes. Dense linkage maps, containing 4,139 single nucleotide polymorphism markers with an average distance of 0.6 and 0.3 cM between markers, were constructed for both parents. The resistance level was evaluated by in vitro inoculation test with R. solanacearum (phylotype I/biovar 4/race 1). Five QTLs (qBWR-1 to -5) were identified on potato chromosomes 1, 3, 7, 10, and 11, and they explained 9.3-18.4% of the phenotypic variance. The resistant parent had resistant alleles in qBWR-2, qBWR-3, and qBWR-4 and susceptible alleles in qBWR-1 and qBWR-5. Accumulation of the resistant alleles in all five QTLs increased the level of resistance compared with that of the resistant parent. This is the first study to identify novel QTLs for bacterial wilt resistance in potato by using genome-wide markers.

Resumption of Direct Oral Anticoagulants in Patients with Acute Spontaneous Intracerebral Hemorrhage.

BACKGROUND: Decisions regarding whether and when to resume direct oral anticoagulants (DOAC) after acute intracerebral hemorrhage (ICH) are challenging. We examined the timing of DOAC resumption and factors that influence decision-making in DOAC resumption. METHODS: We retrospectively analyzed 43 patients with ICH who were treated with DOAC for nonvalvular atrial fibrillation before ICH onset. All patients were divided into 2 groups (resumption of DOAC and no resumption of DOAC) during hospitalization. Clinical backgrounds, laboratory data, and stroke severity were compared between the groups. RESULTS: DOAC were resumed in 19 of 39 (49%) acute ICH survivors and were not resumed in 24 patients, including 4 deceased patients. The National Institutes of Health Stroke Scale score at admission tended to be higher in the no resumption group (median, 17) than in the resumption group (median, 6) (P = .119). The modified Rankin Scale score was slightly poorer in the no resumption group (median, 4) than in the resumption group (median, 3) (P = .070). In the resumption group, DOAC were resumed at a median of 11 days (interquartile range, 5-21 days) after ICH onset. The modified Rankin Scale score at discharge was positively correlated with the days of DOAC resumption (R2 = .31, P = .013). CONCLUSIONS: In half of patients, DOAC were resumed relatively early after ICH onset. Early resumption of DOAC for ICH in patients with nonvalvular atrial fibrillation is considered to be safe. The functional outcome was associated with not only resumption of DOAC but also the timing of resumption.

[Severe coagulation abnormality during treatment for ischemic enteritis in an older patient taking a direct oral anticoagulant].

An 85-year-old woman hospitalized for rehabilitation after cerebral infarction developed persistent bloody diarrhea and was transferred to our hospital (day 1). Contrast-enhanced computed tomography of the abdomen showed edematous thickening extending from the left side of the transverse colon to the rectum, with decreased mucosal enhancement. She was diagnosed with ischemic enteritis. She fasted and was treated with fluids and antibiotics. The bloody diarrhea stopped, and she was restarted on the direct oral anticoagulant (DOAC) edoxaban on day 5. Endoscopy on day 11 showed linear ulceration and severe mucosal edema in the rectum. The diarrhea was persistent, so fasting and fluid therapy were continued. A blood test on day 18 showed significant prolongation of the prothrombin time (≥100 s), International Normalized Ratio (14.03), and activated partial thromboplastin time (87.5 s), as well as a significant increase in protein induced by vitamin K absence-II (12,469 mAU/mL). Her condition was diagnosed as a coagulation abnormality due to vitamin-K deficiency. A vitamin-K preparation was administered immediately, and her coagulation abnormality improved rapidly. In general, DOACs do not require routine monitoring with blood tests. However, frequent monitoring of the coagulation function is required in fasting patients on DOACs because acute coagulation abnormalities can be induced rapidly by vitamin-K deficiency. Given that non-valvular atrial fibrillation and ischemic enteritis are among the most prevalent diseases affecting older people, the likelihood of encountering these diseases in daily clinical practice will increase with the aging of the population. We herein report this instructive case suggesting that a severe coagulation abnormality may develop during treatment for ischemic enteritis in older people taking a DOAC.

CK2 phospho-independent assembly of the Tel2-associated stress-signaling complexes in Schizosaccharomyces pombe.

An evolutionarily conserved protein Tel2 regulates a variety of stress signals. In mammals, TEL2 associates with TTI1 and TTI2 to form the Triple T (TTT: TEL2-TTI1-TTI2) complex as well as with all the phosphatidylinositol 3-kinase-like kinases (PIKKs) and the R2TP (Ruvbl1-Ruvbl2-Tah1-Pih1 in budding yeast)/prefoldin-like complex that associates with HSP90. The phosphorylation of TEL2 by casein kinase 2 (CK2) enables direct binding of PIHD1 (mammalian Pih1) to TEL2 and is important for the stability and the functions of PIKKs. However, the regulatory mechanisms of Tel2 in fission yeast Schizosaccharomyces pombe remain largely unknown. Here, we report that S. pombe Tel2 is phosphorylated by CK2 at Ser490 and Thr493. Tel2 forms the TTT complex with Tti1 and Tti2 and also associates with PIKKs, Rvb2, and Hsp90 in vivo; however, the phosphorylation of Tel2 affects neither the stability of the Tel2-associated proteins nor their association with Tel2. Thus, Tel2 stably associates with its binding partners irrespective of its phosphorylation. Furthermore, the Tel2 phosphorylation by CK2 is not required for the various stress responses to which PIKKs are pivotal. Our results suggest that the Tel2-containing protein complexes are conserved among eukaryotes, but the molecular regulation of their formation has been altered during evolution.

Increased Incidence of Visual Field Abnormalities as Determined by Frequency Doubling Technology Perimetry in High Computer Users Among Japanese Workers: A Retrospective Cohort Study.

BACKGROUND: This retrospective cohort study primarily aimed to investigate the possible association of computer use with visual field abnormalities (VFA) among Japanese workers. METHODS: The study included 2,377 workers (mean age 45.7 [standard deviation, 8.3] years; 2,229 men and 148 women) who initially exhibited no VFA during frequency doubling technology perimetry (FDT) testing. Subjects then underwent annual follow-up FDT testing for 7 years, and VFA were determined using a FDT-test protocol (FDT-VFA). Subjects with FDT-VFA were examined by ophthalmologists. Baseline data about the mean duration of computer use during a 5-year period and refractive errors were obtained via self-administered questionnaire and evaluations for refractive errors (use of eyeglasses or contact lenses), respectively. RESULTS: A Cox proportional hazard analysis demonstrated that heavy computer users (>8 hr/day) had a significantly increased risk of FDT-VFA (hazard ratio [HR] 2.85; 95% confidence interval [CI], 1.26-6.48) relative to light users (<4 hr/day), and this association was strengthened among subjects with refractive errors (HR 4.48; 95% CI, 1.87-10.74). The computer usage history also significantly correlated with FDT-VFA among subject with refractive errors (P < 0.05), and 73.1% of subjects with FDT-VFA and refractive errors were diagnosed with glaucoma or ocular hypertension. CONCLUSIONS: The incidence of FDT-VFA appears to be increased among Japanese workers who are heavy computer users, particularly if they have refractive errors. Further investigations of epidemiology and causality are warranted.

Intensity of Leisure-Time Exercise and Risk of Depressive Symptoms Among Japanese Workers: A Cohort Study.

BACKGROUND: Data on the effect of physical activity intensity on depression is scarce. We investigated the prospective association between intensity of leisure-time exercise and risk of depressive symptoms among Japanese workers. METHODS: The participants were 29,052 employees (24,653 men and 4,399 women) aged 20 to 64 years without psychiatric disease including depressive symptoms at health checkup in 2006-2007 and were followed up until 2014-2015. Details of leisure-time exercise were ascertained via a questionnaire. Depressive states were assessed using a 13-item questionnaire. Multivariable-adjusted hazard ratio of depressive symptoms was estimated using Cox regression analysis. RESULTS: During a mean follow-up of 5.8 years with 168,203 person-years, 6,847 workers developed depressive symptoms. Compared with workers who engaged in no exercise during leisure-time (0 MET-hours per week), hazard ratios (95% confidence intervals) associated with >0 to <7.5, 7.5 to <15.0, and ≥15.0 MET-hours of leisure-time exercise were 0.88 (0.82-0.94), 0.85 (0.76-0.94), and 0.78 (0.68-0.88) among workers who engaged in moderate-intensity exercise alone; 0.93 (0.82-1.06), 0.82 (0.68-0.98), and 0.83 (0.71-0.98) among workers who engaged in vigorous-intensity exercise alone; and 0.96 (0.80-1.15), 0.80 (0.67-0.95), and 0.76 (0.66-0.87) among workers who engaged in both moderate- and vigorous-intensity exercise with adjustment for age, sex, lifestyles, work-related and socioeconomic factors, and body mass index. Additional adjustment for baseline depression score attenuated the inverse association, especially among those who engaged in moderate-intensity exercise alone. CONCLUSIONS: The results suggest that vigorous-intensity exercise alone or vigorous-intensity combined with moderate-intensity exercise would prevent depressive symptoms among Japanese workers.

The Dose of Direct Oral Anticoagulants and Stroke Severity in Patients with Acute Ischemic Stroke and Nonvalvular Atrial Fibrillation.

BACKGROUND: The severity and the functional outcome of patients with stroke occurring during off-label underdosing of direct-acting oral anticoagulants (DOACs) remain uncertain. METHODS: We studied 53 consecutive patients with acute ischemic stroke and nonvalvular atrial fibrillation who were treated with DOACs before the onset of stroke. Thirty patients were treated for primary prevention of stroke and 23 patients were treated for secondary prevention. DOAC treatments were categorized into 3 groups based on the following doses: (1) standard-dose group (n = 17), (2) low-dose group (n = 23), and (3) off-label underdose group (n = 13). RESULTS: Age was significantly older in the low-dose group than in the standard-dose group (P = .026). The standard-dose group and the low-dose group showed higher CHA2DS2-VASc scores (median, 4) compared with the off-label underdose group (median, 3). More than half of the patients had a National Institutes of Health Stroke Scale score of less than 8, and many patients had a good outcome (modified Rankin Scale score ≤1). There were no differences in stroke severity and outcome among the 3 groups. The ratio of being discharged home was the highest in the standard-dose group. CONCLUSIONS: This study shows that patients who have off-label underdosing of DOACs do not develop more severe stroke and a poorer outcome than those with the recommended dose. Careful attention to recommended doses is required for the full benefits from DOACs.

[Recombinant tissue plasminogen activator therapy for acute ischemic stroke in older patients].

AIM: As the number of aged stroke patients increases in Japan, the proportion of older patients who receive recombinant tissue plasminogen activator (rt-PA, 0.6 mg/kg) is also rising. However, the Japanese stroke guideline indicates that rt-PA therapy must be administered very carefully in older patients (i.e. ≥81 years of age) because of serious complications after the therapy. We retrospectively assessed the clinical outcomes of rt-PA therapy in older patients. METHODS: This study included 321 patients who received rt-PA therapy for acute cerebral infarction at our hospital between April 2007 and April 2017. The outcomes (modified Rankin Scale [mRS] score at 3 months after treatment) and symptomatic intracerebral hemorrhaging (sICH) were compared and analyzed between patients ≥81 years of age (group A) and those <81 years of age (group B). In addition, propensity score matching was performed for the factors shown to have significant differences by a univariate analysis in order to adjust for confounding factors, and the outcomes were compared. RESULTS: There were 58 patients in group A (18.1%) and 263 patients in group B (81.9%). The rate of favorable outcomes (mRS 0-1) was lower in group A (12.1%) than in group B (44.1%) (P<0.01). The mortality rate was higher in group A (17.2%) than in group B (4.6%) (P=0.002). No marked differences were observed between the 2 groups regarding the rate of sICH (group A, 3.4%; group B, 3.0%; P=1.00). After propensity score matching, the proportion of patients with favorable outcomes was significantly lower in group A (13.2%) than in group B (36.8%) (P=0.032). There were no marked differences in the mortality rates between the groups (group A, 17.2%; group B, 4.6%) (P=0.200), and no patients in either group had sICH. CONCLUSION: No marked differences in the incidence of ICH were observed between the older and younger groups receiving intravenous rt-PA therapy. However, in terms of efficacy, the proportion of patients with favorable outcomes was significantly lower in the older group than in the younger group.

High Serum Phospholipid Dihomo-γ-Linoleic Acid Concentration and Low Δ5-Desaturase Activity Are Associated with Increased Risk of Type 2 Diabetes among Japanese Adults in the Hitachi Health Study.

Background: The association between the circulating fatty acid (FA) composition and type 2 diabetes (T2D) has been reported in Western populations, but evidence is scarce among Asian populations, including Japanese, who consume large amounts of fish.Objective: The objective of the present study was to prospectively examine the association between circulating concentrations of individual FAs and T2D incidence among Japanese adults.Methods: We conducted a nested case-control study in a cohort of 4754 employees, aged 34-69 y, who attended a comprehensive health checkup in 2008-2009 and donated blood samples for the Hitachi Health Study. During 5 y of follow-up, diabetes was identified on the basis of plasma glucose, glycated hemoglobin, and self-report. Two controls matched to each case by sex, age, and date of checkup were randomly chosen by using density sampling, resulting in 336 cases and 678 controls with FA measurements. GC was used to measure the FA composition in serum phospholipids. Cox proportional hazards regression was used to estimate the HRs and 95% CIs after adjusting for potential confounders. We examined the association of T2D risk with 25 different individual and combinations of FAs.Results: T2D risk was positively associated with serum dihomo-γ-linoleic acid concentration (highest compared with the lowest quartile-HR: 1.49; 95% CI: 1.04, 2.11; P-trend = 0.02) and inversely associated with Δ5-desaturase activity (highest compared with the lowest quartile-HR: 0.72; 95% CI: 0.52, 0.99; P-trend = 0.02), independent of body mass index (BMI). There were also inverse associations between T2D risk with serum total n-6 (ω-6) polyunsaturated fatty acids (PUFAs), linoleic acid, and cis-vaccenic acid, but these were attenuated and became nonsignificant after adjustment for BMI. Serum n-3 (ω-3) PUFAs and saturated fatty acids (SFAs) were not associated with T2D risk.Conclusions: T2D risk was associated with circulating concentrations of the n-6 PUFA dihomo-γ-linoleic acid and Δ5-desaturase activity but not with n-3 PUFA or SFA concentrations in Japanese adults.

Bayesian QTL mapping using genome-wide SSR markers and segregating population derived from a cross of two commercial F1 hybrids of tomato.

KEY MESSAGE: Using newly developed euchromatin-derived genomic SSR markers and a flexible Bayesian mapping method, 13 significant agricultural QTLs were identified in a segregating population derived from a four-way cross of tomato. So far, many QTL mapping studies in tomato have been performed for progeny obtained from crosses between two genetically distant parents, e.g., domesticated tomatoes and wild relatives. However, QTL information of quantitative traits related to yield (e.g., flower or fruit number, and total or average weight of fruits) in such intercross populations would be of limited use for breeding commercial tomato cultivars because individuals in the populations have specific genetic backgrounds underlying extremely different phenotypes between the parents such as large fruit in domesticated tomatoes and small fruit in wild relatives, which may not be reflective of the genetic variation in tomato breeding populations. In this study, we constructed F2 population derived from a cross between two commercial F1 cultivars in tomato to extract QTL information practical for tomato breeding. This cross corresponded to a four-way cross, because the four parental lines of the two F1 cultivars were considered to be the founders. We developed 2510 new expressed sequence tag (EST)-based (euchromatin-derived) genomic SSR markers and selected 262 markers from these new SSR markers and publicly available SSR markers to construct a linkage map. QTL analysis for ten agricultural traits of tomato was performed based on the phenotypes and marker genotypes of F2 plants using a flexible Bayesian method. As results, 13 QTL regions were detected for six traits by the Bayesian method developed in this study.

De Novo Migraine With Aura After Surgical Repair of Aortic Coarctation.

Coarctation of the aorta (CoA) is reported to be associated with an increased risk for migraine. We describe here the case of a 13-year-old female patient who presented migraine with aura after surgical repair of CoA with a stent. As possible reasons for her condition, we postulate host responses to stent placement and/or disturbed cerebral autoregulation related to intracranial hypertension before the surgical repair and hypotension afterward, leading to hypoperfusion. This case demonstrates that de novo migraine with aura can occur after surgical repair of CoA and should be recognized as a potential complication.